Behavior Problems and Cognitive Function in Pediatric Liver Transplant Recipients

BackgroundLiver transplant (LT) is a lifesaving treatment providing excellent clinical outcomes. However, data regarding behavioral and cognitive issues after LT are sparse in Asia. This study aimed to investigate behavior and cognitive problems among pediatric LT recipients.MethodsWe used the Child Behavior Checklist (CBCL) to evaluate behavior problems and/or the Wechsler Intelligence Scale for Children, Third Edition (WISC-III) to assess cognitive function. Participants were children aged 2 to 18 years who were treated with LT for at least 2 years.ResultsWe included 77 children with a median age of 7.8 years (interquartile range, 5.0-10.9). All children were evaluated with the CBCL, and 26 children were available for WISC-III assessment. Approximately one-third (34%) of the children had a total CBCL score above a clinical cutoff for significant behavior problems, and 29% of school-aged children had abnormal competence scores in a clinically significant range. Most of the evaluated children (17 of 26; 65%) had a normal full-scale intelligence quotient. Lower cognitive function was associated with having a single parent (P < .01). Higher behavior problems were associated with lower parental education level (P = .01) and correlated with longer post-transplant duration (Spearman’s rho = 0.443; P < .001).ConclusionsSignificant numbers of children have behavior problems after LT. Most children have normal cognitive function, although a larger sample size is required to confirm this result. Long-term support for cognitive and behavior problems after LT should be implemented, particularly in children with single parents and lower parental education level.     

Primary Multidrug-Resistant Mycobacterium tuberculosis in 2 Regions,Eastern Siberia,Russian Federation

Of 235 Mycobacterium tuberculosis isolates from patients who had not received tuberculosis treatment in the Irkutsk oblast and the Sakha Republic (Yakutia), eastern Siberia, 61 (26%) were multidrug resistant. A novel strain, S 256, clustered among these isolates and carried eis-related kanamycin resistance, indicating a need for locally informed diagnosis and treatment strategies.     

Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study

Nontransfusion-dependent thalassemia (NTDT) patients may develop iron overload and its associated complications despite receiving only occasional or no transfusions. The present 1-year, randomized, double-blind, placebo-controlled THALASSA (Assessment of Exjade in Nontransfusion-Dependent Thalassemia) trial assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients. A total of 166 patients were randomized in a 2:1:2:1 ratio to starting doses of 5 or 10 mg/kg/d of deferasirox or placebo. The means ± SD of the actual deferasirox doses received over the duration of the study in the 5 and 10 mg/kg/d starting dose cohorts were 5.7 ± 1.4 and 11.5 ± 2.9 mg/kg/d, respectively. At 1 year, the liver iron concentration (LIC) decreased significantly compared with placebo (least-squares mean [LSM] ± SEM, -2.33 ± 0.7 mg Fe/g dry weight [dw], P = .001, and -4.18 ± 0.69 mg Fe/g dw, P < .001) for the 5 and 10 mg/kg/d deferasirox groups, respectively (baseline values [means ± SD], 13.11 ± 7.29 and 14.56 ± 7.92 mg Fe/g dw, respectively). Similarly, serum ferritin decreased significantly compared with placebo by LSM -235 and -337 ng/mL for the deferasirox 5 and 10 mg/kg/d groups, respectively (P < .001). In the placebo patients, LIC and serum ferritin increased from baseline by 0.38 mg Fe/g dw and 115 ng/mL (LSM), respectively. The most common drug-related adverse events were nausea (n = 11; 6.6%), rash (n = 8; 4.8%), and diarrhea (n = 6; 3.6%). This is the first randomized study showing that iron chelation with deferasirox significantly reduces iron overload in NTDT patients with a frequency of overall adverse events similar to placebo.     

Surveillance of subtype and genetic variation of the circulating strains of HIV-1 in Thailand

Two HIV-1 strains, CRF01_AE and subtype B', were reported in Thailand during the early years of the epidemic. Recently, an intersubtype recombination of HIV-1 strain was found in Thailand. Eight-hundred and twenty-eight samples collected during years 1995-2004 from high-risk groups in Bangkok, northern, northeastern, and southern region of Thailand were studied. HIV-1 env nucleotide sequences were used for phylogenetic analysis of the circulating HIV-1 strain. By single HIV-1 region (env) genotyping, CRFO1_AE was found in 97.3% and HIV-1 subtype B was found in 2.7%. A predominance of CRF01_AE was found in all geographic regions. Parallel analysis of the HIV-1 gag and env genes demonstrated that 2.1% and 4.0% of recombinant HIV-1 strains were found using p17 and p24 region sequences, respectively. The recombinant gag gene was also found in one southern isolate. Phylogenetic analysis of HIV-1 isolated from 20 provinces in 2002 suggested the northern and northeastern isolates were more related than the southern isolates which had the lowest genetic diversity of 0.13. The GPGQ V3 loop tip was also present in isolates from all regions. The molecular epidemiological data from this study may be useful for surveillance design as well as targeting prevention efforts. It also provides information regarding new antigenic regions of circulating strains responsible for the HIV-1 epidemic in Thailand.     

