JAK2 as Predictor of Therapeutic Response in Patients with Chronic Myeloid Leukemia Treated with Imatinib.

Background: Chronic myeloid leukemia (CML) or chronic granulocytic leukemia is a myeloproliferative neoplasm indicated by the presence of the Philadelphia (Ph+) chromosome. First-line tyrosine kinase inhibitor, imatinib, is the gold standard for treatment. However, there has been known unresponsiveness to treatment, especially due to the involvement of other genes, such as the Janus kinase 2 (JAK2) gene. This study aimed to evaluate the relationships between JAK2 levels and complete hematological response (CHR), as well as early molecular response (EMR) after 3 months of imatinib treatment in patients with chronic phase CML. Methods: Patients with Ph+ CML in the chronic phase (n = 40; mean age, 40 ± 11 years) were recruited to complete assessments consisting of clinical examination and blood test, including evaluation of complete blood counts and the JAK2 levels, at baseline and following 3 months of therapy with imatinib (at an oral dose of 400 mg per day). Subjects were divided into two groups according to the presence of CHR and EMR. Results: JAK2 gene levels, phosphorylated, and total JAK2 proteins at baseline were significantly lower in the group with the presence of CHR and EMR. In addition, baseline JAK2 levels, including JAK2 gene expression, phosphorylated, and total JAK2 proteins, were negatively correlated with the presence of CHR and EMR. Conclusions: Based on these findings, JAK2 levels may be a potential indicator for evaluating treatment response on imatinib due to its role in the pathophysiology of CML.

Significant Inverse Correlation of Serum Levels of Osteoprotegerin (OPG) and Transferrin Saturation in Thalassemia Dependent Transfusion (TDT) Patients.

BACKGROUND: Osteoporosis is a major problem in transfusion-dependent thalassemia patients (TDT) patients. Osteoprotegerin (OPG) is one of several bone markers that are closely associated with osteoporosis in TDT patients. OPG is a glycoprotein that functions as a feedback receptor for the Receptor Activator of Nuclear Factor kappa B Ligand (RANKL), which is an alpha tumor necrosis factor receptor. One of the causes of decreased bone mass density is iron toxicity, which can be identified by showing elevated transferrin saturation. Bone mass dual X-ray absorptiometry (DEXA) is a gold standard for the diagnosis of osteoporosis, these procedures are not commonly available in Indonesia. This study was conducted to analyze the correlation between serum levels of OPG and transferrin saturation in TDT patients. METHODS: A correlational study with a cross-sectional approach analyzed data from TDT patients at Hemato-Oncology Medic Outpatient Clinic, Hasan Sadikin General Hospital, Bandung, Indonesia. Primary data were obtained through blood sampling and anthropometry measurement while secondary data were obtained from the patient's medical records. OPG and transferrin saturation levels were assessed using the ELISA method. Research data were analyzed using the rank Spearman correlation test. RESULTS: Data were collected from 51 research subjects (30 women dan 21 men). The median OPG level was 380 (170-1230) pg/mL and the median transferrin saturation level was 89.4 (66.7 - 96.2)%. Analysis of correlation showed a significant correlation between and transferrin saturation level with a coefficient value of r -0.539 and p-value <0.001. CONCLUSION: There was a significant inverse correlation between OPG with transferrin saturation in TDT patients.

Gender Disparities in Psychological Disturbances and Quality of Life Among Adolescent and Adult Patients with Thalassemia: A Review.

Thalassemia is a chronic disease caused by impaired globin chain synthesis, leading to ineffective erythropoiesis, hemolysis, and chronic anemia. The treatment of patients with thalassemia, including blood transfusion combined with chelation therapy has progressed and improved their survival and prognosis. However, thalassemia-related psychological problems and impaired health-related quality of life (QoL) challenges still exist. Gender is one of the factors that has been suggested, to contribute to the disparities in psychological outcomes. This review article examined the evidence for gender differences in psychological disturbances and QoL in adolescent and adult patients with thalassemia. A non-systematic search of the literature was conducted in PubMed and Google Scholar for English full-text available from 2013 to 2023. We identified 23 studies with a sample size ≥ 100 that examined gender disparities in anxiety, depression, and QoL in adolescent and adult patients with thalassemia (mean prevalence of female = 53.1%; mean age = 28 years). Our review shows that there are gender disparities in psychological distress and QoL in adolescent and adult patients with thalassemia. Statistically significant gender differences were demonstrated in 62% of the psychological and QoL outcomes from 16 studies. Female patients had a higher prevalence of anxiety, depression, and poorer QoL in some studies. However, further studies with sufficient power and design are necessary to confirm the existence of gender disparities in psychological disturbances and QoL outcomes.

