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OBJECTIVES To determine the effectiveness of combined iron supplementation and methylphenidate treatment on attention-deficit/hyperactivity disorder (ADHD) symptoms in children/adolescents with ADHD and iron deficiency compared with methylphenidate alone. METHODS In total, 116 children/adolescents with ADHD were screened for iron deficiency. Participants who exhibited iron deficiency were randomized into 2 groups (ferrous supplementation vs placebo). Vanderbilt ADHD rating scales were completed by parents and teachers at prestudy and poststudy periods. Student's t tests were used to determine improvements of Vanderbilt scores between the groups. RESULTS Among 116 children who participated in this study, 44.8% (52/116) met the criteria for iron deficiency. Of the total 52 participants with iron deficiency, 26 were randomized to the ferrous group and 26 to the placebo group. Most participants in each group had been prescribed short-acting methylphenidate twice daily in the morning and at noon. After a 12-week study period, total parents' Vanderbilt ADHD symptom scores showed a significant improvement between the groups (mean decrement = -3.96 ± 6.79 vs 0 ± 6.54, p = 0.037). However, teachers' Vanderbilt ADHD symptom scores showed no difference between the groups. CONCLUSION Children with ADHD and iron deficiency being on methylphenidate and iron supplementation had shown improvement of ADHD symptoms that were reported by parents.

Pediatric thromboembolism is a rare and heterogenous disease. As a result, there is a paucity of knowledge with regard to natural history, management, and outcomes of most types of pediatric venous and arterial thromboembolism. International research collaboration is needed to fill these knowledge gaps. Not only randomized controlled trials, but also representative observational studies are required to answer all research questions. Therefore, the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis initiated the International Pediatric Thrombosis Network (IPTN). The aims of the IPTN include (1) development of the Throm‐PED registry to facilitate international prospective observational studies, and (2) establishment of a network of pediatric thrombosis centers experienced in effectively conducting clinical trials and observational studies. The IPTN needs dedicated clinicians all over the world and several funding sources to obtain high‐quality research data to reach its ultimate goal of improving care in children with thrombosis. The aim of this communication is to call for active participation in the IPTN to all physicians taking care of children with thrombosis worldwide.

Multi-drug resistant organisms have been emerging among kidney transplant (KT) recipients with bloodstream infections (BSI). The investigation for epidemiology, risk factors and outcome of these infections following KT was initiated.A retrospective study of all adult KT recipients who developed a BSI within the first year after KT in 2016 at a single transplant center was conducted. The cumulative incidence of BSI was estimated with Kaplan-Meier methodology. Clinical characteristics and outcome were extracted. Risk factors were analyzed with Cox proportional hazards models.Among 171 KT recipients, there were 26 (15.2%) episodes of BSI. Fifty-nine percent were men and the mean ± SD age was 43 ± 12 years. The cumulative incidence of BSIs was 10.1% at 1 month, 13.5% at 6 months, and 15.2% at 12 months. Gram-negative bacteria were responsible for 92% of BSIs, Escherichia coli was the most common pathogen (65%) followed by Klebsiella pneumoniae (11%). Among those, 71% were resistant to extended-spectrum cephalosporins. The genitourinary tracts were the predominant source of BSIs (85%). The second kidney transplantation (HR, 4.55; 95% CI, 1.24-16.79 [P = 0.02]) and receiving induction therapy (HR, 3.05; 95% CI, 1.15-8.10 [P 0.03]) were associated with BSI in a multivariate analysis. One patient (4%) developed allograft rejection, allograft failure and death from septic shock.One out of six KT recipients could develop BSI from gram-negative bacteria within the first year after transplant, particularly in those that received the second transplantation or induction therapy.

Recent evidence suggests a role for magnesium as a calcification inhibitor. Increased magnesium abundance may attenuate vascular calcification and promote bone formation.Parallel-group, 1:1-allocation-ratio, quasi-experimental study.The study was conducted at hemodialysis centers in Bangkok, Thailand. Patients receiving maintenance hemodialysis were screened for coronary artery calcification (CAC) and bone mineral density (BMD), and those with a CAC score of ≥300 were included and matched according to the initial CAC score. The intervention and control groups consisted of 20 patients in each arm.A high (1.75 mEq/L) or standard (0.7 mEq/L) dialysate magnesium concentration was delivered for 26 weeks.Changes in the CAC score and BMD and the progression of CAC. The safety outcomes included occurrence of cramps recorded as per usual care.The median CAC score of all patients was 1,792. Serum and ionized magnesium concentrations increased substantially in the high dialysate magnesium group. At the end of the study, the CAC score increased significantly in both the groups, with no significant difference between the groups. The number of participants with CAC progression was comparable between the 2 groups. In exploratory subgroup analyses stratified by the median CAC score, a significant decline in CAC and fewer participants with CAC progression were observed in the subgroup with lower CAC scores that received the high dialysis magnesium concentration. Bone mineral density was largely unchanged in both groups. The number of participants experiencing cramps and the number of episodes of muscle cramps were markedly lower among patients who received the high dialysis magnesium concentration.The participants had severe vascular calcification at baseline; therefore, the findings might not apply to those with less-established calcification. Moreover, cramps were not systematically ascertained.The high dialysis magnesium concentration did not alleviate the progression of CAC or improve BMD in patients with severe calcification receiving hemodialysis; however, muscle cramps were less frequent among those treated with high dialysate magnesium. Further study is required to determine a possible favorable effect of high dialysis magnesium concentration in individuals with mild-to-moderate calcification.

Regular exercise is associated with the production of small amounts of oxidative stress which might promote individual antioxidant capacity contributing to favorable training effects potentially interrelated with skeletal muscle strength. Therefore, the present study was aimed at evaluating effects of an 8-week Qigong exercise training on muscle strengths associated with responses of oxidative stress and antioxidants in young sedentary females. A total of 41 sedentary women were allocated to the Qigong exercise group (QG, N=20) or to the control group (CG, N=21). After 8 weeks of Qigong training, back and leg strength was significantly improved compared to baseline and the CG (P

Hypercalcemia is an uncommon finding in people living with HIV (PLHIV). Causes of hypercalcemia in PLHIV have not been well documented. As such, we studied the causes of hypercalcemia in PLHIV.We conducted a retrospective review of PLHIV who had corrected serum calcium of ≥10.5 mg/dL between 2010 and 2019. Demographic data, associated diseases, and treatment details were collected. Corrected serum calcium levels were compared among the causes of hypercalcemia.A total of 70 of 2168 (3.2%) PLHIV had hypercalcemia. Forty-nine (70.0%) were male with a mean age of 47.7 ± 4.7 years. Only two (2.9%) had symptoms of hypercalcemia. Fifty-four patients had identifiable causes of hypercalcemia; 21 infections (30.0%), 17 solid organ malignancies (24.3%), 14 hematologic malignancies (20.0%), and two other specific causes (2.9%). Mean corrected serum calcium concentrations of PLHIV who had solid organ malignancy, hematologic malignancy, infection, and unknown causes were 12.8 ± 2.1, 11.4 ± 1.0, 11.2 ± 0.6, and 10.8 ± 0.2 mg/dL, respectively. Corrected serum calcium levels were significantly greater in patients who had solid organ malignancy comparing to those with other causes of hypercalcemia (Hypercalcemia in PLHIV is associated with solid organ malignancy, hematologic malignancy, and infection. Most PLHIV with hypercalcemia are asymptomatic. Solid organ malignancy is associated with moderate to severe hypercalcemia, and as such PLHIV presenting with moderate to severe hypercalcemia should be investigated for solid organ malignancy.

Few epidemiological studies of pediatric central nervous system (CNS) tumors have been performed using data from Southeast Asian national registries. Therefore, we aimed to examine data on CNS tumors from the first national childhood CNS tumor registry in Thailand. Newly diagnosed children with benign and malignant primary CNS tumors from 20 nationwide hospitals were included. Two eras in the Thai registry were studied to compare national protocol effectiveness, including 2003–2005 (before establishment of a pediatric CNS tumor protocol) and 2011–2012 (post-establishment). The first study period had 300 patients with an incidence of 7.5/1,000,000 person-years and the second had 168 patients with an incidence of 13.24/1,000,000 person-years. The three most common tumors were gliomas, medulloblastoma/primitive neuroectodermal tumor (PNET), and germ cell tumors. The most common tumor site was the cerebellum, followed by the brainstem and pineal region. Five- and 10-year overall survival (OS) rates were 46.62% (95% confidence interval [CI] 40.85–52.18) and 41.78% (95% CI 36.11–47.34), respectively, for the first period. The second period had a 5-year OS of 64.75% (95% CI 56.70–71.68). OS rates for gliomas, germ cell tumors, medulloblastoma/PNET, and ependymomas were better in the second period than in the first period. The incidence of primary childhood CNS tumors in our study is lower compared with other reports. Improvement of OS in the second study period might be because of establishment of the Thai Pediatric Oncology Group, and national protocols for childhood CNS tumors.

