Donor-type bone marrow aplasia following hematopoietic stem cell transplantation in a child with a novel SAMD9L variant.

Pathogenic variants in the genes SAMD9 (sterile a-motif domain containing protein - 9) and SAMD9L (SAMD9-like) cause bone marrow failure with characteristic syndromic features. We report a case of a previously healthy, 3-year-old boy with no dysmorphology, who presented with severe aplastic anemia and a novel variant in the SAMD9L gene. His father, elder brother and sister who harbored the same variant were completely healthy. In the absence of a matched unrelated donor, he underwent a stem cell transplant from his sister, a 10/10 match. Almost 2 years later he developed donor type aplasia and succumbed to an invasive fungal infection after a failed haplograft from his mother. This case highlights the pathogenicity of this previously undescribed germline variation of uncertain significance in the SAMD9L gene and the value of comprehensive genetic testing for inherited bone marrow failures even in the absence of a positive family history or characteristic congenital abnormalities.

The use of rotational thromboelastometry parameters in understanding the coagulopathy following hump-nosed viper (Hypnale spp) bites: a preliminary study.

BACKGROUND: Hump-nosed vipers (HNV; Hypnale spp) are one of the medically important venomous snakes in Sri Lanka and South-Western regions of India. The haemostatic dysfunction due to HNV bites is poorly characterized by standard diagnostic tests performed to identify coagulopathy. We aimed to determine the usefulness of rotational thromboelastometry (ROTEM) parameters compared to 20-minute whole blood clotting test (WBCT20) and prothrombin time (PT) in understanding the coagulopathy of HNV bites. METHODS: Twenty-three HNV snakebite patients in a prospective study of 127 consecutive snakebites were recruited. After recording details of the clinical presentation, PT/international normalized ratio (INR), WBCT20 and ROTEM delta were performed at presentation. RESULTS: In this preliminary study, none of the patients had clinically apparent bleeding. Coagulopathy was detected by either WBCT20, INR or ROTEM in 13 HNV patients. Eleven had a coagulopathy detectable by ROTEM (either abnormal EXTEM-CT, INTEM-CT or FIBTEM-MCF) but with negative WBCT20. Of them, only two had prolonged INR values. Two patients had positive WBCT20 but with normal ROTEM and INR values. The remaining 10 patients did not show any coagulopathy either by INR, ROTEM or WBCT20. CONCLUSION: In this preliminary study with small number of sample size, ROTEM parameters appeared to be more sensitive to subtle changes in coagulation compared to WBCT20. The clinical utility of detecting these changes and their usefulness in managing snakebite should be explored further in a larger study.

Dissections or prosections: Which method has a better impact on sustainable gross anatomy knowledge?

Background Assessing the level of knowledge of anatomy of undergraduate students four years after their primary anatomy training will give a better indication as to which system of teaching is more effective. We aimed to ascertain which method was more effective at establishing a core of anatomy knowledge that could be recalled after a considerable amount of time. Methods We tested two groups of medical students in their final year on the key concepts of gross anatomy using a question paper that included true-false type questions and identification of anatomical line diagrams. These two batches of students followed a dissection-based curriculum and a newly introduced prosections-based curriculum at the beginning of their medical education. The prosections- based curriculum brought with it a reduction in the in-class teaching and learning activities when compared to the old curriculum. This would in turn reflect how much anatomy knowledge one would possess when they start to practise medicine as a newly qualified doctor and also embark on a postgraduate training programme. The two groups were subjected without prior warning to a question paper that had six questions, each with five true-false statements and four questions on identification and labelling of anatomical line diagrams. Results There was no statistically significant difference in the marks obtained for the true-false type questions between the two groups (p=0.08), but the prosections group obtained higher marks for the diagram identification questions (p=0.02). Conclusion A prosection-based curriculum when compared to a dissection-based curriculum was equally effective at establishing a core of gross anatomy knowledge.

Comparison of rotational thromboelastometry parameters with 20-minute whole blood clotting test as a predictor of envenoming in Russell's viper bite patients.