Generalized Reddish Skin Nodules.

Diagnosis of nodular red lesions is challenging. The differential diagnosis includes dermal nevus, angioma, pyogenic granuloma, amelanotic melanoma, eccrine poroma, Kaposi's sarcoma, skin malignancy or metastasis. Erythema nodosum is one of the common consideration of the red skin nodules, however fully work up should be done to find the right diagnosis.A 60 years old female admitted to our hospital due to pain dark reddish skin nodules since one month. She had continuously high grade fever of 39 Celsius accompanied by arthralgia and fatigue since two months prior to admission and she lost 6 kg of weight in 2 months. On admission, physical examination revealed slight fever, pale conjunctiva, mild hepatosplenomegaly, tender dark red nodules 0.3 to 2 cm, firm edge, at her cheek, abdominal area and both lower extremities. No lymph nodes enlargement was noticed. Her laboratory test showed haemoglobin 9,1 g/dl, WBC 3,040/mL, PLT 149,000/mL, SGOT 48 U/L, SGPT 43 U/L, urea 12.5 mg/dL, creatinine 0.67 mg/dL. She was found to be non-reactive for HBsAg, HCV, and HIV antigens. Urine routine and microscopic examination was unremarkable.Her histopathology of left foot nodule biopsy revealed cutaneous lymphoma. The immunohistochemical (IHC) stain of CD45, CD20, and CD10 were positive, Ki67 were also positive  with >70% tumor cells, while CD3,CD56, CD30, and Granzyme were negative. Her final diagnosed was Cutaneous Diffuse large B cell lymphoma.Primary cutaneous lymphomas of B-cells occur less frequently than primary cutaneous T-cells lymphomas. Primary extra-nodal diffuse large B-Cell lymphoma (DLBCL) can be seen in up to 40% of cases. However skin involvement is less common and in a large cohort of DLBCL cases, skin involvement at presentation was seen only in 3.3% of cases.It characterized by few lesions, in general showing nodules or infiltrations of relatively fast growth and have no itching. The diagnosis is made by the immunohistochemical findings, clinicopathological correlation, and molecular pathology.  The lymphomas have different clinical behaviours despite being identical in morphological appearance. The primary lymphomas presents with local recurrence in up to 68% of the cases and with rare extra-cutaneous dissemination, with an average rate of 5-year survival varying from 89 to 96%. Cutaneous lymphoma should be always become one of considered diagnosed of skin red nodules even it is rare.

The role of chidamide in the treatment of B-cell non-Hodgkin lymphoma: An updated systematic review.

B-cell non-Hodgkin lymphoma (B-NHL) is a lymphoid malignancy derived from B-cells that remains difficult to treat. Moreover, relapses and refractory cases are common. Abnormalities in epigenetic mechanisms, such as imbalanced histone acetylation affecting certain genes, contribute to relapses and refractory cases. Chidamide (tucidinostat) is a novel histone deacetylase inhibitor that can reverse this epigenetic imbalance and has been approved for the treatment of T-cell malignancies. However, the use of chidamide for B-NHL remains limited, and the lack of relevant literature exacerbates this limitation. We conducted this review to summarize the anticancer activity of chidamide against B-NHL and its clinical applications to overcome drug resistance. This systematic review was conducted according to the PRISMA 2020 guidelines, using some keyword combinations from MEDLINE and EBSCO. The inclusion and exclusion criteria were also defined. Of the 131 records retrieved from databases, 16 were included in the review. Nine articles revealed that chidamide limited tumor progression by modifying the tumor microenvironment, stopping the cell cycle, inducing apoptosis and autophagy, and enhancing complement-dependent and antibody-dependent cell-mediated cytotoxicities.According to seven other studies, administering chidamide in combination with another existing therapeutic regimen may benefit not only patients with relapsed/refractory B-NHL, but also those with newly diagnosed B-NHL. Chidamide plays many important roles in limiting B-NHL progression through epigenetic modifications. Thus, combining chidamide with other anticancer drugs may be more beneficial for patients with newly diagnosed and relapsed/refractory B-NHL.