Cardiovascular disease (CVD) is the leading cause of death among patients who have chronic kidney disease (CKD). Nowadays, CKD per se is considered one of the coronary heart disease (CHD) risk equivalents. Apart from traditional CVD risk factors, there are several possible determinants for CVD in patients with CKD, for example, uremic toxins, increased inflammatory stage, abnormal bone mineral metabolism, and positive calcium balance. In this narrative review, we offer a summary of the extensively studied biomarkers for CVD in patients with CKD, including uremic toxins (p-cresol, indoxyl sulfate, and advanced glycated end products), and a novel indicator of arterial stiffness, cardio-ankle vascular index (CAVI), which is an independent prognostic predictor for CVD. For the uremic toxins, we reviewed their metabolisms, particularly, how the reduced renal function in CKD patients affect their clearance and their clearance with dialysis. Also, we pay attention to the recent evidence on how those uremic toxins contribute to CVD and their clinical associations. We do not include the possible treatment targeting at those uremic toxins. As for the novel indicator of arterial stiffness, we reviewed the clinical application of CAVI in comparison to the standard indicator for arterial stiffness, pulse wave velocity.

Patients with severe thalassemia commonly have a survival that is significantly shorter than that of the general population. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only established treatment that is potentially curative, but it is limited by the availability of donors and the medical condition of the patient. To expand the donor pool to include haploidentical related donors, we introduced a program consisting of a pharmacologic pretransplant immune suppression phase (PTIS) and 2 courses of dexamethasone and fludarabine, followed by pretransplant conditioning with fludarabine-i.v. busulfan and post-transplant graft-versus-host disease (GVHD) prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil. We transplanted 83 consecutive transfusion-dependent patients with thalassemia (median age, 12 years; range, 1 to 28 years) with a minimum follow-up of 6 months (median, 15 months; range, 7 to 53 months); the 3-year projected overall and event-free survival is over 96%, and there have been no secondary graft failures. Of the first 31 patients, we had 2 graft failures, both of them occurring in patients with extremely high titers of anti-donor-specific HLA antibodies (anti-DSAs), but after adjusting the PTIS to include bortezomib and rituximab for patients with high titers of anti-DSAs and using pharmacologic dose guidance for busulfan, we had no graft failures in the last 52 patients. Six (7%) of 83 patients developed severe GVHD. We conclude that this is a safe and efficacious approach to allogeneic SCT in thalassemia, yielding results comparable to those available for patients with fully matched donors.

Wiskott-Aldrich syndrome (WAS)/X-linked thrombocytopenia (XLT) is a rare X-linked disease characterized by thrombocytopenia, eczema, and recurrent infection. In addition, WAS/XLT increases incidence of autoimmune diseases and malignancies. We reported 7 male patients, 2 with WAS and 5 with XLT, from 6 different families. Two novel mutations, p.Gly387GlufsTer58 and p.Ala134Asp, were identified in patients with WAS. Both patients had severe clinical phenotypes compatible with classic WAS and developed lethal outcomes with intracranial hemorrhage. Other than that, one patient with XLT developed pineoblastoma.

Rare Brain Tumor Registry., [Background] Embryonal tumours with multi-layered rosettes (ETMRs) are a newly recognised, rare paediatric brain tumour with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and scarce clinical data, disease features and determinants of outcomes for these tumours are poorly defined. We did an integrated clinicopathological and molecular analysis of primary ETMRs to define clinical phenotypes, and to identify prognostic factors of survival and key treatment modalities for this orphan disease., [Methods] Paediatric patients with primary ETMRs and tissue available for analyses were identified from the Rare Brain Tumor Consortium global registry. The institutional histopathological diagnoses were centrally re-reviewed as per the current WHO CNS tumour guidelines, using histopathological and molecular assays. Only patients with complete clinical, treatment, and survival data on Nov 30, 2019, were included in clinicopathological analyses. Among patients who received primary multi-modal curative regimens, event-free survival and overall survival were determined using Cox proportional hazard and log-rank analyses. Univariate and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) with 95% CIs for clinical, molecular, or treatment-related prognostic factors., [Findings] 159 patients had a confirmed molecular diagnosis of primary ETMRs (median age at diagnosis 26 months, IQR 18–36) and were included in our clinicopathological analysis. ETMRs were predominantly non-metastatic (94 [73%] of 128 patients), arising from multiple sites; 84 (55%) of 154 were cerebral tumours and 70 (45%) of 154 arose at sites characteristic of other brain tumours. Hallmark C19MC alterations were seen in 144 (91%) of 159 patients; 15 (9%) were ETMR not otherwise specified. In patients treated with curative intent, event-free survival was 57% (95% CI 47–68) at 6 months and 31% (21–42) at 2 years; overall survival was 29% (20–38) at 2 years and 27% (18–37) at 4 years. Overall survival was associated with non-metastatic disease (HR 0·48, 95% CI 0·28–0·80; p=0·0057) and non-brainstem location (0·42 [0·22–0·81]; p=0·013) on univariate analysis, as well as with gross total resection (0·30, 0·16–0·58; p=0·0014), high-dose chemotherapy (0·35, 0·19–0·67; p=0·0020), and radiotherapy (0·21, 0·10–0·41; p, [Interpretation] Prompt molecular diagnosis and post-surgical treatment with intensive multi-modal therapy tailored to patient-specific risk features could improve ETMR survival., Canadian Institute of Health Research, Canada Research Chair Awards, Australian Lions Childhood Cancer Research Foundation, Spanish Society of Pediatrics, Consejería de Salud y Familias de la Junta de Andalucía, Miracle Marnie, Phoebe Rose Rocks, Tali's Funds, Garron Cancer Centre, Grace's Walk, Meagan's Hug, Brainchild, Nelina's Hope, and Jean Martel Foundation.

Skin diseases are becoming the most prevalent health concern among all nations worldwide. Recognition of skin lesion, abnormal change usually caused by disease or infection in the skin is the first step in diagnosing skin diseases. In dermatology, morphology skin lesions occur due to the disease process's direct result and indicate categorizing a skin lesions' structure and appearance. In this work, we focus on primary skin lesion classification, particularly early-stage detection, and present a deep learning approach to classify images containing skin lesions, macule, nodule, papule, plaque pustule, wheal, and bulla. We applied deep learning techniques for classifying such images into seven classes covering the aforementioned types of lesion. In particular, we performed experiments on pre-trained deep convolutional neural network models to find the most accuracy one. The result shows that the pre-trained model ResNet-50 after the training and testing can achieve satisfactory accuracy of 85.95%.

Background Dialysis patients have an increased risk of mortality. Recently treatment with haemodiafiltration (HDF) has been reported to reduce mortality, particularly cardiovascular mortality, compared to standard high-flux haemodialysis (HD). However, why HDF may offer a survival advantage remains to be determined. So, we conducted a pilot study to explore differences in middle-molecules, inflammation and markers of vascular disease in patients treated by HD and HDF. Methods Observational cross-sectional study measuring serum β2-microglobulin (β2M), Advanced Glycosylation End Products (AGEs) by skin autofluorescence (SAF), oxidative stress with ischaemia modified albumin ratio (IMAR) and peripheral vascular disease assessment using Ankle-Brachial Index (ABI), and arterial stiffness using Cardio-Ankle Vascular Index (CAVI). Results We studied 196 patients, mean age 69.1 ± 12.4 years, 172 (87.8%) treated by HD and 24 (12.2%) by HDF. Age, body mass index, co-morbidity and dialysis vintage were not different between HD and HDF groups. Middle molecules; β2M (31±9.9 vs 31.2±10 ug/mL) and SAF (2.99±0.72 vs 3.0±0.84 AU), ABI (1.06±0.05 vs 1.07±0.10) and CAVI (9.34±1.55 vs 9.35±1.23) were not different, but IMAR was higher in the HD patients (38.4±14.8 vs 31.3 ± 17.4, P = 0.035) Conclusions In this pilot observational study, we found patients treated by HDF had lower oxidative stress as measured by IMAR, with no differences in middle molecules. Lower oxidative stress would be expected to have diverse protective effects on the cardiovascular system Although we found no differences in ABI and CAVI, future studies are required to determine whether reduced oxidative stress translates into clinically relevant differences over time.

