Comparison of Different Types of Oral Adsorbent Therapy in Patients with Chronic Kidney Disease: A Multicenter,Randomized, Phase IV Clinical Trial

PurposeOral adsorbents delay disease progression and improve uremic symptoms in patients with chronic kidney disease (CKD). DW-7202 is a newly developed oral adsorbent with high adsorptive selectivity for uremic toxins. We evaluated patient preference for and adherence to DW-7202 versus AST-120 therapy and compared treatment efficacy and safety in patients with pre-dialysis CKD.Materials and MethodsA seven-center, randomized, open-label, two-way crossover, active-controlled, phase IV clinical trial was conducted. Patients with stable CKD were randomly assigned to receive DW-7202 (capsule type) or AST-120 (granule type) for 12 weeks. The groups then switched to the other adsorbent and took it for the next 12 weeks. Patient preference was the primary outcome. Secondary outcomes included changes in estimated glomerular filtration rate (eGFR) and serum creatinine, cystatin C, and indoxyl sulfate (IS) levels.ResultsSignificantly more patients preferred DW-7202 than AST-120 (p<0.001). Patient adherence improved after switching from AST-120 to DW-7202; there was no apparent change in adherence after switching from DW-7202 to AST-120. Changes in eGFR and serum creatinine, cystatin C, and IS levels were not significantly different according to adsorbent type. There was also no significant difference in the incidences of adverse events during treatment with DW-7202 and AST-120.ConclusionDW-7202 can be considered as an alternative to AST-120 in patients who cannot tolerate or show poor adherence to granule type adsorbents. Further studies to evaluate factors affecting patient preferences and improved adherence are warranted (Clinical trial registration No. {"type":"clinical-trial","attrs":{"text":"NCT02681952","term_id":"NCT02681952"}}NCT02681952).     

Annual changes in radiographic indices of the spine in cerebral palsy patients

Purpose

We estimated the annual changes in radiographic indices of the spine in cerebral palsy (CP) patients and analyzed the factors that influence its progression rate.

Methods

We included CP patients who had undergone whole-spine radiography more than twice and were followed for at least 1 year. The scoliosis Cobb angle, coronal balance, apical vertebral translation, apical rotation, and pelvic obliquity were measured on anteroposterior (AP) radiographs; thoracic kyphosis and lumbar lordosis angles, and sagittal balance was measured on lateral radiographs; and migration percentage was measured on AP hip radiographs to determine hip instability. For each gross motor function classification system (GMFCS) level, the Cobb angles, apical vertebral translation, coronal and sagittal balance, and pelvic obliquity were adjusted by multiple factors with a linear mixed model.

Results

A total of 184 patients (774 radiographs) were included in this study. There was no significant annual change in scoliosis Cobb, thoracic kyphosis, and lumbar lordosis angles in the GMFCS level I–II and III groups. In the GMFCS level IV–V group, there was an annual increase of 3.4° in the scoliosis Cobb angle (p = 0.020). The thoracic kyphosis angle increased by 2.2° (p = 0.018) annually in the GMFCS level IV–V group. Apical vertebral translation increased by 5.4 mm (p = 0.029) annually in the GMFCS level IV–V group. Progression of coronal and sagittal balance and pelvic obliquity with aging were not statistically significant. Sex, hip instability, hip surgery, and triradiate cartilage did not affect the progression of scoliosis and the balance of the spine and pelvis.

Conclusions

The scoliosis Cobb angle, thoracic kyphosis angle, and apical vertebral translation in the GMFCS level IV–V CP patients progressed with age. These findings can predict radiographic progression of scoliosis in CP patients.

