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  1. Low SK, Giannis D, Bahaie NS, Trong BLH, Moris D, Huy NT
    Am. J. Clin. Oncol., 2019 08;42(8):668-674.
    PMID: 31343423 DOI: 10.1097/COC.0000000000000575
    OBJECTIVES: Patients with neuroendocrine tumors (NETs) are at increased risk of mortality from competing causes in light of the improvement in overall survival over recent decades. The purpose of this study was to explore the competing causes of deaths and the risk factors associated with competing mortality.

    MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database was used to identify patients diagnosed with NETs between 1973 and 2015. Risk of competing mortality was estimated by the standardized mortality ratios (SMRs) and by using the Fine and Gray multivariate regression model.

    RESULTS: Of the 29,981 NET patients, 42.5% of the deaths that occurred during follow-up were attributed to competing causes (83.9% from noncancer causes and 16.1% from second primary neoplasms). Overall SMR of competing mortality was 2.50 (95% confidence interval [CI]: 2.43-2.56). The SMR of noncancer causes was 2.65 (95% CI: 2.58-2.73), with the highest risk present within the first year of diagnosis. The SMR of second primary neoplasms was 1.91 (95% CI: 1.79-2.04), with the highest risk observed after 10-year postdiagnosis. A drastic rise in competing mortality was observed in the last decade between 2005 and 2015. Advanced age, black race, small intestinal and gastric NETs, and surgery were significantly associated with competing mortality. Female, pancreatic and recto-anal NETs, distant and regional spread, chemotherapy and radiotherapy were significantly associated with lower competing mortality.

    CONCLUSIONS: Competing mortality plays an increasingly significant role over the years and may hamper efforts made to improve survival outcomes in NET patients.

  2. Low SK, Zayan AH, Istanbuly O, Nguyen Tran MD, Ebied A, Mohamed Tawfik G, et al.
    Leuk Lymphoma, 2019 12;60(14):3406-3416.
    PMID: 31322026 DOI: 10.1080/10428194.2019.1633636
    Primary pulmonary lymphomas (PPLs) are rare lymphoproliferative malignancies arising from the lungs. The prognostic factors and optimal management of PPL have not been clearly defined due to its rarity. This study sought to characterize the significant prognostic factors and develop a validated nomogram for individualized prediction of survival outcomes in patients with PPL. A total of 2325 patients diagnosed with PPL between 1983 and 2010 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Older age at diagnosis, males, Hispanic race, non-marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue histology, Ann Arbor stage IV were significantly associated with worse OS on multivariable analysis. All treatment modalities, including chemotherapy, surgery, and radiotherapy were independent predictors of survival on univariable analysis. The nomogram built demonstrated good discriminative ability and calibration, with the C-index of 0.690 and 0.730 in the training and validation cohorts, respectively.
  3. Pham TS, Reda A, Ngan Nguyen TT, Ng SJ, Huan VT, Viet DC, et al.
    Transfus Apher Sci, 2020 Dec;59(6):102907.
    PMID: 32883595 DOI: 10.1016/j.transci.2020.102907
    We report a case of blood exchange transfusion to treat acute liver failure following hepatitis B infection at the Infectious Disease Department of Children's Hospital No.2 in Ho Chi Minh City, Vietnam. A 3.5-month old baby boy was admitted to the hospital with a presentation of progressively worsening jaundice for the past one month. The patient was diagnosed with hepatitis B infection with a positive HBV DNA quantitative assay. Plasma exchange was indicated in view of progressive liver failure and gradually increasing hepatic coma. However, it was impossible to perform plasmapheresis in this case because the patient was small (in terms of age and weight) and there was no suitable plasma exchange filter. Accordingly, the patient was treated with 3 times of blood exchange transfusion in combination with an antiviral drug, lamivudine. After each blood exchange transfusion, the biochemical values (bilirubin, liver enzymes, and coagulation profile) gradually improved and he was discharged after 1 month of treatment. Blood exchange transfusion is an effective procedure for managing acute liver failure, where plasma exchange is not possible while waiting for the recovery of liver functions or liver transplantation.
  4. Tran L, Radwan I, Minh LHN, Low SK, Hashan MR, Gomaa MD, et al.
    Acta Trop, 2021 Jan 06.
    PMID: 33421421 DOI: 10.1016/j.actatropica.2021.105823
    BACKGROUND AND OBJECTIVES: Modulation of the immune reaction is essential in the development of various diseases, including dengue's "Cytokine Tsunami", an increase in vascular permeability with concomitant severe vascular leakage. We aim to identify the role of T-helper (Th) cells, Th2 and Th7, with their related cytokines in dengue pathogenesis.

