Proportion of Hypogonadism in Transfusion-Dependent Thalassemia Patients and Its Contributing Factors.

BACKGROUND: Beta thalassemia is a lifelong disease involving malformed red blood cells (RBC). One of the disease's complications is hypogonadism, in which adults tend to exhibit regression in sexual characteristics, experience sexual dysfunction, and therefore have a lower quality of life. Around 3-10% of the Indonesian population carries the beta-thalassemia gene. This study aimed to see the proportions of hypogonadism in transfusion-dependent thalassemia patients and its contributing factors. METHODS: This is a cross-sectional study involving 60 male patients admitted to three Indonesian general hospitals from July 2022 to July 2023. All patients were diagnosed with beta-thalassemia via chromatography hemoglobin analysis. We performed a single-time physical examination and laboratory examinations to determine FSH, LH, and free testosterone levels. The correlation between Hb and sexual hormone levels was analyzed using Spearman's rank correlation coefficient. ROC curve analysis was conducted afterward. All statistical analysis was done in SPSS version 29. RESULTS: 31 out of 60 thalassemia patients had hypogonadism. Pre-transfusion Hb count was found to be linearly correlated with FSH (r = 0.388, p = 0.049), LH (r = 0.338, p = 0.008), and free testosterone (r = 0.255, p = 0.049). ROC analysis indicated that pre-transfusion Hb was viable as a predictor for hypogonadism (AUC = 0.655, 65.5% sensitivity, 67.7% specificity). CONCLUSION: We confirmed the role of pre-transfusion Hb count as a potential predictor for hypogonadism due to the tissue hypoxia mechanism and transfusion-related iron overload in TDT patients. Decreased Hb is linearly correlated with FSH, LH, and testosterone levels. Decreased Hb also downregulates these factors.

Gaucher Disease: A First Reported Adult Case in Indonesia.

A 44-year-old female presented with a distended abdomen and fatigue. On physical examination, prominent splenomegaly was found. The laboratory investigations revealed pancytopenia and decreased albumin-globulin ratio. The abdominal ultrasonography revealed splenomegaly, cholelithiasis, and cystitis, and the bone survey showed osteopenia. Differential diagnoses included leukemia, multiple myeloma, and myelofibrosis therefore bone marrow puncture was performed. However, histopathologic examination found Gaucher-like cells in the bone marrow aspiration. The finding of CD68 positivity in Gaucher-like cells by using the immunohistochemistry staining supporting Gaucher disease. To confirm the diagnosis, an examination of glucocerebroside substrate from the patient's blood plasma was performed. Glucosylsphingosine, a deacylated form of glucosylceramide, was markedly elevated. Therefore, the diagnosis of Gaucher disease was confirmed. This is the first reported adult Gaucher case diagnosed in Indonesia.

The association of prognostic awareness with quality of life, spiritual well-being, psychological distress, and pain severity in patients with advanced cancer: Results from the APPROACH Study in Indonesia.

BACKGROUND AND OBJECTIVES: Advanced cancer patients' understanding of their illness is key for making informed treatment decisions. Despite the known importance of patients' awareness of their disease prognosis, it is debatable whether this awareness is positively, negatively, or not associated with clinical and psychological outcomes among patients with advanced cancer. This paper aims to determine the prevalence of and factors associated with prognostic awareness and its association with quality of life (QoL), spiritual well-being, pain control, and psychological distress in patients with advanced cancer in Indonesia. METHODS: This cross-sectional questionnaire-based survey was part of a multicountry study titled "Asian Patient Perspectives Regarding Oncology Awareness, Care and Health (APPROACH)." Patients were asked what they knew about their cancer and treatment. QoL and spiritual well-being were measured using the Functional Assessment of Cancer Therapy - General (FACT-G) and Functional Assessment of Chronic Illness Therapy - Spiritual Well-being (FACIT-Sp) questionnaire. Psychological distress experienced by patients was recorded via the Hospital Anxiety and Depression Scale. Pain severity was also assessed. Data from 160 patients were analyzed using descriptive statistics and multivariable regression models. RESULTS: Of the 160 patients who participated, 55 (34.4%) were unaware of their cancer stage. Those who were aware of their stage of cancer were younger than those who were not aware (45.7 years vs 50.4 years, p = .015). There was no significant difference in spiritual well-being and other domains of QoL between those who were aware and those who were not aware of their advanced cancer stage. There was also no significant difference in anxiety depression or pain severity, even after adjustment for demographic and clinical characteristics. SIGNIFICANT OF RESULTS: Given the high prevalence of patients who wrongly thought their cancer was curable, more could be done to improve disease and prognostic understanding among patients with advanced cancer in Indonesia. Those who were aware of their advanced cancer stage did not have a poorer QoL, nor did they have more anxiety or depression than those who were unaware. This finding suggests that concerns about the negative impact of prognostic disclosure may be unfounded.

