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Caring for children and adolescents with disorders of hemostasis and thrombosis (HAT) has become more specialized and requires a unique skill set that many providers are not able to obtain in standard pediatric hematology/oncology/bone marrow transplant fellowship training programs. The influx of numerous therapeutic advances and increasing medical complexity has expanded the need for experienced HAT providers and subspecialty collaboration in the inpatient setting due to the nuances in the management of patients with HAT complications and concerns. While there are data highlighting the benefits of an inpatient hemostasis, thrombosis, and anticoagulation management service in adult hospitals, there are limited pediatric data supporting such programs. In this article, we summarize the current practices of various pediatric institutions in the inpatient management of HAT patients and provide a consensus opinion for the development of a pediatric inpatient HAT service at tertiary care referral centers.

Studies have shown that religious beliefs and practice play an important role in influencing share price behaviour. Evidence of a Ramadan effect has been documented in Muslim countries suggesting an increase in mean returns as well as a reduction in volatility during the ninth month of the Islamic calendar. In addition to the Ramadan effect, studies have also documented a January effect in Muslim countries. The current study investigates what happens when the Ramadan effect and the January effect occur at the same time. Controlling for the effects of financial crises and time-varying volatility in returns, the results for individual company data from four countries with sizeable Muslim populations indicate higher returns and lower volatility when these two effects overlap, except in one, arguably more Western country, Turkey. Refereed/Peer-reviewed

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.

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.

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.

Since 2004, in a joint project of the Central Institute of Forensic Science (CIFS) and the Department of Correction, Ministry of Justice, CIFS has collected biological samples from prisoners with all offences who will be released within four months to one year. One aspect of this project is to prevent and monitor detained prisoners from repeated offences. Until July 2019, buccal cells on FTA paper were collected from more than 120,000 samples, and analyzed and uploaded to the CIFS DNA database. Presently, the CIFS DNA Database has reached 187,464 profiles, consisting of 16,521 DNA profiles from crime stain samples, 49,210 individuals related to a crime and 121,733 prisoners. Mainly autosomal STR markers were collected in the DNA database. Y-STR markers are also analyzed and uploaded, especially crime stains from sexual assault cases and their potential suspects. Approximately 2150 hits were reported on various offenses such as possession of explosives, unrest, homicide, sexual assault, and drug smuggling. Interestingly, 146 prisoners were found to match against samples from sexual assaults (10), assaults or homicides (23), drug smuggling (79), theft (11), and other crimes (23). All the prisoners were imprisoned and then released few years ago so-called ex-prisoners. The number of match reports demonstrated that some ex-prisoners tend to commit new crimes again or recidivism. Consequently, the DNA database can be applied to monitor repeated offenders and also protect them from false accusation. To expand the capabilities of DNA Database investigations CIFS plans to collect newly registered prisoners and all prisoners in Thailand in order to monitor repeated offenders and perhaps increase the hit rate. However, this report does not intend to state that all prisoners will commit a new crime again.

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.

Bone marrow transplantation (BMT) is the only curable option for thalassemia major, β-thalassemia/HbE. However, some patients still have the risk of hypercoagulable complications. We used a whole blood flow cytometric analysis to measure the circulating microparticle (MP) levels, activated platelets, and leukocyte-platelet aggregates in 59 young β-thalassemia/HbE patients compared with 20- and 28-matched healthy and patients receiving regular blood transfusion (RT), respectively. Results from the studies showed that blood samples from BMT group contained a significantly higher numbers of circulating MPs originated from platelets (ann-V+CD41a+), leukocyte (ann-V+CD45+) and endothelial cells (ann-V+CD146+) when compared to samples from healthy subjects and RT patients. In contrast, the percentages of activated/procoagulant platelets (CD62P and CD142 expressing platelets) were decreased in BMT group. In addition, monocytes forming microaggregates were the major population among other leukocyte-platelet complexes. Different patterns of CD11b, CD62P and CD142 expression on platelet-leukocyte microaggregate surface were also found. These data suggest that circulating MPs together with leukocyte-platelet aggregates may be responsible, in part, in pathogenesis of hypercoagulable state in β-thalassemia/HbE patients who undergone BMT.

Rickettsia felis is an obligate intracellular alpha-proteobacteria and the cause of flea-borne spotted fever (FBSF), an emerging zoonosis of global public health importance, for which dogs and cats have been implicated as potential mammalian reservoirs hosts. The purpose of this study was to determine the prevalence and associated risk factors for R. felis-like species in semi-domesticated cats and their fleas in aim of understanding public health risks posed by cats and their fleas in Bangkok, Thailand. Single whole blood samples (n = 432) and where observed, fleas (n = 234), were collected from cats from 53 temple communities in Bangkok. Fleas were morphologically and genetically identified to a species level. Cat blood and fleas were subjected to a spotted fever group (SFG)-specific PCR targeting the partial outer membrane protein B (ompB). Those that were positive, were further characterised using an R. felis-specific nested PCR targeting the partial citrate synthase A (gltA) gene. All fleas were identified as Ctenocephalides felis felis. In total SFG Rickettsiae were detected in the blood of 82/482 (17.01%) cats and 3/234 fleas (1.28%). DNA sequencing of the partial ompB characterised all positive amplicons from cat blood and their fleas as 100% identical to Rickettsia endosymbiont of Ctenocephalides felis orientis isolate (Rickettsia sp. genotype RF2125) and Rickettsia asemboensis (GenBank accession no. KP256362 and KY650699, respectively). The gltA gene targeting R. felis was successfully amplified from 12/82 PCR-positive cat blood samples and these clustered with 99% bootstrap support with isolates within the Rickettsia sp. genotype RF2125 clade. Cats that were permitted to roam freely inside monasteries were more likely to be infected with R. felis compared with cats confined indoors. The results suggest that cats in Thailand are potential mammalian reservoir hosts for Rickettsia sp. genotype RF2125.