Evaluation of Antibody Response and Adverse Effects following Heterologous COVID-19 Vaccine Booster with mRNA Vaccine among Healthcare Workers in Indonesia.

Background: The administration of the third (or booster) dose of COVID-19 vaccine is important in maintaining protection against SARS-CoV-2 infection or the severity of the disease. In Indonesia, health care workers (HCWs) are among the first to receive a booster dose of the COVID-19 vaccine. In this study, we evaluated the antibody response and adverse events following heterologous booster vaccine using mRNA-1273 among HCWs that were fully vaccinated with inactivated viral vaccine as the priming doses. Methods: 75 HCWs at Dr. Soetomo General Hospital in Surabaya, Indonesia, participated in this study. The level of antibody against the SARS-CoV-2 receptor binding domain was analyzed at 1, 3, and 5 months following the second priming dose and at 1, 3, and 5 months after the booster dose. Results: We found a significantly higher level of antibody response in subjects receiving a booster dose of the mRNA-1273 vaccine compared to those receiving an inactivated viral vaccine as a booster. Interestingly, participants with hypertension and a history of diabetes mellitus showed a lower antibody response following the booster dose. There was a higher frequency of adverse events following injection with the mRNA-1273 vaccine compared to the inactivated viral vaccine, although the overall adverse events were considered minor. Conclusions: A heterologous booster dose using mRNA vaccine resulted in a high antibody response; however, participants with hypertension and diabetes mellitus displayed a lower antibody response.

A review on pulmonary and mediastinal synovial sarcoma.

Sarcoma is defined as a tumor located in the thoracic cavity. However, sarcoma can occur on every side of the body. Synovial sarcoma is a rare soft tissue tumor originating from pluripotent with a high malignancy rate. The most common predilection of synovial sarcoma is in the joints. Primary synovial sarcoma of the lung and mediastinum are rare tumors and generally malignant. There are only a few cases have been reported. Definite diagnosis is made by histopathological, immunohistochemistry, and cytogenetic examination. The management strategy for synovial sarcoma requires multimodality treatment with surgery, chemotherapy, and radiotherapy. However, effective and relatively non-toxic therapy for primary synovial sarcoma is still developed. The five years life expectancy is higher if the patient received adjuvant radiotherapy and/or chemotherapy after surgery.

Ruptured mediastinal mature teratoma with shigellosis empyema: A case report.

INTRODUCTION AND IMPORTANCE: Mediastinal mature teratomas are often benign and asymptomatic, but ruptured mediastinal mature teratoma is rare and induces severe complications. CASE PRESENTATION: A male, 23 year old, complained shorthness of breath, right chest pain, fever, and cough. Radiological examination (X-ray, CT-Scan and MRI) showed mediastinal teratoma and pleural effusion. The patient received supportive therapies, including oxygen, symptomatic therapy, antibiotics, and lateral thoracotomy. Empyema culture was positive for Shigella dysenteriae. He was discharged after thirty-six days of hospitalization in good clinical condition. CLINICAL DISCUSSION: Perforation of mature teratoma is a rare but severe complication. Ruptured mediastinal teratoma can cause extensive pleural adhesions and empyema, making it challenging to perform VATS because of the risk of bleeding and damage to adjacent organs during surgery. CONCLUSION: Ruptured mediastinal mature teratoma has a good prognosis post-surgical partial resection despite tumor attachment to the pericardium and heart.

Incidence of SARS-CoV-2 infection in hospital workers before and after vaccination programme in East Java, Indonesia-A retrospective cohort study.

