Digital Gangrene as a Paraneoplastic Manifestation of Peripheral T-cell Lymphoma Not Otherwise Specified Type.

BACKGROUND: Peripheral T cell lymphoma (PTCL), not otherwise specified (NOS) is a heterogenous group of predominantly nodal T cell lymphomas that generally presents with lymphadenopathy with or without extra nodal involvement. Acral vascular syndrome clinically presents as digital ischemia with Raynaud's phenomenon and acral cyanosis. Although, this condition is commonly associated with connective tissue disorder, smoking and vasculitis, its association with lymphoid malignancy is very rare. Here, we present a case report of a patient with digital gangrene of all toes and fingers as a presenting symptom of PTCL-NOS. CASE DESCRIPTION: A 62 year old male presented with digital ischemia associated with pain, low grade fever, loss of appetite and significant weight loss of 6 kilograms over a period of 3 months. On examination, he was found to have bilateral inguinal and axillary lymph nodes with gangrenous changes over toes and fingers but peripheral pulses were palpable. On evaluation he had anemia, elevated ESR and CRP. CT angiogram revealed thinned out digital arteries with multifocal areas of narrowing. Patient was screened for other causes of digital gangrene and was tested negative for ANCA, ANA, cryoglobulins and viral markers. Lymph node biopsy with IHC was suggestive of peripheral T-cell lymphoma-NOS and was started on CHOP regimen. Lymph nodes size decreased and gangrenous changes resolved. CONCLUSION: Though digital ischemia is a rare paraneoplastic presentation of lymphoma, it should be considered if there is a rapid progression of gangrene. Early initiation of chemotherapy may result in the reduction of further progression of digital gangrene and thus prevent permanent disability. In our patient, progression of gangrene was prevented even though it was an aggressive variant of T cell lymphoma.

The potential of gene therapy for recessive dystrophic epidermolysis bullosa.

Epidermolysis bullosa (EB) encompasses a heterogeneous group of inherited skin fragility disorders, with mutations in genes encoding the basement membrane zone (BMZ) proteins that normally ensure dermal-epidermal integrity. Of the four main EB types, recessive dystrophic EB (RDEB), especially the severe variant, represents one of the most debilitating clinical entities, with recurrent mucocutaneous blistering and ulceration leading to chronic wounds, infections, inflammation, scarring and ultimately cutaneous squamous cell carcinoma, which leads to premature death. Improved understanding of the molecular genetics of EB over the past three decades and advances in biotechnology have led to rapid progress in developing gene and cell-based regenerative therapies for EB. In particular, RDEB is at the vanguard of advances in human clinical trials of advanced therapeutics. Furthermore, the past decade has witnessed the emergence of a real collective, global effort involving academia and industry, supported by international EB patient organizations such as the Dystrophic Epidermolysis Bullosa Research Association (DEBRA), among others, to develop clinically relevant and marketable targeted therapeutics for EB. Thus, there is an increasing need for the practising dermatologist to become familiar with the concept of gene therapy, fundamental differences between various approaches, and their human applications. This review explains the principles of different approaches of gene therapy, summarizes its journey, and discusses its current and future impact in RDEB.

Transient congenital hypothyroidism - too short to be transient.

Congenital hypothyroidism (CH) occurs due to thyroid dysgenesis, thyroid ectopy, and dyshormonogenesis. A proportion of CH is transient which might be due to iodine deficiency/excess or maternal antibody-mediated. Certain forms of dyshormonogenetic defects may cause transient hypothyroidism. Here is a report of a neonate with overt clinical and biochemical hypothyroidism, who on evaluation was found to have dyshormonogenesis with a homozygous mutation in dual oxidase 2 (DUOX2) gene. During infancy, she became euthyroid. Severe in utero deficiency of thyroid hormone, very short duration of hypothyroidism and first-reported mutation of the DUOX2 gene in the Indian subcontinent were interesting features in this infant.

A case of premature and recurrent myocardial infarction associated with ABCA.1 gene mutation.

Coronary heart disease (CHD) is the most important cause of cardiovascular death and when premature, it affects the most productive population of the community. Premature CHD usually has a specific etiology, which on diagnosis, might help in the secondary prevention in that individual. We report a case of young adult with recurrent myocardial infarction, who on evaluation had mildly reduced HDL and Protein C levels with elevated serum homocysteine. Clinical exome identified a possibly pathogenic variant of ABCA1 gene, associated with Tangier disease.

Epidemiology of bloodstream infections in the paediatric population in a Malaysian general hospital over a 2-year period.