CXCL8, MMP1, MMP2, and FN1 Gene Expression and Tumor Extension in Nasopharyngeal Cancer Patients: A Cross-sectional Study.

BACKGROUND: There are correlations between tumor staging, lymph node involvement, and patient survival in Nasopharyngeal cancer (NPC) which is one of the most common types of cancer in Indonesia.  The inflammation process plays a role in tumor progression over the long term and this marked by increased proinflammatory cytokine and gene overexpression. This study aims to identify differentially expressed genes (DEGs) in NPC using T and N staging. METHODS: This is a cross-sectional study of NPC patients in Cipto Mangunkusumo, Jakarta, between 2018 and 2022. DEGs were identified based on the amount of mRNA detected on paraffin blocks with a 1.5- to -1.5-fold change and an adjusted p-value of <0.05. RESULTS: We included 48 subjects. The mean age of subjects was 47.75 (10.48) years, and most were male (77.1%). Non-keratinized squamous cell carcinoma was the most common histopathology type. Differences in the tumor size of the T4 and non-T4 in metastatic (33.3%) group when compared to the non-metastatic (37.5%) group were insignificant (p = 0.763). The proportion of N3 subjects in the metastatic vs non-metastatic group was different significantly (83.3% vs. 50%, p = 0.030). Gene expression analysis showed that C-X-C motif ligand 8 (CXCL8), matrix metalloproteinase-1 (MMP1), matrix metalloproteinase-1 (MMP2), and fibronectin-1 (FN1) genes of the T4 and non-T4 group to be different significantly. CONCLUSION: There was significant finding in the N3 subjects of the metastatic and non-metastatic groups. The DEGs of CXCL8, MMP1, MMP2, and FN1 were statistically significant in the T4 when compared to the non-T4 group.

Efficacy of COVID convalescent plasma therapy in hospitalized moderate coronavirus disease 2019 patients.

INTRODUCTION: Covid Convalescent Plasma (CCP) failed to demonstrate its efficacy in severe and life-threatening coronavirus disease 2019 (COVID-19) cases. However, the role of CCP in hospitalized moderate cases is unclear. This study aims to examine the efficacy of administering CCP to hospitalized moderate coronavirus disease 2019 patients. METHODOLOGY: An open-label randomized controlled clinical trial design was used from November 2020 - August 2021 at two referral hospitals in Jakarta, Indonesia, and the primary outcome was mortality at 14 days. The secondary outcomes were mortality at 28 days, the time-to-discontinuation of supplemental oxygen, and the time-to-hospital discharge. RESULTS: This study recruited 44 subjects, and the intervention arm consisted of 21 respondents who received CCP. The control arm consisted of 23 subjects who received standard-of-care treatment. All subjects survived during the fourteen-day follow-up period, and the 28-day mortality rate in the intervention group was lower than the control (4.8% vs 13.0%; p = 0.16, HR = 4.39 (95% CI = 0.45-42.71). There was no statistically significant difference in the time-to-discontinuation of supplemental oxygen and time-to-hospital discharge. During the total follow-up period (41 days), the mortality rate in the intervention group was also lower than the control (4.8% vs 17.4%, p = 0.13, HR = 5.47, 95% CI = 0.60-49.55). CONCLUSIONS: This study concluded that in hospitalized moderate COVID-19 patients, CCP did not reduce 14-day mortality compared to the control. Mortality during 28 days and total length of stay (41 days) were lower in the CCP group compared to the control, although they did not reach statistical significance.