    MATERIAL AND METHODS: Nine electronic databases and manual search were applied to detect available publications. A meta-analysis using a fixed- or random-effect model was performed to measure standardized mean difference (SMD) with 95% confidence interval (CI). The National Institute of Health (NIH) tools for observational cohort, cross-sectional, and case-control studies were used to examine the risk of bias. The protocol was recorded in PROSPERO with CRD42017060230.

    RESULTS: A total of 38 articles were found including 19 case-control, 11 cross-sectional and 8 prospective cohort studies. We indicated that Th2 cytokines (IL-4, IL-6, IL-8) and Th17 cytokine (IL-17) in dengue patients were notably higher than in a healthy control group in acute phase (SMD = 1.59, 95% CI [0.68, 2.51], p = 0.001; SMD = 1.24, 95% CI [0.41, 2.06], p = 0.003; SMD = 1.13, 95% CI [0.61, 1.66], p<0.0001; SMD = 1.74, 95% CI [0.87, 2.61], p<0.0001), respectively.

    CONCLUSIONS: This study provides evidence of the significant roles of IL-4, IL-6, IL-8, IL-10 and IL-17 in the pathogenesis of developing a severe reaction in dengue fever. However, to fully determine the association of Th cytokines with dengue, it is necessary to perform further studies to assess kinetic levels during the duration of the illness.

  5. Elhusseiny KM, Abd-Elhay FA, Kamel MG, Abd El Hamid Hassan HH, Muhammad El Tanany HH, Hong HT, et al.
    Ann Oncol, 2018 Nov;29 Suppl 9:ix104.
    PMID: 32177708 DOI: 10.1093/annonc/mdy438.035
  6. Abd-Elhay FA, Elhusseiny KM, Kamel MG, Low SK, Sang TK, Mehyar GM, et al.
    Clin Breast Cancer, 2018 12;18(6):e1293-e1310.
    PMID: 30093263 DOI: 10.1016/j.clbc.2018.07.003
    BACKGROUND: Male breast cancer (MBC) is usually diagnosed at late stages and therefore has a worse prognosis than female breast cancer (FBC). MBC is also more likely to have lymph node (LN) involvement than FBC.

    MATERIALS AND METHODS: We sought to determine the prognostic role of the examined lymph node (LN), negative LN (NLN), and positive LN counts and the LN ratio (LNR), defined as (positive LNs/ENLs), on the survival rate among MBC patients. We performed a large population-based study using the data from the Surveillance, Epidemiology, and End Results program.

    RESULTS: Older age, black race, stage IV disease, ≤ 1 NLN, and a > 31.3% LNR were significantly associated with worse survival across all prediction models. Moreover, we demonstrated a decreased risk of mortality in MBC patients across the MBC-specific survival model (hazard ratio, 0.98; 95% confidence interval, 0.96-0.998; P = .03) and 10-year MBC-specific survival model (hazard ratio, 0.98; 95% confidence interval, 0.96-0.999; P = .04).

    CONCLUSION: MBC has had an augmented incidence over the years. We found several independent predictors of MBC survival, including age, race, stage, NLNs, and the LNR. We strongly suggest adding the NLN count and/or LNR into the current staging system. Further studies are needed to provide information on the mechanisms underlying the association between the NLN count and MBC survival and the LNR and MBC survival.

