Effectiveness of transcranial direct current stimulation (tDCS) as adjunctive treatment for chronic headache in adults with clinically stable systemic lupus erythematosus (SHADE): a randomised double-blind multiarm sham controlled clinical trial.

BACKGROUND: Chronic headache is a 'silent' neuropsychiatric systemic lupus erythematosus symptom with heterogeneous prevalence, potentially reaching 54.4%. It may reduce quality of life by increasing the likelihood of depression and sleep disturbance. While pharmacotherapy remains the first-line treatment, the current management is still challenging and needs other non-invasive modalities. An effective, tolerable and disease-specific treatment modality including transcranial direct current stimulation (tDCS) is considered to reduce the frequency of chronic headaches, including in SLE. Until recently, there was no standard protocol for tDCS in treating headaches. METHODS AND ANALYSIS: SHADE is a single-centre randomised double-blind multiarm sham-controlled trial for adults with clinically stable SLE, chronic headaches and without history of traumatic brain injury, brain infection, stroke or brain tumour. Random allocation is conducted to 88 subjects into 3 treatment groups (administration at primary motor, primary sensory and dorsolateral prefrontal cortex) and control group in 1:1:1:1 ratio. The primary endpoint is reduced number of headache days after adjunctive tDCS. The secondary endpoints are reduced headache intensity, increased quality of life, increased sleep quality, decreased depression and reduced analgesics use. The outcome is measured monthly until 3-month postintervention using headache diary, 36-Item Short Form Survey, Chronic Headache Quality of Life Questionnaire, Pittsburgh Sleep Quality Index and Mini International Neuropsychiatry Interview version 10 (MINI ICD 10). Intention-to-treat analysis will be performed to determine the best tDCS electrode placement. ETHICS AND DISSEMINATION: Ethical approval had been obtained from the local Institutional Review Board of Faculty of Medicine Universitas Indonesia. Results will be published through scientific relevant peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05613582.

Effect of adipose derived stromal vascular fraction on leprosy neuropathy: A Preliminary report.

BACKGROUND: Adipose derived stromal vascular fraction (SVF) contains a heterogeneous population of mononuclear cells, progenitor cells and about 1-10% are mesenchymal stromal cells. These cells are an ideal candidate for regenerative medicine for peripheral neuropathy. Leprosy is a disabling disorder with neuropathy, usually with consequences of permanent disability of the extremities. We conducted a preliminary study to evaluate the cell yield, its characteristics and clinical outcomes after SVF injections in four leprosy patients. METHODS: Four post leprosy patients were recruited and evaluated for sensory testing (warm detection, cold detection, vibration, pain and sensation) on the ulnar area of the hand. Liposuction was done and adipose tissue was processed into SVF with a closed system and injected to the ulnar area of the hand at the dorsal and palmar side. Evaluation of sensory testing was done after 3 days, 1 week, 1 month and 3 months following SVF injection. SVF was also characterized using flow cytometry, cell counting, sterility and presence of mycobacteria. RESULTS: The results showed that leprosy patients had a low count of mesenchymal cells and a high amount of CD34/CD45 positive cells. One patient was positive for mycobacteria from his adipose tissue and SVF. Sensory examination after SVF injection showed an improvement in temperature and pain sensation in the palmar and superficial branch. Meanwhile, touch sensation improved on the dorsal branch, and there was no improvement for vibration in all patients. CONCLUSIONS: The results showed that SVF had a potential to improve sensory loss in leprosy patients.

Absence of Association Between Serum Mutant p53 with HbA1c and Insulin in Brain Tumor Patients with Type 2 Diabetes Mellitus.