BACKGROUND: Coagulopathy is an important and common systemic clinical syndrome caused by snake envenoming. The major clinical effect of Russell's viper (RV) envenoming is haematotoxicity. The 20-min whole blood clotting test (WBCT20) is the standard test for identification of envenoming in resource-limited settings. However, its reliability as a diagnostic test has been questioned. Rotational thromboelastometry (ROTEM) assays different phases of clot formation from initiation to fibrinolysis. Our objective was to compare parameters of ROTEM with WBCT20 and the international normalized ratio (INR) as predictors of envenoming in RV bite patients. METHODS: Fifty-three patents with RV bite presenting to Anuradhapura Hospital, Sri Lanka were recruited. Epidemiological and clinical data were obtained. Venous blood samples were collected at admission for ROTEM, INR and WBCT20. RESULTS: A total of 46 of 53 patients with RV bites received antivenom serum (AVS); 74% had a non-clottable WBCT20. All 46 had at least one abnormal ROTEM parameter and 93% had a prolonged EXTEM clotting time (EXTEM-CT). The sensitivity of a prolonged INR was only 55%. CONCLUSIONS: EXTEM-CT is a better predictor of envenoming and the need for AVS than WBCT20 in RV bites (p=0.02). It provides a numerical value that can be used post-AVS to objectively assess the response and decide on further treatment.

An open-source, expert-designed decision tree application to support accurate diagnosis of myeloid malignancies.

Accurate, reproducible diagnoses can be difficult to make in haemato-oncology due to multi-parameter clinical data, complex diagnostic criteria and time-pressured environments. We have designed a decision tree application (DTA) that reflects WHO diagnostic criteria to support accurate diagnoses of myeloid malignancies. The DTA returned the correct diagnoses in 94% of clinical cases tested. The DTA maintained a high level of accuracy in a second validation using artificially generated clinical cases. Optimisations have been made to the DTA based on the validations, and the revised version is now publicly available for use at http://bit.do/ADAtool.

Immunophenotypic characterization of acute lymphoblastic leukemia in a flowcytometry reference centre in Sri Lanka.

BACKGROUND: Acute lymphoblastic leukemia (ALL), is a biologically heterogeneous disease where diagnosis, treatment and prognosis is heavily dependent on the correct characterization of the immunophenotype of each case. OBJECTIVES: To describe the immunophenotypic and laboratory features of a cohort of Sri Lankan children and adults with ALL and to compare them with those reported in other series. METHODS: Records of 229 patients who were suspected of having acute leukaemia and referred for flow cytometry to the Asiri Hospital Sri Lanka, between August 2009 and October 2013 were reviewed. Referrals were from across the country including the National Cancer Institute. RESULTS: Sixty seven percent were children below 12 years of age. 80% had B-lymphoblastic leukaemia (B-ALL), 20% T- lymphoblastic leukaemia (T-ALL). In children, the peak age of diagnosis was between 2-6 years in B-ALL (61%) and 3-6 years (43.7%) in T-ALL. Incidence was commoner in males in all age groups and subtypes except in the adult B ALL group where the incidence was equal. Ninety three percent of paediatric B-ALL and 67% adult B-ALL were CD10 positive common ALL. In T-ALL cytoplasmic expression of CD3 was 100%. nTdT was the most commonly expressed immature marker, in B-ALL - 91% and in T-ALL- 69%. At least one myeloid antigen was present in 34% of B-ALL cases and 60% of T-ALL cases. CONCLUSIONS: This study represents the first immunophenotype based description of ALL in Sri Lanka. Age, sex distribution, ALL subtypes and the immunophenotypic profile of each subtype mirrored those of previous studies.

Awareness of clinical trial registration among healthcare professionals: An observational study.

AIM: Prospective registration in a freely accessible public platform is a key step in the ethical conduct of clinical trials. Little is known of the awareness of clinical trial registration among the scientific community. This study aimed to assess awareness of clinical trial registration among participants attending a medical congress in Sri Lanka. METHODS: Knowledge of trial registration was assessed using a self-administered questionnaire, which spanned domains such as involvement in research, and knowledge and perceptions regarding trial registration. A knowledge score was calculated and correlated with demographic variables. RESULTS: Of 251 survey respondents, 53.4% were male, 74.9% were below the age of 40 years, and 56.6% were currently engaged in research. Registration was considered necessary for trial publication by 73.3%, and 70.5% agreed that trials should be registered prospectively. Most achieved a knowledge score of 'Acceptable' (41%) or 'Good' (19.9%). Mid- or advanced career stages, postgraduate training, current involvement in research, and recent research publications/presentations were correlated with higher knowledge scores (P < 0.05). Beneficial effects considered to be associated with trial registration were access to findings of all trials (61.4%), access to negative results (47.8%), preventing trial duplication (69.3%), and preventing multiple publications (70.1%). Increasing research workload (49.8%), additional restrictions on research conduct (52.2%), and the possibility of 'intellectual theft' (56.2%) were seen as potential negative effects. CONCLUSIONS: Most participants were aware of the need for prospective registration as a requirement for publication of clinical trials. Concerns were expressed regarding several perceived negative effects of trial registration.