HHV6-Associated Hydrocephalus in a Pediatric Hematopoietic Stem Cell Transplant Recipient: An Unusual Presentation.

Human herpesvirus 6 (HHV-6) is a widely spread DNA virus that is ubiquitous and persistent with primary infection occurring in early childhood, with reactivation of the infection a common phenomenon in severely immunocompromised hosts, including hematopoietic stem cell transplant (HSCT) patients, influencing morbidity and mortality. A wide spectrum of clinical presentations is reported in the literature with HHV-6 reactivation including post-transplant limbic encephalitis (PALE). We report the unusual case of a 6-year-old female 107 days postallogenic HSCT due to transfusion dependent beta thalassemia major who developed acute cerebellitis with secondary supratentorial hydrocephalus that required invasive surgical intervention. In addition to accompanying imaging findings, the patient tested positive for HHV-6 by PCR from both serum and CSF samples and demonstrated dramatic improvement with the institution of steroid therapy in addition to ganciclovir treatment. The availability of rapid diagnostic measures in addition to a multidisciplinary approach is crucial to manage HHV-6 encephalitis and associated complications in HSCT patients.

BET Protein Inhibition Regulates Macrophage Chromatin Accessibility and Microbiota-Dependent Colitis.

Introduction: In colitis, macrophage functionality is altered compared to normal homeostatic conditions. Loss of IL-10 signaling results in an inappropriate chronic inflammatory response to bacterial stimulation. It remains unknown if inhibition of bromodomain and extra-terminal domain (BET) proteins alters usage of DNA regulatory elements responsible for driving inflammatory gene expression. We determined if the BET inhibitor, (+)-JQ1, could suppress inflammatory activation of macrophages in Il10-/- mice. Methods: We performed ATAC-seq and RNA-seq on Il10-/- bone marrow-derived macrophages (BMDMs) cultured in the presence and absence of lipopolysaccharide (LPS) with and without treatment with (+)-JQ1 and evaluated changes in chromatin accessibility and gene expression. Germ-free Il10-/- mice were treated with (+)-JQ1, colonized with fecal slurries and underwent histological and molecular evaluation 14-days post colonization. Results: Treatment with (+)-JQ1 suppressed LPS-induced changes in chromatin at distal regulatory elements associated with inflammatory genes, particularly in regions that contain motifs for AP-1 and IRF transcription factors. This resulted in attenuation of inflammatory gene expression. Treatment with (+)-JQ1 in vivo resulted in a mild reduction in colitis severity as compared with vehicle-treated mice. Conclusion: We identified the mechanism of action associated with a new class of compounds that may mitigate aberrant macrophage responses to bacteria in colitis.

Corrigendum to "Chronic Immune Thrombocytopenia and Hashimoto's Hypothyroidism in an Adolescent: Presentation and Implications".

[This corrects the article DOI: 10.1155/2021/6649155.].

Chronic Immune Thrombocytopenia and Hashimoto's Hypothyroidism in an Adolescent: Presentation and Implications.

Immune thrombocytopenia (ITP) is a disorder characterized by immune-mediated destruction of thrombocytes leading to peripheral blood platelet count of <100 × 10^9/L. Primary ITP is a terminology used in the absence of other causes or disorders that may be associated with thrombocytopenia, i.e., isolated thrombocytopenia. The term secondary ITP is used if such diseases coexist. We present here a case of a 14-year-old female diagnosed with immune thrombocytopenia. When her evaluation was not strongly supportive of primary ITP, she was screened and proved to have a concomitant Hashimoto thyroiditis. Contrary to the popular belief about secondary ITP in adult population, treatment of our patient's hypothyroidism did not improve her platelet's count, and the patient needed multiple immunosuppressive medications to improve her condition.

Transcranial Doppler Ultrasound in Peninsular Arab Patients With Sickle Cell Disease.

