Footsteps to Wellness: A Systematic Review and Meta-Analysis of Walking Pace and Coronary Artery Disease Event.

Coronary artery disease (CAD) poses a global health challenge, necessitating effective preventive strategies. Despite the pivotal role of physical activity in cardiovascular health, many fall short of recommended guidelines for daily physical activity. Simple and accessible, walking presents an opportunity, with increased pace emerging as a potential strategy for reducing the risk of cardiovascular diseases. Thus, we aimed to elucidate the potential association between walking pace and the risk of CAD events in adults without a prior history of CAD through a systematic review. We searched PubMed, Scopus, Web of Science, and ScienceDirect without publication date restrictions to identify prospective cohorts that analyzed walking pace and adult CAD events. The literature search conducted from April 02, 2023, to August 21, 2023, identified a total of four studies (six cohorts) for meta-analysis using random-effects models. The Newcastle-Ottawa Scale was used to assess study quality, and data extraction involved two independent reviewers. The analysis calculated overall relative risks (RRs) and 95% confidence intervals (CIs) for those with the quickest walking paces compared to those with the slowest walking paces. A funnel plot analysis for publication bias and subgroup analysis were also conducted. Results from the meta-analysis involving 160,519 participants and 3,351 CAD events demonstrated a 46% decreased risk for those walking at the quickest pace (pooled RR = 0.54, 95% CI = 0.45-0.66). No significant heterogeneity was observed. In conclusion, walking pace emerges as a significant risk factor for CAD events in adults without a prior history of CAD. It serves as a potential screening tool to identify individuals at higher risk. Promoting a faster walking pace as a daily activity may effectively mitigate the burden of CAD.

Relapsed isolated CNS lymphoma treated with radiotherapy and intrathecal methotrexate followed by high-dose intravenous methotrexate, rituximab, and temozolomide: A case report.

Key Clinical Message: Optimized treatments for relapsed isolated CNS lymphoma (RI-SCNSL) remains under investigation. Temozolomide combination-based therapy, which is often used in glioblastoma may be used as potential treatment in RI-SCNSL. Abstract: One of the most common types of non-Hodgkin lymphoma (NHL) is diffuse large B-cell lymphoma (DLBCL). Despite advances in treatment, relapsed isolated CNS lymphoma (RI-SCNSL) from DLBCL remains an issue. The optimal approach in RI-SCNSL remains an area of active investigation as currently there is no high level of evidence for the treatments due to lack of randomized studies. In this case report, we present a DLBCL patient with CNS recurrence treated radiotherapy and intrathecal methotrexate (MTX) followed by intravenous high-dose MTX, rituximab, and temozolomide. To the best of our knowledge, this is the first case report describing RI-SCNSL treated with the regiments above which also include temozolomide which is used for glioblastoma.

Association of metformin use with abdominal aortic aneurysm: A systematic review and meta-analysis.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a cardiovascular disease characterized by a high mortality rate when ruptured. Some studies suggest a potential inverse correlation between AAA and diabetes patients, especially those undergoing metformin treatment. However, this relationship remains unclear. This paper offers a systematic review and meta-analysis with the objective of clarifying the influence of metformin on AAA. METHODS: A search for relevant articles was performed across multiple databases including PubMed, ScienceDirect, Cochrane and Scopus. The focus was on studies that examined the comparative effects of metformin and non-metformin treatments on AAA patients. Data from appropriate studies were consolidated to estimate the effects. Our study encompassed 11 articles, comprising 13 cohorts that compared metformin (n = 32,250) with a control group (n = 116,339). RESULTS: The random effects meta-analysis revealed that metformin was associated with a slower growth rate (weighted mean difference (WMD) -0.86 mm; 95% CI: -1.21 to -0.52; p < 0.01; I2: 81.4%) and fewer AAA-related events (OR: 0.54; 95% CI: 0.34 to 0.86; p = 0.01; I2: 60.9%). The findings suggest that metformin may be linked to a reduced risk of aortic aneurysm. A meta-regression analysis indicated that the association between metformin and AAA growth was significantly influenced by male gender (p = 0.027), but not by age (p = 0.801), hypertension (p = 0.256), DM (p = 0.689), smoking history (p = 0.786), use of lipid-lowering agents (p = 0.715), or baseline diameter (p = 0.291). CONCLUSION: These results hint at a potential role for metformin in limiting annual AAA growth, AAA-related events, and the risk of AAA.