Autologous intraarterial pancreatic bone-marrow mononuclear cells infusion in T2D patients: Changes on beta-cells function, insulin resistance, and inflammatory marker.

BACKGROUND: Type 2 diabetes (T2D) is a progressive disease. Many drugs currently being used for the management of T2D have minimal effect on pancreatic beta cells regeneration. Cell-based therapies might provide potential benefits in this aspect. METHODS: A pilot study in five T2D patients with 12 months follow-up was performed to evaluate the effect of autologous bone marrow mononuclear stem cells (BM-MNCs) infusion into pancreatic arteries on the insulin requirement, beta-cell function, insulin resistance, and systemic inflammatory marker (CRP). RESULTS: The primary endpoint, a 50 % reduction of total insulin doses from baseline, was not achieved in this study. However, a trend of increasing fasting C-peptide (p = 0.07) and C-peptide 60' (p = 0.07) and 90' (p = 0.07) after a mixed-meal tolerance test was observed 12 months post-infusion compared to baseline levels. A similar result was observed for the homeostatic model assessment of beta cell function (HOMA1-B), an index for beta cell function. No improvement was observed for insulin resistance measured by homeostasis model assessment of insulin resistance (HOMA1-IR) and systemic inflammatory parameter. CONCLUSION: Intraarterial pancreatic autologous BM-MNCs infusion might potentially improve beta cell function in T2D patients, although further study is needed to confirm this finding.

The relationship of vascular endothelial growth factor and osteopontin expression with 3-year progression-free survival of locally advanced nasopharyngeal cancer patients treated with platinum-based chemoradiation.

Introduction: The incidence of nasopharyngeal cancer (NPC) is high, with new cases accounting for 5.2% of all malignancies in Indonesia. Most cases are detected at an advanced stage, and recurrences are common. Vascular endothelial growth factor (VEGF) and osteopontin (OPN) are important markers in tumorigenesis that serve as prognostic predictors. This study aims to determine the correlation of VEGF and OPN expression with 3-year progression-free survival (PFS). Material and methods: This retrospective cohort study analyzed 155 patients with locally advanced NPC. Data were obtained from medical records between 2015 and 2017. The locally advanced sample of this disease that met the inclusion criteria was stained with H&E before being prepared in a paraffin block. Furthermore, the immunohistochemistry staining results for VEGF and OPN were observed with ImageJ 1.50i and calculated semi-quantitatively using the histoscore. Results: The 3-year PFS obtained was 39%, with a median of 23 months. Vascular endothelial growth factor expression was detected in 113 of 155 samples (72.9%), while positive OPN expression was discovered in 99 of 155 samples (63.8%). There was a correlation between VEGF (p = 0.747) and OPN expression (p = 0.584) and 3-year PFS. Positive VEGF and OPN expression in the subgroup of patients with stage IVB and N3 tumors was related to improved 3-year PFS (p < 0.05). This was similar to the positive VEGF expression in the subgroup of patients receiving neoadjuvant chemotherapy (p < 0.05). Conclusions: Vascular endothelial growth factor and OPN remained potential prognostic predictors in NPC. Patients with positive VEGF and OPN expression in N3, IVB, and neoadjuvant treatment had significantly improved 3-year PFS.

Palliative Screening Tools to Identify Palliative Care Consultation at Tertiary Hospital.