Background and Aims Cardiovascular calcification is highly prevalent among patients with end-stage renal disease (ESRD). Low normal serum magnesium has been linked to a more severe degree of vascular calcification and a decrease in patient survival. An inhibitory effect of extracellular magnesium on osteogenic transformation of vascular smooth muscle cells and the upregulation of anti-calcification protein have been confirmed in vitro. Increased dialysate magnesium concentration has also been shown to lower calcification propensity of the serum of maintenance hemodialysis (HD) patients. Method This study is an investigator initiated, single-blinded, parallel-group, matched case-control clinical trial that investigated the effect of high dialysate magnesium concentration for 24 weeks on the progression of coronary artery calcification (CAC) in maintenance HD patients. The changes in laboratory data and bone mineral density (BMD) were also examined. Seventy-six ESRD patients underwent CAC screening by multi-slice computed tomography and BMD measurement by dual-x-ray absorptiometry. Only patients with Agatston score>300 were included. They were matched according to the initial CAC score that fell within 20% of one another. Twenty patients were assigned to high dialysate magnesium concentration of 1.75 mEq/L and the matched controls were kept on standard dialysate magnesium concentration of 0.7 mEq/L. CAC and BMD measurements were repeated after 24 weeks. Laboratory data were obtained prior to dialysis at study entry, 8-week intervals during the study and 2 weeks after the study ended. Results There were no significant differences in age, sex, BMI, underlying diseases, dialysis vintage, medications, baseline CAC scores and BMD. The median baseline CAC Agatston score (Volume score) were 1923 (720) and 1672 (785) in the standard and high dialysate groups, respectively. At the end of the study, a significant increase in the CAC score was observed in both groups. Because majority of the included patients had severe calcification burden at baseline, patients were categorized into 2 subgroups using the median baseline CAC Agatston (1600) and Volume scores (700) as cut-offs. Among patients with CAC Agatston score 1600, the severity of CAC worsened in both groups. The progression of CAC was analyzed by the difference between the follow-up and the baseline square root transformed Agatston and Volume scores. In subgroup of patients with less severe calcification, more patients in the standard dialysate magnesium group progressed compared to the high dialysate magnesium group (P=0.03). In subgroup of patients with more severe calcification, the number of progressors were comparable among the 2 groups. Serum and ionized magnesium levels increased substantially during the study and returned to baseline after the return to standard dialysate magnesium concentration. The highest predialysis serum magnesium was 3.8 mg/dL. Most patients who received high dialysate magnesium reported the disappearance of symptoms of muscle cramps (P=0.01) and requested the high dialysate magnesium be continued after the end of the study. There were no significant changes in serum calcium, phosphate or PTH levels. The decline in BMD was observed in both groups but the difference did not reach statistical significance. Conclusion High dialysate magnesium was well tolerated and could ameliorate the progression of CAC in maintenance HD patients with mild to moderate vascular calcification.

A retrospective evaluation of growth in 112 patients (68 males, 44 females) with Hb E (HBB: c.79G>A)/β-thalassemia (β-thal), classified as 88 transfusion-dependent thalassemia (TDT) and 24 non tran...

Antiphospholipid syndrome (APS) is an autoantibody-mediated acquired thrombophilia characterized by venous and/or arterial thromboses, pregnancy morbidity (predominantly repeated fetal losses), and the presence of phospholipid antibodies. The estimated annual incidence of APS is 5 new cases per 100,000 people. The most common thrombotic events in patients with APS in order of frequency are stroke, transient ischemic attack, deep vein thrombosis, and pulmonary embolism. Patients with APS may develop an intracardiac thrombus, which is a life-threatening complication with a high risk of increased morbidity and mortality; however, it is treatable by surgical removal, extensive anticoagulant administration, and prevention of other complications. Catastrophic APS, which is a rare and severe condition diagnosed based on rapidly progressive thromboembolic events involving three or more organs, systems, or tissues, occurs in less than 1% of all patients with APS. We herein report an autopsy case of catastrophic APS in a 12-year-old Thai boy with multiple thromboembolic events including intracardiac thrombus formation with a positive lupus anticoagulant test result. To the best of our knowledge, this is the youngest reported patient with APS to date.

To report outcome of postoperative radiotherapy (RT) in both new and recurrent grade II and III intracranial ependymomas in children treated at Ramathibodi Hospital. Between 2006 and 2017, 24 pediatric intracranial ependymomas treated with postoperative RT were retrospectively reviewed. The median age at diagnosis was 44.5 months (range, 4–165 months). There were 14 (58%) males. Fourteen (58%) patients had infratentorial tumor. The median maximal diameter of tumor at diagnosis was 4.45 cm (range, 2.2–10 cm). Fourteen (58%) patients had anaplastic tumor. Gross total resections were performed in 14 (58%) patients. The median prescribed dose was 54 Gy (range, 45–60 Gy). The median total treatment time was 43 days (range, 37–78 days). The median clinical follow-up time was 44.5 months (range, 1–146 months). There were nine recurrences, five of which occurred at the primary tumor site. The estimated 5-year progression-free survival rate was 56%. The estimated 5-year overall survival rate was 75%. Extent of resection was the only factor associated with improved progression-free survival and overall survival after univariate testing. Six from nine patients with recurrent diseases underwent further surgery or further RT. These six patients had better median overall survival than the three who did not. Acute complication was mostly transient and tolerable. No late radiation effect was found. Postoperative radiation is an effective treatment. GTR is associated with better PFS and OS. Aggressive salvage local treatments for recurrent patients can result in good overall survival. Longer follow-up is needed in account for late relapse.

Purpose: To report a case of fungal keratitis infected by Exserohilum rostratumin a human immunodeficiency virus (HIV) patient. Method: A retrospective study of the HIV patient with keratomycosis caused by E. rostratumwas reviewed for history, clinical characteristics, risk factors, laboratory findings, treatments, and outcomes. Results: A 48-year-old man with HIV infection presented with a history of trauma with an unknown species of insect in the right eye. He also had redness and blurred vision in the right eye. Biomicroscopic examination showed white infiltrate in the right cornea. A feathery edge, satellite lesion, and brownish pigmented deposits in the epithelial surface and anterior stroma were noted. Corneal scraping specimen showed numerous large dematiaceous septate hyphae and polymerase chain reaction (PCR) identified E. rostratum.Treatment was started with 5% natamycin eyedrops and oral itraconazole. The corneal lesion responded well to medication and debridement. Conclusions: Corneal phaeohyphomycosis caused by Exserohilumwas noted in an immunocompromised patient with ocular trauma. A brown pigmented lesion in an otherwise white infiltrate due to Exserohilumwas diagnosed with corneal scrapings and polymerase chain reaction. Antifungal medications and debridement were the mainstay of corneal fungal infection treatment.

Aim In this study, an accuracy survey of intensity-modulated radiation therapy (IMRT) and volumetric arc radiation therapy (VMAT) implementation in radiotherapy centers in Thailand was conducted. Background It is well recognized that there is a need for radiotherapy centers to evaluate the accuracy levels of their current practices, and use the related information to identify opportunities for future development. Materials and methods An end-to-end test using a CIRS thorax phantom was carried out at 8 participating centers. Based on each center's protocol for simulation and planning, linac-based IMRT or VMAT plans were generated following the IAEA (CRP E24017) guidelines. Point doses in the region of PTVs and OARs were obtained from 5 ionization chamber readings and the dose distribution from the radiochromic films. The global gamma indices of the measurement doses and the treatment planning system calculation doses were compared. Results The large majority of the RT centers (6/8) fulfilled the dosimetric goals, with the measured and calculated doses at the specification points agreeing within ±3% for PTV and ±5% for OARS. At 2 centers, TPS underestimated the lung doses by about 6% and spinal cord doses by 8%. The mean percentage gamma pass rates for the 8 centers were 98.29 ± 0.67% (for the 3%/3 mm criterion) and 96.72 ± 0.84% (for the 2%/2 mm criterion). Conclusions The 8 participating RT centers achieved a satisfactory quality level of IMRT/VMAT clinical implementation.

