Disseminated Adenoviral Infection Complicated by Fatal Hemorrhagic Enterocolitis in a Child with Acute Myeloid Leukemia.

Adenovirus infections are common and self-limiting in young children except those with compromised cellular immunity. However, serious adenovirus infections are rare in children with acute leukemia. We report a rare case of a toddler with acute myeloid leukemia who developed a disseminated adenoviral infection complicated by hemorrhagic enterocolitis and septic shock that led to a fatal outcome.

Novel PKLR missense mutation (A300P) causing pyruvate kinase deficiency in an Omani Kindred-PK deficiency masquerading as congenital dyserythropoietic anemia.

We report herein a child with transfusion-dependent chronic anemia, the cause of which was difficult to establish because of his transfusion dependency. The clinical and laboratory features suggested a chronic nonspherocytic hemolytic anemia (CNSHA) with bone marrow features suggestive of congenital dyserythropoietic anemia (CDA). DNA studies, however, revealed the underlying condition to be due to a novel mutation in the PKLR gene responsible for pyruvate kinase deficiency (PKD). Molecular investigations by a targeted next-generation sequencing (t-NGS) using a custom panel of 71 genes involved in the red blood cell (RBC) disorders revealed that the patient was homozygous for a novel missense mutation c.898G>C, p.Ala300Pro, whereas both his parents were heterozygous for the same mutation.

E. coli Monomicrobial Necrotizing Fasciitis in an Iron-Overloaded Adolescent.

Escherichia coli is an extremely unusual cause of monomicrobial necrotizing fasciitis of the extremities in children. We report a transfusion-dependent adolescent boy with iron-overload secondary to congenital dyserythropoietic anemia who developed severe E. coli monomicrobial necrotizing fasciitis of the leg following a minor trauma. Combined surgical, antimicrobial and supportive care resulted in a good outcome.

KMT2A-MLLT3 AML Masquerading as JMML may Disguise Fatal Leukemia.

We present a mortality case showcasing t(9;11)-positive acute myeloid leukemia/juvenile myelomonocytic leukemia (AML/JMML) overlap to shed light on this lethal molecular subtype of AML. In this case, the flawed assumption that JMML was to blame impeded the prompt undertaking of appropriate treatment for AML in our 14-month-old patient. This article aims to scrutinize the catastrophic sequel of such an overlap in leukemia and refutes the contemporary diagnostic methods.

Gender difference in the point prevalence, symptoms, comorbidity, and correlates of depression: findings from the Lagos State Mental Health Survey (LSMHS), Nigeria.

It is still unclear whether the gender difference in the rate of depression cuts across cultures or is specific to some depressive symptoms. This study evaluated the gender difference in current prevalence, symptoms, comorbidity, and correlates of depression in Lagos, Nigeria. A total of 11,246 adult participants (6525 females and 4712 males) in a face-to-face household survey were assessed for symptoms of depression. They were also assessed for symptoms of anxiety, somatic symptoms, alcohol and substance use disorders, and disability. The difference between the point prevalence for symptoms of depression in females (6.3%, s.e 0.3) and males (4.4%, s.e 0.3) was significant (OR 1.28, 95% CI 1.14-1.59). Compared to males, females had significantly higher rates for anhedonia (OR 1.20), hypersomnia (OR 2.15), fatigue (OR 1.49), guilt/worthless feeling (OR 1.41), poor concentration (OR 1.32), psychomotor retardation (OR 1.51), and suicidal ideation (OR 1.32). However, poor appetite (OR 0.69) and comorbidity with alcohol use (OR 0.25) was significantly lower in females compared to males. The significantly higher rates for depression in females were only restricted to below 45 years and higher socioeconomic status. Our study further contributed to the growing literature suggesting that the gender differences in rates of depression not only cut across many cultures, but most pronounced with atypical symptoms, not affected by recall bias and seems to disappear with increasing age. These need to be considered when formulating mental health policies for equitable and acceptable health services.

Current prevalence, comorbidity and associated factors for symptoms of depression and generalised anxiety in the Lagos State Mental Health Survey (LSMHS), Nigeria.

