Medical Journal of Indonesia

The challenges of a small medical journal to have international recognition in Indonesia: editors' perspectives

Hans Joachim Freisleben — 2021-03-25

[No abstract available]

Elevated extracellular CO₂ level affects the adaptive transcriptional response and survival of human peripheral blood mononuclear cells toward hypoxia and oxidative stress

Septelia Inawati Wanandi — 2021-03-25

BACKGROUND High carbon dioxide (CO₂) level from indoor environments, such as classrooms and offices, might cause sick building syndrome. Excessive indoor CO₂ level increases CO₂ level in the blood, and over-accumulation of CO₂ induces an adaptive response that requires modulation of gene expression. This study aimed to investigate the adaptive transcriptional response toward hypoxia and oxidative stress in human peripheral blood mononuclear cells (PBMCs) exposed to elevated CO₂ level in vitro and its association with cell viability.

METHODS PBMCs were treated in 5% CO₂ and 15% CO₂, representatives a high CO₂ level condition for 24 and 48 hours. Extracellular pH (pHe) was measured with a pH meter. The levels of reactive oxygen species were determined by measuring superoxide and hydrogen peroxide with dihydroethidium and dichlorofluorescin-diacetate assay. The mRNA expression levels of hypoxia-inducible factor (HIF)-1α, HIF-2α, nuclear factor (NF)-κB, and manganese superoxide dismutase (MnSOD) were analyzed using a real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell survival was determined by measuring cell viability.

RESULTS pHe increased in 24 hours after 15% CO₂ treatment, and then decreased in 48 hours. Superoxide and hydrogen peroxide levels increased after the 24- and 48-hour of high CO₂ level condition. The expression levels of NF-κB, MnSOD, HIF-1α, and HIF-2α decreased in 24 hours and increased in 48 hours. The increased antioxidant mRNA expression in 48 hours showed that the PBMCs were responsive under high CO₂ conditions. Elevated CO₂ suppressed cell viability significantly in 48 hours.

CONCLUSIONS After 48 hours of high CO₂ level condition, PBMCs showed an upregulation in genes related to hypoxia and oxidative stress to overcome the effects of CO₂ elevation.

Efficacy of adjuvant intrastromal and combination of intrastromal and intracameral voriconazole in Aspergillus fumigatus-induced moderate fungal keratitis in rabbits

Dyah Tjintya Sarika — 2021-03-25

BACKGROUND There is no in vivo evidence for the effectiveness of adjuvant intrastromal and combination of intrastromal and intracameral voriconazole (VCZ) for treating Aspergillus fumigatus keratitis. This study aimed to compare the efficacy of both agents against it.

METHODS A randomized, masked, controlled experimental study was conducted on 11 albino New Zealand white rabbits in which moderate fungal keratitis was induced by inoculating spores of A. fumigatus to the cornea. The rabbits were allocated into 3 groups: 50 μg/0.1 ml intrastromal VCZ injection, 50 μg/0.1 ml intrastromal VCZ and intracameral VCZ injections, and topical VCZ (control). The treatment was given 5 days after inoculation. Epithelial defect, infiltrate size, corneal ulcer depth, and hypopyon were evaluated clinically. Histopathological and mycological examinations were also done 14 days after treatment.

RESULTS All rabbits in the adjuvant treatment groups demonstrated a tendency of a better clinical response with decreasing size of epithelial defect (p = 0.679) and infiltrate (p = 0.755) than in the control group. Direct microscopy, corneal culture, and chop corneal tissue culture were still positive in most of the rabbits from all groups. Histopathological examination showed an increase of inflammatory cells after treatment in all groups, especially in rabbits which were inoculated with A. fumigatus spores in both eyes.

CONCLUSIONS An adjuvant combination of intrastromal and intracameral VCZ showed a tendency of better clinical response for A. fumigatus-induced moderate fungal keratitis in rabbits.

Hydroxychloroquine in the treatment of COVID-19 disease: a systematic review and meta-analysis

Amahirany Manzo-Toledo — 2021-01-26

BACKGROUND Given the urgency of finding a specific treatment for coronavirus disease 2019 (COVID-19), several approaches have been carried out, including the use of chloroquine (CQ) and hydroxychloroquine (HCQ). This study was aimed to systematically evaluate the available evidence on the effectiveness of HCQ in the treatment of COVID-19 disease.