AIMS: This study aims to determine the prevalence of Type 2 Diabetes Mellitus (T2DM) in primary Brain Tumor (BT) subjects and assess the relationship between serum mutant p53 serum and HbA1c and insulin. BACKGROUND: T2DM is known to increase the risk of various types of cancer, which are thought to be caused by hyperglycemia, hyperinsulinemia, and inflammation. A cohort study that looked at more than 500,000 subjects with DM over 11 years showed an increased risk of different types of cancer, including brain tumors. However, several recent studies have shown the opposite. One of the important pathways in the pathogenesis of brain tumors is the p53 pathway, in which mutations in the TP53 gene can cause brain cell growth abnormalities. OBJECTIVE: The first stage involved taking subject data for the period January 2017-November 2020 from the medical records of the RSUPN Dr. Cipto Mangunkusumo Hospital Indonesia to assess the prevalence of T2DM in BT subjects. The second stage was an observational study with a crosssectional design that collected primary data on subjects (n=86) to assess the relationship between serum mutant p53 serum and HbA1c and insulin. METHODS: The analysis of serum mutant p53 serum and insulin was made using the ELISA method, while measurement of HbA1c was made using the boronate affinity method. RESULT: The results show the prevalence of T2DM in BT subjects at Dr. Cipto Mangunkusumo Hospital Indonesia was relatively low (9%). Serum mutant p53 levels in T2DM (1.53 ng/mL ± 0.60) were significantly higher than in BT+T2DM and BT (P < 0.001). The HbA1c value was significantly lower in BT (5.15% ± 0.44) compared to BT+T2DM and T2DM (P < 0.001), while T2DM insulin levels (39.54 IU/mL ± 19.1) were significantly higher than BT+T2DM and BT (P < 0.001). There was no correlation between serum mutant p53 levels and HbA1c and insulin in the three groups. CONCLUSION: The study concludes that the prevalence of BT with T2DM is relatively low (9%) and that serum levels of mutant p53 in T2DM subjects are higher than in subjects with BT, but there is no correlation between serum mutant p53 levels and HbA1c and insulin values. Further research needs to be conducted by analyzing p53 mutants from other specimens, such as brain tumor tissue.

The potential of metformin as an antineoplastic in brain tumors: A systematic review.

Brain tumors are challenging to handle and cause severe mortality and morbidity. The primary therapy for brain tumors, a combination of radiotherapy, chemotherapy (i.e temozolomide), and corticosteroids, is considered inadequate to improve patients' clinical conditions and associated with many adverse effects. There is an urgent need for new compounds or repurposing of existing therapies, which could improve brain tumor patients' prognosis. Metformin, commonly used for type 2 diabetes medication, has been examined for its protective action in cancer, reducing cancer risk and cancer-related mortality. However, its effect on cancer is still in rigorous debate. This study examines recent studies on the effects of metformin in primary brain tumor patients through systematic reviews. The literature search was performed on PubMed, ScienceDirect, and SpringerLink databases for articles published between 2013 and 2020. We selected clinical studies comparing the therapeutic outcomes of brain tumor therapy with and without metformin. The clinical benefits of the drug were assessed through the overall survival (OS) and progression-free survival (PFS) of brain tumor patients. Those studies demonstrated that the combination of metformin with temozolomide given post-radiotherapy resulted in better OS and PFS. Nonetheless, the efficacy and safety of metformin need further clinical testing in the wider population.

Five-Year Cancer Epidemiology at the National Referral Hospital: Hospital-Based Cancer Registry Data in Indonesia.

PURPOSE: In 2016, there were 1,308,061 cases of cancer being treated in Indonesia, with 2.2 trillion rupiahs spent, amounting to $486,960,633 in US dollars (purchasing power parity 2016). The high burden of cancers in Indonesia requires a valid data collection to inform future cancer-related policies. The purpose of this study is to report cancer epidemiological data from 2008 to 2012 based on Hospital-Based Cancer Registry (HBCR) data from Cipto Mangunkusumo Hospital, Indonesia. METHODS: This was a descriptive study with cross-sectional design. Data were collected from Cipto Mangunkusumo Hospital HBCR 2008-2012. Demographical, diagnostic, stages of cancer, and histopathological types of cancer data were extracted. RESULTS: After screening, 18,216 cases were included. A total of 12,438 patients were older than 39 years of age (68.3%), with a female-to-male ratio of 9:5. Most patients have cancers at advanced stages (stages III and IV, 10.2%). The most common sites of cancer were cervix uteri (2,878 cases, 15.8%), breast (2,459 cases, 13.5%), hematopoietic and reticuloendothelial systems (1,422 cases, 7.8%), nasopharynx (1,338 cases, 7.4%), and lymph nodes (1,104 cases, 6.1%). CONCLUSION: From this HBCR, cancer incidence in female was almost twice the incidence in male, largely because of the burden of cervical and breast cancers. The cervix uteri as one of the top five cancer sites based on this HBCR, 2008-2012, are still approximately consistent with Global Cancer Incidence, Mortality and Prevalence 2018, which portrayed that Indonesia has been severely afflicted by cervical cancer cases more than any other Association of Southeast Asian Nations countries. The HBCR could serve as a robust database of epidemiological data for cancer cases in Indonesia.