  7. Hashan MR, Elhusseiny KM, Huu-Hoai L, Tieu TM, Low SK, Minh LHN, et al.
    Acta Trop, 2020 Oct;210:105603.
    PMID: 32598920 DOI: 10.1016/j.actatropica.2020.105603
    We aimed to systematically review evidence pertaining to the safety and efficacy of nitazoxanide in treating infectious diarrhea. On September 21, 2017, we identified relevant studies using 12 databases. The estimates of the included studies were pooled as a risk ratio (RR). We conducted a network and pairwise random-effects meta-analysis for both direct and indirect comparisons of different organisms that are known to cause diarrhea. The primary and secondary analysis outcomes were clinical response until cessation of illness, parasitological response and adverse events. We included 18 studies in our analysis. In cryptosporidiosis, the overall estimate favored nitazoxanide in its clinical response in comparison with placebo RR 1.46 [95% CI 1.22-1.74; P-value <0.0001]. Network meta-analysis among patients with Giardia intestinalis showed an increase in the probability of diarrheal cessation and parasitological responses in comparison with placebo, RR 1.69 [95% CI 1.08-2.64, P-score 0.27] and RR 2.91 [95% CI 1.72-4.91, P-score 0.55] respectively. In Clostridium difficile infection, the network meta-analysis revealed a non-significantly superior clinical response effect of nitazoxanide to metronidazole 31 days after treatment RR 1.21 [95% CI 0.87-1.69, P-score 0.26]. In Entamoeba histolytica, the overall estimate significantly favored nitazoxanide in parasitological response with placebo RR 1.80 [95% CI 1.35-2.40, P-value < 0.001]. We highlighted the effectiveness of nitazoxanide in the cessation of diarrhea caused by Cryptosporidium, Giardia intestinalis and Entamoeba histolytica infection. We also found significant superiority of NTZ to metronidazole in improving the clinical response to G. intestinalis, thus it may be a suitable candidate for treating infection-induced diarrhea. To prove the superiority of NTZ during a C. difficile infection may warrant a larger-scale clinical trial since its superiority was deemed insignificant. We recommend nitazoxanide as an appropriate option for treating infectious diarrhea.
  8. Mathenge PG, Low SK, Vuong NL, Mohamed MYF, Faraj HA, Alieldin GI, et al.
    Parasitol Int, 2020 Feb;74:101919.
    PMID: 31015034 DOI: 10.1016/j.parint.2019.04.016
    BACKGROUND: Malaria parasites have developed resistance to most of the known antimalarial drugs in clinical practice, with reports of artemisinin resistance emerging in South East Asia (SEA). We sort to find the status of artemisinin resistance and efficacy of different modalities of the current artemisinin-based combination therapies (ACTs).

    METHODS: We carried out a systematic search in 11 electronic databases to identify in vivo studies published between 2001 and 2017 that reported artemisinin resistance. This was then followed by A network meta-analysis to compare the efficacy of different ACTs. Quality assessment was performed using the Cochrane Risk of Bias (ROB) tool for randomized controlled trials and National Institute of Health (NIH) tool for cross-sectional studies. The study protocol was registered in PROSPERO under number CRD42018087574.

    RESULTS: With 8400 studies initially identified, 82 were eligible for qualitative and quantitative analysis. Artemisinin resistance was only reported in South East Asia. K13 mutation C580Y was the most abundant mutation associated with resistance having an abundance of 63.1% among all K13 mutations reported. Although the overall network meta-analysis had shown good performance of dihydroartemisinin piperaquine in the early years, a subgroup analysis of the recent years revealed a poor performance of the drug in relation to recrudescence, clinical failure and parasitological failure especially in the artemisinin resistant regions.

    CONCLUSION: With report of high resistance and treatment failure against the leading artemisinin combination therapy in South East Asia, it is imperative that a new drug or a formulation is developed before further spread of resistance.

  9. El-Qushayri AE, Kamel AMA, Faraj HA, Vuong NL, Diab OM, Istanbuly S, et al.
    J Cardiovasc Med (Hagerstown), 2020 May;21(5):359-367.
    PMID: 31815850 DOI: 10.2459/JCM.0000000000000920
    : The aim of the study was to determine the association between pet ownership and cardiovascular risk factors and mortality. Electronic search was conducted through nine databases including PubMed for relevant publications reporting cardiovascular events and mortality among pet owners. Meta-analysis was used to pool the results. Of a total of 2818 reports screened, 26 studies were included in our systematic review and meta-analysis. Higher survival rate was observed in the pet owners group after pooling nonadjusted and adjusted hazard ratios for cardiovascular mortality at 0.73 [95% confidence interval (CI) 0.62-0.86] and 0.81 (0.68-0.97), respectively. A similar trend was observed for the pooled nonadjusted hazard ratio for overall mortality 0.73 (0.62-0.87) but not the adjusted hazard ratio 0.40 (0.04-3.78). Cat owners have a reduction in cardiovascular mortality but not overall mortality after pooling the adjusted hazard ratio 0.79 (0.63-0.99) and 1.04 (0.90-1.21), respectively. However, no significant association between dog owners and survival rate was observed for overall and cardiovascular-specific mortality. Pet owners had significantly lower heart rate (mean difference 95% CI: -2.32 (-3.07 to -1.57), mean arterial pressure -2.60 (-4.25 to -0.95) and SBP -1.69 (-3.06 to -0.31) but not DBP -0.23 (-1.05 to 0.60). No significant difference was observed between pet owners and nonpet owners in prevalence of hypertension. Our study draws attention to the beneficial effects of the human--pet bond; therefore, we recommend pet acquisition for better cardiovascular outcomes after controlling for zoonotics and pet-induced allergies.
  10. Elhusseiny KM, Abd-Elhay FA, Kamel MG, Abd El Hamid Hassan HH, El Tanany HHM, Hieu TH, et al.
    Head Neck, 2019 08;41(8):2625-2635.
    PMID: 30905082 DOI: 10.1002/hed.25742
    BACKGROUND: We aimed to investigate the prognostic role of examined (dissected) lymph nodes (ELNs), negative LNs (NLNs), and positive (metastatic) LNs (PLNs) counts and LN ratio (LNR = PLNs/ELNs×100) in patients with major salivary gland cancer (SGC).