METHODS We searched 3 databases (PubMed, Google Scholar, and ClinicalTrials) until May 31, 2020 for clinical studies in patients diagnosed with COVID-19 comparing conventional treatment with and without HCQ combined with or without azithromycin. The risk of bias assessment and quality evaluation was carried out according to the Cochrane recommendations.

RESULTS 5 articles (1 randomized clinical trial [RCT], 1 non-RCT, and 3 cohort studies) were included. The main outcome measure in 2 articles was the virological conversion determined by reverse transcription-polymerase chain reaction; however, the findings of both studies were contrary. The main objective of the other studies was to determine the effects of HCQ on COVID-19 mortality, and the studies showed similar results. In general, the studies showed methodological limitations, risk of bias, and variable quality. A meta-analysis from 2,041 patients showed the odds ratio of mortality for patients having HCQ and standard care was 1.38 (95% CI 0.93–2.04).

CONCLUSIONS Considering the limited data available and the very low-to-moderate quality of the studies included in this systematic review, the evidence suggests that the HCQ administration does not decrease the risk of death from COVID-19.

A randomized controlled trial of infraorbital block using ketamine 1% for intra- and postoperative analgesia in children for ambulatory cleft lip correction

Andi Ade Wijaya Ramlan — 2021-03-25

BACKGROUND In Indonesia, cleft lip correction surgery is often done as a social program in remote areas with limited resources. This study aimed to assess the effectiveness of ketamine, a cheaper and more accessible alternative, as a local analgesia in infraorbital block and to determine the possibility of ketamine as an alternative local analgesic drug for intraoperative and postoperative periods.

METHODS This was a randomized controlled trial in children aged 2 months to 5 years who underwent cleft lip correction surgery at Cipto Mangunkusumo Hospital in 2016. Subjects were randomly divided into two groups: ketamine and bupivacaine. Standard general anesthesia with endotracheal intubation was performed in each group. Bilateral intraoral infraorbital block was performed using ketamine 1% 0.5 ml or bupivacaine 0.25% 0.5 ml. Postoperative evaluation includes pain scores based on the face, leg, activity, cry, and consolability (FLACC) scale and analgesic duration.

RESULTS A total of 36 subjects were enrolled in this study, with 18 in each group. Both groups received the same total amount of fentanyl addition intraoperatively (p = 1). The postoperative FLACC pain scale scores between the two groups were not different, with p>0.05 in every measurement. The mean duration of postoperative analgesia in the ketamine group was longer than the bupivacaine group (15–13.49 hours, p = 0.031).

CONCLUSIONS Infraorbital block with 1% ketamine 0.5 mg/kg was similarly effective for intraoperative and postoperative analgesia but had a longer duration than that with 0.25% bupivacaine 0.5 ml in ambulatory cleft lip correction.

A randomized controlled trial of combination of peppermint, lavender, and turmeric oil for antipruritic agent in pregnant women

Fransisca Retno Asih — 2021-03-25

BACKGROUND Pruritus is the most common dermatological complaint that occurs during pregnancy, which is around 14–20%. No research related to herbal products to reduce some of the characteristics of pruritus at once has been conducted. This study aimed to assess the effect of blending oil to reduce pruritus based on visual analog scale (VAS).

METHODS This was a single-blind, randomized clinical trial that included 57 pregnant women who were at 25–38 weeks of gestation, had a pruritus during pregnancy, a single pregnancy, a level I and II pruritus and a moderate to severe pruritus based on VAS. Pruritus scores were measured using VAS in both the treatment and control groups. The treatment and control groups applied blending oil and placebo, respectively, twice a day after bathing for 2 weeks. Mann–Whitney U, paired t, and chi-square tests were used for the analysis.

RESULTS Pruritus reduction in pregnant women who received blending oil was higher than those using placebo (61.08% versus 12.41%, p<0.05). 83% of subjects using blending oils had a reduction of pruritus by >25 mm. Pregnant women who used placebo had a six times greater risk of experiencing pruritus than those who used blending oil (RR = 5.8, 95% CI = 2.613–12.874).

CONCLUSIONS Blending oil can be used topically to treat a pruritus in pregnant women.

A prognostic model of excessive lung function decline among Québec apprentices: a cohort exposed to occupational sensitizing agents

Alfi Afadiyanti Parfi — 2021-03-25

BACKGROUND Forced expiratory volume in 1 second (FEV₁) decline as a predictor of lung-related health problems is widely observed, but not fully investigated. This study aimed to develop models to predict FEV₁ decline among apprentices exposed to sensitizing agents.

