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.

The Role of Diet in Influencing the Diversity of Gut Microbiome Related to Lupus Disease Activities: A Systematic Review.

Gut microbiome dysbiosis can affect the host immune system. The balance and activity of the gut microbiome, which are influenced by daily diet, might be associated with disease activity in systemic lupus erythematosus (SLE). Therefore, we conducted a systematic review based on the PRISMA guideline to explore the role and types of diet that affects the gut microbiome related to changes in SLE disease activity. All original and full-text English articles in the last ten years were included using predefined keywords according to PEO (population, exposure, and outcome) design in PubMed. The study subjects were carefully analyzed, including lupus-susceptible mice and humans with SLE on various diets. Children and pregnant women populations were excluded. Of 134 studies found, only seven full-text articles had met the inclusion criteria of which only one study conducted in human. This human study showed that dietary polyphenol as dihydrochalcones and flavanones affected the gut microbiome and ameliorated lupus disease activity. On the contrary, dietary flavones increased Blautia (family: Lachnospiraceae), and that often found in active lupus diseases. Furthermore, six studies in lupus-prone mice models showed that resistant starch (RS), retinoic acid (RA) or all-trans retinoic acid (tRA), and acidic water (AW) had influenced the gut microbiome, leading to an improved lupus development. Conversely, the 2018 commercial rodent diet, vitamin A-retinoic acid (VARA), neutral water (NW), and high tryptophan diet had impacted various microbiomes, resulting in increased lupus activity. Interestingly, several diets have the effect of either increasing or decreasing lupus disease activity depending on the microbiome they affect, such as AW associated with Turicibacter spp., which is frequently found in active lupus disease, and tRA in Bacteroidetes associated with renal pathology. To conclude, diet can influence the gut microbiome, which is related to the disease activity process of SLE.

Myocardial dissection complicating left sinus of Valsalva aneurysm in silent takayasu arteritis.

BACKGROUND: Myocardial dissection (MD) in a left sinus of Valsalva aneurysm (LSVA) is a rare condition that may lead to a fatal complication. Determining the MD etiology is challenging because of various possibilities ranging from congenital to acquired diseases. Here, we discuss an approach for determining the etiology of MD complicating LSVA in Takayasu arteritis (TA) and its treatment. CASE PRESENTATION: A 41-year-old man presented with dyspnea on heavy activities and a history of consciousness loss at the age of 24 years. He was diagnosed with dilated cardiomyopathy and MD complicating LSVA in TA based on combined clinical and pathognomonic diagnostic criteria of TA evaluated using vascular Doppler and computed tomography angiography of the aorta. The patient refused to undergo surgery and received an optimal dose of chronic heart failure therapy, a high-dose steroid, and azathioprine. The patient experienced some improvements in clinical condition, functional outcome, and inflammatory markers at 1-year follow-up. CONCLUSIONS: Clinical criteria and various imaging modalities may be used to determine the etiology of MD complicating LSVA in silent TA. As an alternative to surgery, the optimal medical treatment might result in a satisfactory outcome.

Cutaneous Vasculitis and Generalized Lymphadenopathy Associated with Extended-Spectrum Beta-Lactamase (ESBL)-Producing Escherichia coli Endocarditis: A Rare Case Report.