BACKGROUND: Bloodstream infection (BSI) is a major cause of morbidity and mortality. The classification of infection into community-acquired, hospital-acquired, and healthcare-associated infection provides an educated guess on the possible aetiological agents and appropriate empirical antimicrobial therapy to be instituted. This study aims to determine the aetiological agents, the antimicrobial susceptibility patterns, and the classification of infections among the paediatric population. MATERIALS & METHODS: This study was conducted in Hospital Kuala Lumpur, Malaysia from January 2016 to December 2017. A total of 303 isolates were included in this study which was obtained from 238 patients. The patients' microbiological worksheets and medical notes were reviewed to determine the antimicrobial susceptibility patterns, demographic data, classification of infection, and outcome (survival versus death). RESULTS: Most of the patients were in the age group of one to less than five years old (41%) with 58% male and 85% Malay patients. Common causes of BSI were Staphylococcus aureus (17%), followed by Klebsiella pneumoniae (15%), Acinetobacter baumanii (10%), Pseudomonas aeruginosa (10%), and Escherichia coli (6%). Sixty percent of BSI episodes were caused by gram-negative bacteria, 34% by gram-positive bacteria, and 6% by fungi. Most of the infections were classified as hospital-acquired infections (72%), followed by healthcareassociated (20%) and community-acquired infections (8%). There were 33% of methicillin-resistant Staphylococcus aureus, 53% of extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae, and 33% ESBL producing Escherichia coli. The overall case fatality rate (CFR) was 27% with the highest CFR caused by Serratia marcescens (53.3%). CONCLUSIONS: The majority of paediatric bloodstream infections are hospital-acquired. Improvement in prevention strategies and revisions in antibiotic policies are important to overcome it.

Fatty liver in a two days old neonate.

Neonatal death due to inborn error of metabolism (IEM) is rare in Malaysia. We report a sudden neonate death just a few hours after being discharged from the hospital. The deceased was a two-day-old baby boy and was asymptomatic until his demise. He was fed with expressed breast milk and formula milk. Autopsy revealed fatty changes of the liver and an enlarged heart. Laboratory investigation confirmed very long chain Acyl-CoA dehydrogenase deficiency which resulted in his death. Autopsy of sudden unexpected death in neonate should include investigation for inborn error of metabolism. Fatty liver and enlarged heart could give a clue for the diagnosis.

Cellulitis in human brucellosis: An atypical presentation.

INTRODUCTION: Brucellosis is a zoonotic disease with variable clinical manifestations and atypical presentation in humans. Human brucellosis cases are not seen often in Malaysia. CASE REPORT: This is a case report of 19 years old gentleman who presented with fever, lower limb redness, pain and swelling. He was initially treated as cellulitis. However, based on the recovery of Brucella melitensis from his blood culture, he was later diagnosed to have brucellosis. He had a history of consumption of fresh goat's milk and uncooked meat which could have been the possible modes of transmission. Brucella serology IgM and IgG were both positive, and anti-Brucella immunocapture agglutination test (BrucellaCapt) was also positive with a titer of 1:2560. He was treated with six weeks of oral doxycycline 100 mg twice daily and oral rifampin 450 mg twice daily. DISCUSSION: This is a case of human brucellosis with atypical cutaneous involvement.

Sudden cardiac death in a young adult man due to spontaneous coronary artery dissection.

Spontaneous coronary artery dissection is a rare event and commonly associated with pregnancy and female gender. This condition can reduce or completely obstruct the blood flow to the heart, causing a myocardial ischaemia, abnormalities in heart rhythm or sudden death. We present a case of a 28-year-old Indian male with no previous medical illness who complained sudden onset of chest pain prior to his death. Autopsy revealed a left anterior descending coronary artery dissection associated with plaque rupture. The anterior wall of left ventricle showed contraction band necrosis. There was also atheroma present in the right coronary artery which was insignificant. Histologically, dissection was associated with atherosclerosis. There was no evidence of vasculitis. The cause of death was given as coronary artery dissection due to coronary artery atherosclerosis.

Host-mediated RNAi of a Notch-like receptor gene in Meloidogyne incognita induces nematode resistance.

