Developing and validating of Ramathibodi Appendicitis Score (RAMA-AS) for diagnosis of appendicitis in suspected appendicitis patients

Background

Diagnosis of appendicitis is still clinically challenging where resources are limited. The purpose of this study was to develop and externally validate Ramathibodi Appendicitis Score (RAMA-AS) in aiding diagnosis of appendicitis.

Methods

A two-phase cross-sectional study (i.e., derivation and validation) was conducted at Ramathibodi Hospital (for derivation) and at Thammasat University Hospital and Chaiyaphum Hospital (for validation). Patients with abdominal pain and suspected of having appendicitis were enrolled. Multiple logistic regression was applied to develop a parsimonious model. Calibration and discrimination performances were assessed. In addition, our RAMA-AS was compared with Alvarado’s score performances using ROC curve analysis.

Results

The RAMA-AS consisted of three domains with seven predictors including symptoms (i.e., progression of pain, aggravation of pain, and migration of pain), signs (i.e., fever and rebound tenderness), and laboratory tests (i.e., white blood cell count (WBC) and neutrophil). The model fitted well with data, and it performed better discrimination than the Alvarado score with C-statistics of 0.842 (95% CI 0.804, 0.881) versus 0.760 (0.710, 0.810). Internal validation by bootstrap yielded Sommer’s D of 0.686 (0.608, 0.763) and C-statistics of 0.848 (0.846, 0.849). The C-statistics of two external validations were 0.853 (0.791, 0.915) and 0.813 (0.736, 0.892) with fair calibrations.

Conclusion

RAMA-AS should be a useful tool for aiding diagnosis of appendicitis with good calibration and discrimination performances.

     

Allogeneic peripheral blood stem cell transplantation in children with homozygous beta-thalassemia and severe beta-thalassemia/hemoglobin E disease

To determine the outcome of children with homozygous beta-thalassemia (beta/beta) and severe beta-thalassemia/hemoglobin E disease (beta/E) who underwent allogeneic peripheral blood stem cell transplantation (PBSCT). The authors conducted a cohort study of allogeneic PBSCT in beta/beta and beta/E patients who had 6/6 or 5/6 HLA-matched sibling donors. All patients received a conditioning regimen including busulfan and cyclophosphamide, except one who received busul-fan and cyclophosphamide plus antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and methotrexate for eight patients and cyclosporine and mycophenolate mofetil for one patient. Donors received G-CSF for 4 days before leukapheresis collections. There were five beta/beta and four beta/E patients in this study. The median age was 9 years (range 1.5-10 years). The median CD34+ cell count was 7.4 x 10(6) cells/kg recipient body weight. All patients achieved neutrophil and platelet engraftment with a median time of 15 days and 21 days respectively. Acute GVHD grade 2 to 4 appeared in four patients (grade 2, n = 3; grade 4, n = 1). Three patients developed chronic GVHD (limited, n = 2; extensive, n = 1). All patients were alive with a median follow-up time of 23 months (range 7-52 months). Neither graft failure nor graft rejection was observed. Allogeneic PBSCT is feasible for children with beta/beta and beta/E, although the incidence of GVHD was apparently high compared with bone marrow transplant study in Thais.     

CCND1 polymorphism and age of onset of hepatoblastoma

Cyclin D1, encoded by the gene CCND1, is a major regulator of the cell cycle transition from G1 phase to S phase. A CCND1 polymorphism (G to A) at codon 242, the boundary of exon 4 and intron 4, affects splicing such that exon 5 is not expressed in the A allele. Since exon 5 is involved in rapid turnover, the variant cyclin D1 corresponding to the A allele may have a longer half-life. A previous study demonstrated that in families with hereditary nonpolyposis colorectal cancer, the age of onset of colorectal cancer varied according to variation at this polymorphic site. We examined this CCND1polymorphism in a series hepatoblastoma, a childhood liver cancer that shares other molecular features with colon cancer. We determined in an analysis of 84 children with hepatoblastoma that the G/A exon 4 polymorphism in CCND1 is correlated with the age of onset of hepatoblastomas. The A/A genotype is associated with an earlier age of onset compared to the G/A or G/G genotype. The median age of patients with the G/G genotype was 22 months, compared to 17 months in patients with the G/A genotype and 11 months for the A/A genotype. These findings suggest that the CCND1 A polymorphism may contribute to tumor development in children with hepatoblastoma.     

Expression of monocyte markers in HIV-1 infected individuals with or without HIV associated dementia and normal controls in Bangkok Thailand

HIV Associated Dementia (HAD) is a complication of HIV infection in developed countries and is still poorly defined in resource-limited settings. In this study we investigated the expression of the monocyte phenotype CD14CD16HLADR and the inflammatory profiles in monocytes supernatants by surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF) mass spectrometry in a cohort of HAD and non-HAD Thai volunteers prior to the initiation of ARV. The CD14CD16HLADR phenotype was significantly increased in monocytes from HAD and non-HAD versus negative controls, but there was no difference in phenotype and in the secretion protein profiles between the two seropositive groups. In addition, monocytes supernatants from HAD and non-HAD did not induced apoptosis or cell death in brain aggregate culture. In conclusion it appears that HAD in Thai individuals has a different immunological profile then in North America cohorts.     

Immune tolerance in a haemophilia A patient with high inhibitor using locally prepared lyophilized cryoprecipitate

The immune tolerance in a 12-year-old haemophilia A patient was carried out at the Faculty of Medicine, Ramathibodi Hospital, Bangkok in 1998. His inhibitor titres ranged from 10 to 3450 Bethesda units (BU). He suffered from serious bleeding episodes requiring prolonged hospitalization and the disarticulation of the left knee joint. After obtaining informed consent, locally prepared lyophilized cryoprecipitate (LC), heat treated at 60 degrees C for 25 h, was given in a dose of 13 units kg-1 body weight of factor VIII three times per week. His inhibitor was increased from 15 to 580 BU within the first 4 weeks of immune tolerance. Finally, it was decreased to 40 BU in the 36th week. The only adverse effect was seroconversion of anti-hepatitis C virus after receiving 108 bottles of LC for 36 weeks. In conclusion, the locally prepared LC was able to control the bleeding episodes in a haemophilia A patient with high inhibitor. To our knowledge, this is the first reported case in Thailand.     

Hypercalcemia and altered biochemical bone markers in post-bone marrow transplantation osteopetrosis: a case report and literature review

Autosomal recessive osteopetrosis is a rare disorder of bone resorption defect that results in generalized sclerotic bones and bone marrow failure. Allogeneic BMT is the only treatment for cure. One of the complications following a successful BMT is hypercalcemia that is a unique complication in this group of patients. We report a three-yr-old boy with osteopetrosis who developed hypercalcemia following the successful BMT. His maximal calcium level was 13.3 mg/dL. Markedly increased both bone formation and resorption markers were demonstrated along with hypercalcemia. These findings indicated an active donor-derived osteoclastic function and thus bone resorption following the successful donor engraftment in the patient. Treatment with hyperhydration, furosemide and bone resorption inhibitors, calcitonin, and bisphosphonate led to normalization of the serum calcium level. Bone resorption but not bone formation marker was persistently elevated despite having normocalcemia during a 16.5-month follow-up period.