    METHODS: Data were retrieved for major SGC patients diagnosed between 1988 and 2011 from Surveillance, Epidemiology, and End Results program.

    RESULTS: We have included 5446 patients with major SGC. Most patients had parotid gland cancer (84.61%). Patients having >18 ELNs, >4 PLNs, and >33.33% LNR were associated with a worse survival. Moreover, older age, male patients, grade IV, distant stage, unmarried patients, submandibular gland cancer, and received chemotherapy but not received surgery were significantly associated with a worse survival.

    CONCLUSIONS: We demonstrated that patients with >18 ELNs and >4 PLNs counts, and >33.33% LNR were high-risk group patients. We strongly suggest adding the ELNs and PLNs counts and/or LNR into the current staging system.

  11. Sharma A, U V, Dong V, Raut A, Tawfik GM, Ng SJ, et al.
    Clin Med (Lond), 2021 Mar;21(Suppl 2):25-26.
    PMID: 34078684 DOI: 10.7861/clinmed.21-2-s25
  12. Le TTB, Vasanthakumaran T, Thi Hien HN, Hung IC, Luu MN, Khan ZA, et al.
    Rev Med Virol, 2023 Jan;33(1):e2398.
    PMID: 36150052 DOI: 10.1002/rmv.2398
    The emergence of the SARS-CoV-2 Omicron variant (B.1.1.529) has created great global distress. This variant of concern shows multiple sublineages, importantly B.1.1.529.1 (BA.1), BA.1 + R346K (BA.1.1), and B.1.1.529.2 (BA.2), each with unique properties. However, little is known about this new variant, specifically its sub-variants. A narrative review was conducted to summarise the latest findings on transmissibility, clinical manifestations, diagnosis, and efficacy of current vaccines and treatments. Omicron has shown two times higher transmission rates than Delta and above ten times more infectious than other variants over a similar period. With more than 30 mutations in the spike protein's receptor-binding domain, there is reduced detection by conventional RT-PCR and rapid antigen tests. Moreover, the two-dose vaccine effectiveness against Delta and Omicron variants was found to be approximately 21%, suggesting an urgent need for a booster dose to prevent the possibility of breakthrough infections. However, the current vaccines remain highly efficacious against severe disease, hospitalisation, and mortality. Japanese preliminary lab data elucidated that the Omicron sublineage BA.2 shows a higher illness severity than BA.1. To date, the clinical management of Omicron remains unchanged, except for monoclonal antibodies. Thus far, only Bebtelovimab could sufficiently treat all three sub-variants of Omicron. Further studies are warranted to understand the complexity of Omicron and its sub-variants. Such research is necessary to improve the management and prevention of Omicron infection.
  13. Qarawi ATA, Ng SJ, Gad A, Luu MN, Al-Ahdal TMA, Sharma A, et al.
    Front Public Health, 2021;9:580427.
    PMID: 34277529 DOI: 10.3389/fpubh.2021.580427
    Background: The outbreak of Coronavirus disease (COVID-19) caused by a novel coronavirus (named SARS-CoV-2) has gained attention globally and has been recognized as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) due to the rapidly increasing number of deaths and confirmed cases. Health care workers (HCWs) are vulnerable to this crisis as they are the first frontline to receive and manage COVID-19 patients. In this multicenter multinational survey, we aim to assess the level of awareness and preparedness of hospital staff regarding COVID-19 all over the world. Methods: From February to March 2020, the web-based or paper-based survey to gather information about the hospital staff's awareness and preparedness in the participants' countries will be carried out using a structured questionnaire based on the United States Centers for Disease Control and Prevention (CDC) checklist and delivered to participants by the local collaborators for each hospital. As of March 2020, we recruited 374 hospitals from 58 countries that could adhere to this protocol as approved by their Institutional Review Boards (IRB) or Ethics Committees (EC). Discussion: The awareness and preparedness of HCWs against COVID-19 are of utmost importance not only to protect themselves from infection, but also to control the virus transmission in healthcare facilities and to manage the disease, especially in the context of manpower lacking and hospital overload during the pandemic. The results of this survey can be used to inform hospitals about the awareness and preparedness of their health staff regarding COVID-19, so appropriate policies and practice guidelines can be implemented to improve their capabilities of facing this crisis and other future pandemic-prone diseases.
  14. Huy NT, Chico RM, Huan VT, Shaikhkhalil HW, Uyen VNT, Qarawi ATA, et al.
    PLoS One, 2021;16(12):e0258348.
    PMID: 34936646 DOI: 10.1371/journal.pone.0258348
    BACKGROUND: Since the COVID-19 pandemic began, there have been concerns related to the preparedness of healthcare workers (HCWs). This study aimed to describe the level of awareness and preparedness of hospital HCWs at the time of the first wave.