GLP-1 (abnormal germline proliferation) is a Notch-like receptor protein that plays an essential role in pharyngeal development. In this study, an orthologue of Caenorhabditis elegans glp-1 was identified in Meloidogyne incognita. A computational analysis revealed that the orthologue contained almost all the domains present in the C. elegans gene: specifically, the LIN-12/Notch repeat, the ankyrin repeat, a transmembrane domain and different ligand-binding motifs were present in orthologue, but the epidermal growth factor-like motif was not observed. An expression analysis showed differential expression of glp-1 throughout the life cycle of M. incognita, with relatively higher expression in the egg stage. To evaluate the silencing efficacy of Mi-glp-1, transgenic Arabidopsis plants carrying double-stranded RNA constructs of glp-1 were generated, and infection of these plants with M. incognita resulted in a 47-50% reduction in the numbers of galls, females and egg masses. Females obtained from the transgenic RNAi lines exhibited 40-60% reductions in the transcript levels of the targeted glp-1 gene compared with females isolated from the control plants. Second-generation juveniles (J2s), which were descendants of the infected females from the transgenic lines, showed aberrant phenotypes. These J2s exhibited a significant decrease in the overall distance from the stylet to the metacorpus region, and this effect was accompanied by disruption around the metacorporeal bulb of the pharynx. The present study suggests a role for this gene in organ (pharynx) development during embryogenesis in M. incognita and its potential use as a target in the management of nematode infestations in plants.

Association of the drug of abuse in road traffic collision death in Hospital Kuala Lumpur.

INTRODUCTION: The role of pathologist not only confined in performing post mortem but also can assist in prevention. The aim of this study to determine the prevalence and association of drug of abuse (DoA) in road traffic collision (RTC) at Hospital Kuala Lumpur. METHODS: This is a retrospective study of post mortem cases at Hospital Kuala Lumpur from 2014 to 2016. Deaths from RTC were included while decomposed and homicide cases were excluded. We performed Spearman Correlation statistical test to relate RTC and positive DoA results. RESULTS: A total of 523 RTC cases were identified in which either blood or urine or both samples were taken for toxicology. 93 cases were positive for both DoA and therapeutic drugs. A total of 37 cases were positive for DoA. Alcohol was present in 5 out of 37 DoA positive cases. Most of the cases seen among 16 to 45 years old (69%) and predominantly in males (93.1%). 29 out of 37 were motorcyclist and the rest were pillion rider and pedestrian. Spearman Correlation statistical test showed a negative relationship between RTC and positive DoA results. DISCUSSION AND CONCLUSION: Majority of the DoA cases in RTC were identified in the younger age group and among the motorcyclist. Spearman Correlation statistical test showed that more cases of DoA died in natural or suicidal manner compared to RTC. However, this doesn't reflect the true association of DoA in RTC. This is because of mainly two factors which the delayed effect of DoA that gives negative toxicology test and also the influence of other road users on DoA.

Adult extracorporeal membrane oxygenation: an international survey of transfusion and anticoagulation techniques.

BACKGROUND AND OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is a method of life support for either isolated cardiac failure or respiratory failure, with or without cardiac failure. When used for hemodynamic support, the ECMO circuit presents a non-endothelialized, artificial surface to blood inciting an inflammatory response which activates haemostatic pathways. Anticoagulation may complicate a pre-existing coagulopathy and/or inadequate surgical hemostasis of varying severity. There is no standardized method to achieve and monitor anticoagulation or guide transfusion therapy during ECMO. We tested the hypothesis that institutions across the world conduct similar management of anticoagulation and transfusion during adult ECMO support. METHODS: This is a descriptive, self-reporting cross-sectional survey of anticoagulation and transfusion practice for patients age 18 or older on ECMO. This 38 multiple-choice question survey was sent to 166 institutions, internationally, utilizing adult ECMO. About 32·4% (54) of institutions responded. Responses were anonymously collected. Descriptive analyses were calculated. RESULTS: Our findings indicate there appears to be a significant practice variation among institutions regarding anticoagulation and transfusion during adult ECMO support. DISCUSSION: The lack of standard practices among institutions may reflect a paucity of data regarding optimal anticoagulation and transfusion for patients requiring ECMO. Standardized protocols for anticoagulation and transfusion may help increase quality of care for and reduce morbidity, mortality and cost to patients and healthcare centres. Further study is required for standardized, high quality care.

Safe and effective: anti-tumour necrosis factor therapy use in pregnant patients with Crohn disease and ulcerative colitis.

Biological therapy, particularly the anti-tumour necrosis factor (TNF) antibodies, infliximab and adalimumab, are used for the maintenance of remission for patients with inflammatory bowel diseases (IBD). We present 21 pregnancies in IBD patients exposed to anti-TNF agents between 2007 and 2014. Our study demonstrates that anti-TNF therapy is safe and effective in pregnancy. Rates of foetal complications are similar to IBD cohorts from the pre anti-TNF era.

Placental involvement by non-Hodgkin lymphoma in a Crohn disease patient on long-term thiopurine therapy.

We report the first published case of aggressive diffuse large B-cell (non-Hodgkin) lymphoma in a 35-year-old pregnant woman who had Crohn disease and was taking long-term thiopurine therapy: the patient developed placental insufficiency, and there was intrauterine fetal death.