The role of high dose vitamin d and glutathione supplementation in COVID-19 treatment: A case series.

COVID-19 has been affecting millions of people worldwide and becoming a global public health burden. Therefore, exploring treatment options is essential to help flatten the curve and reduce hospitalization time. This is a case series of ten COVID-19 patients in Jakarta and Tangerang, Indonesia, who received a high dose of vitamin D and glutathione supplementation daily. Within 5-7 days of treatment, all patients were confirmed COVID-19 negative. To date, this is the first report from Indonesia describing the potential benefit of supplementing vitamin D and glutathione concurrently in improving clinical conditions and expediting the recovery time of COVID-19 patients.

The effects of aspirin on the outcome of COVID-19: A systematic review and meta-analysis.

BACKGROUND: Repurposing the use of aspirin to treat hospitalized patients with COVID-19 is a sensible approach. However, several previous studies showed conflicting results. This meta-analysis was aimed to assess the effect of aspirin on the outcome in patients with COVID-19. METHODS: Systematic search using relevant keywords was carried out via several electronic databases until February 21, 2021. Research studies on adults COVID-19 patients with documentation on the use of aspirin and reported our outcomes of interest were included in the analysis. Our main outcome of interest was all types of mortality, while the incidence of thrombosis and bleeding were considered as secondary outcomes. Estimated risk estimates of the included studies were then pooled using DerSimonian-Laird random-effect models regardless heterogeneity. RESULTS: Seven studies with a total of 34,415 patients were included in this systematic review and meta-analysis. The use of aspirin was associated with a reduced risk of mortality (RR 0.56, 95% CI 0.38-0.81, P = 0.002; I2: 68%, P = 0.005). Sensitivity analysis by differentiating in-hospital (active aspirin prescription) and pre-hospital use of aspirin could significantly reduce the heterogeneity (I2: 1%, P = 0.4). Only one study reported the incidence of major bleeding between aspirin and non-aspirin users (6.1% vs. 7.6%, P = 0.61). The association between the use of aspirin and the incidence of thrombosis were contradictory in two studies. CONCLUSION: The use of aspirin was significantly associated with a reduced risk of mortality among patients with COVID-19. Due to limited studies, the effect of aspirin on the incidence of thrombosis and bleeding in patients with COVID-19 could not be drawn definitively.

The use of Janus Kinase inhibitors in hospitalized patients with COVID-19: Systematic review and meta-analysis.

BACKGROUND: The evidence of using JAK inhibitors among hospitalized patients with COVID-19 is conflicting. The systematic review and meta-analysis aimed to address the efficacy of Janus Kinase (JAK) Inhibitors in reducing risk of mortality among hospitalized patients with COVID-19. METHODS: Several electronic databases, including PubMed, EuropePMC, and the Cochrane Central Register of Controlled Trials, with relevant keywords "COVID-19″ AND ("JAK inhibitor" OR "Ruxolitinib" OR "Tofacitinib" OR "Fedratinib" OR "Baricitinib") AND ("Severe" OR "Mortality"), were used to perform a systematic literature search up to December 11, 2020. All studies pertinent to the predetermined eligibility criteria were included in the analysis. Our outcome of interest was all types of mortality, clinical improvement, and clinical deterioration. Dichotomous variables of our outcomes of interest were analyzed using Maentel-Haenszel formula to obtain odds ratios (ORs) and 95% confidence intervals (CI) with random-effects modeling regardless of heterogeneity. RESULTS: Five studies with a total of 1190 patients and were included in this systematic review and meta-analysis. The use of JAK inhibitors was associated with a reduced risk of mortality (OR 0.51, 95% CI 0.28-0.93, P = 0.02; I2: 7.8%, P = 0.354) and clinical improvement (OR 1.76, 95% CI 1.05-2.95, P = 0.032; I2: 26.4%, P = 0.253). The use of JAK inhibitors was not associated with a reduced risk of clinical deterioration (OR 0.58, 95% CI 0.28-1.19, P = 0.136; I2: 24.1%, P = 0.267). CONCLUSION: The use of JAK inhibitors was significantly associated with a reduced risk of mortality, and clinical improvement in hospitalized patients with COVID-19.