BACKGROUND: The need of palliative care is increasing, but it is not all achievable. It is necessary to identify palliative patients in order to provide the proper care according to the needs of the patients. Cipto Mangunkusumo Hospital has been making the identification using a palliative-patient screening questionnaire, but no performance assessment has been carried out on the screening tool. This study aimed to evaluate the performance of the screening-tool questionnaire used on palliative-care patients at Cipto Mangunkusumo Hospital in order to assess the need of palliative-care consultation and to find out the optimal cut-off point of palliative care screening tools. METHODS: The design of this study is cross-sectional and was conducted at Cipto Mangunkusumo National Central Public Hospital in July - October 2019. The sampling was collected by consecutive sampling. The reliability test was performed by the intraclass correlation coefficient (ICC). The internal consistency was measured by the Cronbach's-Alpha coefficient. The criterion-validity test was run by an evaluation using the Pearson test. RESULTS: There were 64 subjects collected, the largest age group was 51-70 years (50%). Cancer was the main disease found in most of the subjects (56 people / 87.5%). The most common comorbidity was kidney disease (11 people). The most common palliative score distribution was 6 (15 people). The average score was 7.51. The mortality rate at the hospital was 51.6%, 33 patients from a total of 64 patients. From the palliative score distribution curve, the AUC value was 0.687 with a 95% CI (0.557-0.818). The optimal cut-off point was 8. All patients were palliative according to expert opinion based on WHO criteria. CONCLUSION: The performance of this tool is sufficient to screen palliative patients in a terminal and complex condition, but requires improvements to screen for patients who need early palliative care. The optimal cut-off point to determine the limit of consultation on palliative patients is found at score 8.

MUM1 Expression versus Hans Algorithm to Predict Prognosis in Indonesian Diffuse Large B-Cell Lymphoma Patients Receiving R-CHOP.

Background: Treatment response in diffuse large B-cell lymphoma (DLBCL) is heterogenous. The Hans algorithm (using 30% cut-offs for CD10, BCL6, and MUM1 protein expression) has been the most favored method to categorize DLBCL into germinal center B-cell (GCB) and non-GCB subtypes in order to predict prognosis. However, the algorithm's ability to prognosticate is not always consistent. Methods: This retrospective cohort study was conducted on DLBCL patients receiving R-CHOP therapy at Dr. Cipto Mangunkusumo Hospital, Jakarta from 2014 to 2017. We aimed to compare the prognostic value of Hans algorithm as well as the protein levels of CD10, BCL6, MUM1, and Ki67 at different cut-offs. Ninety-two patients were classified based on Hans algorithm and various proteins at different cut-off values were analyzed with regard to event-free survival at 24 months using survival analysis. The cut-off values were then compared using receiver operating characteristic curves. Results: A significant survival difference was observed with MUM1 expression cut-off of 50% or more (log rank p = 0.035). CD10, BCL6, Ki67, and Hans algorithm showed AUCs below or near 0.5 (0.405, 0.436, 0.498, and 0.413, respectively), whereas MUM1 showed an AUC of 0.835, in predicting events within 24 months. MUM-1 cut-off of 70.5% yielded an optimal trade-off for sensitivity and specificity. Conclusion: MUM1 expression of 50% or more can help predict prognosis in DLBCL patients receiving R-CHOP therapy and can be considered as for use as a single marker to predict prognosis.

The role of IL-6, ferritin, and coagulopathy in Covid-19 clinical progression.

Background In COVID-19, the release of pro-inflammatory mediators in the cytokine storm, primarily interleukin-6 (IL-6), has been hypothesized to induce pulmonary intravascular coagulation. However, the relationship between IL-6 and coagulopathy remains unclear in COVID-19 progression. We aimed to investigate the correlation of IL-6 with D-dimer, fibrinogen, prothrombin time (PT), and ferritin. Furthermore, we also analyzed the effect of those parameters on the worsening of COVID-19 patients. Methods A prospective cohort study was conducted in moderate and severe COVID-19 patients from June 2020 to January 2021. A serial evaluation of IL-6, D-dimer, fibrinogen, ferritin, and PT was performed and correlated with the patient's condition at admission and on the 14th day. The outcomes (improvement, worsening, or discharged patients) were recorded during the study. Results Of 374 patients, 73 study subjects (61 severe and 12 moderate COVID-19) were included in this study. A total of 35 out of 61 severe and one out of 12 moderate illness subjects had experienced worsening. Spearman-rank correlation of IL-6 with with ferritin, D-dimer, fibrinogen, and PT was 0.08 ( p=0.5), -0.13 ( p=0.27), 0.01 ( p=0.91), and 0.03 ( p=0.77), respectively. In ROC analysis, D-dimer (74,77%) and IL-6 (71,32%) were the highest among other variables (>60%). Conclusions In COVID-19 patients, there was a correlation between elevated IL-6 and D-dimer levels with disease deterioration. There was no correlation between elevated IL-6 levels with ferritin, D-dimer, fibrinogen, and PT levels. Therefore, changes in IL-6 and D-dimer can predict worsening in moderate and severe COVID-19 patients.