OBJECTIVES: Transcranial Doppler ultrasound is used to identify patients with sickle cell disease (SCD) at risk for stroke. We performed transcranial Doppler studies in patients from 4 countries in the Arabian Peninsula (Kuwait, Oman, Iraq, and United Arab Emirates) to document the prevalence of abnormal transcranial Doppler findings. METHODS: The patients were recruited from outpatient clinics and studied in a steady state. Transcranial Doppler examinations were performed with standard equipment by experienced operators. The time-averaged maximum mean velocity (TAMMV) was documented in the arteries of the circle of Willis. The hemoglobin (Hb) genotype was confirmed, and the fetal Hb level and complete blood counts were determined. RESULTS: There were 415 patients in the study, aged 2 to 18 years (mean ± SD, 8.6 ± 3.5 years). None of the patients had an abnormal TAMMV (ie, > 200 cm/s), whereas only 13 (3.1%), all from Iraq, had conditional values (170-200 cm/s) in the right middle cerebral artery and 7 (1.7%) in the left middle cerebral artery. There were no consistent TAMMV differences among male and female patients or in patients with different Hb genotypes (sickle cell anemia, sickle cell ß0- thalassemia, and sickle D). The use of hydroxyurea was associated with a lower TAMMV, whereas a blood transfusion history had no influence. Total hemoglobin, reticulocyte count, serum bilirubin, and fetal Hb values showed varying degrees of association with the TAMMV in the different vessels. CONCLUSIONS: This study has demonstrated the rarity of abnormal transcranial Doppler findings among Peninsular Arab patients with SCD. The guidelines for transcranial Doppler screening in this population need further studies and recommendations.

A Proposed Clinical Evaluation of a Simulation Environment for Magnetically-Driven Active Endoscopic Capsules.

Background A simulation environment for magnetically-driven, active endoscopic capsules (Abu-Kheil Y, Seneviratne L, Dias J, A simulation environment for active endoscopic capsules. 2017 IEEE 30th international symposium on Computer Based Medical Systems (CBMS), Thessaloniki, pp 714-719, 2017), can perform four main operations: capsule tele- operation, tracking of a specific region of interest, haptic feedback for capsule navigation and virtual reality navigation.Methods The main operations of the simulation environment can be clinically evaluated. In this paper, we proposed a clinical evaluation for the main functions of the simulation environment. There main testing procedures for the navigation strategies are proposed; i) vision-based tele-operation, ii) vision/haptic-based navigation without head control, and iii) vision/haptic-based navigation with head control. The navigation ways can be compared with each other in terms of introduction time, visualization and procedure comfort. Human-subject studies are to be conducted in which 20 students and 12 expert gastroenterologists participated.

Colonic epithelial miR-31 associates with the development of Crohn's phenotypes.

BACKGROUND: Crohn's disease (CD) is highly heterogeneous, due in large part to variability in cellular processes that underlie the natural history of CD, thereby confounding effective therapy. There is a critical need to advance understanding of the cellular mechanisms that drive CD heterogeneity. METHODS: We performed small RNA sequencing of adult colon tissue from CD and NIBD controls. Colonic epithelial cells and immune cells were isolated from colonic tissues, and microRNA-31 (miR-31) expression was measured. miR-31 expression was measured in colonoid cultures generated from controls and patients with CD. We performed small RNA-sequencing of formalin-fixed paraffin-embedded colon and ileum biopsies from treatment-naive pediatric patients with CD and controls and collected data on disease features and outcomes. RESULTS: Small RNA-sequencing and microRNA profiling in the colon revealed 2 distinct molecular subtypes, each with different clinical associations. Notably, we found that miR-31 expression was a driver of these 2 subtypes and, further, that miR-31 expression was particularly pronounced in epithelial cells. Colonoids revealed that miR-31 expression differences are preserved in this ex vivo system. In adult patients, low colonic miR-31 expression levels at the time of surgery were associated with worse disease outcome as measured by need for an end ileostomy and recurrence of disease in the neoterminal ileum. In pediatric patients, lower miR-31 expression at the time of diagnosis was associated with future development of fibrostenotic ileal CD requiring surgeryCONCLUSIONS. These findings represent an important step forward in designing more effective clinical trials and developing personalized CD therapies. FUNDING: This work was supported by CCF Career Development Award (SZS), R01-ES024983 from NIEHS (SZS and TSF), 1R01DK104828-01A1 from NIDDK (SZS and TSF), P01-DK094779-01A1 from NIDDK (SZS), P30-DK034987 from NIDDK (SZS), 1-16-ACE-47 ADA Pathway Award (PS), UNC Nutrition Obesity Research Center Pilot & Feasibility Grant P30DK056350 (PS), CCF PRO-KIIDS NETWORK (SZS and PS), UNC CGIBD T32 Training Grant from NIDDK (JBB), T32 Training Grant (5T32GM007092-42) from NIGMS (MH), and SHARE from the Helmsley Trust (SZS). The UNC Translational Pathology Laboratory is supported, in part, by grants from the National Cancer Institute (3P30CA016086) and the UNC University Cancer Research Fund (UCRF) (PS).

