Non-Hodgkin's Lymphoma: An Unusual Cause of Shoulder Pain.

Shoulder pain is a common complaint seen in the orthopedic clinic. Here, we report a rare case of primary extranodal ileocecal with exceedingly rare right shoulder deltoid non-Hodgkin's lymphoma (NHL). A 67-year-old female presented with abdominal swelling for four months associated with loss of appetite, loss of weight, and night sweats. Abdominal contrast-enhanced CT and cecal biopsy confirmed the diagnosis of ileocecal NHL. A right hemicolectomy was performed, and the patient completed six cycles of chemotherapy. The patient developed right shoulder pain with swelling three months later and was diagnosed with a relapse ileocecal lymphoma with dissemination to the right deltoid muscle after a repeat positron emission tomography scan. Clinicians need to consider NHL as a differential diagnosis in evaluating shoulder pain or swelling even though it is exceedingly rare. A partial or non-response to chemotherapy with dissemination to skeletal muscle carries a poor prognosis.

Genomic Alterations, Gene Expression Profiles and Functional Enrichment of Normal-Karyotype Acute Myeloid Leukaemia Based on Targeted Next-Generation Sequencing.

Characterising genomic variants is paramount in understanding the pathogenesis and heterogeneity of normal-karyotype acute myeloid leukaemia (AML-NK). In this study, clinically significant genomic biomarkers were ascertained using targeted DNA sequencing and RNA sequencing on eight AML-NK patients' samples collected at disease presentation and after complete remission. In silico and Sanger sequencing validations were performed to validate variants of interest, and they were followed by the performance of functional and pathway enrichment analyses for overrepresentation analysis of genes with somatic variants. Somatic variants involving 26 genes were identified and classified as follows: 18/42 (42.9%) as pathogenic, 4/42 (9.5%) as likely pathogenic, 4/42 (9.5%) as variants of unknown significance, 7/42 (16.7%) as likely benign and 9/42 (21.4%) as benign. Nine novel somatic variants were discovered, of which three were likely pathogenic, in the CEBPA gene with significant association with its upregulation. Transcription misregulation in cancer tops the affected pathways involving upstream genes (CEBPA and RUNX1) that were deregulated in most patients during disease presentation and were closely related to the most enriched molecular function gene ontology category, DNA-binding transcription activator activity RNA polymerase II-specific (GO:0001228). In summary, this study elucidated putative variants and their gene expression profiles along with functional and pathway enrichment in AML-NK patients.

Validating lactate dehydrogenase (LDH) as a component of the PLASMIC predictive tool (PLASMIC-LDH).

Background: The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of <10%. Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis. Methods: Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients' ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score. Results: 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of <10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%. Conclusion: Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.

Mortality outcomes and survival patterns of patients with myeloproliferative neoplasms in Malaysia.

BACKGROUND: Prognostication of myeloproliferative neoplasm (MPN) has always been challenging, even with the advent of Janus kinase 2 (JAK2 V617F) molecular studies. The survival pattern of patients diagnosed with MPN in developing countries is still undetermined. MATERIALS AND METHODS: The national MPN registry conducted from 2009 to 2015 in Malaysia provided a comprehensive insight into the demographics, clinical characteristics and laboratory parameters of patients diagnosed with MPN nationwide. The study analysed the survival patterns and mortality outcomes and risk among 671 patients diagnosed with essential thrombocythaemia (ET), polycythaemia vera (PV), primary myelofibrosis (PMF) and unclassified MPN (MPN-U). Mortality status was traced and confirmed until the end of December 2018, with right censoring applied to patients alive beyond that. RESULTS: The analysed cohort consisted of 283 (42.2%) ET, 269 (40.1%) PV, 62 (9.2%) PMF and 57 (8.5%) MPN-U incident cases with diagnosis made between 2007 and 2015. The majority of patients were male (52.3%) and Malay (48.9%), except for ET, in which the majority of patients were female (60.1%) and of Chinese origin (47.0%). Female patients were found to have significantly better overall survival (OS) rates in ET (p = 0.0285) and MPN-U (p = 0.0070). Patients with JAK2 V617F mutation were found to have marginally inferior OS over time. Multivariable Cox regression identified patients with increased age [hazard ratio (HR) 1.055, 95% CI 1.031; 1.064], reduced haemoglobin (HB) level (HR 0.886, 95% CI 0.831; 0.945, p = 0.0002), being male (HR 1.545, 95% CI 1.077; 2.217, p = 0.0182), and having MPN-U (HR 2.383, 95% CI 1.261; 4.503, p = 0.0075) and PMF (HR 1.975, 95% CI 1.054; 3.701, p = 0.0335) at increased risk for worse mortality outcomes. CONCLUSION: Myeloproliferative neoplasm reduces patient survival. The degree of impact on survival varies according to sub-type, sex, bone marrow fibrosis and HB levels. The JAK2 V617F mutation was not found to affect the survival pattern or mortality outcome significantly.

A Rare Case of Posterior Interosseous Nerve Palsy Post-venepuncture.