Factors that Influence 2-Year Progression-Free Survival Among Head and Neck Cancer Patients.

OBJECTIVES: The majority of patients with head and neck cancer (HNC) come to the hospital at advanced stages. This research was conducted to determine the mortality, 2-year progression-free survival (PFS) and factors that influenced PFS of HNC patients. METHODS: A retrospective cohort study was conducted among locally advanced HNC patients who underwent chemoradiation for the first time at RSCM from January 2015 to December 2017. Data were retrieved through medical records. Laboratory data were taken 2-4 weeks prior and 2-4 weeks after chemoradiation. PFS observation started from the first day of chemoradiation until disease progression or death. PFS data were recorded in two groups: ≤ 2 years and > 2 years. The Chi-square test was used for bivariate analysis with the Fischer-exact test as an alternative. Variables will be further tested using multivariate logistic regression tests. RESULTS: Among 216 subjects, there were 103 (47.69%) patients who did not reach overall survival (OS) > 2 years. There were 108 (50%) patients who had PFS > 2 years. Based on the results of multivariate analysis, it was found that smoking, hemoglobin level ≤ 12 g/dl, ECOG (Eastern Cooperative Oncology Group) 1-2, and negative therapeutic response were associated with poor PFS. Hazard ratio (HR) for 2-year PFS for Brinkman index > 250 was 1.36 (95% CI 0.93-2.00; p = 0.02); HR for Hb ≤ 12 g/dl was 1.65 (95% CI 1.13-2.42; p = 0.01); HR for ECOG 1-2 was 4.05 (95% CI 1.49-11.00; p < 0.01); and HR for negative therapeutic response was 2.37 (95% CI 1.43-3.94; p < 0.01). CONCLUSION: Mortality of HNC patients within 2 years is 47.69%, with a 2-year PFS reaching 50%. Cigarette smoking, low hemoglobin levels, poor performance status, and negative therapeutic response (non-responders) negatively affect the 2-year PFS.

Role of Pretreatment Hemoglobin-to-Platelet Ratio in Predicting Survival Outcome of Locally Advanced Nasopharyngeal Carcinoma Patients.

BACKGROUND: The three-year survival rate of locally advanced nasopharyngeal carcinoma (NPC) patients in Indonesia is lower than in other Asian countries. Calculation of hemoglobin-to-platelet ratio (HPR) may become a more practical predictor than the ratios using leukocyte cell components. Yet, no study has been conducted to investigate the potential of HPR in predicting survival outcomes in locally advanced nasopharyngeal cancer patients. OBJECTIVE: To determine the role of pretreatment hemoglobin-to-platelet ratio in predicting the three-year overall survival (OS) of locally advanced NPC. METHOD: A retrospective cohort study followed up on 289 locally advanced NPC patients who had undergone therapy at the Dr. Cipto Mangunkusumo National General Hospital between January 2012 and October 2016. HPR cut-off was determined using ROC. Subjects were classified into two groups according to the HPR value. Kaplan-Meier curve was utilized to illustrate patients' three-year survival, and Cox regression test analyzed confounding variables to yield an adjusted hazard ratio (HR). RESULTS: The optimal cut-off for HPR was 0.362 (AUC 0.6228, 95% CI: 0.56-0.69, sensitivity 61.27%, specificity 60.34%). Of the subjects, 48.44% had HPR ≤ 0.362, and they had a higher three-year mortality rate than those with HPR > 0.362 (50% vs. 31.54%). In bivariate analysis, HPR ≤ 0.362 and age ≥ 60 significantly showed a worse three-year OS (p value = 0.003 and 0.075, respectively). In multivariate analysis, we concluded that a pretreatment HPR ≤ 0.362 was an independent negative predictor of three-year OS in locally advanced NPC patients (adjusted HR 1.82; 95% CI: 1.25-2.65). CONCLUSION: Pretreatment HPR ≤ 0.362 was a negative predictor of three-year OS in locally advanced nasopharyngeal cancer patients.