BACKGROUND: Depression and anxiety are very prevalent, highly co-morbid, burdensome with huge treatment gaps in low and middle-income countries (LMICs). This study aimed to estimate the current prevalence of symptoms of depression and generalised anxiety, examine co-morbid conditions and associated sociodemographic factors in Lagos state, Nigeria. METHODS: A face to face household survey completed by 11,246 adult participants (age 18-75years). Clinically significant symptoms of depression, generalised anxiety and somatic symptoms were assessed using the specific modules of the Patient Health Questionnaire (PHQ) respectively. Alcohol use, substance use and disability were assessed with the Alcohol Use Disorders Identification Test-short form (AUDIT-C), the Mini International Neuropsychiatric Interview (M.I.N.I) and the WHO Disability Assessment Schedule (WHODAS 2.0) respectively. RESULTS: The mean age was 36.75 (sd 12.3) years and there were 6525 (58.0%) females. The weighted current prevalence of symptoms of depression, generalised anxiety and combined depression/generalised anxiety were 5.5% (se 0.3), 3.5% (se 0.2) and 1.2% (se 0.1) respectively. About 20.9% of all cases of depressive symptoms have co-morbidity with symptoms of generalised anxiety. Symptoms of depression and generalised anxiety had high co-morbidity with somatic symptoms, alcohol use problems and disability but not substance use disorders. Being female, not married (especially separated/divorced or widowed) and unemployment were significantly associated with presence of either symptoms of depression or generalised anxiety. CONCLUSION: Our findings suggest that despite the popularity of cross-national surveys, there is need for individual countries and states to generate complimentary local data to plan effective local response to close the huge treatment gap for common mental disorders.

Human Parvovirus B19 in Children with Sickle Cell Disease; Poking the Spleen.

Parvovirus is a known culprit of transient red cell aplasia (TRCA) in children with sickle cell disease (SCD). Few reports have previously described the association between the virus and acute splenic sequestration crisis (ASSC) in the same patient. Here, we are shedding light on such a potentially serious combination by reporting two cases of siblings with SCD complicated with concurrent ASSC and TRCA and presenting a review of the relevant literature.

Effect of 2 Models of Care and Factors Predicting Patients' Adherence to Doctor's Appointment Attendance in Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.

BACKGROUND: Provision of antiretroviral therapy in resource limited settings has put pressure on the available infrastructure. OBJECTIVES: The study examined patients' adherence to Doctor's appointment attendance after an intervention changing the model of care and factors that predicted adherence. METHODS: Observational study was carried out over four years. The model of care was changed in the last year and the effect assessed. SPSS version 15.0 was used for analysis. Predictors of adherence were determined using logistic regression model. RESULTS: Over half 148 (59.7%) of the patients were females, with a mean age of 40.4±8.8 years and baseline CD4 cells of 143.5±92.7cells/microliters. "Adherence" rates were 51.3% in 2007, 35.9% in 2008 and 14.9% in 2009 giving patients' average adherence to Doctor's appointment attendance of 34.03%. Intervention changing the model of care in 2010 recorded an adherence rate of 93.1%. CONCLUSIONS: The change in model of care greatly improved patients' "adherence". Patients' knowledge of management, adherence, and smoking and drinking habits were identified as statistically significant predictors of adherence.

Prevalence and associated factors for suicidal ideation in the Lagos State Mental Health Survey, Nigeria.

BACKGROUND: To combat the increasing rate of suicide, basic data on suicidal behaviours reflecting the uniqueness of the locality are needed in sub-Saharan Africa. AIMS: To assess the prevalence of suicidal ideation and associated factors. METHOD: Adults (n=11 246) from the five administrative divisions of Lagos State completed questionnaires detailing suicidal ideation, socio-demographic details, common mental disorders (depression, anxiety and somatic symptoms), alcohol and psychoactive substance use disorders and disability. RESULTS: The weighted prevalence of current suicidal ideation was 7.28% (s.e. 0.27). Independently associated factors were older age, being female, not married, low occupational group, depression, anxiety, somatic symptoms and disability. CONCLUSIONS: Despite the validity of cross-national surveys, there is need for individual countries to generate complementary local data to explain variability in rates and risk factors in order to plan for suicide prevention or develop timely and effective response. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Impact of Burden of Thalassemia Major on Health-related Quality of Life in Omani Children.