Cytomegalovirus Infection in Patient with Clear Cell Renal Cell Carcinoma.

Introduction: Cytomegalovirus (CMV) infection is a widespread condition that can affect individuals of all ages. Most cases of CMV infection are mild and resolve on their own. However, in immunocompromised individuals, such as post-transplant patients or those with cancer, severe infections can occur. While there have been several studies on CMV infection in post-transplant patients, there is limited literature on CMV infection in cancer, particularly in kidney cancer. Case Report. In this case report, we present the case of a 61-year-old man with clear cell renal cell carcinoma who underwent targeted therapy with the receptor tyrosine kinase (RTK) inhibitor lenvatinib and the mammalian target of rapamycin (mTOR) inhibitor everolimus. The patient was hospitalized for 26 days and admitted to the intensive care unit (ICU) due to shortness of breath, decreased oxygen saturation, and irregular breathing. Cytomegalovirus polymerase chain reaction (PCR) test results were positive. Given the high prevalence of CMV infection in developing countries, it is likely that the patient had a reactivation of CMV. As such, the patient was subsequently treated with ganciclovir for 14 days and showed improvement in symptoms such as shortness of breath, cough, fever, and increased oxygen saturation. Following recovery, the patient received maintenance therapy with oral valganciclovir for 7 days. No further symptoms appeared during subsequent cancer treatments. Conclusion: Cancer patients who are undergoing treatment are at a higher risk for developing opportunistic infections, which can result in morbidity and mortality. Therefore, healthcare professionals should be aware of the possibility of CMV infection in cancer patients and be prepared to diagnose and treat the infection, particularly in areas where the prevalence of CMV infection is high.

A Comparative Analysis of the Efficacy and Safety of Hot Snare Polypectomy and Cold Snare Polypectomy for Removing Small Colorectal Polyps: A Systematic Review and Meta-Analysis.

Both cold snare polypectomy (CSP) and hot snare polypectomy (HSP) have been shown to be effective methods for removing small colorectal polyps, but the optimal method for achieving complete resection remains unclear. To address this issue, we conducted a systematic search of relevant articles using databases such as PubMed, ProQuest, and EBSCOhost. The search criteria included randomized controlled trials that compared CSP and HSP for small colorectal polyps ≤10 mm and the articles were screened based on specific inclusion and exclusion criteria. The data were analyzed using RevMan software (version 5.4; Cochrane Collaboration, London, United Kingdom), and meta-analysis was performed with outcomes measured using pooled odds ratios (OR) and 95% confidence intervals (CI). The Mantel-Haenszel random effect model was used to calculate the OR. We selected a total of 14 randomized controlled trials involving 11601 polyps for analysis. Pooled analysis showed no statistically significant difference in the incomplete resection rate between CSP and HSP (OR: 1.22; 95% CI: 0.88-1.73, p-value: 0.27; I2: 51%), en bloc resection rate (OR: 0.66; 95%CI: 0.38-1.13; p: 0.13; I2: 60%), and polyp retrieval rate (OR: 0.97; 95%CI: 0.59-1.57; p: 0.89; I2: 17%). For safety endpoints, there is no statistically significant difference in intraprocedural bleeding rate between CSP and HSP per patient analysis (OR: 2.37, 95% CI: 0.74-7.54; p: 0.95; I2: 74%) and per polyp basis (OR: 1.84, 95% CI: 0.72-4.72; p: 0.20; I2: 85%). CSP had lower OR for the delayed bleeding outcome when compared with the HSP group per patient basis (OR: 0.42; 95% CI: 0.2-0.86; p: 0.02; I2: 25%), but not in the per polyp analysis (OR: 0.59; 95% CI: 0.12-3; p: 0.53; I2: 0%). Total polypectomy time was significantly shorter in the CSP group (mean difference: -0.81 minutes; 95% CI: -0.96, -0.66; p:<0.00001; I2: 0%). Thus, CSP is both an efficacious and safe method for removing small colorectal polyps. Therefore, it can be recommended as a suitable alternative to HSP for the removal of small colorectal polyps. However, more studies are necessary to evaluate any long-term differences between the two methods such as polyp recurrence rates.

