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.

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.

Prolonged ICU Stay in Severe and Critically-Ill COVID-19 Patients Who Received Convalescent Plasma Therapy.

Background: Convalescent plasma administration in severe and critically-ill COVID-19 patients have been proven to not provide improvement in patients' outcome, yet it is still widely used in countries with limited resources due to its high availability and safety. This study aims to investigate its effects on ICU mortality, ICU length of stay (LoS), and improvement of oxygen support requirements. Methods: Data of all severe and critically-ill patients in our COVID-19 ICU was collected retrospectively between May and November 2020. We dichotomized the variables and compared outcome data of 48 patients, who received convalescent plasma to 131 patients, receiving standard of care. Data were analyzed using multiple logistic regression to make prediction models of mortality, length of stay, and oxygen support device requirement. Result: Overall mortality rate in our COVID-19 ICU was 55.3%, with a median overall length of stay of 8 (4-11) days. Less patients that received convalescent plasma presented with the need for mechanical ventilation on ICU admission (p < 0.001), but with comparable PaO2 to FiO2 (P/F) ratio (p=0.95). Factors that confounded mortality were obesity (aOR = 14.1; 95% CI (1.25, 166.7); p=0.032), mechanical ventilation (aOR = 333; 95% CI (4.5,1,000); p < 0.001), higher neutrophil-to-lymphocyte ratio (NLR) (aOR = 7.32; 95% CI (1.82, 29.4); p=0.005), and lower P/F ratio (aOR = 7.70; 95% CI (2.04, 29.4); p=0.003). ICU LoS was longer in patients, who had prior history of hypertension (aOR = 2.14; 95% CI (1.05, 4.35); p=0.036) and received convalescent plasma (aOR = 3.88; 95% CI (1.77, 8.05); p < 0.001). Deceased patients, who received convalescent plasma, stayed longer in the ICU with a mean length of stay of 12.87 ± 5.7 days versus 8.13 ± 4.8 days with a significant difference (U = 434; p < 0.000). The chance of improved oxygen support requirements was lower in obese patients (aOR = 9.18; 95%CI (2.0, 42.1); p < 0.004), mechanically ventilated patients (aOR = 13.15; 95% CI (3.75, 46.09); p < 0.001), patients with higher NLR (aOR = 2.5; 95% CI (1.07, 5.85); p=0.034), and lower P/F ratio (aOR = 2.76; 95% CI (1.1, 6.91); p=0.031). Conclusion: The length of stay of patients in the convalescent plasma group was significantly longer than the control group. There was no effect of convalescent plasma in ICU mortality and no improvement was observed in terms of oxygen support requirements.

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.

Hematologic and coagulopathy parameter as a survival predictor among moderate to severe COVID-19 patients in non- ICU ward: a single-center study at the main referral hospital in Surabaya, East Java, Indonesia.

Background : This research aimed to examine and analyze risk factors for death, hematologic parameters and coagulation in COVID-19 patients at RSUD Dr. Soetomo Surabaya, one of the referral centers for probable COVID-19 patient cases in East Java. Method : This was a retrospective analytical study by taking secondary data on patients with probable COVID-19 cases who were treated in hospital isolation rooms from May to September, 2020. Result : Of 538 probable COVID-19 patients, 217  tested positive, with an average age of 52.11±13.12 years, and there were 38 death cases. Hematologic parameters, such as white blood cell, neutrophil and lymphocyte counts, were significantly different in the deceased group. On the other hand, coagulation parameters, consisting of D-dimer, CRP, PT, and aPTT showed significantly similar value in the deceased group. Univatiate analysis concluded that chronic kidney disease, diabetes mellitus, coronary heart disease, WBC, NLR, and PPT counts could predict the mortality, while multivariate analysis revealed that coronary heart disease was the only significant independent predictor of mortality. Conclusion : This research shows that hematologic and coagulation parameters were increased in the majority of COVID-19 patients and the deceased group. While the number of neutrophils and WBC increases, the number of lymphocytes decreases significantly with increasing disease severity. Coronary heart disease is an independent predictor of mortality.

Drug utilization study and cost analysis of adult ß-thalassemia major patient therapy at Dr. Soetomo General Hospital Surabaya.

