Derivation and validation of novel integrated inpatient mortality prediction score for COVID-19 (IMPACT) using clinical, laboratory, and AI-processed radiological parameter upon admission: a multicentre study.

Limited studies explore the use of AI for COVID-19 prognostication. This study investigates the relationship between AI-aided radiographic parameters, clinical and laboratory data, and mortality in hospitalized COVID-19 patients. We conducted a multicentre retrospective study. The derivation and validation cohort comprised of 512 and 137 confirmed COVID-19 patients, respectively. Variable selection for constructing an in-hospital mortality scoring model was performed using the least absolute shrinkage and selection operator, followed by logistic regression. The accuracy of the scoring model was assessed using the area under the receiver operating characteristic curve. The final model included eight variables: anosmia (OR: 0.280; 95%CI 0.095-0.826), dyspnoea (OR: 1.684; 95%CI 1.049-2.705), loss of consciousness (OR: 4.593; 95%CI 1.702-12.396), mean arterial pressure (OR: 0.928; 95%CI 0.900-0.957), peripheral oxygen saturation (OR: 0.981; 95%CI 0.967-0.996), neutrophil % (OR: 1.034; 95%CI 1.013-1.055), serum urea (OR: 1.018; 95%CI 1.010-1.026), affected lung area score (OR: 1.026; 95%CI 1.014-1.038). The Integrated Inpatient Mortality Prediction Score for COVID-19 (IMPACT) demonstrated a predictive value of 0.815 (95% CI 0.774-0.856) in the derivation cohort. Internal validation resulted in an AUROC of 0.770 (95% CI 0.661-0.879). Our study provides valuable evidence of the real-world application of AI in clinical settings. However, it is imperative to conduct prospective validation of our findings, preferably utilizing a control group and extending the application to broader populations.

Brown Tumour in Chronic Kidney Disease: Revisiting an Old Disease with a New Perspective.

Osteitis fibrosa cystica (OFC) and Brown Tumours are two related but distinct types of bone lesions that result from the overactivity of osteoclasts and are most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors, such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation, may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions, placing them in the spectrum of RAS-MAPK-driven neoplasms, which were until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumours, such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumours includes clinical symptoms involving chronic bone pain and laboratory findings of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically, both lesions are characterized by clustered osteoclasts in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumours.

Current Insights into Cellular Determinants of Peritoneal Fibrosis in Peritoneal Dialysis: A Narrative Review.

Peritoneal fibrosis is the final process of progressive changes in the peritoneal membrane due to chronic inflammation and infection. It is one of the main causes of discontinuation of peritoneal dialysis (PD), apart from peritonitis and cardiovascular complications. Over time, morphological changes occur in the peritoneal membranes of patients who use PD. Of those are mesothelial-to-mesenchymal transition (MMT), neoangiogenesis, sub-mesothelial fibrosis, and hyalinizing vasculopathy. Several key molecules are involved in the complex pathophysiology of peritoneal fibrosis, including advanced glycosylation end products (AGEs), transforming growth factor beta (TGF-ß), and vascular endothelial growth factor (VEGF). This narrative review will first discuss the physiology of the peritoneum and PD. Next, the multifaceted pathophysiology of peritoneal fibrosis, including the effects of hyperglycemia and diabetes mellitus on the peritoneal membrane, and the promising biomarkers of peritoneal fibrosis will be reviewed. Finally, the current and future management of peritoneal fibrosis will be discussed, including the potential benefits of new-generation glucose-lowering medications to prevent or slow down the progression of peritoneal fibrosis.

Markers of Renal Complications in Beta Thalassemia Patients with Iron Overload Receiving Chelation Agent Therapy: A Systematic Review.

Objective: The emerging renal complications in beta-thalassemia patients have raised the global exchange of views. Despite better survival due to blood transfusion and iron chelation therapy, the previously unrecognized renal complication remain a burden of disease affecting this population -the primary concern on how iron overload and chelation therapy correlated with renal impairment is still controversial. Early detection and diagnosis is crucial in preventing further kidney damage. Therefore, a systematic review was performed to identify markers of kidney complications in beta thalassemia patients with iron overload receiving chelation therapy. Methods: Searches of PubMed, Scopus, Science Direct, and Web of Science were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to identify studies of literature reporting renal outcome in ß-TM patients with iron overload and receiving chelation therapy. The eligible 17 studies were obtained. Results: uNGAL/NGAL, uNAG/NAG, uKIM-1 are markers that can be used as predictor of renal tubular damage in early renal complications, while Cystatin C and uß2MG showed further damage at the glomerular level. Discussion and Conclusion: The renal complication in beta-thalassemia patients with iron overload receiving chelating agent therapy may progress to kidney disease. Early detection using accurate biological markers is a substantial issue that deserves further evaluation to determine prevention and management.