Coronary stenosis is a consequence of atherosclerotic plaque progression that is associated with impaired fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor 1 (PAI-1) are fibrinolysis inhibitors whose levels are influenced by acquired conditions and by polymorphisms. This study therefore aimed to investigate the association of TAFI and PAI-1 gene polymorphisms with severity of coronary stenosis in subjects with stable coronary artery disease (CAD).A total of 327 subjects suspected with CAD who underwent a coronary angiogram were recruited. Gensini score was applied to stratify the severity of coronary stenosis. Based on the Gensini score, the subjects were categorized into low-medium (20) or high (≥20) groups. The study polymorphisms included TAFI Ala147Thr (505G/A), Thr325Ile (1040C/T), +1542C/G, +1583T/A and PAI-1 -675 4G/5G. Most polymorphisms were genotyped by allele-specific polymerase chain reaction, except for TAFI Thr325Ile that was genotyped by polymerase chain reaction-restriction fragment length polymorphism.A significant increase in the Gensini score was found in TAFI 505A and +1583A allele carriers. Binary regression analysis revealed the independent association of the TAFI 505G/A and +1583T/A polymorphisms with a high Gensini score [adjusted OR = 1.67 (95% CI: 1.03, 2.73) and 1.69 (95% CI: 1.04, 2.76), respectively]. Neither the homozygous PAI-1 -675 4G/4G nor the heterozygous 4G/5G was associated with a high Gensini score.The results indicated the contribution of TAFI polymorphisms to atherosclerosis progression and severity of coronary stenosis in stable CAD.

Background The food industry can influence individual and population level food consumption behaviours, shape public preferences and interfere with government policy on obesity prevention and NCDs. This paper identifies the Corporate Political Activity (CPA) of major food companies in Thailand which relate to obesity and NCDs. Methods Using the INFORMAS framework to classify CPA, we reviewed publicly available information by 12 food companies between August 2011 and July 2016 in order to identify, analyse and classify the CPA contents. Semi-structured interviews with 17 key stakeholders who are experts in this field supplemented evidence from the document review. Data analysis applied a thematic approach. Results Food industry in Thailand applied a variety of CPA strategies and practices. The two most common strategies were constituency building and information and messaging. Conclusion The diverse range of CPA strategies which influence government policy and public opinion can undermine efforts to prevent obesity and diet-related NCDs. We recommend systematic monitoring of their CPA, strengthening mechanisms to hold the food industry accountable for their role in protecting and promoting the nutrition and health of the population, introducing mandatory registration of lobbyists, mandatory disclosure of political donations, and stronger oversight of conflicts of interest among the government actors. Electronic supplementary material The online version of this article (10.1186/s12992-018-0432-z) contains supplementary material, which is available to authorized users.

Background Patients with thalassemia encounter increased consumption of zinc (Zn) and copper (Cu) from chronic hemolysis and increased excretion from iron chelation. Iron-enriched diet restriction may result in low Zn and Cu intakes. Recent data on Zn and Cu status among Thai pediatric patients with thalassemia are lacking. This study aimed to identify frequencies and determine risk factors of Zn and Cu deficiencies among patients with thalassemia. Methods Patients with transfusion-dependent thalassemia (TDT) receiving iron chelation ≥12 months and nonTDT (NTDT) aged 2–20 years were recruited. Serum Zn and Cu were measured. Dietary intakes were ascertained by interviews. Results A total of 209 patients (TDT = 126, NTDT = 83) were enrolled. Zn deficiency seemed to be associated with disease severity as median (IQR) Zn level of TDT was lower than that of NTDT [77 (69−85) vs. 80 (72−88) mcg/dL, p = 0.05], while higher frequency of Zn deficiency was identified in the former (24 % vs. 14 %). In TDT, Zn deficiency was associated with patients >10 years (OR 4.6; 95 %CI 1.1–6.4, p = 0.03), which likely resulted from combined low dietary Zn intake, prolonged exposures to hemolysis and iron chelators. Frequencies of Cu deficiency were similarly low in TDT and NTDT (8% and 7%) with comparable median (IQR) Cu levels of 103 (90−124) and 110 (92−132) mcg/dL, respectively (p = 0.13). Cu levels were inversely associated with age (r=-0.65 and r=-0.62 in TDT and NTDT, respectively; p Conclusion Compared with younger patients, Zn and Cu deficiencies were more common among patients with thalassemia >10 years. Age was a major factor associated with both Zn and Cu deficiencies.

The diagnosis of MYH9 disorder is guided by recognizing granulocyte Dohle body-like inclusion bodies and large/giant platelets in the peripheral blood smear. Immunofluorescence study of nonmuscle myosin heavy chain IIA is a sensitive screening method for diagnosis of MYH9 disorder. The diagnosis can then be confirmed by genetic analysis. A total of 67 patients with macrothrombocytopenia were included, of which 11 patients (16%), aged 4 months to 22 years, were ultimately diagnosed with MYH9 disorder. One novel mutation in exon 30 at c.4338T>C (p.F1446A) was detected. This mutation was associated with nonhematologic manifestations presenting in late adolescence with cataracts, hearing loss, and hematuria.

Background: Hemoglobin H (HbH) is usually recognized as mild thalassemia. However, a wide range of clinical manifestations, from fatal hydrops fetalis to asymptomatic mild anemia, is observed. A severity scoring system to guide the management of patients with HbH is needed. Objective: To develop a scoring system to predict the necessity of regular transfusion among patients with HbH. Methods: Patients were classified into 2 groups according to transfusion requirement: severe among transfusion-dependent thalassemia (TDT) and nonsevere among nontransfusion-dependent thalassemia (NTDT). Clinical and hematological parameters associated with transfusion dependency were identified and β-coefficients of significant parameters from multiple logistic regression analysis were used to develop a scoring system. Results: A total of 247 pediatric patients (24 severe, 223 nonsevere) with a median age of 14.3 (IQR 9.9-18.4) years were included. Multiple logistic regression analysis revealed 3 significant parameters associated with regular transfusion requirement including 1) age at diagnosis

Hemostatic changes and endothelial activations have been recognized in β-thalassemic patients after matched-donor hematopoietic stem cell transplantation (HSCT) but there are limited studies for haploidentical HSCT. This report demonstrates that the levels of hemostatic and endothelial markers, including thrombin antithrombin complex, prothrombin fragment, D-dimer, von Willebrand factor antigen and thrombomodulin levels, were not significantly different between haploidentical and matched-donor HSCT patients.

BackgroundETMRs are a newly recognized rare paediatric brain tumor with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and limited clinical data, disease features and determinants of outcome are poorly defined. We performed an integrated clinico-pathologic and molecular analyses of 159 primary ETMRs to define clinical phenotypes, identify predictors of survival and critical treatment modalities for this orphan disease.MethodsPrimary ETMR patients were identified from the Rare Brain Tumor Consortium (rarebraintumorconsortium.ca) global registry using histopathologic and molecular assays. Event-Free (EFS) and Overall Survival (OS) for 108 patients treated with curative multi-modal regimens were determined using Cox proportional hazard and log rank analyses.FindingsETMRs were predominantly non-metastatic (73%) tumors arising from multiple sites; 55% were cerebral tumors, 45% arose at sites characteristic of other brain tumors. Hallmark C19MC alterations were seen in 91%; 9% were ETMR-NOS. Survival and hazard analyses showed a 6 month median EFS and 2-4yr OS of 27-29% with metastatic disease (HR=0.44, 95% CI 0.26-0.74; p=0.002) and brainstem location (HR=0.40, 95% CI 0.021-0.75; p=0.005) correlating with adverse OS. Gross total resection (GTR: HR=0.38, 95% CI 0.21-0.68; p=0.001), high dose chemotherapy (HDC: HR=0.55, 95% CI 0.31-0.97; p=0.04) and radiation (RT: HR=0.32, 95% CI 0.16-0.60; p=InterpretationPrompt molecular diagnosis and post-surgical treatment with multi-modal therapy tailored to patient-specific risk features improves ETMR survival.FundingThis work was supported by the Canadian Institute of Health Research Grant No. 137011, Canada Research Chair Awards to AH. Funds from Miracle Marnie, Phoebe Rose Rocks, Tali’s Funds, Garron Cancer Centre, Grace’s Walk, Meagan’s Walk, Nelina’s Hope and Jean Martel Foundation are gratefully acknowledged. SK and PS were respectively supported by the Australian Lions Children’s Cancer Foundation and the Spanish Society of Pediatrics, Consejería de Salud y Familias de la Junta de Andalucía Project EF-0451-2017.