Undifferentiated sarcoma of the liver: a rare pediatric tumor.

Undifferentiated embryonal sarcoma of the liver (UESL) is an uncommon hepatic tumor of mesenchymal origin recognized as a unique clinicopathologic entity since 1978. UESL has historically been considered an aggressive neoplasm with an unfavorable prognosis. Survival has improved using recent multimodal approaches, designed for patients with soft tissue sarcomas at other sites. Several small series have reported survival of up to 70% of children. We report a case of a 12-year-old boy from the United Arab Emirates who relapsed after complete surgical resection and was then successfully treated with re-resection followed by chemotherapy and radiotherapy. With a follow-up of 5 years, he is well and asymptomatic, and is leading a healthy life. This case emphasizes the fact that these poorly prognostic tumors may benefit from post-surgery chemotherapy. This case illustrates the improved survival of UESL patients following the multimodality therapy with a relatively long follow-up. This is the first case of UESL reported in this region of the world.

Hepatic Sinusoidal Obstruction Syndrome in a child after chemotherapy for medulloblastoma.

Hepatic Sinusoidal Obstruction Syndrome (HSOS), the new name given to veno-occlusive disease (VOD) of the liver, is a well-known complication of high-dose chemotherapy employed with hematopoietic stem cell transplantation, but it has rarely been observed in children who receive conventional chemotherapy. HSOS following standard chemotherapy has been reported in patients receiving vincristine, actinomycin D, and cyclophosphamide for the treatment of Wilms tumor and more rarely rhabdomyosarcoma. We report a 14-year-old boy with high risk medulloblastoma treated with craniospinal radiation followed by chemotherapy, who experienced severe HSOS after only one course of chemotherapy including carboplatin, vincristine, and cyclophosphamide. To our knowledge, this is the second report of HSOS after standard dose chemotherapy for brain tumor in childhood.

Reversal of iron-induced dilated cardiomyopathy during therapy with deferasirox in beta-thalassemia.

A 15-year-old male with beta-thalassemia major developed dilated cardiomyopathy secondary to iron-overload (Z-scores of left ventricle (LV) dimensions >3, ejection fraction (EF) 33%). Treatment with deferoxamine was unsuccessful, presumably due to poor compliance. After 15 months of using deferasirox (DFX), LV end-diastolic dimension normalized (Z-scores <2), and EF improved to 58%. We conclude that treatment with DFX resulted in a reversal of iron-induced cardiomyopathy.

Allogeneic stem cell transplantation for Glanzmann thrombasthenia.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by normal platelet count, but lack of platelet aggregation. The molecular basis is linked to quantitative and/or qualitative abnormalities of the membrane glycoprotein IIb/IIIa complexes. Usually it is associated with mild bleeding but may lead to severe and potentially fatal hemorrhages. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. However, because of the risks associated with HSCT, it is generally not recommended unless there are life threatening hemorrhages, or the patient has developed refractoriness to platelet transfusion due to antibody formation. Herein, we report an 11-year-old female from United Arab Emirates (UAE) with severe GT and anti platelet alloimmunization successfully treated with HSCT from her HLA-identical sibling.

The molecular epidemiology of Stenotrophomonas maltophilia bacteraemia in a tertiary referral hospital in the United Arab Emirates 2000-2004.

BACKGROUND: Stenotrophomonas maltophilia is recognised as an important cause of nosocomial infection, especially in immunocompromised patients, resulting in significant morbidity and mortality. The treatment of S. maltophilia infection presents a therapeutic challenge. The precise modes of transmission of S. maltophilia in the hospital environment are not known and such knowledge is essential to target interventions to prevent spread. There are few published data on the patterns of nosocomial infection in the United Arab Emirates (UAE). A recent study showed that S. maltophilia is an established cause of bloodstream infection in Tawam Hospital in the UAE. Little is known about its epidemiology in the hospital. METHODS: We describe the clinical characteristics of 25 episodes of S. maltophilia bacteraemia which occurred from 2000-2004. The strains were characterised using pulsed field gel electrophoresis (PFGE). RESULTS: All episodes were hospital-acquired and malignancy and central venous catheters were predisposing factors. Catheter-associated infection comprised 88% infection. Catheter removal was important for the successful management of catheter-associated infection. The results of PFGE suggested that there were as many strains as patients. S. maltophilia strains isolated from the same patient had indistinguishable PFGE profiles. CONCLUSION: PFGE is a valid and reproducible typing method for S. maltophilia. The precise sources and modes of spread of S. maltophilia in the hospital are still not known. Knowledge that person to person transmission was not a major mode of transmission enabled infection control interventions for S. maltophilia to be targeted more effectively.