To improve treatment outcome in young patients with homozygous ß-thalassemia, evaluation of factors associated with health-related quality of life (HRQoL) is essential to develop clinical, counseling, social, and school support programs. This study was performed to evaluate HRQoL in Omani children with thalassemia who have not been previously evaluated. All patients with thalassemia (5 to 18 y) on regular hypertransfusion from August 2013 to February 2014 were included. Demographic-clinical information was obtained from electronic patient records. The 23-item Pediatric Quality of Life Inventory (PedsQL) 4.0 with 4 multidimensional scales and 3 summary scores was used to assess HRQoL by both patients and caregivers. Statistical analysis was performed using SPSS version 19. Delayed age at diagnosis and delayed initiation of chelation were independently associated with a negative impact on total PedsQL scores; children with higher pretransfusion hemoglobin and lower serum ferritin levels scored better overall. Patients self-rated their HRQoL scores lower as compared with caregivers. Although physical health was more affected than psychosocial health function from both patients' (72.26±22.34 vs. 74.55±18.25) and caregivers' (69.91±19.86 vs. 78.83±18.45) perspective, school functioning domain (68.05±21.30 and 69.71±18.96) scored the lowest. Low ratings for physical health and school functioning highlight the importance of adequate transfusion together with the need for a multidisciplinary teamwork by health care providers, social workers, counselors, family members, and school authorities to provide psychosocial support to prevent mental issues and improve academic performance in these young patients.

Impact of Mannose-Binding Protein Gene Polymorphisms in Omani Sickle Cell Disease Patients.

OBJECTIVES: Our aim was to study mannose-binding protein (MBP) polymorphisms in exonic and promoter region and correlate it with associated infections and vasoocculsive (VOC) episodes in sickle cell disease (SCD) patients since MBP plays an important role in innate immunity by activating the complement system. METHODS: We studied the genetic polymorphisms in the Exon 1 (alleles A/O) and promoter region (alleles Y/X; H/L, P/Q) of the MBL2 gene, in SCD patients as an increased incidence of infections is seen in these patients. A PCR-based, targeted genomic DNA sequencing of MBL2 was used to study 68 SCD Omani patients and 44 controls (healthy voluntary blood donors). RESULTS: In SCD patients, the frequency of the genotype related to the high production of MBL was 0.35 (YA/YA) and for intermediate/low production was 0.65 (YA/XA, XA/XA, YA/YO, XA/YO, YO/YO). The observed frequencies of MBL2 gene promoter polymorphism (-221, Y/X) were 44.4% and 20.5% for the heterozygous genotype Y/X and 3.2% and 2.2% for the homozygous (X/X) respectively between SCD patients and controls. MBL2 Exon1 gene mutations were 29.4% and 50% for the heterozygous genotype A/O and 5.9% and 6.8% respectively for the homozygous (O/O) genotype between SCD patients and controls. The distribution of variant MBL2 gene polymorphisms did not show any correlation in SCD patients with or without VOC attacks (p=0.16; OR -0.486; CI=0.177 -1.33), however, it was correlated with infections (p=0.0162; OR -3.55; CI 1.25-10.04). CONCLUSIONS: Although the frequency of the genotypes and haplotypes of MBL2 in SCD patients did not differ from controls, overall in the SCD patient cohort the increased representation of variant alleles was significantly correlated with infections (p<0.05). However, these variant MBL2 polymorphisms did not seem to play a significant role in the VOC episodes in this SCD cohort.

Single Breath-Hold Physiotherapy Technique: Effective tool for T2* magnetic resonance imaging in young patients with thalassaemia major.

Magnetic resonance imaging using T2* (MRI T2*) is a highly sensitive and non-invasive technique for the detection of tissue iron load. Although the single breath-hold multi-echo T2* technique has been available at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, since 2006, it could not be performed on younger patients due to their inability to hold their breath after expiration. This study was carried out between May 2007 and May 2015 and assessed 50 SQUH thalassaemic patients aged 7-17 years old. Seven of these patients underwent baseline and one-year follow-up MRI T2* scans before receiving physiotherapy training. Subsequently, all patients were trained by a physiotherapist to hold their breath for approximately 15-20 seconds at the end of expiration before undergoing baseline and one-year follow-up MRI T2* scans. Failure rates for the pre- and post-training groups were 6.0% and 42.8%, respectively. These results indicate that the training of thalassaemic patients in breath-hold techniques is beneficial and increases rates of compliance for MRI T2* scans.

Single dose darbepoetin alfa is useful in reducing red cell transfusions in leukemic children receiving chemotherapy.