Acute flaccid paralysis in Indonesian adult due to suspected familial hypokalemia paralysis: A rare case.

Background: Familial hypokalemic periodic paralysis (FHPP) is rare, so its management is essential to report. Case presentation: A 25-year-old Indonesian woman complained of feeling weak in both hands and legs, but the heaviest in both legs. The patient has several family members with similar complaints. The patient experienced decreased muscle strength in the upper extremity of 4/4 and the lower extremity of 3/3. Laboratory investigation showed potassium of 2.0 mmol/L, and the patient was given KCL of 50 mEq/24 hours, KSR of 3 × 600 mg/24 hours for 3 days, and a high potassium diet. The next few days, potassium levels increased, and the patient was treated as an outpatient. Discussion: Early diagnosis and management of acute flaccid paralysis (AFP) due to FHPP are very effective in low-resource settings. Conclusion: Finding the cause of AFP is essential for better management.

The Role of Plasma Interleukin-6 Levels on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk Scores in Javanese Patients with Chronic Kidney Disease.

Interleukin-6 (IL-6) has been identified as an important pro-inflammatory factor involved in mediating the severity of chronic kidney disease (CKD). This study sought to determine the effect of plasma IL-6 levels on atherosclerotic cardiovascular disease (ASCVD) and cardiovascular mortality risk scores in Javanese CKD patients. We also analyzed the frequency of IL-6 G174C single nucleotide polymorphism (SNP) in the population. This study was a cross-sectional study involving seventy-three patients of Javanese ethnic origin with stable chronic kidney disease. We assessed the ASCVD risk score, cardiovascular mortality score, genotyping of IL-6 G174C SNP, and plasma IL-6 levels in these patients. The genotype distribution and allele frequencies of the IL-6 G174C SNP were predominated by the G genotype/allele (GG: 97.26%, GC: 1.37%, CC: 1.37%, G-allele: 97.95%, and C-allele: 2.05%). Despite the fact that plasma IL-6 levels did not directly affect cardiovascular mortality risk, further analysis revealed its direct effect on the ASCVD risk score (path coefficient = 0.184, p = 0.043, 95% CI = 0.018−0.380), which in turn affected cardiovascular mortality risk (path coefficient = 0.851, p = <0.01, 95% CI = 0.714−0.925). In conclusion, plasma IL-6 levels play important roles on ASCVD risk and cardiovascular mortality risk in Javanese patients with CKD.

The Effect of Angiotensin Converting Enzyme (ACE) I/D Polymorphism on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk in Non-Hemodialyzed Chronic Kidney Disease: The Mediating Role of Plasma ACE Level.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

Predictive Value of Sequential Organ Failure Assessment, Quick Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II, and New Early Warning Signs Scores Estimate Mortality of COVID-19 Patients Requiring Intensive Care Unit.

Introduction: Various mortality predictive score models for coronavirus disease-2019 (COVID-19) have been deliberated. We studied how sequential organ failure assessment (SOFA), quick sequential organ failure assessment (qSOFA), acute physiology and chronic health evaluation II (APACHE II), and new early warning signs (NEWS-2) scores estimate mortality in COVID-19 patients. Materials and methods: We conducted a prospective cohort study of 53 patients with moderate-to-severe COVID-19. We calculated qSOFA, SOFA, APACHE II, and NEWS-2 on initial admission and re-evaluated on day 5. We performed logistic regression analysis to differentiate the predictors of qSOFA, SOFA, APACHE II, and NEWS-2 scores on mortality. Result: qSOFA, SOFA, APACHE II, and NEWS-2 scores on day 5 exhibited a difference between survivors and nonsurvivors (p <0.05), also between ICU and non-ICU admission (p <0.05). The initial NEWS-2 revealed a higher AUC value than the qSOFA, APACHE II, and SOFA score in estimating mortality (0.867; 0.83; 0.822; 0.794). In ICU, APACHE II score revealed a higher AUC value than the SOFA, NEWS-2, and qSOFA score (0.853; 0.832; 0.813; 0.809). Concurrently, evaluation on day 5 showed that qSOFA AUC had higher scores than the NEWS-2, APACHE II, and SOFA (0.979; 0.965; 0.939; 0.933) in predicting mortality, while SOFA and APACHE II AUC were higher in ICU admission than NEWS-2 and qSOFA (0.968; 0.964; 0.939; 0.934). According to the cutoff score, APACHE II on day 5 revealed the highest sensitivity and specificity in predicting the mortality (sensitivity 95.7%, specificity 86.7%). Conclusion: All scores signify good predictive values on COVID-19 patients mortality following the evaluation on the day 5. Nonetheless, APACHE-II appears to be the best at predicting mortality and ICU admission rate. How to cite this article: Asmarawati TP, Suryantoro SD, Rosyid AN, Marfiani E, Windradi C, Mahdi BA, et al. Predictive Value of Sequential Organ Failure Assessment, Quick Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II, and New Early Warning Signs Scores Estimate Mortality of COVID-19 Patients Requiring Intensive Care Unit. Indian J Crit Care Med 2022;26(4):464-471.