Tocilizumab as a Treatment for 'Cytokine Storm Syndrome' in COVID-19: A Case Report.

Coronavirus disease 19 (COVID-19) which is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has been a problem worldwide, particularly due to the high rate of transmission and wide range of clinical manifestations. Acute respiratory distress syndrome (ARDS) and multiorgan failure are the most common events observed in severe cases and can be fatal. Cytokine storm syndrome emerges as one of the possibilities for the development of ARDS and multiorgan failure in severe cases of COVID-19. This case report describes a case of a 53-year-old male patient who has been diagnosed with COVID-19. Further evaluation in this patient showed that there was a marked increase in IL-6 level in blood accompanied with hyperferritinemia, which was in accordance with the characteristic of cytokine storm syndrome. Patient was treated with tocilizumab, a monoclonal antibody and is an antagonist to IL-6 receptor. The binding between tocilizumab and IL-6 receptors effectively inhibit and manage cytokine storm syndrome. Although this case report reported the efficacy of tocilizumab in managing cytokine storm syndrome, tocilizumab has several adverse effects requiring close monitoring. Further clinical randomized control trial is required to evaluate the efficacy and safety of tocilizumab administration in participants with various clinical characteristics and greater number of subjects.

Comprehensive analysis of peripheral T-cell and natural killer/T-cell lymphoma in Asian patients: A multinational, multicenter, prospective registry study in Asia.

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are uncommon and their frequency is regionally heterogeneous. Several studies have been conducted to evaluate the clinical features and treatment outcomes of this disease entity, but the majority of these were conducted in limited areas, making it difficult to comprehensively analyze their relative frequency and clinical features. Furthermore, no consensus treatment for PTCLs has been established. Therefore, we conducted an Asia-specific study to understand the relative frequency of PTCLs and assess treatments and their outcomes in Asian patients. METHODS: We performed a multinational, multicenter, prospective registry of adult patients with PTCLs that was named as the International Cooperative non-Hodgkin T-cell lymphoma prospective registry study where thirty-two institutes from six Asian countries and territories (Korea, China, Taiwan, Singapore, Malaysia, and Indonesia) participated. FINDINGS: A total of 486 patients were registered between April 2016 and February 2019, and more than a half of patients (57%) had stage III or IV. Extranodal natural killer (NK)/T- cell lymphoma was the most common subtype (n = 139,28.6%), followed by angioimmunoblastic T-cell lymphoma (AITL, n = 120,24.7%), PTCL-not otherwise specified (PTCL-NOS, n = 101,20.8%), ALK-positive anaplastic large cell lymphoma (ALCL, n = 34,6.9%), and ALK-negative ALCL (n = 30,6.2%). The median progression-free survival (PFS) and overall survival (OS) were 21.1 months (95% CI,10.6-31.6) and 83.6 months (95% CI, 56.7-110.5), respectively. Upfront use of combined treatment with chemotherapy and radiotherapy showed better PFS than chemotherapy alone in localized ENKTL whereas consolidation with upfront autologous stem cell transplantation (SCT) provided longer PFS in advance stage ENKTL. In patients with PTCLs other than ENKTL, anthracycline-containing chemotherapies were widely used, but the outcome of those regimens was not satisfactory, and upfront autologous SCT was not significantly associated with survival benefit, either. The treatment outcome of salvage chemotherapy was disappointing, and none of the salvage strategies showed superiority to one another. INTERPRETATION: This multinational, multicenter study identified the relative frequency of each subtype of PTCLs across Asian countries, and the survival outcomes according to the therapeutic strategies currently used. FUNDING: Samsung Biomedical Research Institute.