Objective This study aimed to explore real-world evidence on health resource use (HRU) spending on patients with haemophilia and inhibitor. Materials and methods Medical records from 1990 to 2019 of patients with haemophilia and inhibitor from three comprehensive haemophilia treatment centres were retrospectively retrieved. Results In all, 31 patients with haemophilia (A = 30, B = 1) and inhibitor ≥5 BU were included. The mean initial inhibitor of 95.4 BU was detected at the mean age of 6.7 years. The mean number of annual hospitalisations was 3.9. A total of 795 bleeding episodes (major =125, minor =670) were evaluated. The treatment included bypassing agents or plasma exchange before administering high-dose factor VIII concentrate and intervention or surgery. Six patients succumbed to bleeding at the mean age of 17.2 years. Nineteen surviving patients experienced multiple morbidity except six patients with successful and partially successful immune tolerance induction (ITI). The mean (SD) annual total medical consumption for episodic treatment and successful ITI per patient with haemophilia A were 30,804 (81,332) USD and 55,531 (100,566) USD, respectively. Only episodic treatment was paid by the government budget for limited amounts of bypassing agents. Conclusion Management for patients with haemophilia and inhibitor exhibiting severe bleeding is challenging for medical personnel in countries having limited resources over decades. The real-world data will be used to negotiate with the government to increase budget for adequate bypassing agents or nonreplacement therapy and to include ITI in the national haemophilia treatment.

Background Observational studies indicate that children hospitalized with COVID-19-related illness, like adults, are at increased risk for venous thromboembolism (VTE). A multicenter phase 2 clinical trial of anticoagulant thromboprophylaxis in children hospitalized with COVID-19-related illness has recently been initiated in the United States. To date, there remains a paucity of high-quality evidence to inform clinical practice world-wide. Therefore, the objective of this scientific statement is to provide consensus-based recommendations on the use of anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illnesses, and to identify priorities for future research. Methods We surveyed 20 pediatric hematologists and pediatric critical care physicians from several continents who were identified by Pediatric/Neonatal Hemostasis and Thrombosis Subcommittee leadership as having experience and expertise in the use of anticoagulant thromboprophylaxis and/or the management of COVID-19-related illness in children. A comprehensive review of the literature on COVID-19 in children was also performed. Results Response rate was 90%. Based on consensus of expert opinions, we suggest the administration of low-dose low molecular weight heparin subcutaneously twice-daily as anticoagulant thromboprophylaxis (in the absence of contraindications, and in combination with mechanical thromboprophylaxis with sequential compression devices, where feasible) in children hospitalized for COVID-19-related illness (including the multisystem inflammatory syndrome in children [MIS-C]) who have markedly elevated D-dimer levels or superimposed clinical risk factors for hospitalassociated VTE. For children who are clinically unstable or have severe renal impairment, we suggest the use of unfractionated heparin by continuous intravenous infusion as anticoagulant thromboprophylaxis. In addition, continued efforts to characterize VTE risk and risk factors in children with COVID-19, as well as to evaluate the safety and efficacy of anticoagulant thromboprophylaxis strategies in children hospitalized with COVID-19-related illness (including MIS-C) via cooperative multicenter trials, were identified among several key priorities for future research. Conclusion These consensus-based recommendations on the use of anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illnesses and priorities for future research will be updated as high-quality evidence emerges.

Background and Aims Haemodialysis (HD) is one of the life-saving procedures which prolonged life of chronic kidney disease stage 5, however, the long-termed complications such as cardiovascular disease (CVD), immune and endothelial dysfunction are commonly occurred. The high incidence of CVD in haemodialysis patient associated with traditional and non-traditional risk factors. The novel non-traditional risk factors such as p-cresol, Advance Glycosylation End Products (AGEs), Ankle-Brachial Index (ABI), Cardio-Ankle Vascular Index (CAVI). The ischemic modified albumin (IMA) is the new marker for cardiovascular disease in various populations including haemodialysis. We aimed to explored the factors associate with higher IMA in chronic haemodialysis patients. Method Cross sectional study 196 chronic haemodialysis patients were collected blood sample for Ischemic modified albumin (IMA), measured Ankle-Brachial Index (ABI), Cardio-Ankle Vascular Index (CAVI), and skin autofluorescence advanced glycosylation end products (SAF). Results 53% were female, 21% were smoker, 57% were diabetes, 93% were hypertension, 33% were coronary artery disease, 12% on HDF. Mean Age were 69.2±13.2 year, ABI 1.1±0.15, CAVI 9.3±1.5, SAF 3.1±0.8 arbitrary unit, IMA 37.5±15.2 U/ml, and serum albumin 3.7±0.4 g/dl. In multivariate adjustment showed factors associate with higher IMA were low ABI (B co-efficiency -13.4, P=0.049) and high serum albumin (B co-efficiency 1.68, P=0.000002). Conclusion Lower ABI and high serum albumin associate with higher IMA. The finding underlines the association between the atherosclerosis, vascular endothelial function and cardiac injury in haemodialysis. These results should be confirmed and explored in larger and longer clinical trials. Figure Regression analysis of factors associate with IMA accumulation.

Masked hypertension defined as having normal office blood pressure (BP) but hypertension detected by continuous BP monitoring has been observed in children and adolescents with type 1 diabetes (T1D). However, no study has evaluated whether masked hypertension is associated with glycemic variability (GV) in these patients. We hypothesized that masked hypertension might be associated with high GV in patients with T1D.This cross-sectional study performed continuous glucose monitoring (CGM) in parallel with ambulatory blood pressure monitoring (ABPM) in T1D patients aged 6-21 years. Patients who had known hypertension were excluded. CGM data from the same day as ABPM was calculated for GV including standard deviation (SD), coefficient of variation (CV) of glucose levels, and unstable glycemia which was defined as having a CV of glucose levels ≥ 36%.Thirty-three patients had complete ABPM and CGM data. Mean (SD) age was 13.8 (3.8) years and mean (SD) duration of T1D was 5.4 (3.6) years. All patients had normal office BP, but ABPM showed masked hypertension in 9 patients (27%). In comparison with normotensive patients, patients with masked hypertension had longer duration of T1D (7.4 vs. 4.6 years, p = 0.049), higher insulin requirement (1.2 vs. 0.9 units/kg/day, p = 0.049), and higher SD of glucose (70.3 vs. 47.9 mg/dl, p = 0.038). Masked hypertension group had a greater number of patients (71% vs. 19%, p = 0.02) with unstable glycemia. Multivariate analysis revealed that unstable glycemia was associated with masked hypertension.The presence of unstable glycemia in children and adolescents with T1D is associated with masked hypertension. Graphical abstract.

Background: Vascular complications are the major morbid consequences of type 2 diabetes mellitus (T2DM). The transcription factor 7-like 2 (TCF7L2), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), and inwardly-rectifying potassium channel, subfamily J, member 11 gene (KCNJ11) are common T2DM susceptibility genes in various populations. However, the associations between polymorphisms in these genes and diabetic complications are controversial. This study aimed to investigate the effects of combined gene-polymorphisms within TCF7L2, KCNQ1, and KCNJ11 on vascular complications in Thai subjects with T2DM.Methods: We conducted a case-control study comprising 960 T2DM patients and 740 non-diabetes controls. Single nucleotide polymorphisms in TCF7L2, KCNQ1, and KCNJ11 were genotyped and evaluated for their association with diabetic vascular complications.Results: The gene variants TCF7L2 rs290487-T, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-C were associated with increased risk of T2DM. TCF7L2 rs7903146-C, TCF7L2 rs290487-C, KCNQ1 rs2237892-T, and KCNQ1 rs2237897-T revealed an association with hypertension. The specific combination of risk-alleles that have effects on T2DM and hypertension, TCF7L2 rs7903146-C, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-T, as genetic risk score (GRS), pronounced significant association with coronary artery disease (CAD), cumulative nephropathy and CAD, and cumulative microvascular and macrovascular complications (respective odds ratios [ORs] with 95% confidence interval [95% CI], comparing between GRS 2–3 and GRS 5–6, were 7.31 [2.03 to 26.35], 3.92 [1.75 to 8.76], and 2.33 [1.13 to 4.79]).Conclusion: This study demonstrated, for the first time, the effect conferred by specific combined genetic variants in TCF7L2 and KCNQ1 on diabetic vascular complications, predominantly with nephropathy and CAD. Such a specific pattern of gene variant combination may implicate in the progression of T2DM and life-threatening vascular complications.