The role of erythropoiesis-stimulating agents (ESAs) in the management of chemotherapy-induced anemia (CIA) is becoming increasingly recognized in the field of medical oncology, with paucity of data in pediatrics. We evaluated the efficacy and tolerability of a single-dose darbepoetin alfa, a long-acting ESA, given to 35 pediatric acute lymphoblastic leukemia (ALL) children during induction chemotherapy. Compared to a retrospective control group, the studied patients have required significantly less units of packed red blood cells (0.88 units/patient in the studied group versus 2.04 units in controls), with no major side effects. We recommend further prospective double-blinded studies with more tailored dosing regimens in pediatric ALL cases and solid tumors.

Optimizing Hydroxyurea use in children with sickle cell disease: low dose regimen is effective.

BACKGROUND AND OBJECTIVES: Hydroxyurea (HU) is the standard treatment for severely affected children with sickle cell disease (SCD). Starting dose is 15-20 mg/kg/day that can be escalated up to 35 mg/kg/day. Ethnic neutropenia is common in this area of the world that requires judicious usage of myelosuppressive drugs. Aim was to assess the efficacy of a lower initial dose of HU and cautious dose escalation regimen in patients with SCD. METHODS: We assessed 161 patients with SCD on HU, at Sultan Qaboos University Hospital (SQUH), Muscat, Oman, retrospectively from 1998 to 2008 and prospectively from 2009 to 2011. Starting dose of HU was 10-12 mg/kg/day, adjusted based on response or side effects. Patients were divided into two groups according to the dose of HU (10-15.9 mg/kg/day and 16-26 mg/kg/day). RESULTS: Nineteen patients were excluded for various reasons. Forty-four children were in the low-dose group and 98 were in the high-dose group. There was significant reduction in the annual number of admissions due to vaso-occlusive crisis in both groups (P < 0.001). However, the difference between the two groups was statistically insignificant (P > 0.05). In addition, there was an observed clinical improvement regarding the acute chest syndrome (ACS). Both groups had comparable significant improvements in their laboratory markers [e.g., hemoglobin (Hb), Mean Corpuscular Volume (MCV), and absolute neutrophil count (ANC)]. All 142 patients tolerated the treatment well. Reversible toxicities occurred in both low- and high-dose groups. CONCLUSION: In SCD patients, low-dose regimen of HU is a feasible option that ensured safety and yet did not affect efficacy.

Comparative assessment of deferiprone and deferasirox in thalassemia major patients in the first two decades-single centre experience.

Iron overload is mainly responsible for the morbidity and mortality in patients with beta thalassemia major (TM). Our aim was to compare treatment outcomes with oral iron chelators, deferiprone (DFP), and deferasirox (DFX) in the first two decades on therapy. Seventy patients with TM (mean age ± SD, 7.9 ± 4.2; range 1.5-17 years) attending the pediatric day care unit for regular transfusional support were enrolled in this cross-sectional cohort study. The patients were treated either with DFP at the dose of 75-100 mg/kg/d in three divided doses after food or DFX at the dose of 25-40 mg/kg/d as single dose before food. Mean serum ferritin (±SD) was lower in patients below 10 years (n = 44) at 1283 (±600) ng/mL when compared with patients ≥10 years (n = 19) at 1546 (±589) ng/mL. There was no significant difference in mean serum ferritin (±SD) level in patients receiving DFP (1360 ± 589) versus DFX (1260 ± 641) in this cohort, P > 0.05. 67% of the patients had Vitamin D deficiency (<50 umol/L). Our results show comparable efficacy of DFP and DFX with regards to iron chelation as estimated by serial serum ferritin levels; however, MRI T2* values were higher in the DFP-treated patients compared to DFX treatment.

Prepubertal Hypertransfusion in Thalassemia Intermedia: A Case Report of Sustained Positive Effects on Growth, Splenic Function and Endocrine Parameters.

We report a known case of thalassemia intermedia (Hb Dhofar) who in spite of mild thalassemic facies, attained his normal genetic height, pubertal maturity and improved self-image with minimal splenomegaly through a hypertransfusion/chelation regimen that was started just before puberty and maintained for 5 years. As there are no clear guidelines in the management of patients with thalassemia intermedia, the option of hypertransfusion/chelation during the pubertal growth spurt may alleviate some of the complications associated with thalassemia intermedia.

Orbital infarction in sickle cell disease.