Cutaneous T-cell lymphoma in Asian patients: a multinational, multicenter, prospective registry study in Asia.

Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0-122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3-4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.

Autologous Bone-Marrow vs. Peripheral Blood Mononuclear Cells Therapy for Peripheral Artery Disease in Diabetic Patients.

Diabetes mellitus (DM) remains one of the most important risk factors for peripheral artery disease (PAD), with approximately 20% of DM patients older than 40 years old are affected with PAD. The current standard management for severe PAD is endovascular intervention with or without surgical bypass. Unfortunately, up to 40% of patients are unable to undergo these revascularization therapies due to excessive surgical risk or adverse vascular side effects. Stem cell therapy has emerged as a novel therapeutic strategy for these 'no-option' patients. Several types of stem cells are utilized for PAD therapy, including bone marrow mononuclear cells (BMMNC) and peripheral blood mononuclear cells (PBMNC). Many studies have reported the safety of BMMNC and PBMNC, as well as its efficacy in reducing ischemic pain, ulcer size, pain-free walking distance, ankle-brachial index (ABI), and transcutaneous oxygen pressure (TcPO2). However, the capacity to establish the efficacy of reducing major amputation rates, amputation free survival, and all-cause mortality is limited, as shown by several randomized placebo-controlled trials. The present literature review will focus on comparing safety and efficacy between BMMNC and PBMNC as cell-based management in diabetic patients with PAD who are not suitable for revascularization therapy.

The Difference in the Cyclin D1 Expression in Advanced Stage Nasopharyngeal Cancer based on Treatment Response: A Retrospective Cohort Study.

BACKGROUND: nasopharyngeal cancer (NPC) is the most common type of head and neck cancer in Indonesia (28.4%). Reports showed that 18.9% of cases came with advanced stage. Chemotherapy play important role in advanced stage. However, patients with the same stage of the disease may have different treatment response, likely due to the different tumor biological characteristics. Cyclin D1 is a protein involved in the cell cycle, which will stimulate proliferation. This study aimed to examine the proportion of cyclin D1 in NPC and its association with treatment response. METHODS: a retrospective cohort study was conducted on advanced NPC patients that underwent chemotherapy at Cipto Mangunkusumo Hospital from 2015 until 2018. Cyclin D1 immunohistochemistry staining was done by antigen retrieval methods using the cyclin D1 NovocastraTM monoclonal antibody. The cyclin D1 expression was evaluated with h-score. Treatment response was reviewed based on the RECIST 1.1 criteria. RESULTS: fifteen subjects (48.4%) had a positive expression of cyclin D1. Higher proportion of cyclin D1 positive was found in responsive group compare with non-responsive group (66.7% vs. 33.3%, p = 0.032). Statistically significant difference in mean h-score was observed between the subjects who responded and those who did not respond (116.24 SD57.80 vs. 77.97 SD45.27, p = 0.048). CONCLUSION: this study suggests that a higher expression of cyclin D1 is associated with a good treatment response in NPC patients.

Undifferentiated Nasopharyngeal Carcinoma Presenting with Shoulder Mass.

Nasopharyngeal cancer (NPC) is the most common cancer among head and neck cancer that usually presented with unilateral neck mass. Unusual symptoms of NPC can lead us to diagnosis misleading and delayed definitive treatment. We present a case of NPC with bone metastasis in the shoulder. A 33-year-old female presented with right shoulder mass caused by undifferentiated carcinoma of unknown primary, based on biopsy of shoulder mass. After four months, she was complaining painless neck swelling, headache, and hearing impairment in the left ear. Bone MRI showed malignant bone tumour in the right humerus. Neck CT scan showed mass in the nasopharyngeal and bilateral lymphadenopathy. Biopsy in nasopharyngeal revealed undifferentiated carcinoma of nasopharyngeal cancer (WHO-3 type A). The patient was diagnosed as NPC stage IVb and thus was treated with palliative chemotherapy. After three cycles of cisplatin docetaxel, patient condition improved.