METHODS Of 692 apprentices recruited and followed in 3.6–17.3 years, 292 were exposed to low-molecular weight agents. The analysis was restricted to 357 apprentices with complete lung function assessment at the end of their training with a minimum of 5-year follow-up. According to the American Thoracic Society guideline, a mean FEV₁ decline >60 ml/year was defined as “accelerated.” Descriptive statistics and Cox regression analysis were utilized to determine its predictors. To develop the prognostic models, we used a logistic regression analysis adjusted for the follow-up duration. The accuracy of the models was quantified using calibration and discrimination measures.

RESULTS Of 357 subjects, 62 (17.4%) had an excessive FEV₁ decline post-apprenticeship. The questionnaire model (model 1), which included male sex, wheezing, and exposure to isocyanate or animal allergens during the apprenticeship, showed a reasonable discriminative ability (area under the receiver operating characteristics curve [AUC] of 0.67, 95% CI = 0.59–0.75). Adding the percent-predicted FEV₁ value at the end of apprenticeship significantly increased the discriminative ability of the model (model 4) (AUC = 0.762, 95% CI = 0.694–0.829) with a good calibration and reasonable internal validity.

CONCLUSIONS We developed a model for accelerated lung function decline with a good accuracy and internal validity. However, external validation of the model is necessary.

Validation of EuroSCORE II to predict mortality in post-cardiac surgery patients in East Java tertiary hospital

Yan Efrata Sembiring — 2021-03-31

BACKGROUND The European system for cardiac operative risk evaluation (EuroSCORE) II is one of the established risk models used to predict mortality after cardiac surgery. However, its application as a mortality predictor for Indonesian adult cardiac surgery is still unknown. This study aimed to examine the validation of EuroSCORE II in predicting the mortality following adult cardiac surgery in Indonesian adults.

METHODS This retrospective cohort study collected data from the medical records and the database of the Department of Thoracic Cardiac and Vascular Surgery at Soetomo General Hospital, Surabaya. Data on the EuroSCORE II variables were collected for patients aged >18 years who underwent coronary artery bypass, heart valve, heart tumors, aortic surgeries, or a combination of these surgeries between January 2016 and December 2018. In-hospital mortality prediction was calculated using the online calculator at www.euroscore.org. The calibration of the EuroSCORE II model was conducted using the Hosmer–Lemeshow test, and discrimination analysis was done using receiver operating characteristic (ROC) curves with area under the ROC curve (AUC) calculation.

RESULTS A total of 213 patients met the inclusion criteria and were analyzed for this study. Mortality was 8.9%. The predicted and actual mortalities were 1.74% and 8.9%, respectively. The significance (p-value) of the Hosmer–Lemeshow test was 0.55, indicating good calibration. The AUC of ROC curve was 0.85 (95% CI = 0.77–0.92, p<0.001), suggesting good discrimination.

CONCLUSIONS EuroSCORE II has a good calibration and discrimination for cardiac surgery in Indonesian adults.

Factors associated with delay in diagnosis among tuberculosis patients in the north of Iran

Mahmood Moosazadeh — 2021-03-25

BACKGROUND Recognizing factors that affect delay in diagnosis in patients with pulmonary tuberculosis (TB) is critical. This study aimed to identify such factors among TB patients in the north of Iran.

METHODS In this retrospective cohort study, we reviewed patient’s medical records from the TB registration system of the Health Deputy of Mazandaran University of Medical Sciences, Sari, Iran that was responsible for the TB registry in the province from 2007 to 2017. All hospitals affiliated with the university, including private hospitals, reported TB cases directly to the health deputy. Patient’s gender, age, TB smear result, TB type, imprisonment, diabetes, nationality, residence area, and drug use were considered factors of delay in diagnosis, which was defined as a delay of >30 days between symptom onset and diagnosis. Data from 3,453 patients were analyzed using the chi-square test and logistic regression models.

RESULTS The frequency of patients with delay in diagnosis was 67.7%. There was no association between delay in diagnosis and gender (p = 0.194), TB type (p = 0.140), and diabetes (p = 0.198). On the other hand, old age (≥60 years) was related to delay in diagnosis (OR = 1.37; 95% CI = 1.12–1.68; p = 0.002). The chance of delay in diagnosis in prisoners was lower than in non-prisoners (OR = 0.62; 95% CI = 0.46–0.82; p = 0.001).