Situs inversus abdominus in association with congenital duodenal obstruction: a report of two cases and review of the literature.

This report describes two newborns with persistent bile-stained vomiting. Their radiological investigations revealed the existence of situs inversus and duodenal obstruction. In one, the duodenal obstruction was partial, secondary to a duodenal diaphragm with a central aperture, whereas the other child had complete duodenal atresia as well as Fallot's tetralogy. Such an association is extremely rare, with only 18 cases reported so far in the literature. Embryological aspects, investigations, and treatment are also discussed.

Vincristine-induced urinary bladder paralysis.

The authors describe the development of bladder paralysis in a child with acute lymphoblastic leukemia undergoing maintenance chemotherapy. Immediately before the adverse clinical event, the child had received vincristine intravenously and triple therapy with hydrocortisone, cytosine arabinoside, and methotrexate intrathecally and had begun a 5-day pulse of prednisolone. The authors conclude that the ensuing reversible bladder paralysis was related to the vincristine. The clinical event resolved, and vincristine was deleted from the child's subsequent therapy until full recovery was achieved. The authors advise recognition of this problem and discontinuation of the vincristine if transient bladder paralysis develops until symptoms completely disappear.

Congenital peripheral primitive neuroectodermal tumor refractory to treatment.

The authors report an unusual case of an infant presenting with a congenital peripheral primitive neuroectodermal tumor (PPNET) of the left hand refractory to treatment. A newborn girl was born with a large bluish-red mass of 4.5 cm diameter protruding into the palm and the dorsum of the left hand. Tumor biopsy confirmed the diagnosis of PPNET. The initial metastatic workup for the detection of metastases was negative. Four cycles of chemotherapy according to CCSG 7881/POG 8850 regimen B were given. Despite this aggressive chemotherapy the tumor grew to involve the entire left hand. The left hand was amputated, and then two cycles of topotecan/cyclophosphamide were given. Five months later extensive metastases developed, involving the brain, lungs, liver, and skeleton, and the child died at the age of 2.5 years. PPNET presenting at birth is uncommon; presentation in the hand is unusual, and the fact that it did not respond to treatment is still more uncommon.

Congenital duodenal diaphragm in eight children.

BACKGROUND: Congenital duodenal obstruction (CDO) is a common and usually easy to diagnose cause of intestinal obstruction in the newborn, except when the cause of the obstruction is a duodenal diaphragm. We describe our experience with eight children who had intrinsic duodenal obstruction secondary to a duodenal diaphragm. METHODS: The medical records of 22 children with the diagnosis of congenital intrinsic duodenal obstruction were reviewed for age at diagnosis, sex, gestation, birth weight, clinical features, associated anomalies, method of diagnosis, treatment and outcome. Operative findings and procedures were obtained from the operative notes. RESULTS: Eight of the 22 children (36.4%) had congenital duodenal diaphragm (CDD). In all children, the diagnosis was made from plain abdominal X-ray, which showed the classic double-bubble appearance, and barium meal, which showed duodenal obstruction. Four patients had associated anomalies, including two with Down's syndrome. Intraoperatively, five patients were found to have duodenal diaphragm with a central hole, while the other three had complete duodenal diaphragms. Postoperatively, all patients did well. Six required total parenteral nutrition. CONCLUSIONS: The 100% survival rate among these children is comparable to that in Western countries, and can be attributed to the lack of major associated abnormalities, good perioperative management, and the availability of total parenteral nutrition.

The triad of seizures, hypertension, and neuroblastoma: the first described case.

The combination of seizures, hypertensive encephalopathy, and neuroblastoma has not been described before. The authors report one case, which is not only of interest in its own right, but also emphasizes the importance of including blood pressure measurement in the clinical examination of children, especially when hypertension could be the cause of the symptoms.

Morbidity in neonates of mothers who have ingested aflatoxins.

This study was undertaken to assess whether aflatoxin M(1) concentrations in newborn infants correlated with those of their mothers and to determine whether the presence of aflatoxin M(1) in cord blood was associated with an increase in morbidity in the newborn. There was a strong correlation (r =0.797, p <0.0001) between mothers' and cord blood levels of aflatoxin. There was also a strong negative correlation between aflatoxin levels and birthweight (r =-0.565, p <0.001) but there was no association between aflatoxin M(1) concentration in maternal or cord blood and rates of jaundice or infection.