OBJECTIVES: The main therapy of ß-thalassemia major are blood transfusion and iron chelation drugs. However, those therapies also have some adverse effects and problems such as iron overload, transfusion reactions, nutritional deficiencies, and patient compliance problems. Those arising problems also have an impact on therapy cost. Hence, this study was designed to analyze drug utilization study and cost of therapy in ß-thalassemia major adult patients at Dr. Soetomo General Hospital Surabaya. METHODS: This research was conducted in descriptive observational-retrospective design using secondary data obtained from patient's medical records and billing registrations from January 1-December 31, 2019. RESULTS: There were 18 patients out of 233 patients that were analyzed. Deferasirox was the most administered drug with doses between 500 mg/day-1,500 mg/day while deferiprone was ranged between 1,500 and 4,500 mg/day. Patients also received transfusion reaction drugs with dexamethasone injection 5 mg/ml which was administered the most. The most administered supplement was folic acid 1 mg. Patients had an increase in serum ferritin due to low compliance. Deferasirox had the most adherence number of patients with decrease of serum ferritin. The two highest costs of direct medical components were top-up medicines and consumable medical supplies. Overall, the hospital gained profit from national health insurance claims. CONCLUSIONS: The most administered chelating agent was deferasirox. Deferasirox also had the most adherence number of patients with decreased number of serum ferritin. However, deferasirox also yielded the highest cost. Yet, overall, the hospital gained profit from national health insurance claims.

The Association between Plasma miRNA-21 Levels with Overall 1-year Survival Rate of Breast Cancer Patients at Various Stages.

BACKGROUND: miRNA 21 exhibits an increased expression in breast cancer (BC). However, its relationship with the 1-year survival of breast cancer patients is still disputable and under serious discussion. METHODS: Cohort prospective study involving 49 breast cancer patients was done, comprising 26 in early stage and 23 in end-stage. We evaluated miRNA-21 values and observed its association with mortality within 1 year. RESULTS: In general, there was a correlation between the increase in miRNA-21 levels and the mortality rate of breast cancer patients (r = 0.651; p <0.05). In the early stages, the increase in miRNA-21 values was not associated with breast cancer mortality (r= 0.25; p=0.218), but in the later stages, we found that the increase in miRNA-21 had a correlation with mortality (r=0.866; p=<0, 05). In advanced stage, high level of miRNA-21 had high asscociation with mortality rate (HR 17,27 95%CI 7,37-40,69). CONCLUSION: The increase in miRNA-21 values is associated with the 1-year survival of breast cancer patients.

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.

Relationship between trough level of tyrosine kinase inhibitor (imatinib and nilotinib) and BCR-ABL ratios in an Indonesian chronic-phase chronic myeloid leukemia (CML) population.

Objectives Among Chronic Myeloid Leukemia (CML) patients treated with Tyrosine Kinase Inhibitor (TKI-imatinib-nilotinib), some showed a suboptimal response. Based on pharmacokinetic studies, TKI trough level ( C m i n ∞ ${C}_{min}\hat{\infty }$ ) is associated with clinical outcomes, reflected by the BCR-ABL ratio. However, the interindividual pharmacokinetic variability of imatinib and nilotinib is found to be moderate-high. This study aims to analyze the relationship between TKI C m i n ∞   ${C}_{min}\hat{\infty }$ and BCL-ABL ratio in chronic-phase CML patients. Methods Cross-sectional study to CML chronic-phase patients treated with imatinib 400 mg daily or nilotinib 400 or 800 mg daily for ≥12 months. The exclusion criteria were therapy discontinuation within 29 days (imatinib) or 8 days (nilotinib) before the sampling day. Blood samples were drawn 1 h before the next dose. Imatinib-nilotinib C m i n ∞ ${C}_{min}\hat{\infty }$ and BCR-ABL ratio were measured using HPLC and RT-qPCR. The relationship was analyzed using bivariate correlation Spearman's rho test. Results Twenty-three imatinib and 11 nilotinib patients met the inclusion criteria. The mean imatinib and nilotinib C m i n ∞ ${C}_{min}\hat{\infty }$ were 1,065.46 ± 765.71 and 1,445 ± 1,010.35 ng/mL respectively. There were large interindividual variations in both groups (71.87% vs. 69.88%). Half of the patients in each group were found to reach C m i n ∞ ${C}_{min}\hat{\infty }$ target (≥1.000 ng/mL, imatinib; ≥800 ng/mL nilotinib), but only 12 (35,29%) of them result in BCR-ABL ratio ≤0.1%. C m i n ∞   ${C}_{min}\hat{\infty }$ imatinib was found to be significantly associated with BCR-ABL ratio. But, not with the nilotinib group. Conclusions There were high interindividual variations of imatinib and nilotinib correlated with BCR-ABL ratio, but no correlation in nilotinib.