Background: The incidence of the Coronavirus Disease 2019 (COVID-19) among healthcare workers (HCWs) is widespread. It is important to understand COVID-19 characteristics among HCWs before and after vaccination. We evaluated the incidence of COVID-19 among HCWs in East Java, Indonesia comparing the characteristics of the disease between the pre- vs post-vaccination periods. Methods: A retrospective observational study was conducted among HCWs in two major hospitals in East Java, Indonesia, between April 01, 2020, and Oct 31, 2021. All HCWs were offered vaccination with inactivated viral vaccine (CoronaVac) from Jan 15, 2021. Therefore, we divided the time of the study into the pre-vaccination period (between April 01, 2020, and Jan 14, 2021) and post-vaccination period (between Jan 15 and Oct 31, 2021). We then compared the pattern of COVID-19 infections, and hospitalisations between these periods. Findings: A total of 434 (15.1%) and 649 (22.6%) SARS-CoV-2 infections were reported among study participants (n = 2878) during the pre-vaccination and post-vaccination periods, respectively. The vaccine effectiveness was 73.3% during the first 3-4 months after vaccination but this decreased to 17.6% at 6-7 months after vaccination, which coincided with the emergence of the delta variant. The overall hospitalisation rate was reduced from 23.5% in the pre-vaccination period to 14.3% in the post-vaccination period. Hypertension appeared to be the strongest risk factor affecting hospitalisation in the pre-vaccination period. However, the risk due to hypertension was reduced in the post-vaccination period. Interpretation: The risk to contract COVID-19 remains high among HCWs in East Java, Indonesia. Vaccination is important to reduce infection and hospitalisation. It is essentially important to evaluate the characteristics of COVID-19 infection, hospitalisation, the impact of co-morbidities and vaccine effectiveness in order to improve the measures applied in protecting HCWs during the pandemic. Funding: Mandate Research Grant No:1043/UN3.15/PT/2021, Universitas Airlangga, Indonesia.

Respinos: A Portable Device for Remote Vital Signs Monitoring of COVID-19 Patients.

The rapidly increasing number of COVID-19 patients has posed a massive burden on many healthcare systems worldwide. Moreover, the limited availability of diagnostic and treatment equipment makes it difficult to treat patients in the hospital. To reduce the burden and maintain the quality of care, asymptomatic patients or patients with mild symptoms are advised to self-isolate at home. However, self-isolated patients need to be continuously monitored as their health can turn into critical condition within a short time. Therefore, a portable device that can remotely monitor the condition and progression of the health of these patients is urgently needed. Here we present a portable device, called Respinos, that can monitor multiparameter vital signs including respiratory rate, heart rate, body temperature, and SpO2. It can also operate as a spirometer that measures forced vital capacity (FVC), forced expiratory volume (FEV), FEV in the first second (FEV1), and peak expiratory flow Rate (PEFR) parameters which are useful for detecting pulmonary diseases. The spirometer is designed in the form of a tube that can be ergonomically inflated by the patient, and is equipped with an accurate and disposable turbine based air flow sensor to evaluate the patient's respiratory condition. Respinos uses rechargeable batteries and wirelessly connects to a mobile application whereby the patient's condition can be monitored in real-time and consulted with doctors via chat. Extensive comparison against medical-grade reference devices showed good performance of Respinos. Overall results demonstrate the potential of Respinos for remote patient monitoring during and post pandemic.

Global Prevalence and Potential Influencing Factors of COVID-19 Vaccination Hesitancy: A Meta-Analysis.

Countries worldwide have deployed mass COVID-19 vaccination drives, but there are people who are hesitant to receive the vaccine. Studies assessing the factors associated with COVID-19 vaccination hesitancy are inconclusive. This study aimed to assess the global prevalence of COVID-19 vaccination hesitancy and determine the potential factors associated with such hesitancy. We performed an organized search for relevant articles in PubMed, Scopus, and Web of Science. Extraction of the required information was performed for each study. A single-arm meta-analysis was performed to determine the global prevalence of COVID-19 vaccination hesitancy; the potential factors related to vaccine hesitancy were analyzed using a Z-test. A total of 56 articles were included in our analysis. We found that the global prevalence of COVID-19 vaccination hesitancy was 25%. Being a woman, being a 50-year-old or younger, being single, being unemployed, living in a household with five or more individuals, having an educational attainment lower than an undergraduate degree, having a non-healthcare-related job and considering COVID-19 vaccines to be unsafe were associated with a higher risk of vaccination hesitancy. In contrast, living with children at home, maintaining physical distancing norms, having ever tested for COVID-19, and having a history of influenza vaccination in the past few years were associated with a lower risk of hesitancy to COVID-19 vaccination. Our study provides valuable information on COVID-19 vaccination hesitancy, and we recommend special interventions in the sub-populations with increased risk to reduce COVID-19 vaccine hesitancy.