Detection of infectious spleen and kidney necrosis virus (ISKNV) and turbot reddish body iridovirus (TRBIV) from archival ornamental fish samples.

Although infections caused by megalocytiviruses have been reported from a wide range of finfish species for several decades, molecular characterisation of the viruses involved has been undertaken only on more recent cases. Sequence analysis of the major capsid protein and adenosine triphosphatase genes is reported here from formalin-fixed, paraffin-embedded material from 2 archival ornamental fish cases from 1986 and 1988 in conjunction with data for a range of genes from fresh frozen tissues from 5 cases obtained from 1991 through to 2010. Turbot reddish body iridovirus (TRBIV) genotype megalocytiviruses, previously not documented in ornamental fish, were detected in samples from 1986, 1988 and 1991. In contrast, megalocytiviruses from 1996 onwards, including those characterised from 2002, 2006 and 2010 in this study, were almost indistinguishable from infectious spleen and kidney necrosis virus (ISKNV). Three of the species infected with TRBIV-like megalocytiviruses from 1986 to 1991, viz. dwarf gourami Trichogaster lalius (formerly Colisa lalia), freshwater angelfish Pterophyllum scalare and oscar Astronotus ocellatus, were infected with ISKNV genotype megalocytiviruses from 2002 to 2010. The detection of a TRBIV genotype isolate in ornamental fish from 1986 represents the index case, confirmed by molecular sequence data, for the genus Megalocytivirus.

Spondyloarthropathy in inflammatory bowel disease patients on TNF inhibitors.

BACKGROUND: Musculoskeletal symptoms are the most common extra-intestinal manifestation associated with inflammatory bowel disease (IBD). Spondyloarthritis (SpA) is an umbrella term applied to a group of rheumatic diseases with some features in common and others distinct from other inflammatory arthritides. AIM: To determine self-reported prevalence of SpA associated musculoskeletal manifestations in an IBD cohort on tumour necrosis factor (TNF) inhibitors using a questionnaire incorporating Assessment of SpondyloArthritis International Society (ASAS) criteria. METHODS: Consecutive IBD patients on TNF inhibitors attending a single IBD centre (May-September 2011) were asked to complete a SpA questionnaire. Data collected included SpA and IBD variables, demographics, concurrent medications, co-morbidities and autoimmune serology. RESULTS: The 140-patient cohort included 96 suffering from Crohn disease and 44 from ulcerative colitis. The mean age of disease onset was 29.3 years and 45% were men. Concurrent or past history of inflammatory back pain was reported by 29% subjects. Using the imaging and clinical arms of the ASAS criteria, 30% and 14% subjects respectively had axial SpA. Arthritis was reported by 34%, enthesitis 17%, dactylitis 4%, uveitis 6%, psoriasis 6% and a family history of SpA in 39%. Peripheral SpA was present in 41% by the ASAS criteria. There were no differences in these frequencies between Crohn disease and ulcerative colitis. A positive antinuclear antibodies (>1:80) was found in 19% before commencement of TNF inhibitor therapy and increased to 78% on therapy. Clinical drug-induced lupus erythematosus was uncommon (4%) and was characterised by new clinical signs and symptoms, including arthralgia, rash with elevated dsDNA titres and positive antinuclear antibodies. CONCLUSIONS: Inflammatory bowel disease patients on TNF inhibitors frequently reported musculoskeletal manifestations. Increased recognition of SpA occurred with use of an SpA self-reported questionnaire in IBD patients: this could alter management and improve patient outcomes. Clinical drug-induced lupus erythematosus was uncommon.

Early predictors of colectomy and long-term maintenance of remission in ulcerative colitis patients treated using anti-tumour necrosis factor therapy.