Forward head posture (FHP) is a problem with muscle imbalance around neck and shoulder girdle. The FHP might be a silent threat for young adults in their later stages of life. An impact of the FHP on muscle activities in upright posture has been well established; however, how it influences neck and shoulder muscle activities in side lying-position has been still elusive. This study was aimed to investigate electrical muscle activities (% maximum voluntary contraction, %MVC) on both upper and lower sides of 4 neck and shoulder muscles—sternocleidomastoid (SCM), upper trapezius (UT), middle trapezius (MT) and lower trapezius (LT) using surface electromyography (EMG) in 34 participants (normal head posture (NHP) group, aged 21.24±0.97 years old, n=17; and FHP group, aged 20.83±1.20 years old, n=17). Each participant performed side-lying position with a self-selected pillow for 5-min of acclimatization and another 12-min for EMG recordings. Results showed that there was no significant difference between %MVC on upper and lower sides of all muscles in both groups. In contrast, the %MVC of the trapezius muscles on the upper side of the FHP group were significantly higher than the NHP group i.e., 1.26±0.76 vs 0.79±0.44 in UT; and 3.06±1.86 vs 1.74±1.14 in LT, respectively. Despite symmetrical activation of bilateral muscles can be seen in both groups; however, the FHP could induce over activation of UT and LT while resting in side-sleeping position. Therefore, selective technique to minimize muscle activation during resting position might be required as preventive regimen for this group of young adults

Pretransplant desensitization protocols, including plasmapheresis, intravenous immunoglobulin, induction antibody therapy, and intensive maintenance immunosuppression, are generally employed in kidney transplant recipients who have positive status for donor-specific anti-HLA antibody (DSA). To avoid serious infectious complications, the authors designed a novel low-dose protocol in Thai patients undergoing DSA+ living-related kidney transplantation (LRKT).A retrospective cohort study of the patients who underwent DSA+ LRKT was conducted. The novel protocol consisted of 3 to 5 sessions of pretransplant double-filtration plasmapheresis (DFPP) with or without low-dose intravenous immunoglobulin together with low-dose anti-thymocyte globulin (ATG) induction (1-1.5 mg/kg/d for 3-4 days) and low-dose tacrolimus (Tac) (trough level 5-10 ng/mL), mycophenolate, and prednisolone.The study included 17 patients. The lymphocyte crossmatch via complement-dependent cytotoxicity was negative in 12 patients and positive for B cell immunoglobulin M in 5 patients. The novel desensitization protocol resulted in a decrease of at least 50% of DSA mean fluorescence intensity from baseline (from 4320 ± 549 before DFPP to 1601 ± 350 before transplantation, P .005) and successful kidney transplantation with good allograft function in all cases. Early DSA rebound was observed in 3 patients after transplantation, and kidney biopsy revealed subclinical antibody-mediated rejection in 1 patient and diffuse C4d staining without cell infiltration in 2 patients. There were good long-term outcomes in patient and graft survival (100% and 94.1%, respectively). Only 1 allograft loss occurred because of nonadherence. The majority of patients have stable allograft function with serum creatinine less than 1.5 mg/dL. However, infections, including CMV and other organisms, were commonly observed.Desensitization protocol with DFPP, low-dose ATG, and Tac provides excellent outcomes in living donor kidney transplantation in highly sensitized Asian populations.

An incidence of cisplatin-induced acute kidney injury (AKI) of 34% has been reported in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, delayed cisplatin-induced nephrotoxicity and long-term renal outcomes remain poorly studied. Patients with LA-HNSCC who underwent definitive or postoperative cisplatin-based chemoradiotherapy (CRT) were included. Acute kidney disease (AKD) was defined as newly developed estimated glomerular filtration rate (eGFR) 50% increase in serum creatinine for

Yuda Sutherasan,1 Pongdhep Theerawit,1 Alongkot Suporn,2 Arkom Nongnuch,3 Pariya Phanachet,4 Chomsri Kositchaiwat5 1Division of Pulmonary and Pulmonary Critical Care Medicine, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Renal Unit, Department of Medicine, Faculty of Medicine Ramathibodi Hospital Mahidol University, Bangkok, Thailand; 4Division of Nutrition and Biochemical Medicine, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 5Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Purpose: The aim of this study was to evaluate the impact of a hospital protocol in response to patient deterioration in general wards, stratified using the national early warning score (NEWS), on primary patient outcomes of in-hospital mortality and percentage of patients transferred to the intensive care unit (ICU).Patients and methods: We conducted a prospective observational cohort study among adult medical patients admitted to a university hospital in Bangkok. A 4-month pre-protocol period (November 2015 to February 2016) was assigned to a control group and a protocol period (March 2016 to June 2016) was allocated to a protocol group. On admission, vital signs (respiratory rate, pulse rate, systolic blood pressure, and temperature), oxygen saturation, presence of oxygen supplementation, and neurological status were used to calculate NEWS. Patients were categorized as low, moderate, or high risk based on the NEWS. During protocol period, when patients’ conditions are critical and they are at imminent risk, the NEWS detects the event and triggers a systematic response. The response enables closed monitoring and early treatment by expert physicians to rapidly stabilize and triage the patient to a location where services meet the patient’s needs. Primary outcomes were compared between the pre-protocol and protocol groups using historical controls for the intervention, which is the availability of NEWS to staff and an associated escalation pathway.Results: A total of 1,145 patients were included in the analysis: 564 patients in the pre-protocol group and 581 in the protocol group. The mean NEWS of patients at admission was higher in the protocol group than in the pre-protocol group (2.4±2.4 vs 1.77±2.158; P

Increasing urea clearance by hemodialysis (HD) has not improved patient survival. Hemodiafiltration (HDF) has been reported to reduce cardiovascular mortality. HDF increases middle sized solute clearances. Advanced glycosylation end products (AGEs) are associated with increased cardiovascular mortality. We wished to determine whether HDF reduces AGEs. Skin auto-fluorescence (SAF) measures circulating AGEs deposited in the skin. We compared SAF measurements 12 months apart in high flux HD and HDF patients. At enrollment SAF was not different (HD 3.34 ± 0.71 vs. HDF 3.48 ± 1.05 AU). At seven months after completion of SAF measurement, one hemodiafiltration center returned to hemodialysis, and one hemodialysis center converted to hemodiafiltration. In the 66 patients treated solely by high flux HD, SAF increased (3.36 ± 0.71 to 3.82 ± 0.88 AU, P 0.9). SAF increased in 34 patients switching from HDF to high flux HD (3.52 ± 0.94 vs. 3.88 ± 1.05, P 0.3). On multivariate analysis, SAF was associated with older age (β coefficient 0.013, P = 0.002), prescription of insulin (β 0.29, P = 0.016), lanthanum (β 0.36, P = 0.004), and warfarin (β 0.62, P = 0.012), whereas vegetarian diet and > 250 mL/day residual urine volume were negatively associated with SAF (β -0.58, P = 0.002 and β -0.26, P = 0.033 respectively). Residual urine output and vegetarian diet were associated with lower AGE deposition. Whereas SAF increased over time in patients treated with high flux HD, there was no statistical change in SAF in those exclusively treated by HDF.

Introduction: Intrinsic foot muscle weakness is a crucial cause of balance deficit in the elderly, which leads to a limited range of motion from the fear of falling and subsequently decreases the quality of life. Muscle strengthening via transcutaneous electrical stimulation (TENS) is an effective intervention; however, its effects on elderly people have rarely been reported. This study was conducted to investigate the effects of TENS on navicular height, balance, and fear of falling. Method: In this study, forty-eight participants aged 65–75 years were included and were randomly divided into two groups: the TENS and control groups. Before and after 4 weeks of training, navicular height, balance, and fear of falling were measured. Result: After 4 weeks of training, navicular height significantly increased in both groups (p < 0.05); however, the increase was higher in the TENS group (p = 0.035). The TENS group had a better improvement in balance in all four directions—front, back, left, and right (p < 0.05). However, postural balance improvements in the control group were observed in three directions only—front, back, and left (p < 0.05)—without any significant difference between the two groups. Furthermore, the TENS group decreased the scale of fear of falling after 4 weeks of training (p = 0.039). Conclusion: In summary, the results of this study can be used as part of the muscle strengthening via ES for decreasing the risk of falls or fear of falling in the elderly.