Wrist drop post-venepuncture is uncommon. There has been reported cases of direct injury to the radial nerve during venepuncture but to our knowledge, there has never been a case of posterior interosseous nerve (PIN) injury. A 34-year female, right hand dominant homemaker, with a newly diagnosed diabetes mellitus, was admitted for diabetic ketoacidosis. There was difficult access with multiple attempts in her blood taking over the antebrachial fossa and forearm. Thereafter, she was unable to fully extend her wrist, fingers and thumb with an intact sensation. The electrophysiological study was suggestive of demyelinating right radial neuropathy at the elbow. Despite the transient blood taking session, patient developed neuropraxia, which only resolved after four months. We wish to report this case of unusual presentation of a PIN palsy post- routine venepuncture, which can result in high morbidity to a patient. Key Words: Posterior interosseous nerve syndrome, venepuncture, neuropraxia, wrist drop.

An Unusual Case of Chronic Partial Quadriceps Tear in a Child: A Case Report.

Quadriceps tendon rupture usually occurs in adults and is rare in children. A six-year-old boy was playing at home and had a fall. He was unable to extend his right knee but there was no gap felt over the patella tendon or quadriceps. He was first seen by a family doctor and presented late to the surgeon three months after the injury. Radiographs and ultrasound were performed. The magnetic resonance imaging confirmed the findings of partial quadriceps tear. The patient was put in a cylinder case with the knee in extension for two months. Six months post-injury, he regained full range of motion without any complications. We present an unusual case of partial quadriceps tear in an otherwise healthy six-year-old boy that was treated successfully despite a delayed presentation. Besides a high index of suspicion, magnetic resonance imaging is a good modality to detect partial quadriceps tear in children.

The epidemiology and clinical characteristics of myeloproliferative neoplasms in Malaysia.

BACKGROUND: The evolution of molecular studies in myeloproliferative neoplasms (MPN) has enlightened us the understanding of this complex disease consisting of polycythaemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The epidemiology is well described in the western world but not in Asian countries like Malaysia. MATERIALS AND METHODS: This retrospective national registry of MPN was conducted from year 2009 to 2015 in Malaysia. RESULTS: A total of 1010 patients were registered over a period of 5 years. The mean age was 54 years with male predominance. The ethnic distribution revealed that Chinese had a relatively high weighted incidence proportion (43.2%), followed by Indian (23.8%), Malay (15.8%) and other ethnic groups (17.2%). The types of MPN reported were 40.4% of ET (n = 408), 38.1% of PV (n = 385), 9.2% of PMF (n = 93), 3.1% of hypereosinophilic syndrome (HES) (n = 31) and 7.9% of unclassifiable MPN (MPN-U) (n = 80). Splenomegaly was only palpable clinically in 32.2% of patients. The positive JAK2 V617F mutation was present in 644 patients with 46.6% in PV, 36.0% in ET, 9.0% in PMF, and 7.4% in MPN-U, and had significantly lower haemoglobin (p < 0.001), haematocrit (p < 0.001) and white blood cells (WBC) (p < 0.001) than those with negative mutation. Significant differences in platelet and WBC count were detected in ethnic groups and MPN sub-types. There were more arterial thrombosis events seen in those with JAK2 V617F mutation as compared to venous thrombosis events (23.1% vs 4.4%). The bleeding rate was only 6.6%. Among the risk factors, previous thrombosis, old age (≥ 60 years) and hypertension were significantly correlated to positive JAK2 V617F mutation. The arterial thrombosis event is associated with higher presenting HB, HCT and PLT while the bleeding event is associated with lower presenting HB, HCT but higher PLT. The presence of JAK2 V617F mutation is associated with higher risk of arterial thrombosis. CONCLUSION: Chinese ethnicity is associated with higher rates of MPN. The history of thrombosis, age ≥ 60 years and hypertension are risk factors that can be correlated to JAK2 V617F mutation. This study is instrumental for policy makers to ensure preventive strategies can be implemented in future.

Clinical characteristics and outcomes of thrombotic microangiopathy in Malaysia.

BACKGROUND: Thrombotic microangiopathy (TMA) with non-deficient ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) outcome is unknown hence the survival analysis correlating with ADAMTS-13 activity is conducted in Malaysia. METHODS: This was a retrospective epidemiological study involving all cases of TMA from 2012-2016. RESULTS: We evaluated 243 patients with a median age of 34.2 years; 57.6% were female. Majority of the patients were Malay (62.5%), followed by Chinese (23.5%) and Indian (8.6%). The proportion of patients with thrombotic thrombocytopenic purpura (TTP) was 20.9%, 72.2% of which were acquired while 27.8% were congenital. Patients with ADAMTS-13 activity ≥5% had a four-fold higher odds of mortality compared to those with ADAMTS-13 activity <5% (odds ratio: 4.133, P=0.0425). The mortality rate was 22.6% (N=55). Most cases had secondary etiologies (42.5%), followed by acquired TTP (16.6%), atypical hemolytic uremic syndrome (HUS) or HUS (12.8%) and congenital TTP (6.4%). Patients with secondary TMA had inferior overall survival (P=0.0387). The secondary causes comprised systemic lupus erythematosus (30%), infection (29%), pregnancy (10%), transplant (8%), malignancy (6%), and drugs (3%). Transplant-associated TMA had the worst OS (P=0.0016) among the secondary causes. Plasma exchange, methylprednisolone and intravenous immunoglobulin were recorded as first-line treatments in 162 patients, while rituximab, bortezomib, vincristine, azathioprine, cyclophosphamide, cyclosporine, and tacrolimus were described in 78 patients as second-line treatment. CONCLUSION: This study showed that TMA without ADAMTS-13 deficiency yielded inferior outcomes compared to TMA with severeADAMTS-13 deficiency, although this difference was not statistically significant.