CONCLUSIONS Old age was a risk factor for delay in diagnosis, and interestingly, prisoners had been diagnosed significantly faster.

Middle cerebral artery territory infarction in a COVID-19 patient: a case report

Rizaldy Pinzon — 2020-11-14

Coronavirus disease 2019 (COVID-19) mainly invades the respiratory system, yet previous reports have shown unusual manifestations of COVID-19, including cerebrovascular events. However, detailed case reports are still lacking. A 57-year-old male presented with sudden unconsciousness and right side lateralization for 6 hours before hospital admission. His test results were positive for severe acute respiratory syndrome coronavirus 2 infection. The head computed tomography (CT) scan showed infarction within the middle cerebral artery region. The scan was repeated 48 hours after admission and showed a massive infarct in the left hemisphere with hemorrhagic transformation. A chest CT showed the appearance of bronchopneumonia with ground-glass opacities in both lungs. The patient's condition was rapidly deteriorating, and he died on the third day after admission. Our findings suggest that ischemic vascular events may simultaneously develop due to the progression of COVID-19. A hypercoagulable state and vascular endothelial dysfunction have been proposed as complications of COVID-19 and are risk factors of thrombotic vascular events.

A case of third degree hemorrhagic shock due to total subacute uterine inversion after delivery

William Timotius Wahono — 2021-02-11

Uterine inversion is a rare, but life-threatening obstetric emergency. We describe a case of total subacute uterine inversion in settings with limited resources. A multiparous (P4) 29-year-old woman with history of delivery assisted by a traditional birth attendant who used the fundal pressure technique 4 days before admission was referred due to postpartum hemorrhage. She had low blood pressure, tachycardia, and lethargic. A protruding mass from the vaginal introitus with active bleeding was visible. She diagnosed with third degree hemorrhagic shock due to total subacute uterine inversion. Resuscitation was initiated immediately and manual uterine repositioning was performed under general anesthesia. After two failed attempts, a laparotomy was performed to apply traction to the round ligaments and an incision on the cervical ring by using Allis clamps. The inversion was resolved. Next, subtotal hysterectomy was done to stop bleeding and infection.

Xanthine oxidase inhibition in SARS-CoV-2 infection: the mechanism and potency of allopurinol and febuxostat in COVID-19 management

Irandi Putra Pratomo — 2020-11-24

The number of coronavirus disease 2019 (COVID-19) infection cases has been increasing globally, including in Indonesia. Definitive therapy for COVID-19 has not yet been found; hence, repurposed drugs for COVID-19 have been considered and have been practiced by several researchers in the world. This literature review investigates the action of xanthine oxidase as a component of the biomolecular pathway against severe acute respiratory syndrome-related coronavirus-2, the cause of COVID-19, and describes the mechanism and potential of uric acid drugs (allopurinol and febuxostat) as prophylaxis and curative therapy for COVID-19.

Rapid advancement in cancer genomic big data in the pursuit of precision oncology

Tiara Bunga Mayang Permata — 2021-01-13

In the current big data era, massive genomic cancer data are available for open access from anywhere in the world. They are obtained from popular platforms, such as The Cancer Genome Atlas, which provides genetic information from clinical samples, and Cancer Cell Line Encyclopedia, which offers genomic data of cancer cell lines. For convenient analysis, user-friendly tools, such as the Tumor Immune Estimation Resource (TIMER), which can be used to analyze tumor-infiltrating immune cells comprehensively, are also emerging. In clinical practice, clinical sequencing has been recommended for patients with cancer in many countries. Despite its many challenges, it enables the application of precision medicine, especially in medical oncology. In this review, several efforts devoted to accomplishing precision oncology and applying big data for use in Indonesia are discussed. Utilizing open access genomic data in writing research articles is also described.

Corrigendum: A randomized clinical trial of freeze-dried amniotic membrane transplantation and conjunctival-limbal graft for pterygium excision and evaluation of conjunctival inflammation marker in tears

Made Susiyanti — 2021-03-31

[This corrects the article DOI: 10.13181/mji.oa.203818]

Erratum: Amniotic membrane transplantation for infectious corneal ulcer treatment: a cohort retrospective study

Vega Casalita — 2021-03-31

[This corrects the article DOI: 10.13181/mji.oa.203849]

Front & Back Matter

Medical Journal of Indonesia — 2021-03-31