Cytotoxicity of Simvastatin in Human Breast Cancer MCF-7 and MDA-MB-231 Cell Lines.

OBJECTIVE: Statins, 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors, have been shown to be effective in the treatment of cardiovascular disease. Recent reports demonstrate an anticancer effect induced by statins on lung and prostate cancer cells. The present study aimed to investigate the therapeutic potential of Simvastatin can serve as chemotherapeutic agent against human breast cancer MCF-7 and MDA-MB-231 cell lines. METHODS: The cytotoxic effect of simvastatin against breast cancer cells were evaluated using MTT assay. The related mechanism of cell death was further determined by trypan blue staining, morphological changes observation, and drug combination index. RESULTS: The results showed that simvastatin treatment substantially induced cell death in a dose-dependent and time-dependent manner on MCF-7 and MDA-MB-231 cells. Simvastatin exhibited a highly cytotoxic effect on MCF7 and MDA-MB-231 with half-maximal (50%) inhibitory concentration (IC50) 8.9 µM and 4.5 µM respectively. Consistently, we observed antiproliferative effect of Simvastatin was associated with apoptosis on breast cancer cell lines by determination of morphological changes. Moreover, this drug demonstrated a synergistic activity with doxorubicin on triggering cell death in MCF7 cells, but not in MDA-MB-231. CONCLUSION: Simvastatin has a potent cytotoxic effect resulting in the death of human breast cancer MCF-7 and MDA-MB-231 cell lines, demonstrating its potential as a new candidate for cancer drug.
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Challenge in diagnosis of COVID-19 in hemodialysis patient: a case report and brief review of the literature.

Diagnosis of COVID-19 in end-stage kidney disease (ESKD) patients on hemodialysis is challenging,  as the symptoms are often atypical. Herein, we reported a confimed case of COVID-19 in a patient on maintenance hemodialysis. A 38-year-old man with ESKD on regular hemodialysis initially presented with progressive shortness of breath and dry cough, without fever. He had lymphopenia, and chest X-ray suggested pulmonary edema with cardiomegaly and suspected bilateral bronchopneumonia. The patient clinically improved after 7 days of hospitalization, and was subsequently discharged from hospital. Ten days after being discharged, the patient was re-admitted with progressive shortness of breath and dry cough, without fever. SARS-CoV-2 infection was later confirmed by a qualitative RT-PCR test and the diagnosis COVID-19 pneumonia was established. We presented a case of atypical presentation of COVID-19 in an ESKD patient on maintenance hemodialysis with a brief review of the current literature.

Typhonium flagelliforme extract induce apoptosis in breast cancer stem cells by suppressing survivin.

CONTEXT: Breast cancer stem cells (bCSCs) are a small population of cancer-initiating cells within breast cancer, characterized as CD44+ CD24-/low. bCSCs develop apoptosis resistance by expressing survivin and suppressing caspase-9 and caspase-3 expression. Typhonium flagelliforme tuber extract (TFTe) can induce apoptosis in several types of cancer cells; however, the effects of TFTe to induce the bCSCs remain unclear. AIMS: This study aimed to investigate the effects of TFTe on apoptosis induction in bCSCs through the suppression of survivin and the exhibition of caspase-9 and caspase-3. SETTINGS AND DESIGN: This study employed a posttest only, control group design. SUBJECTS AND METHODS: To analyze the apoptotic index, TFTe, at concentrations of 25 (Tf1d), 50.89 (Tf2d), and 100 µg/mL (Tf3d) were used to treat bCSCs for 24 h, in a humidified incubator containing 5% CO2, at 37°C. The control group was exposed to dimethyl sulfoxide. Apoptosis was measured by propidium iodide and acridine orange double-staining, and the expression levels of survivin, caspase-9, and caspase-3 were assessed by immunocytochemistry. STATISTICAL ANALYSIS USED: Differences were analyzed by the independent Student's t-test, to compare two groups, and the Kruskal-Wallis test, to compare more than two groups. P < 0.05 was considered statistically significant. RESULTS: TFTe inhibited bCSC proliferation, with an IC50 value of 50.89 µg/mL, and significantly induced apoptosis in bCSCs (P < 0.001). TFTe also significantly decreased the expression levels of survivin in bCSCs (P < 0.001) and increased the expression levels of caspase-9 and caspase-3 (P < 0.001). CONCLUSIONS: TFTe can induce apoptosis in bCSCs by decreasing survivin expression levels and increasing the levels of caspase-9 and caspase-3.