Chronic Myeloid Leukemia, from Pathophysiology to Treatment-Free Remission: A Narrative Literature Review.

Chronic myeloid leukemia (CML) is one of the most common leukemias occurring in the adult population. The course of CML is divided into three phases: the chronic phase, the acceleration phase, and the blast phase. Pathophysiology of CML revolves around Philadelphia chromosome that constitutively activate tyrosine kinase through BCR-ABL1 oncoprotein. In the era of tyrosine kinase inhibitors (TKIs), CML patients now have a similar life expectancy to people without CML, and it is now very rare for CML patients to progress to the blast phase. Only a small proportion of CML patients have resistance to TKI, caused by BCR-ABL1 point mutations. CML patients with TKI resistance should be treated with second or third generation TKI, depending on the BCR-ABL1 mutation. Recently, many studies have shown that it is possible for CML patients who achieve a long-term deep molecular response to stop TKIs treatment and maintain remission. This review aimed to provide an overview of CML, including its pathophysiology, clinical manifestations, the role of stem cells, CML treatments, and treatment-free remission.

Pneumonia Deterioration Occurring After C-section in a Preeclamptic Patient: A Case Report.

Pneumonia is a type of lung infection that can be caused by bacteria, viruses, or fungi. It is a serious condition that can affect people of all ages, but it is more dangerous for certain populations, such as the elderly, young children, and people with weakened immune systems. Pneumonia can cause higher risk in patients undergoing surgery, including C-sections. In this case report, we present a pregnant woman who was scheduled for a C-section due to preeclampsia and was initially suspected of concomitant pneumonia. The patient successfully underwent the C-section, but unfortunately experienced a deterioration in her pneumonia after the surgery. She was later admitted to ICU and placed on mechanical ventilation due to the deterioration. Despite the acknowledged risks, including the possibility of death, the patient's family chose to bring the patient home due to their belief that there had been no improvement in the patient's condition and a feeling of resignation. In conclusion, pregnant patients who have pneumonia may require an emergency C-section due to several conditions such as preeclampsia, and the C-section can be conducted successfully. However, it is important for physicians to be aware of the potential for the worsening of pneumonia postoperatively. Post-operative pneumonia is a serious condition that can have a significant impact on the health of patients who have undergone a C-section.

Surgical Complications in Myeloproliferative Neoplasm Patient with Essential Thrombocythemia: A Case Report.

Introduction: Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) which could complicate surgical procedures due to thrombosis and spontaneous bleeding. However, currently, there is neither concrete guideline nor prerequisite for ET patients who underwent operations. Case Report: A 48 year-old-female was admitted to the emergency unit on 21 February 2020 due to vomiting and inability to pass gas/stool. The patient previously had an operation for uterine myoma two weeks before which showed thrombocyte count of 688,000/mm3. The patient was previously diagnosed with essential thrombocythemia with positive JAK2V617 point mutation on 24 June 2019. Laboratory examination showed thrombocyte 1,134,000/mm3 and leukocyte 22,700/mm3 suggestive of neutrophilia. CT scan showed fluid collection with blood density in the abdomen and pelvis. She was then diagnosed with obstructive ileus due to abdominal abscess and intestine adhesion. Adhesiolysis by laparoscopy was performed on 29 February 2020 with thrombocyte count of 727,000/mm3. Patient was able to pass flatus and defecate three days post-surgery. However, a decrease of hemoglobin to 8.2 g/dL on 3 March 2020 with thrombocyte count of 700,000/mm3 was suggestive of internal bleeding. She was discharged three weeks post-surgery after improvement of clinical condition with thrombocyte count of 850,000/mm3. She was given hydroxyurea 1000 mg once every two days, aspirin 80 mg OD, anagrelide 1 mg OD, and amlodipine 10 mg OD. Conclusion: Myeloproliferative disease patients with high thrombocyte count are subjected to increased risk of thrombotic complications in perioperative settings, thus perioperative management and risk assessment are important to improve quality of life and prevent complications. Surgery in MPN patients with elevated thrombocytes may be considered if the benefits outweigh the risks. More studies in this field should be conducted in-order to provide more data for a guideline or systematic review/meta-analyses.

Factors Associated With Candidiasis in Systemic Lupus Erythematosus Patients in Cipto Mangunkusumo National General Hospital: A Single-Center Case-Control Study.