Hypertension is associated with antibody response and breakthrough infection in health care workers following vaccination with inactivated SARS-CoV-2.

Several types of vaccines have been developed to prevent the coronavirus disease 2019 (COVID-19). It is important to understand whether demographic and clinical variables affect the effectiveness of various types of vaccines. This study analysed the association between demographic/clinical factors, antibody response and vaccine effectiveness in healthcare workers vaccinated with inactivated virus. We enrolled 101 healthcare workers who received two doses of inactivated viral vaccine (CoronaVac). Blood samples were analysed at 1, 3, and 5 months after the second dose of vaccination. Data regarding demographic characteristics, medical histories, and clinical parameters were collected by interview and medical examination. In a separate retrospective study, we analysed the incidence of vaccine breakthrough infection on 2714 healthcare workers who received two doses of inactivated viral vaccine. Medical histories and demographic data were collected using a structured self-reported questionnaire. We found that antibody titres markedly increased at 1 month after vaccination but gradually decreased at 3-5 months post-vaccination. We observed a significant association between age (≥40 years) and antibody level, whereas sex and body mass index (BMI) exhibited no effect on antibody titres. Amongst clinical variables analysed, high blood pressure and history of hypertension were significantly correlated with lower antibody titres. Consistently, we found a significant association in the retrospective study between hypertension and the incidence of breakthrough infection. In conclusion, our results showed that hypertension is associated with lower antibody titres and breakthrough infection following COVID-19 vaccination. Thus, blood pressure control might be important to improve the efficacy of inactivated virus vaccine.

The prevalence, predictors and outcomes of acute liver injury among patients with COVID-19: A systematic review and meta-analysis.

The data on the predictors and prognosis of acute liver injury (ALI) among patients in coronavirus disease 2019 (COVID-19) patients are limited. The aim of this study was to determine the prevalence, predictors and outcomes of ALI among patients with COVID-19. A systematic review was conducted up to 10 June 2021. The relevant papers were searched from PubMed, Embase, Cochrane and Web of Science, and the data were analysed using a Z test. A total of 1331 papers were identified and 16 papers consisting of 1254 COVID-19 with ALI and 4999 COVID-19 without ALI were analysed. The cumulative prevalence of ALI among patients with COVID-19 was 22.8%. Male and having low lymphocyte levels were more likely to be associated with ALI compared with female and having higher lymphocyte level, odds ratio (OR): 2.70; 95% confidence interval (CI): 2.03, 3.60 and mean difference (MD) -125; 95% CI: -207, -43, respectively. COVID-19 patients with ALI had higher risk of developing severe COVID-19 compared with those without ALI (OR: 3.61; 95% CI: 2.60, 5.02). Our findings may serve as the additional evaluation for the management of ALI in COVID-19 patients.

Sequential Co-infection of Heligmosomoides polygyrus and Mycobacterium tuberculosis Determine Lung Macrophage Polarization and Histopathological Changes.

BACKGROUND: Tuberculosis is a chronic infection caused by Mycobacterium tuberculosis (M.tb), which needs proper macrophage activation for control. It has been debated whether the co-infection with helminth will affect the immune response to mycobacterial infection. OBJECTIVE: To determine the effect of sequential co-infection of Heligmosomoides polygyrus (H.pg) nematodes and M.tb on T cell responses, macrophages polarization and lung histopathological changes. METHOD: This study used 49 mice divided into 7 treatment groups, with different sequence of infection of M.tb via inhalation and H.pg via oral ingestion for 8 and 16 weeks. T cells response in the lung, intestine, and peripheral blood were determined by flow cytometry. Cytokines (IL-4, IFN-γ, TGB-ß1, and IL-10) were measured in peripheral blood using ELISA. Lung macrophage polarization were determined by the expression of iNOS (M1) or Arginase 1 (M2). Mycobacterial count were done in lung tissue. Lung histopathology were measured using Dorman's semiquantitative score assessing peribronchiolitis, perivasculitis, alveolitis, and granuloma formation. RESULT: M.tb infection induced Th1 response and M1 macrophage polarization, while H.pg infection induced Th2 and M2 polarization. In sequential co-infection, the final polarization of macrophage was dictated by the sequence of co-infection. However, all groups with M.tb infection showed the same degree of mycobacterial count in lung tissues and lung tissue histopathological changes. CONCLUSION: Sequential co-infection of H.pg and M.tb induces different T cell response which leads to different macrophage polarization in lung tissue. Helminth infection induced M2 lung macrophage polarization, but did not cause different mycobacterial count nor lung histopathological changes.