The Use of Therapeutic-Dose Anticoagulation and Its Effect on Mortality in Patients With COVID-19: A Systematic Review.

The incidence of venous thromboembolism (VTE) events in patients with COVID-19 treated with a standard thromboprophylaxis dose of anticoagulants remains high. We conducted a systematic review in order to explore the association between therapeutic-dose anticoagulation and its effect on mortality in patients with COVID-19. A systematic search was carried out using the electronic databases of PubMed, EuropePMC, and the Cochrane Central Database, using specific keywords. All articles that fulfilled the inclusion criteria were included in the qualitative analysis. There were 8 observational studies included in the final qualitative analysis. Quality assessment using the Newcastle-Ottawa Scale (NOS) showed a mean score of 7.5 ± 1.06, indicating moderate to high quality of the studies. Three retrospective cohort studies reported a reduction in the mortality rate, while 6 other studies showed no mortality benefits among patients with COVID-19 treated with therapeutic-dose anticoagulation. There was a slight tendency toward a reduction in the mortality rate among mechanically-ventilated patients with COVID-19 receiving therapeutic-dose anticoagulation. Bleeding events and thrombotic complications among patients receiving therapeutic-dose anticoagulation were reported in 3 studies. Although it is too soon to draw any conclusions, this systematic review draws attention to current evidence regarding the association between therapeutic-dose anticoagulation and its effect on mortality in patients with COVID-19.

The Correlation of KRAS Gene Expression and P53 Immunoexpression in Colorectal Adenocarcinoma.

BACKGROUND: Colorectal Adenocarcinoma (ADCCR) is the third most cancer not only in the world but also in Indonesia. There were 623 cases of ADCCR at Dr Hasan Sadikin hospital within 2015-2017. Both KRAS and TP53 mutation are known as genes which involve in carcinogenesis through the same pathway, namely the chromosomal instability pathway. In West Java, researches focusing on mutation KRAS and p53 also a correlation between both biomarkers among ADCCR patients are still limited. AIM: Therefore, this research aimed to perceive a correlation between KRAS gene expression with p53 immunoexpression in ADCCR. METHODS: Cross section research design was performed to 62 cases of ADCCR as paraffin block taken from 4 hospitals in West Java, including Dr Hasan Sadikin hospital Bandung, Santosa hospital Bandung, Borromeus hospital Bandung and Syamsudin hospital Sukabumi from January 1st 2014 to 31s November 2018. KRAS mutation gene data taken from secondary data at molecular laboratory in Ciptomangunkusumo Hospital Jakarta and Dr Sardjito Hospital Jogjakarta, while the detection of p53 immunoexpression data using immunohistochemical staining was carried out in the Laboratorium of Anatomical Pathology of Padjadjaran University (Dr Hasan Sadikin Hospital). All data were analysed using Chi-Square test with p-value < 0,05 of significant level then proceeded with Stata ver.11 for windows. RESULTS: The results of this study showed that KRAS gene expressions from 62 sample consist of 39 wild type KRAS (62.39%) and 23 mutant KRAS (37.1%). The p53 immunoexpression consists of 27 negative cases (non-mutant p53) and 35 mutant p53, which includes 10 cases as focal expression (16.33%) and 25 cases as diffuse expressions (40.33%). There is a significant association between KRAS gene expression and p53 immunoexpressions in ADCCR (p = 0.04), with mild positive correlation (Rho 0.28). CONCLUSION: This study concluded that KRAS and p53 mutations are involved in carcinogenesis, and the p53 mutation is a more dominant risk factor than KRAS mutation among West Java people. P53 mutations with diffuse pattern tend to express mutant KRAS while p53 negative and having a focal pattern tend to express wt KRAS.

Paraneoplastic Arthritis in a Patient with Non-Hodgkin's Lymphoma.

