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.

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.

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.

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.

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).

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.

The Role of Ursodeoxycholic Acid in Acute Viral Hepatitis: an Evidence-based Case Report.

AIM: to review the role of ursodeoxycholic acid in acute viral hepatitis. METHODS: following literature searching according to the clinical question on Pubmed and Cochrane Library. After filtered with our inclusion and exclusion criteria, one meta-analysis and two randomized clinical trials are obtained. Through critical appraisal, it was concluded that the articles meet the criteria for validity and relevance. RESULTS: the article found that there is a positive effect of ursodeoxycholic acid on the activity of serum transaminases and cholestasis indexes. However, there is insufficient evidence to support or to refute effects of ursodeoxycholic acid on disease's course as well as the viral load. CONCLUSION: better method of clinical trials are needed to obtain a valid and applicable result for daily practice.

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.

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.

Hypertensive crises in the adolescent: evaluation of suspected renovascular hypertension.

Hypertensive crises can be divided into two categories as hypertensive emergency and hypertensive urgency. Most authorities have defined hypertensive emergency as a situation that requires immediate reduction in blood pressure (BP) with parenteral agents because of acute or progressive target organ damage, whereas hypertensive urgency is a situation with markedly elevated BP but without severe symptoms or progressive target organ damage, wherein the BP should be reduced within hours, often with oral agents. Adolescent with hypertension should be suspected of having renovascular hypertension in spite of other causes. This case is presenting a 16-year-old boy with hypertensive crises due to suspected renovascular hypertension. His blood pressure was 240/120 at admission with hypertensive retinopathy grade III and there was increase in creatinine after administering ACE-inhibitor but his renal arteriography revealed normal, other physical examination and laboratory findings was normal. Regarding these findings, the conclusion was this patient got essential hypertension. As many hypertensive crises occur in any ages, clinicians should aware the possibility of renovascular hypertension in young patients with hypertensive crises. An early detection and urgent treatment are needed to prevent the implication of progressive target organ damage.

Reactivation of hepatitis B virus associated with chemotherapy and immunosuppressive agent.

Hepatitis B virus (HBV) reactivation after chemotherapy or immunosuppressive therapy is a serious cause of liver-related morbidity and mortality. The mechanism of HBV reactivation is still unclear, but it is believed due to the suppression of immune response hence increasing the viral load. No uniform diagnostic criteria are available, HBV reactivation can be confirmed by an increase in serum HBV-DNA level. There are many consensus regarding this issue, including the type and duration of nucleoside analogue therapy which need to be understood as not all chronic hepatitis B patients will lead to HBV reactivation. Recently, there has been an increased awareness of reactivation of occult hepatitis B virus, especially in hepatitis B virus endemic area, including Indonesia as part of Asia Pacific region. Preempative antiviral therapy was the best approach to prevent the HBV reactivation.

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 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.

Acute liver failure related to chemotherapy.

Hepatitis B virus (HBV) reactivation is a serious but preventable complication of immunosuppression. Chemotherapy in patients with lymphoma without specific anti-HBV prophylaxis leads to significant impairment of liver function and results in an overall liver-related mortality of greater than 5%. Prevention is a better approach than intervention at the time of reactivation. The cause of death is usually HBV-related fulminant liver failure. We reported a case of a male patient aged 42 years old who was present with acute liver failure related to chemotherapy for treatment of gastric lymphoma. He was later known as having chronic carrier hepatitis B, with high elevated transaminases and hyperbilirubinemia and signs of decompensated liver. The patient was admitted to High Care Unit for best supportive care but his condition was deteriorating and eventually died eventhough he had been already given antiviral agent.

Diagnosis and treatment update: cholangiocarcinoma.

Cholangiocarcinoma is a rare and very aggressive neoplasm that arises from the biliary epithelium, constitutes approximately 2% of all reported cancer, and accounts for about 3% of all gastrointestinal malignancies. Up to date, there are many modalities to diagnosis and treat with a range of sensitivity and specificity, and also the advantage and disadvantage of its modality. As a physician, we should be able to assess and choose promptly which modality is best for our patient, even for paliative care. Treatment modalities are surgery and non-surgery like adjuvant chemotherapy, radiation, chemoradiation, radiotherapy, TACE, 5-FU chemoinfusion, intralesion PEI, photodynamic therapy, liver transplantation, and paliative therapy. The choice of treatment varies individually. Radical surgery remains the optimal therapy and offering a potential for cure. Overall prognosis in these patients is poor and survival is limited to a few months.

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.

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.

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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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.

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.