BACKGROUND: Anti-tumour necrosis factor (TNF) agents are used as induction and maintenance therapy in ulcerative colitis (UC) refractory to standard therapy and as rescue therapy in acute severe UC (ASUC). AIMS: To determine long-term outcomes including colectomy rates, predictors of maintenance of response and remission, risk of serious adverse events by reviewing 12-year clinical experience from a single centre in Australia. METHODS: Seventy-one patients with moderate-severe UC (Mayo score ≥6) (n = 52) and ASUC (n = 19) treated with anti-TNF agents were included. Primary end-points were colectomy at 12 weeks and colectomy-free survival at last follow up. Secondary endpoints included clinical response (decrease in Mayo score of ≥3) and remission (Mayo score ≤2). RESULTS: Colectomy at 12 weeks was 1%, and colectomy-free survival was 69%. Using full Mayo score, at 3 months, 32/37 (87%) refractory and 9/12 (75%) ASUC patients responded to anti-TNF therapy; 19/37 (51%) refractory and 8/12 (67%) ASUC patients were in remission. Long-term response rates (mean follow up 37.4 months) were 24/44 (55%) and 11/15 (73%) in refractory and ASUC groups respectively. Long-term remission rates were 43% in refractory and 60% in ASUC patients. Twenty two of 71 (31%) underwent colectomy (mean time 50.4 months). Clinical non-response at 3 months was a predictor of colectomy (hazard ratio = 9.346; P = 0.001). ASUC predicted long-term maintenance of response (odds ratio 19.4; P = 0.013) and remission (odds ratio 6.13; P = 0.037). Two of 71 patients had serious infections. CONCLUSIONS: Anti-TNF therapy is effective in both refractory and ASUC. We argue that early anti-TNF therapy may improve outcome in UC.

Hepatosplenic T-cell lymphoma, immunosuppressive agents and biologicals: what are the risks?

We present three cases of the rare hepatosplenic T-cell lymphoma (HSTCL); two patients suffering from Crohn disease who developed HSTCL on azathioprine without exposure to biologicals, and a third patient who had psoriasis treated using etanercept, cyclosporine and methotrexate. The evidence for an association between HSTCL and immunosuppressive drugs and biologicals is reviewed. We argue for improved pharmacovigilance processes to help determine the benefit to risk ratios for the use of these and other new agents.

Management of CSF leak following spinal surgery.

PURPOSE: Postoperative CSF leak is a known complication of spinal surgery especially after surgery for neural tube defects (NTD). The problem can metamorphose into a severe infection. This article hopes to shed some light on the management of these problems and suggests precautions so as to reduce their occurrence. MATERIALS AND METHODS: A retrospective analysis of 102 children, between the ages of 1 day and 12 years, operated for various spinal pathologies, over the past 2.5 years by the same surgeon (CB) was done. The various methods of dural closure were noted. The methods of management of postoperative CSF leaks were analysed, and the patients were followed till discharge. RESULTS: The incidence of CSF leak was found to be 12.7%. The methods of management included lumbar drain only (n = 7), lumbar drain with re-exploration (n = 3), lumbar drain followed by lumboperitoneal shunt (n = 2) and only lumboperitoneal shunt (n = 1). The use of fibrin glue did not seem to significantly prevent the incidence of CSF leak in cases. CONCLUSIONS: Primary and meticulous dural closure is sine qua non in preventing postoperative CSF leak. A lumbar drain is a convenient and economical method of managing the problem initially failing which more invasive methods like re-exploration may be employed.

Detection and molecular characterization of infectious spleen and kidney necrosis virus from major ornamental fish breeding states in Peninsular Malaysia.

'Gold standard' OIE reference PCR assay was utilized to detect the presence of infectious spleen and kidney necrosis virus (ISKNV) in freshwater ornamental fish from Malaysia. From total of 210 ornamental fish samples representing 14 species, ISKNV was detected in 36 samples representing 5 fish species. All positive cases did not show any clinical signs of ISKNV. Three restriction enzymes analyses showed that the fish were infected by identical strains of the same virus species within Megalocytivirus genus. Major capsid protein (MCP) genes of 10 ISKNV strains were sequenced and compared with 9 other reference nucleotide sequences acquired from GenBank. Sequence analysis of MCP gene showed that all strains detected in this study were closely related to the reference ISKNV with nucleotide sequence identity that was ranging from 99.8% to 100%. In addition, phylogenetic analysis of MCP gene revealed that viruses from genus Megalocytivirus can be divided into three genotypes: genotype 1 include reference ISKNV and all other strains that were detected in this study, genotype 2 include viruses closely related to red sea bream iridovirus (RSIV), and genotype 3 include viruses closely related turbot reddish body iridovirus (TRBIV).

Clostridial aortitis causing ruptured dissecting aneurysm in a young adult female.

Ruptured dissecting aortic aneurysm more commonly occur in men in the 40 to 70 age group, and most commonly is associated with atherosclerosis. Uncommon causes are previous heart surgery, connective tissue disorders and aortitis. Despite its rarity, Clostridium spp aortitis progresses very rapidly with a mortality rate of approximately 79% in adults, typically occurring within 48 hours of infection. We present a case of sudden death due to clostridial aortitis causing ruptured aortic dissection in an apparently healthy adult female, 7 weeks post-spontaneous vaginal delivery. This case highlights the pathology of aortic dissection and cystic media necrosis as presentations of clostridium spp infection in young female adult.