Prognosticating 2-Year Survival Rate of Breast Cancer Patients Through Plasma miRNA-21 and Other Associating Factors.

Background: miRNA-21, one of breast cancer (BC) predictive markers, is now gaining cardinal attention from researchers worldwide to evaluate BC patients' survival rate. However, cancer staging, hormonal status, and other BC markers still have to be discussed. We aim to determine the relationship between miRNA-21 and associating factors such as BC staging, other tumor markers, and hormonal status to predict the 2-year survival rate of BC patients. Methods: We conducted a prospective cohort study on 49 BC patients (26 early stage, 23 advanced stage). Apart from cancer staging, we also examined CEA, Ca15-3, and hormonal status (ER, PR, Her2) and correlated them with miRNA-21 to predict 2-year survival rate. We did bivariate, multivariate, and survival analyses to determine the link between miRNA-21 and those factors to prognosticate on 2-year survival rate. Results: There are significances between advanced and loco-regional stage (p < 0.001); high and low miRNA-21 (p = 0.002) and CA 15-3 (p = 0.001), and low survival rate in patients with ER/PR-Her2- status (p=0.0015). Cox proportional hazard showed miRNA-21 (Adjusted HR 1.41; 95% CI = 1.205-1.632), cancer stage (Adjusted HR 9.5; 95% CI = 1.378-20.683), and CA15-3 (Adjusted HR 4.64; 95% CI = 1.548-13.931) affected patients' mortality within 2 years. Conclusion: Low two-year survival rate depends on miRNA-21, cancer stage, CA15-3, and ER/PR-Her2-. Cancer stage is robustly associated with miRNA-21 in predicting 2-year survival rate.

High Sensitivity Troponin T as Complementary Modality for Determining Doxorubicin Regimen Cardiotoxicity in Non-Hodgkin Lymphoma Patients.

Purpose: This study aims to evaluate the role of high-sensitivity troponin T (hsTnT) as a complementary tool for determining cardiotoxicity in non-Hodgkin lymphoma (NHL) patients receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen chemotherapy. Methods: We included 35 patients diagnosed with NHL who received CHOP chemotherapy. Left ventricular ejection fraction (LVEF) and hsTnT were measured at two time points: before the first cycle (pre-test) and after the fourth cycle (post-test). The LVEF and hsTnT were analysed using IBM SPSS version 24 through the paired-sample T-test, Wilcoxon signed-rank test, Pearson's correlation and Spearman's correlation. Results: There was a significant difference in both LVEF and hsTnT between pre-chemotherapy and post-4th chemotherapy cycles (P = 0.001). However, more contrast difference from the baseline value of hsTnT compared to LVEF could be observed. LVEF did not detect any deterioration in myocardial function. However, 10 out of 35 subjects exhibit hsTnT higher than the 99th percentile of the population (>14 pg/ml), suggesting that myocardial injury (MI) could be detected. There was no correlation between LVEF and hsTnT (P > 0.05). Conclusion: HsTnT, together with LVEF, could complement each other and offer better coverage for detecting cardiotoxicity during the administration of CHOP in NHL patients. An insignificant correlation between hsTnT and LVEF showed that cardiotoxicity existed in a broad spectrum including cellular damage and functional impairment, as hsTnT represents cellular damage, and LVEF reflects heart functional capacity.