Association between convalescent plasma and the risk of mortality among patients with COVID-19: a meta-analysis.

Background: Convalescent plasma (CCP) has been used for treating some infectious diseases; however, the efficacy of CCP in coronavirus disease 2019 (COVID-19) remains controversial. The aim of this research was to assess the efficacy of CCP as an adjunctive treatment in COVID-19 patients. Methods: Four bibliographic databases and a preprint database were searched for potentially relevant articles. Mortality rates between patients treated with standard treatment and standard treatment with CCP were compared using a Z test. Results: A total of 1,937 patients treated with CCP and 3,405 patients without CCP retrieved from 12 studies were included. The risk of mortality was 1.92-fold higher in patients without CCP compared to patients treated with CCP (OR: 1.92; 95%CI: 1.33, 2.77; p=0.0005). In severe COVID-19 sub-group analysis, we found that patients without the CCP had a 1.32 times higher risk of mortality than those treated with the CCP (OR: 1.32; 95%CI: 1.09, 1.60; p=0.0040). Conclusions: CCP, as adjunctive therapy, reduces the mortality rate among COVID-19 patients.

Hemoptysis in a patient with pulmonary aspergilloma and type 2 diabetes mellitus: A rare case in an Indonesian adult.

BACKGROUND: The success rate of surgery on aspergilloma is quite low since aspergilloma generally spreads throughout the lung cavity. CASE PRESENTATION: A 45-year-old woman with a past history of type 2 diabetes mellitus presented with chronic hemoptysis. Clinical presentation and work up revealed a left lung aspergilloma, with x-ray and CT-scan showing a mass in the upper lobe of left lung and FNAB showing Aspergillus sp. The patient underwent thoracotomy with left superior lobectomy. Histopathological examination of specimens showed hyphae with septa. The patient had postoperatively controlled pleural effusions. DISCUSSION: T2DM is a risk factor for Aspergillus sp infection because it is immunocompromised when hyperglycemia occurs. Pulmonary aspergilloma has a poor prognosis during surgery. Removing aspergilloma in the lung cavity and maintaining blood glucose levels can provide a good prognosis. Keeping the amount of fluid from increasing is the main focus of post-surgery. CONCLUSION: Pulmonary aspergilloma that only occurs in one lung lobe has a good prognosis after surgery.

Comparison of Detection of Epidermal Growth Factor Receptor (EFGR) Gene Mutation in Peripheral Blood Plasma (Liquid Biopsy) with Cytological Specimens in Lung Adenocarcinoma Patients.

The ctDNA plasma testing is one of the methods to examine biomarkers for lung adenocarcinoma in order to detect a mutation of epidermal growth factor receptor (EGFR) gene. The advantages of ctDNA testing over tissue biopsy and lung tumor cytology include less invasive, faster result, cheaper, and minimum risk of complication for the patient. We analyzed and compare the detection of EFGR mutation in peripheral blood plasma (liquid biopsy) with cytological specimens of patients with lung adenocarcinoma. We conducted ctDNA plasma testing in 124 lung adenocarcinoma patients who visited our hospital from January to December 2018. The ctDNA testing results were compared with the results of EGFR detection from the previous cytological specimen examination. Most of the patients were males, aged 55-59 years, nonsmokers, and had stage IVA lung adenocarcinoma, with most metastasis found in the pleura. We found a correlation between EGFR prevalence with nonsmoking status and patient's age. The ctDNA plasma testing detected 27.4% common EGFR mutation and 72.6% wild-type EGFR. The figures of EGFR mutation detection from cytological specimens were 47.6% and 52.4%, respectively. Compared to cytological specimens, the EGFR mutation detection in ctDNA had a sensitivity of 48.3%, with a specificity of 90.9%, PPV of 82.35%, NPV of 66.7%, and 70.97% concordance rate. EGFR mutation with cytological specimen examination was more accurate than ctDNA.

Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 widely varies from asymptomatic infection to severe pneumonia and systemic inflammatory disease. It is thought that host genetic variability may affect the host's response to the virus infection and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load. RESULTS: We genotyped 95 patients with COVID-19 hospitalised in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 genetic variant and the severity of the disease. However, we identified a significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19. CONCLUSION: Our data indicate a possible association between TMPRSS2 p.Val160Met polymorphism and SARS-CoV-2 infectivity and the outcome of COVID-19.

The predictors of high titer of anti-SARS-CoV-2 antibody of convalescent plasma donors.

BACKGROUND: Recent evidence suggested that the higher titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody from convalescent plasma donors contributed to the clinical improvement in coronavirus disease 2019 (COVID-19) patients. However, the titers of anti-SARS-CoV-2 antibodies varied in each individual, and the precise factors that might govern such variation have not been elucidated. OBJECTIVES: To assess the factors associated with high titers of anti-SARS-CoV-2 antibody among COVID-19 convalescent plasma (CCP) donors. METHODS: A cross-sectional study was conducted in Saiful Anwar General Hospital, Malang, Indonesia. Information of interest including demographic characteristics, clinical symptoms, comorbidities, laboratory findings, and the titers of anti-SARS-CoV-2 antibody among COVID-19 CCP donors were collected. The correlation was assessed using multiple logistic regression. RESULTS: A total of 50 COVID-19 CCP donors with the titers of anti-SARS-CoV-2 antibody of more than 1:320 and 33 donors with the titers of less than 1:320 were analyzed. Our analysis revealed that CCP donors with history of cough, fever, dyspnea, and pneumonia significantly had higher titers of anti-SARS-CoV-2 antibody compared to asymptomatic donors. Moreover, CCP donors with elevated levels of eosinophils and immature granulocytes and low levels of albumins had higher levels of anti-SARS-CoV-2 antibody. The titer of antibody was not affected by comorbidities of donors. CONCLUSIONS: CPP donors who had experience of symptomatic COVID-19 with high eosinophils level, high immature granulocytes and low albumin level have higher titers of anti-SARS-COV-2 antibody than those who experienced asymptomatic COVID-19. Our current findings may be used as the additional baseline criteria for selecting the donors of CCP for the management of COVID-19.

The association between therapeutic plasma exchange and the risk of mortality among patients critically ill with COVID-19: a meta-analysis.

Background: Cytokine storm has been widely known to contribute to the development of the critical condition in patients with coronavirus disease 2019 (COVID-19), and studies had been conducted to assess the potential aspect of cytokine storm elimination by performing therapeutic plasma exchange (TPE). However, contradictory findings were observed. The objective of this study was to assess the association between TPE and the reduction of mortality of critically ill COVID-19 patients. Methods: A meta-analysis was conducted by collecting data from PubMed, Scopus, and Web of Science. Data on the mortality rate of critically ill COVID-19 patients treated with TPE plus standard of care and that of patients treated with standard of care alone were analyzed using a Z test. Results: We included a total of four papers assessing the association between TPE and the risk of mortality among critically ill COVID-19 patients. Our findings suggested that critically ill COVID-19 patients treated with TPE had lower risk of mortality compared to those without TPE treatment. Conclusion: Our study has identified the potential benefits of TPE in reducing the risk of mortality among critically ill COVID-19 patients.

Bone marrow-derived mesenchymal stem cells attenuate pulmonary inflammation and lung damage caused by highly pathogenic avian influenza A/H5N1 virus in BALB/c mice.