Relationship between hypercoagulable state and erythrocyte phosphatidylserine exposure in splenectomized haemoglobin E/beta-thalassaemic patients

Small pulmonary arterial thromboses can occur following splenectomy of patients with haemoglobin E/beta-thalassaemia (Hb E/beta-thal). We compared plasma markers of coagulation activation in vivo and red blood cell (RBC) markers of procoagulant activity in 15 Hb E/beta-thal patients who were not splenectomized (NS), 15 who had been splenectomized (S), and 15 normal controls (NC). Levels of plasma thrombin-antithrombin III complex (TAT) were significantly higher in the S group than in either the NS or the NC groups, and levels of prothrombin fragment 1.2 (F 1.2) were significantly higher in the S than in the NC group. Diluted Russell's viper venom clotting times were significantly shorter when RBCs from group S patients were added to the assay compared with RBCs from the NC group. Phosphatidylserine (PS) expression (% of annexin V-positive RBCs) on the outer leaflet of RBC membrane of both 'larger'- and 'smaller'-sized RBCs was significantly higher for the S than the NC group. The RBC PS expression of the S and the NS groups, respectively, accounted for 25 x 3% (P = 0 x 174) and 6.3% (P = 0 x 675) of the variation in plasma TAT levels. Our findings indicated that, when compared with NC, splenectomized patients with Hb E/beta-thal were in a chronic low-grade hypercoagulable state associated with increased numbers of circulating PS exposed RBCs. This condition may have a role in the risk of these patients for pulmonary arterial thromboses.     

Correction of hypercoagulability and amelioration of pulmonary arterial hypertension by chronic blood transfusion in an asplenic hemoglobin E/beta-thalassemia patient

Chronic transfusion of packed red blood cells, in addition to other ongoing treatment with warfarin, acetyl salicylic acid, desferrioxamine, and other supportive measures, was given to a splenectomized hemoglobin E/beta-thalassemia woman with pulmonary arterial hypertension (PHT). Serial measurements of plasma thrombin-antithrombin III complex (TAT) levels and right-sided cardiac catheterization were used to monitor changes after treatment. Reduction of plasma TAT levels from 7.5 to 3.8 microg/L (normal, 3 +/- 2.4 microg/L), pulmonary vascular resistance (PVR) from 553.8 to 238.6 dyne.sec.cm(-5) (normal, 67 +/- 30 dyne.sec.cm(-5)), and mean pulmonary arterial pressure from 51 to 32 mm Hg (normal, 9 to 19 mm Hg) occurred in tandem. Normalization of blood hypercoagulability as reflected in plasma TAT level by chronic blood transfusion was the likely basis for improvement of increased PVR, being secondary to thrombotic pulmonary arteriopathy and subsequently PHT.     

A randomized,double-blind study of two combined oral contraceptives containing the same progestogen,but different estrogens

An investigation correlating scanning electron microscopic observations with sperm penetration tests carried out on cervical mucus under the influence of low-dose continuous progestogen (Norgestrienone) is presented. The results demonstrate that such type of contraceptive is involved in drastic alterations of mid-cycle cervical mucus at the macromolecular level. The meshwork which constitutes the infrastructure of the cervical secretion appears to be greatly tightened as a result of the treatment, thus giving the woof a general appearance typical of cervical mucus in the late luteal phase. The immobilizing effect of such modified mucus on spermatozoa is demonstrated and the duration of effectiveness after the administration of a last pill on the morning of day 13 is determined.     