BACKGROUND: Infection has been a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. One of the infections encountered in SLE patients is candidiasis. Therefore, we aimed to conduct a case-control study to explore the risk factors associated with candidiasis in SLE patients in our center. METHODS: Medical records of 20 SLE patients with fungal infection were obtained, and a case-control study was conducted with an age and sex-matched control group of 20 patients. Data were obtained from the Cipto Mangunkusumo National General Hospital. SLE confirmatory diagnosis was based on Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria. Patients with comorbidities of various chronic diseases (diabetes, HIV, and chronic kidney disease) were excluded. Statistical analysis was conducted using the Mann-Whitney U test with statistical significance defined as a p-value < 0.05. RESULT: Based on the analysis, a maximum corticosteroid dose of 24 (4-250) mg/day for the last one year was associated with the development of fungal infection (p = 0.047). Lower absolute lymphocyte count (748 cells/mm³ versus 1635 cells/mm³) was also associated with the occurrence of candidiasis in SLE patients (p = 0.008). CONCLUSION: Physicians should be aware that corticosteroid use in SLE patients may cause candidiasis. Monitoring of maximum corticosteroid dose and absolute lymphocyte count is important to help prevent candidiasis. Patients should also be educated regarding the risk of candidiasis from corticosteroid use.

Efficacy and safety profile of COVID-19 mRNA vaccine in patients with hematological malignancies: Systematic review and meta-analysis.

Patient populations, including those with hematological malignancies, have different responses to COVID-19 vaccines. This study aimed to quantitatively analyze the efficacy and safety of COVID-19 mRNA vaccines in patients with hematological malignancies. Studies reporting on the efficacy and safety of COVID-19 mRNA vaccines in cohorts with hematological malignancies compared to healthy controls were systematically searched in four databases. Meta-analysis and subgroup analyses were performed to generate quantitative synthesis. Fifteen studies with 2,055 cohorts with hematological malignancies and 1,105 healthy subjects as control were included. After two doses of COVID-19 vaccination, only 60% of cohorts with hematological malignancies were seroconverted compared to healthy controls (RR 0.60; 95%CI 0.50-0.71). A single dose of the vaccine resulted in a significantly lower seroconversion rate (RR 0.30; 95%CI 0.16-0.54). Non-Hodgkin lymphoma cohorts had the lowest rate of seroconversion (RR 0.5; 95%CI 0.35-0.71) and those who received active treatments had lower immunological responses (RR 0.59; 95%CI 0.46-0.75). Antibody titers were lower in cohorts with hematological malignancies without any differences in adverse effects in both groups. In conclusion, cohorts with hematological malignancies showed a lower seroconversion rate and antibody titers after receiving COVID-19 mRNA vaccines. The type of malignancy and the status of treatment had a significant impact on the response to vaccination. The vaccines were shown to be safe for both patients with hematological malignancies and healthy controls. Booster doses and stricter health protocols might be beneficial for patient populations.

Predisposing Factors of Tuberculosis Infection in Systemic Lupus Erythematosus Patients: A Single-Center Case-Control Study.

INTRODUCTION: Indonesia has the second-highest tuberculosis cases in the world, according to the global WHO tuberculosis report, amounting to approximately 10% of the world's tuberculosis cases. Systemic lupus erythematosus (SLE) patients are at an increased risk for tuberculosis infection. This research aims to analyze the association between corticosteroid pulse dose, corticosteroid cumulative dose, SLE disease duration, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and lupus nephritis status with the development of tuberculosis in SLE patients. METHODS: This research was a matched case-control study to identify risk factors of tuberculosis infection in SLE patients. Data were taken from medical records of Cipto Mangunkusumo National General Hospital, a national tertiary hospital. Inclusion criteria were patients who meet the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria of SLE in the period of 2012-2016 or patients who meet the SLICC 2012 SLE criteria and developed tuberculosis between 2012 and 2016. Statistical analyses used were bivariate analysis and correlation analysis. All statistical analyses were conducted using SPSS software (IBM Corp., Armonk, NY). All statistical analyses were defined as statistically significant when the p-value was less than 0.05. RESULTS: A total of 48 SLE patients were included from medical records consisting of 24 SLE patients with tuberculosis infection and controls of 24 SLE patients without tuberculosis infection. In this study, it was observed that the presence of lupus nephritis (p = 0.001), administration of pulse corticosteroids (p = 0.048), high corticosteroid cumulative dose (p = 0.001), and high SLEDAI score (p = 0.003) were associated with tuberculosis infection. Correlation analysis showed that all of these variables had a weak positive correlation with tuberculosis infection in SLE patients. CONCLUSION: SLE patients with lupus nephritis, administration of pulse corticosteroids, high cumulative corticosteroid dose, and high SLEDAI score have a higher risk of tuberculosis infection. Clinicians and patients should be aware of these risk factors in SLE patients to prevent tuberculosis infection. Corticosteroid pulse dose should be avoided in SLE patients and if it is needed, tuberculosis prophylaxis may be considered.