Background: Valproic acid (VPA), an anti-epileptic drug, can cause male subfertility. However, the degree to which testicular and epididymal histopathologies and androgen receptor (AR) expression are changed under VPA treatment has never been reported. Objective: To investigate the histopathological changes and AR protein levels of testis and epididymis in VPA-treated rats for every single day. Materials and Methods: Sixty-four adult male Wistar rats were divided into control and VPA-treated groups (n=8/ each). Treated rats were injected with 500 mg/ kgBW, intraperitoneally, VPA for 10 consecutive days. At the end of every experimental day, all reproductive parameters including histology by hematoxylin and eosin staining and protein expression of AR by Immuno-Western blot in testis and epididymis were examined. Results: VPA-treated rats showed dramatically changes in testicular and epididymal histopathologies compared to control group. The multinucleated giant cells and sloughing of germ cells were observed on day 6. The germ cell disintegration and increased intercellular spaces of seminiferous tubular epithelium appeared in days 7-10 of VPA treatment. Additionally, extensive multinucleated giant cells and complete exfoliation were clearly found from days 8-10. Such exfoliated germ cells were clearly seen in its epididymal lumen at day 10. The increasing rate of sperm concentration was approximately 32.31% of that in control group at day 10 (p=0.03). Moreover, the protein expressions of testicular and epididymal AR (% intensity/ 80 µg protein lysate) was decreased in VPA-treated rats compared with control. Conclusion: VPA treatment induces histologic changes of germ cell epithelium in seminiferous tubules and decreases the expression of testicular and epididymal androgen receptors.

The p.R147W mutation, the c.C6152T in exon 7, causing a change in amino acid from arginine to tryptophan of the PROC gene has been reported as a common mutation in Taiwanese populations with venous thromboembolism (VTE). The present study aimed to identify the prevalence of p.R147W in the Thai population and children with TE and the risk of developing TE. Patients aged ≤18 years diagnosed with TE were enrolled. The PROC gene was amplified by polymerase chain reaction using a specific primer in exon 7. The restriction fragment length polymorphism was designed using MwoI restriction enzyme. A total of 184 patients and 690 controls were enrolled. The most common diagnosis of TE was arterial ischemic stroke (AIS), at 100 (54.3%), followed by VTE, at 38 (20.6%), and cerebral venous sinus thrombosis (CVST), at 23 (12.5%). The prevalence of heterozygous and homozygous p.R147W in patients and controls was 9.5% versus 5.8% and 2.7% versus 0.1%, respectively. Heterozygous p.R147W had odds ratios (ORs) of 1.8 (95% confidence interval [CI]: 1.0-3.2, P = .04), 3.2 (95% CI: 1.2-8.2, P = .009), and 4.5 (95% CI: 1.6-12.8, P = .002) of developing overall TE, VTE, and CVST, respectively. Homozygous p.R147W had ORs of 20.2 (95% CI: 2.3-173.7, P < .001), 21.4 (95% CI: 2.2-207.9, P < .001), and 43.3 (95% CI: 3.8-490.6, P < .001) of developing overall TE, AIS, and CVST, respectively. This study suggested that p.R147W is a common mutation and increased risk of TE in Thai children.

The outcome of children with high-grade gliomas (HGGs) treated with radiation and adjuvant chemotherapy remains poor. The expression of epidermal growth factor receptor (EGFR) has been established in children with HGGs. This report demonstrated the outcomes of adjuvant nimotuzumab, an EGFR inhibitor, with irinotecan in pediatric HGGs. Children with newly diagnosed HGGs were enrolled. Two weeks after surgery, nimotuzumab with a dose of 150 mg/m2 was given every week during radiation. After completion of radiation, a 4-week cycle of nimotuzumab (150 mg/m2) at week 1 and 3 and irinotecan (125 mg/m2) at week 1, 2, and 3 was given. Sixteen patients (5 females, 11 males), with a mean ± SD age of 8.2 ± 3.5 years were included. Tumors were located at the supratentorial region (50.0%), infratentorial region (43.8%), and both locations (6.2%). The 5-year PFS and OS were 19.9 ± 11.6 and 31.5 ± 13.0%, respectively. Median times of PFS and OS were 1.8 and 1.9 years, respectively. Prognostic factors related to good outcome were the location of tumor at the supratentorial region or outside brainstem and the extension of surgery. Side effects were minimal, with grade 1 anemia in three patients and diarrhea in one patient. Although, the adjuvant regimen of nimotuzumab and irinotecan slightly increases the overall outcome when compared to the historical study, the advantages of this protocol were minimal side effect, short period of hospitalization, and improved OS in patients who received extensive surgery.

Aims: To compare insulin sensitivity, β-cell function and iron status biomarkers in non-transfusion-dependent thalassaemia (NTDT) with iron excess during pre- and post-iron chelation. Methods: Subjects with NTDT, aged older than 10 years, with serum ferritin >300 ng/ml, were included. Iron chelation with deferasirox (10 mg/kg/day) was prescribed daily for 6 months. Results: Ten patients with a median age of 17.4 years were enrolled. The comparison between pre- and post-chelation demonstrated significantly lower iron load: median serum ferritin (551.4 vs. 486.2 ng/ml, p = 0.047), median TIBC (211.5 vs. 233.5 µg/dl, p = 0.009) and median non-transferrin binding iron (5.5 vs. 1.4 µM, p = 0.005). All patients had a normal oral glucose tolerance test (OGTT) both pre- and post-chelation. However, fasting plasma glucose was significantly reduced after iron chelation (85.0 vs.79.5 mg/dl, p = 0.047). MRI revealed no significant changes of iron accumulation in the heart and liver after chelation, but there was a significantly lower iron load in the pancreas, assessed by higher T2* at post-chelation compared with pre-chelation (41.9 vs. 36.7 ms, p = 0.047). No adverse events were detected. Conclusions: A trend towards improving insulin sensitivity and β-cell function as well as a reduced pancreatic iron load was observed following 6 months of iron chelation (TCTR20160523003).

Background Induction chemotherapy with carboplatin followed by radiotherapy has been used for many years for treating intracranial germ-cell tumors (IC-GCTs) in Thailand. The objective of this study was to assess treatment outcomes, focusing on survival and ototoxicity. Methods The outcomes of all patients with IC-GCT treated at Ramathibodi Hospital and the Prasat Neurological Institute between 2000 and 2017 were reviewed and analyzed, including all patient characteristics and treatment modalities. Five-year overall survival (OS) and event-free survival (EFS) were analyzed using the Kaplan-Meier method, and factors affecting survival were compared using the log-rank test. Results Fifty-three patients age 1-14 years (median, 11 years) were included in this study. The median follow-up time was 63 months. The 5-year EFS and OS rates were 94.3% and 96.2% for all patients, respectively. No statistical difference in OS or EFS was observed between the data of recipients in the carboplatin-based and historical cisplatin-based therapies in our institutes. Concerning radiotherapy, omission of radiotherapy or focal irradiation results in worse long-term survival outcomes, but reduction in dose of radiotherapy to less than 40 Gy did not cause any negative impact on survival rates. Furthermore, carboplatin was associated with lower rates of hearing loss than cisplatin (5.7% vs 87.5%). Conclusions Induction chemotherapy with carboplatin-based regimens was associated with excellent survival rates and low ototoxicity in patients with IC-GCT. Radiotherapy should be given to all patients with a minimal volume equivalent to whole-ventricular radiotherapy, during which doses of lower than 40 Gy can be effectively used.

Background Sleep disturbance is common among chronic haemodialysis patients, which leads to poor quality of life, in addition to increased instances of morbidity and mortality. Hypervolemia has been linked to sleep problems observed in chronic haemodialysis patients, which suggests that optimising one’s fluid status could improve the sleep quality of this patient group. In our study, we subjectively examined and objectively measured sleep parameters, using actigraphy recordings, the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and Epworth Sleepiness Scale (ESS), in order to compare bioelectrical impedance analysis (BIA)-guided and standard clinical-guided dry weight adjustment. Methods We randomly selected 19 chronic haemodialysis patients with subclinical hypervolemia, defined as a clinically euvolemic status, despite the ratio of extracellular water to total body water being more than 0.4 in BIA. Furthermore, these patients, who were poor sleepers (PSQI > 5), were assigned to either a BIA-guided dry weight group (BIA group) or a standard clinical-guided one (clinical group). The primary outcome was changes in sleep actigraphy parameters between the groups at 1, 3, and 6 months. Changes observed in the PSQI and ESS score between the two groups over the same period of time were the secondary endpoints. Results The mean age of the participants was 63.53 ± 11.12 years, and 42% of them were male. All sleep parameters measured by means of actigraphy were not significantly different between the two groups. Interestingly, at 3 and 6 months, the subjective sleep quality significantly improved in the BIA group, as reflected by a greater decline in the PSQI score, in comparison with the clinical group (3 months: mean difference − 1.82 [− 3.13 to − 0.51], P = 0.006; 6 months: mean difference − 3.16 [− 4.49 to − 1.83], P