A rare case: Vesicoureteral reflux in Indonesian young adult with neurogenic bladder and chronic kidney disease stage 4.

BACKGROUND: Vesicoureteral reflux (VUR) is one of the main causes of chronic kidney disease (CKD) in adolescence and young adult. It can be a congenital or an acquired anomaly and its uncommon in adult life. CASE PRESENTATION: A 19th years old male with neurogenic bladder, VUR grade 4, CKD stage 4, malnutrition, and short stature. Radiological examinations show a spastic neurogenic bladder, cystitis, right VUR grade 4. Abdominal ultrasonography (USG) results were bilateral severe hydronephrosis due to post-renal causes. This patient had a history of myelocele excision at the age of 1.5 years. He had recurrent urinary tract infection with CKD stage 4. DISCUSSION: The diagnosis of VUR and neurogenic bladder in CKD stage 4 is a rare case in nephrology. CONCLUSION: Indonesian male confirms of diagnosis VUR grade 4, neurogenic bladder, and CKD stage 4.

Dietary management of haemodialysis patients with chronic kidney disease and malnourishment.

BACKGROUND AND OBJECTIVES: Dietary supplementation for haemodialyzed (HD) patients with chronic kidney disease (CKD) and its benefits for the anthropometric profiles remain contentious. This study analysed changes in the albumin levels and anthropometric profiles of HD patients within 3 months of nutritional therapy. METHODS AND STUDY DESIGN: Sixty-three malnourished HD patients (Subjective Global Assessment nutrition status B or C) were enrolled. Twenty patients received counselling, 17 patients received oral therapy, 26 patients received intradialytic parenteral nutrition (IDPN), and were evaluated at month 0, month 1, and month 3. Five patients withdrew before completing the trial. The patients' albumin levels and anthropometric profiles (biceps and triceps skinfold thickness, upper arm circumference, body weight, and body mass index) were analysed before and after treatment. We performed multivariate analysis to determine the effect of each treatment on serum albumin and anthropometric profiles. RESULTS: At months 1 and 3, nutritional therapy was associated with different mean serum albumin level among three nutritional intervention groups (p<0.05). Significant increases in serum albumin, upper arm circumference, and triceps and biceps skinfold thickness were identified in the counselling and IDPN groups. Multivariate linear regression revealed significant differences between oral and nonoral groups in albumin and biceps and triceps skinfold thickness at months 1 and 3. These variables were affected by age and duration of haemodialysis (p<0.05). CONCLUSIONS: Nutritional therapy for malnourished CKD patients receiving HD ameliorated serum albumin and their anthropometric profiles within 3 months.

Severe COVID-19 infection in a kidney transplant recipient treated with lopinavir/ritonavir, hydroxychloroquine and dexamethasone.

Severe COVID-19 infection management for a recipient of kidney transplant has debatable prognosis and treatment. We described the case of a COVID-19 infected 70 year old female, previously had renal transplantation in 2017. The patient took immunosuppressive agents as routine drugs for transplant recipient status and received lopinavir/ritonavir, hydroxychloroquine, and dexamethasone daily at the hospitalization. Specific question arises about renal transplant recipients being infected by COVID-19 - whether the infection will get worse compared to those without immunosuppresive agent. In this case, author decided to stop the immunosuppressive agent followed administration of combination lopinavir/ritonavir, hydroxychloroquine, and dexamethasone that gives a good clinical impact change to patient's condition after once getting worsened and mechanically ventilated. Nevertheless, the assessment of risk and benefit in continuing immunosuppressive drugs is concurrently essential due to the prevention of transplant rejection.

The clinical impact of bacterial co-infection among moderate, severe and critically ill COVID-19 patients in the second referral hospital in Surabaya.

Background: Data on the prevalence of bacterial co-infections among COVID-19 patients are limited, especially in our country, Indonesia. We aimed to assess the rate of bacterial co-infections in hospitalized COVID-19 patients and report the most common microorganisms involved and the antibiotic use in these patients. Methods: This study is a retrospective cohort study, among COVID-19 adult patients admitted to Universitas Airlangga Hospital Surabaya from 14 March-30 September 2020. The bacterial infection is defined based on clinical assessment, laboratory parameters, and microbiology results. Results: A total of 218 patients with moderate to critical illness and confirmed COVID-19 were included in this study. Bacterial infection was confirmed in 43 patients (19.7%). COVID-19 patients with bacterial infections had longer hospital length of stay (17.6 ± 6.62 vs 13.31±7.12), a higher proportion of respiratory failure, intensive care treatment, and ventilator use. COVID-19 patients with bacterial infection had a worse prognosis than those without bacterial infection (p<0.04). The empirical antibiotic was given to 75.2% of the patients. Gram-negative bacteria were commonly found as causative agents in this study (n = 39; 70.37%). Conclusion: COVID-19 patients with bacterial infection have a longer length of stay and worse outcomes. Healthcare-associated infections during intensive care treatment for COVID-19 patients must be carefully prevented.