    METHODS: This multinational, multicenter, cross-sectional survey was conducted among hospital HCWs from February to May 2020. We used a hierarchical logistic regression multivariate analysis to adjust the influence of variables based on awareness and preparedness. We then used association rule mining to identify relationships between HCW confidence in handling suspected COVID-19 patients and prior COVID-19 case-management training.

    RESULTS: We surveyed 24,653 HCWs from 371 hospitals across 57 countries and received 17,302 responses from 70.2% HCWs overall. The median COVID-19 preparedness score was 11.0 (interquartile range [IQR] = 6.0-14.0) and the median awareness score was 29.6 (IQR = 26.6-32.6). HCWs at COVID-19 designated facilities with previous outbreak experience, or HCWs who were trained for dealing with the SARS-CoV-2 outbreak, had significantly higher levels of preparedness and awareness (p<0.001). Association rule mining suggests that nurses and doctors who had a 'great-extent-of-confidence' in handling suspected COVID-19 patients had participated in COVID-19 training courses. Male participants (mean difference = 0.34; 95% CI = 0.22, 0.46; p<0.001) and nurses (mean difference = 0.67; 95% CI = 0.53, 0.81; p<0.001) had higher preparedness scores compared to women participants and doctors.

    INTERPRETATION: There was an unsurprising high level of awareness and preparedness among HCWs who participated in COVID-19 training courses. However, disparity existed along the lines of gender and type of HCW. It is unknown whether the difference in COVID-19 preparedness that we detected early in the pandemic may have translated into disproportionate SARS-CoV-2 burden of disease by gender or HCW type.

  15. Luu MN, Imoto A, Matsuo Y, Huy NT, Qarawi A, Alhady STM, et al.
    PLoS One, 2024;19(3):e0280144.
    PMID: 38489310 DOI: 10.1371/journal.pone.0280144
    INTRODUCTION: In the context of collective efforts taken in Japan to control the spread of COVID-19, the state of emergency and social distancing have caused a negative impact on the mental health of all residents, including foreign communities in Japan. This study aimed to evaluate the level of anxiety and its associated factors among non-Japanese residents residing in Japan during the COVID-19 pandemic.

    METHODS: A web-based survey in 13 languages was conducted among non-Japanese residents living in Japan during the COVID-19 situation. The State-Trait Anxiety Inventory assessed the level of anxiety-State (STAI-S) scores prorated from its six-item version. The multivariable logistic regression using the Akaike Information Criterion (AIC) method was performed to identify the associated factors of anxiety among participants.

    RESULTS: From January to March 2021, we collected 392 responses. A total of 357 valid responses were analyzed. 54.6% of participants suffered from clinically significant anxiety (CSA). In multivariable logistic model analysis, the CSA status or the high level of anxiety was associated with three factors, including having troubles/difficulties in learning or working, decreased sleep duration, and decreased overall physical health (p<0.05).

    CONCLUSION: Our study suggests several possible risk factors of anxiety among non-Japanese residents living in Japan undergoing the COVID-19 pandemic, including the troubles or difficulties in learning or working, the decrease in sleep duration, and the decrease in overall physical health.

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