BACKGROUND: The highly pathogenic avian influenza A/H5N1 virus is one of the causative agents of acute lung injury (ALI) with high mortality rate. Studies on therapeutic administration of bone marrow-derived mesenchymal stem cells (MSCs) in ALI caused by the viral infection have been limited in number and have shown conflicting results. The aim of the present investigation is to evaluate the therapeutic potential of MSC administration in A/H5N1-caused ALI, using a mouse model. METHODS: MSCs were prepared from the bone marrow of 9 to 12 week-old BALB/c mice. An H5N1 virus of A/turkey/East Java/Av154/2013 was intranasally inoculated into BALB/c mice. On days 2, 4, and 6 after virus inoculation, MSCs were intravenously administered into the mice. To evaluate effects of the treatment, we examined for lung alveolar protein as an indicator for lung injury, PaO2/FiO2 ratio for lung functioning, and lung histopathology. Expressions of NF-κB, RAGE (transmembrane receptor for damage associated molecular patterns), TNFα, IL-1ß, Sftpc (alveolar cell type II marker), and Aqp5+ (alveolar cell type I marker) were examined by immunohistochemistry. In addition, body weight, virus growth in lung and brain, and duration of survival were measured. RESULTS: The administration of MSCs lowered the level of lung damage in the virus-infected mice, as shown by measuring lung alveolar protein, PaO2/FiO2 ratio, and histopathological score. In the MSC-treated group, the expressions of NF-κB, RAGE, TNFα, and IL-1ß were significantly suppressed in comparison with a mock-treated group, while those of Sftpc and Aqp5+ were enhanced. Body weight, virus growth, and survival period were not significantly different between the groups. CONCLUSION: The administration of MSCs prevented further lung injury and inflammation, and enhanced alveolar cell type II and I regeneration, while it did not significantly affect viral proliferation and mouse morbidity and mortality. The results suggested that MSC administration was a promissing strategy for treatment of acute lung injuries caused by the highly pathogenic avian influenza A/H5N1 virus, although further optimization and combination use of anti-viral drugs will be obviously required to achieve the goal of reducing mortality.

Comparison of Virulence and Lethality in Mice for Avian Influenza Viruses of Two A/H5N1 and One A/H3N6 Isolated from Poultry during Year 2013-2014 in Indonesia.

In Indonesia, the highly pathogenic avian influenza A/H5N1 virus has become endemic and has been linked with direct transmission to humans. From 2013 to 2014, we isolated avian influenza A/H5N1 and A/H3N6 viruses from poultry in Indonesia. This study aimed to reveal their pathogenicity in mammals using a mouse model. Three of the isolates, Av154 of A/H5N1 clade 2.3.2.1c, Av240 of A/H5N1 clade 2.1.3.2b, and Av39 of A/H3N6, were inoculated into BALB/c mice. To assess morbidity and mortality, we measured body weight daily and monitored survival for 20 d. Av154- and Av240-infected mice lost 25% of their starting body weight by day 7, while Av39-infected mice did not. Most of the Av154-infected mice died on day 8, while the majority of the Av240-infected mice survived until day 20. A 50% mouse lethal dose was calculated to be 2.0 × 101 50% egg infectious doses for Av154, 1.1 × 105 for Av240 and > 3.2 × 106 for Av39. The Av154 virus was highly virulent and lethal in mice without prior adaptation, suggesting its high pathogenic potential in mammals. The Av240 virus was highly virulent but modestly lethal, whereas the Av39 virus was neither virulent nor lethal. Several mammalian adaptive markers of amino acid residues were associated with the highly virulent and lethal phenotypes of the Av154 virus.

T790M mutations identified by circulating tumor DNA test in lung adenocarcinoma patients who progressed on first-line epidermal growth factor receptor-tyrosine kinase inhibitors.

BACKGROUND: Plasma circulating tumor deoxyribonucleic acid (ctDNA) test is an alternative method to detect the T790M mutation. Compared to conventional tumor rebiopsy, ctDNA possesses several advantages including less invasive, faster, lower costs, and having minimal risk of complications for patients. OBJECTIVE: The main objective of the study is to identify the prevalence of T790M mutations in lung adenocarcinoma patients who progressed after tyrosine kinase inhibitors (TKIs) therapy using ctDNA examination. MATERIALS AND METHODS: This was a retrospective cohort study based on medical records of lung adenocarcinoma patients in the Oncology Outpatient Clinic of Dr. Soetomo General Hospital within the period of January 2017-June 2018. Patients who progressed after receiving first-line epidermal growth factor receptor-TKI (EGFR-TKI) undergone plasma ctDNA examination and genotyping using digital platforms (Droplet Digital™ PCR) method. RESULTS: In total, there were 39 patients who met the criteria for ctDNA testing. Thirty-three patients (84.6%) received first-line gefitinib, while the other six (15.4%) received erlotinib. The T790M mutations were detected in 46.2% of patients. In addition, EGFR common mutation in exon 19 and exon 21 were detected in 87.2% of patients. Median progression-free survival of patients receiving first-line gefitinib or erlotinib were both around 9 months and did not differ significantly. CONCLUSIONS: CtDNA examination successfully detected T790M mutation in a certain proportion of lung adenocarcinoma patients who progressed after first-line EGFR-TKI without the need for difficult and invasive rebiopsy.