Background Oxidative stress modulates insulin resistant-related atherogenic dyslipidemia: hypertriglyceridemia (HTG) and low high-density lipoprotein cholesterol (HDL-C) level. Gene polymorphisms in superoxide dismutase (SOD2 and SOD3), glutathione peroxidase-3 (GPX3), and glutathione S-transferase theta-1 (GSTT1) may enable oxidative stress-related lipid abnormalities and severity of coronary atherosclerosis. The present study investigated the associations of antioxidant-related gene polymorphisms with atherogenic dyslipidemia and atherosclerotic severity in subjects with high risk of coronary artery disease (CAD). Methods Study population comprises of 396 subjects with high risk of CAD. Gene polymorphisms: SOD2 rs4880, SOD3 rs2536512 and rs2855262, GPX rs3828599, and GSTT1 (deletion) were evaluated the associations with HTG, low HDL-C, high TG/HDL-C ratio, and severity of coronary atherosclerosis. Results SOD2 rs4880-CC, SOD3 rs2536512-AA, rs2855262-CC, and GPX3 rs3828599-AA, but not GSTT1-/- individually increased risk of HTG combined with low HDL-C level. With a combination of five risk-genotypes as a genetic risk score (GRS), GRS ≥ 6 increased risks of low HDL-C, high TG/HDL-C ratio, and HTG combined with low HDL-C, comparing with GRS 0–2 [respective adjusted ORs (95% CI) = 2.70 (1.24–5.85), 3.11 (1.55–6.23), and 5.73 (2.22–14.77)]. Gene polymorphisms, though, were not directly associated with severity of coronary atherosclerosis; high TG/HDL-C ratio was associated with coronary atherosclerotic severity [OR = 2.26 (95% CI [1.17–4.34])]. Conclusion Combined polymorphisms in antioxidant-related genes increased the risk of dyslipidemia related to atherosclerotic severity, suggesting the combined antioxidant-related gene polymorphisms as predictor of atherogenic dyslipidemia.

NRF2 is a transcription factor which, during oxidative stress, activates transcription of its target antioxidant genes. Polymorphisms in NRF2 and its target antioxidant genes: HMOX-1, NQO1, and MT, have been associated with cardiovascular diseases (CVDs) and diabetes in various ethnic groups, however, with variable results. The aim of this study was to investigate the association of NRF2, HMOX-1, NQO1, and MT gene polymorphisms with CVD risk factors in Thais. The study was conducted in two groups: group with high-risk for coronary artery disease (CAD) and health check-up group. Polymorphisms in NRF2 (rs6721961), NQO1 (rs1800566), MT1A (rs11640851), and HMOX-1 (rs2071746) were genotyped. Expressions of NRF2, HMOX-1, and NQO1 were also determined. In high-risk group, NRF2 rs6721961-TT was associated with CAD [OR (95% CI) 5.07 (1.42–18.10)] and severity of coronary atherosclerosis [Gensini score > 32, OR (95% CI) 4.31 (1.67–11.09)]; rs6721961 GT and TT revealed significant association with lower mRNA expression than GG (p = 0.021). NQO1 rs1800566 also revealed association with CAD, only in female. Combined effect of NQO1-rs1800566, HMOX1-rs2071746, and MT1A-rs11640851 was evaluated on the risks of DM and hypertension. With a combination of risk alleles as genetic risk score (GRS), the highest GRS (score 6) increased risk for hypertension, comparing with GRS 0–2 [OR (95% CI) 1.89 (1.02–3.49)]; group with score 5–6 revealed association with risk of DM [OR (95% CI) 1.481 (1.08–2.04)]. In conclusion, NRF2 rs6721961 associated with CAD and severity of coronary atherosclerosis. NQO1 rs1800566 also associated with CAD, only in female. Combined polymorphisms of three NRF2-regulated genes increased risk of DM and hypertension.

Oxidative stress plays a critical role in the pathophysiology of hypertension (HT) and the progression of atherosclerotic coronary artery disease (CAD). Genetic variations in superoxide dismutase (SOD), glutathione peroxidase 3 (GPX3), paraoxonase 1 (PON1) and glutathione S-transferase theta 1 (GSTT1) may modulate their gene functions, affecting protein functions. These changes could have an impact on the pathogenesis of HT and progression of CAD. The present study investigated the associations of individual and combined antioxidant-related gene polymorphisms with the incidence of HT and severity of CAD. Two study populations were enrolled. The HT-associated study comprised 735 control and 735 hypertensive subjects (mean age 59.3 ± 9.0 years), matched for age and sex. The CAD study, hospital-based subjects (mean age 62.1 ± 9.5 years), included 279 CAD patients and 165 non-CAD subjects. Gene polymorphisms were identified in genomic DNA using polymerase chain reaction (PCR)-based technique. Genetic variations were assessed for their associations with HT and severity of CAD. Antioxidant gene variants, SOD3 rs2536512-GG, GPX3 rs3828599-GG, PON1 rs705379-TT, and GSTT1−/− and +/−, were independently associated with the incidence of HT. A combination of four HT-associated genotypes, as a genetic risk score (GRS), revealed an association of GRS 5 and GRS ≥ 6 with increased susceptibility to HT and CAD, and further with multivessel coronary atherosclerosis (multivessel CAD) compared with GRS 0–2 [respective ORs(95% CI) for GRS ≥ 6 = 2.37 (1.46–3.85), 3.26 (1.29–8.25), and 4.36 (1.36–14.0)]. Combined polymorphisms in these four antioxidant-related genes were associated with the incidences of HT and CAD, and with the severity of coronary atherosclerosis.

Background We studied long-term outcomes and prognostic features of Thai children with acute lymphoblastic leukemia treated with modified St Jude Children’s Research Hospital (SJCRH) protocols. Patients and Methods Pediatric patients newly diagnosed with acute lymphoblastic leukemia were included. From 1997 to 2003, the first group received modified Total Therapy XIIIB (previous protocol). From 2004 to 2014, the latter had modified Total Therapy XV (current protocol). Results In 250 patients, the event-free survival rates (± standard error) of the previous protocol (n = 95) were 82.8 ± 3.9%, 81.7 ± 4.0%, and 81.7 ± 4.0% at 5, 10, and 15 years, respectively; current protocol event-free survival rates (n = 155) were 84 ± 3.0%, 80.8 ± 3.4%, and 80.8 ± 3.4%, respectively. Previous protocol overall survival rates for the same years were 89.2 ± 3.2%, 84.8 ± 3.8%, and 84.8 ± 3.8%, and for the current protocol were 90 ± 2.5%, 86.9 ± 3.2%, and 83.7 ± 4.4%. Previous protocol relapses were 10.5% (10 patients), with 7 having isolated hematologic and 3 isolated/combined central nervous system relapses. Current protocol relapses were 9.7% (15 patients), with 7 having isolated hematologic, 6 isolated/combined central nervous system, and 2 extramedullary relapses. Patients with leukocyte counts over 100 × 109/L and who had disease classified as high risk had worse event-free survival using the previous protocol. However, only initial leukocyte counts of ≥ 100 × 109/L predicted adverse outcomes under the current protocol. Minimal residual disease positivity was a prognostic factor of worse overall survival only for previous protocol patients. Conclusion Favorable outcomes of childhood acute lymphoblastic leukemia occurred using adapted SJCRH protocols, perhaps because of multidisciplinary care teams and improved parent advocacy. Inferior outcomes might be prevented by addressing predictive factors to ameliorate monitoring and care.

INTRODUCTION Low grade glioma (LGG) is the most common central nervous system (CNS) tumor in children accounted for 30–50%. Regarding benign characteristic of disease, surgical management remains the mainstay of treatment. However, surgical approach is limited in some conditions such as location at brainstem or infiltrative tumor. Chemotherapy and radiation treatments have been included in order to control tumor progression. The 5-years survival rate is approach 90% especially in patients who receive complete resection. However, the outcome of children with LGG in low to middle income is limited. Therefore, the aim of the study was to determine long-term outcome of children with newly diagnosed LGG. METHODS A retrospective study enrolled children aged RESULTS A total of 40 patients, female to male ratio was 1:1.35 and mean (SD) for age was 6.7 (4.0) years. The most common location was optic chiasmatic pathway (42.5%), followed by suprasellar region (25.0%). Sixty percent of patients received at least partial tumor removal. Chemotherapy and radiation had been used in 70% and 10.0% respectively. The 10-year progression free survival was 74.1±11.4% and overall survival was 96.2±3.8%. SUMMARY: Treatment of Pediatric LGG mainly required surgical management, however, chemotherapy and radiation had been used in progressive disease. The outcome was excellent.