     

ACVR1 Gene Mutation in Sporadic Korean Patients with Fibrodysplasia Ossificans Progressiva

Fibrodysplasia ossificans progressiva (FOP; OMIM 135100) is a rare but extremely disabling genetic disorder of the skeletal system, and is characterized by the progressive development of ectopic ossification of skeletal muscles and subsequent joint ankylosis. The c.617G>A; p.R206H point mutation in the activin A type I receptor (ACVR1) gene has been reported to be a causative mutation of FOP. In the present study, mutation analysis of the ACVR1 gene was performed in 12 patients diagnosed or suspected to have FOP. All patients tested had a de novo heterozygous point mutation of c.617G>A; p.R206H in ACVR1. Mutation analysis confirmed a diagnosis of FOP in patients with ambiguous features, and thus, could be used for diagnostic purposes. Early confirmation through mutation analysis would allow medical professionals to advise on the avoidance of provoking events to delay catastrophic flare-ups of ectopic ossifications.     

Colposcopy in microinvasive carcinoma of the cervix—an enigma of diagnosis

Summary. Colposcopy and the complementary roles of cervical cytology and biopsy in the diagnosis of microinvasive carcinoma of the cervix were assessed in 26 patients. The cervical cytology indicated cervical intraepithelial neoplasia in 16 (62%) and invasive carcinoma in 10 (38%) patients. A correct colposcopic diagnosis of microinvasive carcinoma was made in only seven (30%) patients while 12 (46%) were diagnosed as having preinvasive carcinoma and four (15%) as having invasive carcinoma. Atypical vessels, characteristic of invasion, were found in less than a third of patients. Microinvasion, therefore, may not be evident on colposcopy alone. Multiple large biopsies under colposcopic guidance are useful with cone biopsy as a back-up.     

Deformity correction of knee and leg lengthening by Ilizarov method in hypophosphatemic rickets: outcomes and significance of serum phosphate level

The authors evaluated 14 patients with hypophosphatemic rickets who underwent correction of a knee deformity along with a leg lengthening by the Ilizarov method. Deformity correction alone was performed in 8 femora and 4 tibiae-fibulae, and concomitant deformity correction and limb lengthening (>1.0 cm) in 9 femora and 19 tibiae-fibulae. The healing index correlated with the biochemical parameters. Knee deformities were satisfactorily corrected in all patients except one. There was a statistically significant negative correlation between the healing index and the serum phosphate level: those who had a serum phosphate level higher than 2.5 mg/dL showed a relatively rapid regenerate bone healing compared with those with less than 2.5 mg/dL. The authors conclude that a serum phosphate level of 2.5 mg/dL as a cut-off point should be considered in deciding whether deformity correction alone or with a concomitant leg lengthening should be undertaken.     

Both the epitope specificity and isotype are important in the antitumor effect of monoclonal antibodies against Her-2/neu antigen

The Her-2/neu oncogene, which encodes a growth factor receptor, was implicated in the malignancy of human adenocarcinomas. Antibodies directed to this molecule have been previously shown to have an antitumor effect in vivo. In an attempt to understand the mechanisms of the antitumor activity, we generated 2 monoclonal antibodies (mAbs), HRO G1 and HRT G1, that recognize different epitopes on Her-2/neu. Both of the mAbs bound HER2/neu on the tumor surface, resulting in phosphorylation of HER2/neu. We also generated IgG2a and IgG2b mAbs from these 2 mAbs, respectively. The results of in vitro studies showed that these anti-Her-2/neu mAbs could not inhibit the growth of the tumor cells that express Her-2/neu molecules by themselves. However, in an antibody-dependent cellular cytotoxicity study using mouse splenocytes as effector cells, HRT mAbs had antitumor activities superior to those of HRO mAbs, indicating that the epitope specificity may also partake in antibody-dependent cellular cytotoxicity with antibody isotype. In a complement-dependent cytotoxicity study, the IgG2a and IgG2b mAbs showed stronger effects than IgG1 isotype mAbs irrespective of the epitope specificities. The results of in vivo studies also showed that HRT mAbs had superior antitumor activity to those of HRO mAbs. The antitumor activity was most prominent in the HRT G2b isotype among HRT mAbs. HRT G1 also showed a moderate antitumor effect, while HRT G2a showed only slight inhibition effect. These data indicate that both the epitope specificity and the differences in Fc region of mAbs could play important roles in the antitumor activities.