Role of Anti-B-Cell Maturation Antigen (BCMA) in the Management of Multiple Myeloma.

Over the past few decades, treatment options have become more advanced for multiple myeloma (MM), one of the most prevalent hematological cancers; however, multiple myeloma remains an incurable disease due to its poor response to therapy and high rates of resistance, which cause relapsed/refractory or multiple myeloma. Researchers have described anti-BCMA (B-cell maturation antigen) as a promising treatment regimen that targets the BCMA biomarker in the affected plasma cells. BCMA is a protein that is specifically expressed in plasma-cell neoplasms by using several mechanisms, such as CAR T cells (Chimeric Antigen Receptor T cells), antibody-drug conjugates, and bispecific T-cell engagers, thus allowing for a rapid response in the treatment of resistant or relapsed/refractory multiple myeloma patients. Anti-BCMA treatment is novel and specific in its mechanisms of action, with noninferior complete responses, higher overall survival rates, and fewer reported adverse events compared to other currently available treatment of MM. In this review, we compared anti-BCMA mechanisms with those of previously available therapies, such as those using immunomodulators and proteasome inhibitors, and discussed the advantages of using anti-BCMA as a potential first-line treatment for multiple myeloma patients.

Comparison of the Efficacy and Safety of Rivaroxaban and Enoxaparin as Thromboprophylaxis Agents for Orthopedic Surgery-Systematic Review and Meta-Analysis.

Venous thromboembolism (VTE) is a serious complication that can occur during and after postoperative treatment, including in treatment after orthopedic surgery. The current guidelines for VTE prophylaxis in postoperative patients recommend the use of LMWHs, one of which is enoxaparin. Another recommendation for use in pharmacological VTE prophylaxis is rivaroxaban, which has better efficacy than enoxaparin but a higher bleeding risk. The aim of this systematic review is to provide an update on the profile of rivaroxaban for VTE prophylaxis after orthopedic surgery. PubMed, SCOPUS, EMBASE, and EBSCOhost were searched up until May 2022. The outcome sought was efficacy and safety, described by the incidence of VTE and incidence of bleeding, respectively. Five randomized controlled trials (RCT) were finally included. Rivaroxaban was confirmed to have better efficacy by significantly reducing the risk of VTE and all-cause mortality (RR = 0.38; 95% CI = 0.27-0.54) compared to enoxaparin. However, regarding the safety variable, no significant difference was found between the incidence of major bleeding in rivaroxaban and enoxaparin (RR = 0.97; 95% CI = 0.56-1.68). The results of the analysis show that rivaroxaban has better efficacy than enoxaparin but the same safety profile, so when used, the bleeding of patients should still be monitored.

Prevalence of Anemia and Factors Associated With Handgrip Strength in Indonesian Elderly Population.