Plasma drug activity assay for treatment optimization in tuberculosis patients

Low antituberculosis (TB) drug levels are common, but their clinical significance remains unclear, and methods of measurement are resource intensive. Subjects initiating treatment for sputum smear-positive pulmonary TB were enrolled from Kibong'oto National TB Hospital, Tanzania, and levels of isoniazid, rifampin, ethambutol, and pyrazinamide were measured at the time of typical peak plasma concentration (C(2 h)). To evaluate the significance of the effect of observed drug levels on Mycobacterium tuberculosis growth, a plasma TB drug activity (TDA) assay was developed using the Bactec MGIT system. Time to detection of plasma-cocultured M. tuberculosis versus time to detection of control growth was defined as a TDA ratio. TDA assays were later performed using the subject's own M. tuberculosis isolate and C(2 h) plasma from the Tanzanian cohort and compared to drug levels and clinical outcomes. Sixteen subjects with a mean age of 37.8 years ± 10.7 were enrolled. Fourteen (88%) had C(2 h) rifampin levels and 11 (69%) had isoniazid levels below 90% of the lower limit of the expected range. Plasma spiked with various concentrations of antituberculosis medications found TDA assay results to be unaffected by ethambutol or pyrazinamide. Yet with a range of isoniazid and rifampin concentrations, TDA exhibited a statistically significant correlation with drug level and drug MIC, and a TDA of ~1.0 indicated the presence of multidrug-resistant TB. In Tanzania, low (≤ 2.0) TDA was significantly associated with both lower isoniazid and rifampin C(2 h) levels, and very low (≤ 1.5) TDA corresponded to a trend toward lack of cure. Study of TDA compared to additional clinical outcomes and as a therapeutic management tool is warranted.     

Inflammatory bowel disease in Thai children: presentations and outcomes of treatment

Inflammatory bowel disease (IBD) is characterized by idiopathic chronic intestinal inflammation, due to abnormalities in gastrointestinal immunoregulation. Pediatric IBD has been rarely reported in Thailand. We describe eight children, five girls and three boys, who were diagnosed with IBD at Ramathibodi Hospital during 1999-2005 and had a follow-up of more than one year. Four cases had Crohn's disease (CD) and four cases had ulcerative colitis (UC). The ages at diagnosis ranged from 3.5 to 15.5 years. Diagnosis of IBD was delayed for more than 12 months in five patients. Five out of eight patients had early onset of disease, before 6 years of age. The manifestations included chronic diarrhea, abdominal pain, rectal bleeding and perianal lesions. The common extraintestinal manifestations were oral ulcer, anemia, weight loss and failure to thrive. Most patients had moderate to severe diseases and ileocolic fistula developed in one patient with CD. The disease was controlled with 5-aminosalicylic acid and corticosteroid in most patients. Four patients required additional therapy with azathioprine. Infliximab was used in two patients who were chronically steroid-dependent CD, one also had persistent ileocolic fistula and both patients responded well. During the follow-up period ranging from 1.1 to 5.8 years, three patients remained growth retardation; all had early onset of disease before 6 years of age, long duration of symptoms of more than 3 years before diagnosis and had multiple relapses. It is concluded that there is an increasing number of IBD in Thai children during the recent years. Most patients had moderate to severe diseases. Early onset of disease, delay in diagnosis and treatment are responsible for more complications, particularly persistent growth impairment. Early recognition of IBD and treatment are essential for a satisfactory long-term outcome.     

Diarrhea in pediatric recipients of solid organ or bone marrow transplants

Diarrhea is common in adults after solid organ transplantation (SOT) and bone marrow transplantation (BMT), but data in children are limited. Therefore, we aimed to determine the incidence and etiology of pediatric early-onset diarrhea in post SOT and BMT.We reviewed children aged 6 months to 18 years who underwent liver transplantation, kidney transplantation or BMT between January 2015 and December 2019 with duration of diarrhea > 72 hours within the first 6 months after transplantation. Clinical data and diarrheal course were collected. Regression analyses were performed to define factors associated with the interested outcomes.Among 252 transplanted patients, 168 patients (66.6%) had 289 documented episodes of diarrhea. A diagnosis of 68.2% of post-transplant diarrhea remained ‘indefinite’. Enteric infection in SOT and gastrointestinal acute graft-versus-host disease (GI-aGVHD) in BMT were the commonly identified etiologies. Among 182 episodes among BMT children, skin rash was more pronounced when compared the ones with diarrhea > 7 days vs ≤ 7 days (odds ratio [OR] 13.9; 95% CI 1.8, 107.6). Males were more likely to develop GI-aGVHD as compared to females (OR 8.9). We found that GI-aGVHD was more common in the ones with skin rash and the presence of white blood cells in stool examination (OR 8.4 and 3.1, respectively). Deaths occurred in 7.7%.Two-thirds of post-transplant children experienced at least one episode of early-onset diarrhea, of which the etiology mainly remains undefined. Various clinical factors of prolonged/chronic diarrhea and GI-aGVHD may help clinicians when managing these children.