Karnofsky Performance Scale and Neurological Assessment of Neuro-Oncology Scale as Early Predictor in Glioma.

OBJECTIVE: Glioma is one of the most frequent and disabling primary brain tumour. Patients are not only dealing with survival, but also quality of life, which remains another major concern. Karnofsky Performance Scale (KPS) is one of the most commonly used scale to assess patients' quality of life. A recent scale, known as Neurological Assessment of Neuro-Oncology Scale, has surfaced to examine neurological disability caused by brain tumour. Previous study showed this scale to be superior to KPS in predicting survival. However, these scales have never been used to foresee functional scale improvement during disease progression. We sought to determine whether initial KPS and NANO Scale can predict functional scale improvement 2 months after surgery. METHODS: Patients with glioma grade II-IV were included in the study. IDH mutation and MGMT methylation were tested. KPS and NANO scale were examined before surgery and 2 months after surgery. Favorable outcome (FO) was defined as improvement in functional scale 2 months after surgery. Patients initial functional scales were analyzed towards favorable outcome. RESULTS: Glioma WHO grade II, III and IV was found in 17 patients (36.2%), 3 patients (6.4%) and 27 patients (57.4%) respectively. Median KPS before and 2 months after surgery were 50 (30-80) and 60 (0-100), whereas median NANO scale before and 2 months after surgery were 5 (0-12) and 3 (0-12). Favorable outcome was found in 63.8% (KPS) and 78.7% (NANO Scale). Patients initial functional scales were significantly related to FO. CONCLUSION: Good initial functional scales are 4 to 5 times likely of having a favorable outcome 2 months after surgery.

Burden of cancer pain in developing countries: a narrative literature review.

Cancer pain is one of the most common, feared, debilitating, and often undertreated symptoms among cancer patients. It needs attention since it has a significant impact on the quality of life (QoL) of the patients. Also, since cancer has emerged as a major health problem in developing countries, there is a need to strengthen preventive strategies for effective cancer pain management and provide comfort to cancer patients. Nonetheless, various barriers limit developing countries toward optimal cancer pain management. To bridge the gap between adequate pain management and burden of cancer pain in developing countries, a comprehensive understanding of the limitations faced and the prevalence of cancer pain should be addressed. The aim of this literature review is to provide a deeper understanding on the factors associated with cancer pain as well as barriers toward optimal cancer pain management in developing countries. Some of the barriers addressed were administrative, judicial, economic, and professional barriers. Also, estimates on the prevalence of cancer pain and detrimental effects of pain on the QoL of cancer patients have been addressed. In summary, pain, which is one of the most debilitating symptoms of cancer, remains uncontrolled and undertreated in developing countries. It has a profound impact on the patient's QoL and can have physical, psychological, and social consequences; therefore, it needs to be managed urgently and appropriately. Most importantly, optimal treatment of cancer pain should be highlighted as a priority in developing countries and concerted efforts should be made to eliminate different barriers discussed in this review for effective and humane care.

Underutilization of anticoagulant for venous thromboembolism prophylaxis in three hospitals in Jakarta.

AIM: to assess the current use of anticoagulants and implementation of International Guidelines in venous thromboembolism (VTE) prophylaxis in hospitalized patients with acute medical illnesses in Jakarta, Indonesia. METHODS: a multicenter, prospective, disease registry, recruiting patients diagnosed as acutely ill medical diseases and other medical conditions at risk of VTE, with in-hospital immobilization for at least 3 days. RESULTS: of 401 patients, 46.9% received anticoagulants which included unfractionated heparin (64.4%), fondaparinux (11.7%), enoxaparin (9.6%), warfarin (3.7%), and combination of anticoagulants (10.6%). VTE prophylaxis using physical and mechanical method was used in 81.3% of patients, either as a single modality or in combination with anticoagulants. During hospitalization, VTE were found in 3.2% patients; 10 patients (2.5%) had lower limb events and 3 patients (0.75%) had a suspected pulmonary embolism. The main reference international guidelines used were AHA/ASA 2007 (47.4%), followed by ACCP 2008 (21.7%). CONCLUSION: the study showed underutilization of prophylaxis anticoagulants in which mechanical thromboprophylaxis either alone or combination with anticoagulants was the most commonly used. Unfractionated heparin was the preferable choice. The most commonly used guideline was AHA/ASA 2007. VTE thromboprophylaxis in medically ill patients needs to be encouraged.