INTRODUCTION: Anemia is a common blood disorder in the elderly which is associated with numerous poor medical outcomes. However, there is currently no study that assesses anemia prevalence of the Indonesian elderly population aged ≥60 years old in multiple provinces and analyzes its association with handgrip muscle strength using a large sample size. AIM: We aimed to elucidate the prevalence of anemia and analyze factors associated with handgrip strength in elderly. METHOD: This was a cross-sectional study using data from the Indonesian Family Life Survey-5 (IFLS-5). All participants aged ≥60 years old were included in this study. Exclusion criteria were: (1) respondents who refused to take health measurements (hemoglobin (Hb) level, handgrip strength, weight, stature, and waist circumference); (2) respondents with incomplete or missing data; (3) respondents with history of stroke; and (4) respondents with history of pain, swelling, inflammation, injury, and surgery on one or both hands within the last 6 months. The dependent variable for this study was handgrip strength. Subjects were classified as weak if the handgrip strength was <28 kg for men and <18 kg for women based on classification from the Asian Working Group for Sarcopenia (AWGS) 2019. The independent variables were Hb level, gender, age, body mass index (BMI), waist circumference, smoking history, comorbidities, and current use of drug therapies. Based on WHO standard, male and female participants with Hb less than 13 g/dL and 12 g/dL, respectively, are defined as anemic. Statistical analyses used included correlation, bivariate logistic regression, and multivariate logistic regression. RESULT: A total of 3192 individuals were selected for analysis. Overall, 38.8% of participants had anemia, and the prevalence of anemia increases with age. A total of 56.30% of participants aged  ≥80 years had anemia. There was a positive correlation between Hb level and handgrip strength in the Indonesian elderly population (r: 0.349; p value: <0.001). Multivariate analysis showed that anemia was significantly associated with weak handgrip strength (OR: 1.557; 95% CI: 1.314-1.846; p value: <0.001).  Age ≥ 80 years (OR: 5.234), age 70-79 years (OR: 3.152), low BMI (OR: 1.827), and hypertension (OR: 1.340) were associated with weak handgrip strength in multivariate analysis. CONCLUSION: The prevalence of anemia in the Indonesian elderly was 38.8% and anemia was associated with weak handgrip strength. The association of anemia with weak handgrip strength is more pronounced in males and the elderly aged ≥80 years.

Abdominal Tuberculosis Mimicking Ovarian Cancer: A Case Report and Review of the Literature.

Introduction: Tuberculosis (TB) is a disease with high morbidity and mortality resulting from infection by Mycobacterium tuberculosis. TB can disseminate to any organ system of the body resulting in extrapulmonary tuberculosis. Interestingly, CA-125, which is a biomarker for some cancer, also rises in benign diseases such as pulmonary and extrapulmonary tuberculosis which may complicate diagnosis. In this case report, we present an abdominal tuberculosis patient that was initially presented as ovarian cancer. Case Report: A 30-year-old woman admitted to the emergency department with chief complaint of fatigue and shortness of breath since 3 months ago. She had lost around 20 kg weight in the past 5 months. She was previously suspected with ovarian cancer because of the characteristic features of malignancy, high levels of CA-125, and positive PET scan. She was later diagnosed with abdominal TB. Subsequently, the patient was given anti-TB drugs, and the patient showed clinical improvement. Conclusion: In the case of an elevated CA-125, clinicians should consider extrapulmonary TB as a differential diagnosis of ovarian cancer, especially in countries with high burden of tuberculosis.

Association of Somatic Gene Mutations with Risk of Transformation into Acute Myeloid Leukemia in Patients with Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis.

OBJECTIVES: we aim to conduct a systematic review and meta-analysis in population of adult MDS patients to elucidate the role of these genes in AML transformation risk. MATERIALS AND METHODS: The protocol for this systematic review and meta-analysis was registered in the international prospective register of systematic reviews (PROSPERO) with ID number of CRD42020218581. Systematic literature search was conducted by all authors up to October 2021 on: (1) PubMed, (2) EBSCOhost, (3) Scopus, (4) JSTOR, and (5) grey literatures. Hand-searching for relevant articles was also conducted. The following keywords with their synonyms and combinations using Boolean operators were applied to all database: "myelodysplastic syndrome", SRSF2", "SF3B1", "U2AF1", "ASXL1", "DNMT3A", "TET2", "IDH1", "IDH2", "RUNX1", "acute myeloid leukemia progression", and "leukemia free survival". Outcome was measured using hazard ratio (HR). RESULTS: We identified 14 articles to be used for this systematic review and meta-analysis. There was no statistically significant difference in AML transformation risk between U2AF1 mutant and U2AF1 wildtype MDS patients (HR: 1.41; 95% CI: 0.95-2.07, p=0.08, I2=0%). Pooled HR showed that patients with SRSF2 mutation had higher risk of AML transformation (HR 2.62; 95% CI: 1.54-4.45; p= .0004; I2= 55%). The pooled HR for SF3B1 was 0.48 (95% CI: 0.22-1.06, p=0.07, I2=55%). Mutations of TET2, ASXL1, and EZH2 were not associated with AML transformation. Meanwhile, DNMT3A mutations were associated with AML transformation with pooled HR of 2.73 (95% CI: 1.43-5.21; p= 0.08; I2: 67%). The pooled HR for IDH genes was smaller (HR: 2.92; 95%CI: 1.21-7.06; p=0.02; I2:65%). Patients with RUNX1 mutation were associated with AML transformation (HR: 1.85; 95%CI: 1.11-3.09; p=0.02; I2:38%). CONCLUSION: Based from our analyses, MDS patients with mutations of SRSF2, DNMT3A, IDH, and RUNX1 have higher hazard ratio for AML transformation.