Optimal use of tocilizumab for severe and critical COVID-19: a systematic review and meta-analysis.

Background: Several studies have revealed the potential use of tocilizumab in treating COVID-19 since no therapy has yet been approved for COVID-19 pneumonia. Tocilizumab may provide clinical benefits for cytokine release syndrome in COVID-19 patients. Methods: We searched for relevant studies in PubMed, Embase, Medline, and Cochrane published from March to October 2020 to evaluate optimal use and baseline criteria for administration of tocilizumab in severe and critically ill COVID-19 patients. Research involving patients with confirmed SARS-CoV-2 infection, treated with tocilizumab and compared with the standard of care (SOC) was included in this study. We conducted a systematic review to find data about the risks and benefits of tocilizumab and outcomes from different baseline criteria for administration of tocilizumab as a treatment for severe and critically ill COVID-19 patients. Results: A total of 26 studies, consisting of 23 retrospective studies, one prospective study, and two randomised controlled trials with 2112 patients enrolled in the tocilizumab group and 6160 patients in the SOC group, were included in this meta-analysis. Compared to the SOC, tocilizumab showed benefits for all-cause mortality events and a shorter time until death after first intervention but showed no difference in hospital length of stay. Upon subgroup analysis, tocilizumab showed fewer all-cause mortality events when CRP level ≥100 mg/L, P/F ratio 200-300 mmHg, and P/F ratio <200 mmHg. However, tocilizumab showed a longer length of stay when CRP <100 mg/L than the SOC. Conclusion: This meta-analysis demonstrated that tocilizumab has a positive effect on all-cause mortality. It should be cautiously administrated for optimal results and tailored to the patient's eligibility criteria.

Case Report: Priapism as The Clinical Presenting Feature of Chronic Myeloid Leukemia: Case Report and 20-Year Literature Review.

Priapism in chronic myeloid leukemia (CML) appears to be an infrequent manifestation as well as a crucial emergency. Here, we report an 18-year-old male presenting with a persistent erection of penis for 20 days. We evaluate and compare the reported cases during the past 20 years discussing the management of CML patients experiencing priapism. Cytoreductive therapy followed by leukapheresis, the administration of tyrosine kinase inhibitor, and intra-cavernosal blood aspiration may resolve the symptoms of priapism. Early intervention for cytoreduction and aspiration are the pivotal keys to successfully impeding the complications.

Correlation between anti-hypertensive drugs and disease progression among moderate, severe, and critically ill COVID-19 patients in the second referral hospital in Surabaya: A retrospective cohort study.

Background: Hypertension, as the comorbidity accompanying COVID-19, is related to angiotensin-converting enzyme 2 receptor (ACE-2R) and endothelial dysregulation which have an important role in blood pressure regulation. Other anti-hypertensive agents are believed to trigger the hyperinflammation process. We aimed to figure out the association between the use of anti-hypertensive drugs and the disease progression of COVID-19 patients.   Methods: This study is an observational cohort study among COVID-19 adult patients from moderate to critically ill admitted to Universitas Airlangga Hospital (UAH) Surabaya with history of hypertension and receiving anti-hypertensive drugs.   Results: Patients receiving beta blockers only had a longer length of stay than angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ACEI/ARB) or calcium channel blockers alone (17, 13.36, and 13.73 respectively), had the higher rate of intensive care unit (ICU) admission than ACEi/ARB (p 0.04), and had the highest mortality rate (54.55%). There were no significant differences in length of stay, ICU admission, mortality rate, and days of death among the single, double, and triple anti-hypertensive groups. The mortality rate in groups taking ACEi/ARB was lower than other combination.   Conclusions: Hypertension can increase the severity of COVID-19. The use of ACEI/ARBs in ACE-2 receptor regulation which is thought to aggravate the condition of COVID-19 patients has not yet been proven. This is consistent with findings in other anti-hypertensive groups.