Predictors of COVID-19 severity: a systematic review and meta-analysis.

Background: The unpredictability of the progression of coronavirus disease 2019 (COVID-19) may be attributed to the low precision of the tools used to predict the prognosis of this disease. Objective: To identify the predictors associated with poor clinical outcomes in patients with COVID-19. Methods: Relevant articles from PubMed, Embase, Cochrane, and Web of Science were searched as of April 5, 2020. The quality of the included papers was appraised using the Newcastle-Ottawa scale (NOS). Data of interest were collected and evaluated for their compatibility for the meta-analysis. Cumulative calculations to determine the correlation and effect estimates were performed using the Z test. Results: In total, 19 papers recording 1,934 mild and 1,644 severe cases of COVID-19 were included. Based on the initial evaluation, 62 potential risk factors were identified for the meta-analysis. Several comorbidities, including chronic respiratory disease, cardiovascular disease, diabetes mellitus, and hypertension were observed more frequent among patients with severe COVID-19 than with the mild ones. Compared to the mild form, severe COVID-19 was associated with symptoms such as dyspnea, anorexia, fatigue, increased respiratory rate, and high systolic blood pressure. Lower levels of lymphocytes and hemoglobin; elevated levels of leukocytes, aspartate aminotransferase, alanine aminotransferase, blood creatinine, blood urea nitrogen, high-sensitivity troponin, creatine kinase, high-sensitivity C-reactive protein, interleukin 6, D-dimer, ferritin, lactate dehydrogenase, and procalcitonin; and a high erythrocyte sedimentation rate were also associated with severe COVID-19. Conclusion: More than 30 risk factors are associated with a higher risk of severe COVID-19. These may serve as useful baseline parameters in the development of prediction tools for COVID-19 prognosis.

Multidrug-Resistant Infections Among Hospitalized Adults With Community-Acquired Pneumonia In An Indonesian Tertiary Referral Hospital.

OBJECTIVES: To evaluate the clinical and microbiological appearance among hospitalized pneumonia patients focusing on resistance and risk factors for mortality in a referral hospital. PATIENTS AND METHODS: The study was an observational retrospective study on patients with CAP from 2014 to 2016 at Dr Soetomo referral hospital of Surabaya, Indonesia. All positive cultures with antimicrobial susceptibility results from blood and respiratory specimens were included. Patients infected with drug-susceptible pathogens and MDR organisms were also assessed in terms of clinical characteristics, day-3 clinical improvement, and 14-day mortality. RESULTS: Of 202 isolates, 181 possessed antimicrobial susceptibility data. S. pneumoniae was the most prevalent pathogen causing CAP (18.3%). Most patients were empirically treated with ceftriaxone (n=75; 41.4%). Among beta-lactam antibiotics, the susceptibility to the third-generation cephalosporins remained relatively high, between 67.4% and 82.3%, compared with the other beta-lactams such as amoxicillin/clavulanate and ampicillin/sulbactam (a sensitivity rate of 36.5% and 47.5, respectively). For carbapenem antibiotics, imipenem and meropenem susceptibility was 69.6% and 82.3% respectively. Approximately 22% of isolates were identified as MDR that showed significant differences in clinical outcomes of 14-day mortality rates (p<0.001). Notably, patients with day-3 improvement had a lower risk of mortality (OR= 0.06; 95% CI= 0.02-0.19). CONCLUSION: One-fifth of causative agents among hospitalized CAP cases were identified as MDR organisms. The pathogens of MDR and non-MDR CAP remain susceptible to the third-generation cephalosporins. Together with additional consideration of culture findings and Pneumonia Severity Index (PSI) assessment, a 3-day clinical assessment is essential to predict the prognosis of 14-day mortality.