Comparison of early mortality between leukapheresis and non-leukapheresis in adult acute myeloid leukemia patients with hyperleukocytosis: a systematic review and meta-analysis.

OBJECTIVES: One of the treatment modalities that can be used for hyperleukocytosis is leukapheresis. However, the result of studies showing the benefit of early mortality through the use of leukapheresis versus no leukapheresis is still inconclusive. Hence, we aimed to conduct a systematic review with meta-analysis to determine the effect of leukapheresis on early mortality in AML patients with hyperleukocytosis. METHODS: We conducted a literature search on five databases (PubMed, EBSCOhost, Scopus, Clinicalkey, and JSTOR) up to October 2021 for studies comparing early mortality outcomes between hyperleukocytosis AML patients treated with leukapheresis versus no leukapheresis. Summary odds ratios (OR) and 95% confidence intervals (CI) were calculated using random-effects models. Heterogeneity tests were presented in I2 value and publication bias was analyzed using a funnel plot. RESULTS: Eleven retrospective cohort studies were eligible based on the inclusion and exclusion criteria. Pooled analysis showed that there was no significant difference in early mortality between patients receiving leukapheresis and not receiving leukapheresis in studies using hyperleukocytosis cutoff of 95,000/mm3 or 100,000/mm3 (OR: 1.17; 95% CI: 0.74-1.86; p: 0.50; I2: 0%). Similarly, studies using hyperleukocytosis cutoff of 50,000/mm3 also showed no benefits of early mortality (OR: 0.67; 95% CI: 0.43-1.05; p: 0.08; I2: 0%). Most of the studies used had a moderate risk of bias due to being observational studies. Funnel plot showed an indication of publication bias on studies using hyperleukocytosis cutoff of ≥50,000/mm3. CONCLUSION: The use of leukapheresis does not provide early mortality benefit in adult AML patients with hyperleukocytosis.

Diagnosis and Management of Acquired Hemophilia A: Case Reports and a Literature Review.

BACKGROUND: Acquired hemophilia A (AHA) is a potentially life-threatening autoimmune hemostatic disorder where autoantibodies that disrupt the functions of factor VIII (FVIII) are present in the circulation. The early diagnosis of AHA is difficult since the symptoms of AHA differ from those of congenital hemophilia A. Furthermore, the management of AHA is also more complex due to the presence of autoantibodies against FVIII (FVIII inhibitors). Here, we present three case reports and conduct a literature review of AHA with the aim to increase awareness and knowledge regarding the diagnosis and treatment of AHA. Case Presentations. We present three patients diagnosed with AHA in these case reports. The first patient was a young female, while the second and third patients were middle-aged and elderly males, respectively. All patients presented with a chief complaint of bruises without hemarthrosis and a history of bleeding. Laboratory examinations of the patients revealed isolated prolonged aPTT, normal PT, and the presence of autoantibodies against factor VIII, which are characteristics of AHA. Patients were then treated with corticosteroids to reduce the titer level of autoantibodies and received factor VIII transfusion to stop bleeding. CONCLUSION: AHA can be suspected in patients presenting with symptoms of bruises without hemarthrosis and without the history of bleeding. Isolated aPTT elevation with normal PT should raise high suspicion of AHA. The presence of FVIII inhibitors can help to confirm the diagnosis of AHA. Treatment consists of factor VIII transfusion and corticosteroid therapy. Bypassing agents are recommended as an alternative to FVIII transfusion.

Diagnostic Value of Neutrophil Lymphocyte Ratio and D-Dimer as Biological Markers of Deep Vein Thrombosis in Patients Presenting with Unilateral Limb Edema.