Paraneoplastic syndromes are a group of disorders associated with benign or malignant tumors but not related to mass effect or invasion directly. Paraneoplastic syndromes may affect any organic system of the human body, such as endocrine, neurologic, dermatologic, hematologic, rheumatologic. Paraneoplastic rheumatic syndromes are not quite common, about 7-10% of paraneoplastic syndromes, and may mimic rheumatic diseases. We present an interesting case of paraneoplastic arthritis in a woman with non-Hodgkin's lymphoma.

Giant Scrotal Hydrocele and Bilateral Leg Lymphedema as Clinical Manifestation of Chronic Lymphatic Filariasis.

A 51-year-old male came with the complaint of recurrent swelling in the scrotum and legs. Swelling of the scrotum first appeared 17 years ago in the left scrotum approximately the same size as an apple and underwent surgery. However, 2 years after surgery, the swelling reemerged and gradually increase in size in both scrotums. Left leg swelling began to emerge 5 years ago followed by right leg 3 years after. The patient lives in Sarmi regency Papua province (endemic).

Chronic Hypoparathyroidism Due to Partial Thyroidectomy with Intracranial Calcification.

A 57 year old female came with the complaint of recurrent headache, often fatigue, and sometimes feel numbs and rigid in her extremities, no other symptom was noted. Her body weight is stable and she was in menopausal state. She had a history of partial thyroidectomy 20 years ago and continues thiamazole 2.5 mg with seldom regular consult to physician. From the physical examination, the patient had a scar from thyroid surgery and other organs were in the normal condition. From laboratory examination, there was slight normocytic normochromic anemia (Hb: 10.7 gr/dL), normal fT4: 1.21 ng/dL (0.7-1.48 ng/dL), slightly low Calcium: 8.3 mg/dL (8.5-10.2 mg/dL), others were within normal limit but there was no Phosphorus level data. She was currently on medication: thiamazole 2.5 mg once daily, CaCO3 500 mg once daily, and alfacalcidol 1 mcg once daily, to prevent the rigid and numbness that she felt before. For further investigation, we performed a PTH test with result of hypoparathyroidism with parathyroid hormone 7 pg/mL (15-65 pg/mL) and brain CT-scan with result there was a symmetrical bilateral calcification in radiate corona, frontal lobes, temporal lobes, basal ganglia, thalamic, and dentate nuclei of cerebelli. There was no data about the histopathology examination of the thyroid tumor because the patient did not keep the data. The mechanism of intracranial calcification in hypoparathyroidism, more often seen in pseudohypoparathyroidism than in idiopathic hypoparathyroidism, has not been completely elucidated. It may be related more to the duration of hypocalcaemia and hyperphosphataemia than parathyroid hormone itself. Hyperphosphataemia promotes ectopic calcification in brain tissue in hypoparathyroidism. Intracranial calcification is one of the features of chronic hypocalcemia, and the calcifications typically involve basal ganglia, thalami, and the cerebellum.

Scoring System Development and Added Value of Albuminuria to Estimate Carotid Intima-media Thickness (CIMT) in Type 2 Diabetes Mellitus Patients.

AIM: to develop a scoring system and measure the diagnostic added value of albuminuria to estimate CIMT. METHODS: cross-sectional study was done in Endocrine Outpatient Clinic Cipto Mangunkusumo Hospital between March-May 2012 in T2DM patients without history of cerebrocardiovascular event, CKD stage ≥ III, and smoking. Bivariate analysis and multivariate (logistic regression) analysis was done, followed by developing the scoring system. RESULTS: from 71 subjects, there were 67.6% with increased CIMT and 73.3% with albuminuria. From 48 subjects with increased CIMT, 87.5% had albuminuria. Albuminuria measurement had high sensitivity (87.5%). Adding albuminuria measurement will increase the AUC as 2.3%. Estimation score for duration of DM, hypertension, dyslipidemia were as follows 1, 2, 1 respectively. Probability score of increased CIMT for score <2, 2, and >2 was as follows 15%, 57%, and 90%. CONCLUSION: albuminuria measurement increase the diagnostic value of CIMT. Scoring system can be used as a screening tool to estimate the increased of CIMT in type 2 DM patients without history of cerebrocardiovascular event, CKD stage ≥ III, and smoking.