PURPOSE: To determine the role of hematological and genetic factors in the development of orbital infarction in sickle cell disease. DESIGN: Retrospective, noncomparative case series. METHODS: Fourteen sickle cell disease patients were diagnosed with orbital infarction during a vaso-occlusive crisis. Clinical and radiological findings were reviewed retrospectively. Sickle cell disease patients without orbital infarction were recruited as controls after matching for disease severity. Sickle haplotypes were determined for all patients. Differences between groups were evaluated statistically. RESULTS: Patients with orbital infarction in sickle cell disease presented with acute periorbital pain and swelling with or without proptosis, ophthalmoplegia, and visual impairment during a vaso-occlusive crisis. Radiological findings included orbital soft tissue swelling (100%), hematoma (orbital, 36%; intracranial, 21%), and abnormal bone marrow intensities. Severity of orbital involvement was unrelated to that of the systemic disease (Pearson correlation coefficient, -0.1567). Affected patients predominantly had the Benin haplotype (P < .00782). CONCLUSIONS: Orbital infarction is a potential threat to vision in sickle cell disease patients. Magnetic resonance imaging is more specific than computed tomography or nuclear scintigraphy in the evaluation of orbital changes. The degree of severity of the orbital manifestations appears unrelated to the severity of sickle cell disease. Patients with the Benin haplotype are more likely to develop orbital infarction during vaso-occlusive crises.

Novel spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis in ethnic Omani patients.

Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive immune disorder, characterized by fever, hepatosplenomegaly, pancytopenia, hypertriglyceridemia, hypofibrinogenemia, markedly elevated levels of inflammatory cytokines, and impaired cytotoxic activity of lymphocytes. FHL is often fatal in early infancy. Histologic features include organ infiltration by activated macrophages and lymphocytes. Four genetic loci (FHL1, 2, 3, and 4) have been identified, of which FHL2 involves mutations in the perforin gene and is present in 20-50% of patients with FHL. We herein report the first comprehensive molecular analysis of 16 unrelated cases of FHL in ethnic Omanis. Using direct DNA sequencing analysis in 11 families, seven different mutations were identified in the coding region of the perforin gene, of which five were novel. Perforin gene defects do not seem to be involved in one-third of the cases of FHL in ethnic Omanis.

Identification of prognosis markers in pediatric high-risk acute lymphoblastic leukemia.

Gene expression profiling may improve the understanding of the biology behind relapse in pediatric acute lymphoblastic leukemia. Using suppression subtractive hybridization (SSH), cDNA concatenated sequencing (CCS), and reverse transcriptase real-time quantitative polymerase chain reaction (RT-RQ-PCR) on high-risk patient samples with nondeterminant chromosomal translocation, the authors identified 3 genes that were significantly overexpressed in the nonrelapsed patients: the calcium/calmodulin-dependent serine protein kinase (CASK), subunit 2 of the cofactor required for SP1 transcriptional activation (CRSP2), and granzyme K (GZMK). The level of expression of these biomarkers may help identify patients with potentially good prognosis within a group otherwise at high risk of relapse.

An inframe perforin gene deletion in familial hemophagocytic lymphohistiocytosis is associated with perforin expression.

Familial hemophagocytic lymphohistiocytosis is an autosomal recessive disease of early childhood manifested by hypercytokinemia and organ infiltration of macrophages and activated lymphocytes, and it is characterized by a fulminant clinical course. The molecular mechanism underlying this disease appears to be a deregulation of apoptosis of activated T cells and macrophages. Approximately 20-40% of patients with familial hemophagocytic lymphohistiocytosis reported worldwide had a perforin gene mutation. We report herein a novel perforin variant in the homozygous state in an Omani boy who was diagnosed 44 days after birth. Sequence analysis of the perforin gene coding region revealed a 12-base pair deletion (codon 284-287) resulting in the deletion of four amino acids in the membrane attack complex domain of the protein. This deletion maintains the reading frame of the perforin mRNA. Both parents were heterozygotes for this molecular defect. Flow-cytometric analysis revealed intracellular perforin expression at the lower end of the normal range in the cytotoxic T cells (CD3+/CD8+) and (CD3+/CD56+) and in around 50% of the natural killer cells (CD3-/CD56+). This is an additional example of a perforin variant which is associated with a significant level of cellular perforin expression and thus confirms that drastic reduction in its expression is not a constant feature in familial hemophagocytic lymphohistiocytosis type 2.