INTRODUCTION: Patients with deep vein thrombosis (DVT) pose high morbidity and mortality risk thus needing fast and accurate diagnosis. Wells clinical prediction scores with D-dimer testing are traditionally used to rule out patients with low probability of DVT. However, D-dimer testing has a few limitations regarding its relatively low specificity. Neutrophil-lymphocyte ratio (NLR), a marker of inflammation, was found to increase in DVT. Hence, we aimed to evaluate the role of NLR for DVT diagnosis. METHODS: Data were collected from medical records of patients with suspected DVT at Cipto Mangunkusumo National General Hospital during January-December 2014. Diagnosis of DVT was conducted using lower limb ultrasonography. Diagnostic values for NLR, D-dimer, and NLR + D-dimer were determined by receiver operating characteristic (ROC) analysis to obtain area under the curve (AUC), sensitivity, specificity, negative predictive value, and positive predictive values. Sensitivity and specificity analyses of NLR and D-dimer were also conducted based on Wells score and divided into groups of low and high probability of DVT. RESULTS: The AUC values for NLR, D-dimer, and NLR + D-dimer were 72.6%, 70.4%, and 76.1%, respectively. The optimal cut-off value determined for NLR was 5.12 with sensitivity of 67.7%, specificity of 67.9%, PPV of 68.85%, and NPV of 64.91% in differentiating subjects with and without DVT. This study also found that D-dimer had sensitivity of 69.4%, specificity of 71.4%, PPV of 72.88%, and NPV of 67.8%. Meanwhile, the NLR + D-dimer combination had sensitivity of 66.1% and specificity of 72.6%. Multivariate analysis showed that NLR (OR: 2.636; 95% CI: 1.144-6.076; p: 0.023) and D-dimer (OR: 4.175; 95% CI: 1.810-9.633; p: 0.001) were associated with DVT. CONCLUSION: NLR value has wider AUC than D-Dimer and is relatively easier to obtain and does not require specific assay, thus enabling rapid evaluation of symptomatic patients suspected of having DVT. Adding NLR to D-dimer increased AUC to detect DVT. Therefore, NLR could serve as a complementary diagnostic tool for D-dimer to exclude DVT, especially in low clinical probability patients.

Leukapheresis Does Not Improve Early Survival Outcome of Acute Myeloid Leukemia with Leukostasis Patients - A Dual-Center Retrospective Cohort Study.

INTRODUCTION: Leukostasis is a medical emergency with high mortality which often occurs in acute myeloid leukemia patients with hyperleukocytosis. One of the therapies that can be used for leukostasis in acute myeloid leukemia is leukapheresis. However, whether leukapheresis can provide better survival benefit when compared with patients not receiving leukapheresis is still unclear. Hence, we aimed to evaluate the effect of chemotherapy plus leukapheresis combination versus chemotherapy only on 28-day survival of acute myeloid leukemia patients with leukostasis. METHODS: This study was a dual-center retrospective cohort using secondary data from medical records collected from November 2018 to March 2019. Inclusion criteria were adult patients aged 18 years old or above, diagnosed with acute leukemia with hyperleukocytosis status defined by WBC count greater than 100,000/uL, and with symptoms of leukostasis. One-month survival analysis was conducted using Kaplan-Meier curve method. Univariate and multivariate analyses were then conducted using Cox proportional hazards model to obtain value of hazard ratio (HR) with a 95% confidence interval (CI). RESULTS: A total of 38 patients were obtained for analysis. The median overall survival was 25 days (95% CI: 17.001-32.999 days) in the chemotherapy only group and 20 days (95% CI: 1.497-38.503) in the chemotherapy with leukapheresis group. The use of leukapheresis did not affect 28-day survival (HR: 1.140; 95% CI: 0.396-3.283; p value: 0.809) and 7-day survival (HR: 1.073; 95% CI: 0.277-4.152; p value: 0.919). In the multivariate analysis, age ≥60 years, blast percentage ≥90%, creatinine ≥1.4 mg/dL, and presence of disseminated intravascular coagulation were associated with worse 28-day survival. CONCLUSION: AML patients with leukostasis who received both chemotherapy and leukapheresis did not have better 28-day survival and 7-day survival when compared with patients receiving chemotherapy only. Old age, high blast percentage, high creatinine, and presence of disseminated intravascular coagulation were prognostic factors for worse 28-day survival.