Characteristics of Palliative Patients, Insights of Patients and Families, and the Impact of Estimated Survival Time on Therapy Decisions.

BACKGROUND: chronic and terminal diseases require holistic therapy that covers the biopsychosocial aspect, and it can be found in palliative therapy. Patients who receive palliative therapy exhibit very diverse profiles. As such, researchers are keen to study the general characteristics of palliative patients. In addition, researchers will also assess the patient's and their family's insight that influences the success of the therapy and the impact of estimated survival time in making treatment decisions. METHODS: this research used cross-sectional descriptive analytic study and secondary data of 300 palliative patients who consult to Psychosomatic Palliative Team at Dr. Cipto Mangunkusumo Hospital. The data were processed using SPSS version 25. The data processed included: sociodemographic characteristics, length of stay, incidence of death in hospital, DNR cases, the patient's and their family's insight, and the impact of estimated survival time on treatment decisions. RESULTS: most palliative patients were women (52.0%) aged 51 - 60 years (27.0%), unemployed (29.0%), and suffered from cancer (55.3%). In addition, the patients were generally treated for less than 1 month (83.6%), died in the hospital (37.3%), and consented to DNR orders (36.7%). These DNR cases are highly correlated to the family's understanding regarding the prognosis of the patient's condition (p = 0.022). The family's understanding of the diagnosis, prognosis, and treatment goals (92.3%, 81.3%, and 87.7%) was better than the patient's (79.0%, 64.0%, and 69.7%). Furthermore, no link was found between the therapy choice (optimal, withholding, and withdrawing therapies) with the patient's estimated survival time (p = 0.174). CONCLUSION: female, elderly, and cancer patients most often get palliative therapy. The consent for DNR orders to palliative patient is notably frequent. Currently, the family's insight is much better than the patient's, which means that health care providers need to improve patient education and information. In addition, patients and families generally still opt for optimal therapy despite low estimated survival time.

Feasibility of Qualitative Testing of BCR-ABL and JAK2 V617F in Suspected Myeloproliperative Neoplasm (MPN) Using RT-PCR Reversed Dot Blot Hybridization (RT-PCR RDB).

BACKGROUND: Defining the presence of BCR-ABL transcript in suspected myeloproliferative neoplasm is essential in establishing chronic myeloid leukemia. In the absence of BCR-ABL, the conventional diagnostic algorithm recommends JAK2 V617F mutation testing to support diagnosis of other MPN diseases such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis. In certain cases of thrombocythemia, simultaneous upfront testing of both BCR-ABL and JAK2 may be desirable. We wanted to test the feasibility of multiplex detection of BCR-ABL transcript variants and JAK2 V617F mutation simultaneously using the reverse transcriptase polymerase chain reaction (RT-PCR)-based reverse dot-blot hybridization (RDB) method. MATERIAL AND METHODS: Separate biotinylated RT-PCR primers were designed to amplify specific BCR-ABL transcripts and JAK2 V617F mutant alleles. Specific hybridization of RT-PCR products with arrays of membrane-bound probes followed by colorimetric development would allow simultaneous visualization of BCR-ABL and/or JAK2 mutant transcripts in a given specimen. To validate the RDB method, we used cDNA specimens previously referred to our laboratory for routine clinical testing of BCR-ABL and/or JAK2. RESULTS: The limit of detection or analytical sensitivity of the RDB method using cDNA specimens was 0.5% and 6.25% in detecting BCR-ABL and JAK2 mutant transcripts, respectively. The diagnostic specificity and sensitivity to detect BCR-ABL and JAK2 were 100% and 92.3% (N = 38); and 100% and 100% (N = 27), respectively. RDB also detected BCR-ABL transcripts in 22% of JAK2 V617F mutation-positive samples (N = 14). CONCLUSIONS: RT-PCR RDB is a promising qualitative multiplex method to detect BCR-ABL and JAK2 mutant transcripts simultaneously.