INTRODUCTION: Infective endocarditis (IE) has been known as the great imitator due to variable clinical manifestation, making its diagnosis challenging. A missed diagnosis could lead to inappropriate therapy. We presented a rare case of blood culture-negative infective endocarditis (BCNIE) due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli manifest with cutaneous vasculitis and generalized lymphadenopathy. We highlighted its diagnostic challenge and management. CASE ILLUSTRATION AND DISCUSSION: A 36-year-old male with known asymptomatic ruptured sinus of Valsalva (SOV) presented with fever of unknown origin for six months, fatigue, weight loss with a history of multiple hospitalizations. The physical examination revealed a continuous murmur at Erb's point, cutaneous vasculitis, and bilateral inguinal lymphadenopathy. The laboratory result was leukocytosis and elevated C-Reactive Protein (CRP). Generalized lymphadenopathy was detected from the thorax and abdominal Computed Tomography (CT) Scans. Positive Anti Nuclear Antibody (ANA) Indirect Immunofluorescence (IF) speckled pattern led us to consider an autoimmune as the etiology, but we still considered IE as a differential diagnosis due to history of structural heart disease. Detection of multiple tiny oscillating masses at the tricuspid valve from the echocardiogram and cardiac CT led to possible IE diagnosis. Negative three consecutive blood cultures led the diagnosis to BCNIE. Surgery was performed to evacuate the vegetations, repair the SOV, and tricuspid valve replacement with a bioprosthetic valve. These results in improvement of the patient's condition. ESBL-producing Escherichia coli yielded in tissue culture made the diagnosis of IE became definite. CONCLUSION: ESBL-producing Escherichia coli should be considered as the etiology of BCNIE. Cutaneous vasculitis and generalized lymphadenopathy as a manifestation of IE could lead to diagnostic confusion. A thorough investigation will help clinician to avoid delay or inappropriate treatment that could be detrimental for the patient.

Cut off point of neutrophil-to-lymphocyte ratio as a marker of active disease in systemic lupus erythematosus.

AIM: We aimed to measure sensitivity, specificity, and to determine the cut-off value (COV) ratio of neutrophil-to-lymphocyte (NLR) in patients with active systemic lupus erythematosus (SLE). METHODS: A cross sectional study was conducted using the retrospective data from Hasan Sadikin Lupus Registry (HSLR). The inclusion criteria were SLE patients aged 18 years or older who had documented data of neutrophil, lymphocyte, and SLE disease activity index (SLEDAI). Patients with infections, malignancies, and other inflammatory diseases recorded in registry were excluded. SLEDAI with a score of ≤ 4 is considered inactive and score of > 4 is considered active. The neutrophil-to-lymphocyte ratio was calculated by dividing the absolute number of neutrophils by the absoulte number of lymphocytes. Receiver Operating Characteristic (ROC) curve was used to analyze and determine optimal COV of NLR. RESULTS: The total sample in this study were 112 subjects with a dominant of female (95.54%) and the mean age of 34.45 ± 9.40 years. The median of SLEDAI was 4.5 with a range from 0 to 16, while the median of NLR was 2.68 with a range of 0.59 to 19.02. The ROC analysis showed the optimal cut-off in this study was 2.94 with sensitivity and specificity as high as 60.71% and 76.79%, respectively. CONCLUSION: Neutrophil-to-lymphocyte ratio with cut off value of 2.94 can be used to determine active disease of systemic lupus eythematousus.

Lethal Arrhythmia (Torsade de Pointes) in COVID-19: An Event Synergistically Induced by Viral Associated Cardiac Injury, Hyperinflammatory Response, and Treatment Drug?

Arrhythmias in patients with coronavirus disease 2019 (COVID-19) are prevalent and deserve special attention because they are associated with an increased risk of fatal outcome. The mechanism of arrhythmia in COVID-19 remains unclear. Here, we report our first case of confirmed COVID-19 with documented Torsade de Pointes (TdP). A 64-year-old woman, previously healthy, presented to our emergency department with progressive shortness of breath, dry cough, and 1 week of fever. She was treated with chloroquine phosphate, meropenem, and ciprofloxacin. After 5 days of admission, her condition deteriorated and she was admitted to the intensive care unit. The patient had two episodes of malignant arrhythmias within 24 hours. The former was TdP, and the latter was a fatal pulseless ventricular tachycardia that occured even after chloroquine was discontinued. There was evidence of cardiac injury shown by increased serum level of troponin I. We propose a synergistic concept of lethal arrhythmia due to direct severe acute respiratory syndrome coronavirus (SARS-CoV)-2-associated cardiac injury, hyperinflammatory response, and drug-induced arrhythmia.

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.