Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: a randomized phase-2 trial.

BACKGROUND: The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. METHODS: The present phase-2, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevated serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. RESULTS: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in the proportion of courses with increased serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465) nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than that in group A. No adverse events related to magnesium administration were observed. CONCLUSIONS: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients. TRIAL REGISTRATION: JRCT ( https://jrct.niph.go.jp/ ) Identifier UMIN000029215 jRCTs031180251. UMIN-CTR ( http://www.umin.ac.jp/icdr/index.html ) Identifier UMIN000029215.

Analgesic efficacy of continuous wound infiltration compared with continuous intravenous fentanyl after gynaecological surgery: a non-inferiority, randomised controlled trial.

OBJECTIVE: The present trial aimed to prove the non-inferiority of the analgesic efficacy of continuous wound infiltration (CWI) to that of continuous intravenous fentanyl (IV) and to compare the safety of the two methods. METHODS: This trial was a prospective, single-centre, two-arm, non-inferiority, randomised controlled trial. Patients participating in the trial were randomised to a CWI group or an IV group. The VAS (visual analogue scale), additional analgesic usage and side effects were then compared between the groups. RESULTS: In total, 61 patients were enrolled; two in CWI were excluded, leaving 59 (30 in the CWI group and 29 in the IV group) for analysis. The difference in the VAS score at 24 h (CWI group - IV group) was -3.2 (95% confidence interval [CI] -14.7 to 8.2), which was less than the non-inferiority margin of 15. The mean amount of total fentanyl use at postoperative hour 48 was 1395 (95% CI 886-1903) µg in the CWI group and 3186 (95% CI 2716-3658) µg in the IV group. The amount of other analgesics and the incidence of adverse effects did not differ significantly between the groups. CONCLUSION: CWI was non-inferior to IV in terms of its analgesic effect, and has an opioid sparing effect in open gynaecological surgery.

Epidemiology of biopsy-proven Henoch-Schönlein purpura nephritis in children: A nationwide survey in Japan.

BACKGROUND: Little is known about the epidemiology of Henoch-Schönlein purpura nephritis (HSPN). METHODS: We conducted a nationwide epidemiological survey of Japanese children aged 1 to 15 years with HSPN. Children who were newly diagnosed with HSPN by biopsy between January 2013 and December 2015 were eligible for the survey to clarify the incidence of HSPN. We also conducted an institutional survey on kidney biopsy criteria and treatment protocols. RESULTS: A total of 353 of 412 institutions (85.7%) responded to the questionnaire. Of the 353 institutions, 174 reported to perform kidney biopsies at their institutions, and 563 children were diagnosed with HSPN. Considering the collection rate, the estimated incidence of biopsy-proven HSPN was 1.32 cases/100,000 children per year. The median age at biopsy was 7.0 years, and the male-to-female ratio was 1.2:1. The kidney biopsy criteria and treatment protocols for HSPN were as follows. Patients with acute kidney injury underwent biopsy at least one month after onset. For patients without kidney dysfunction, the timing for biopsy was determined by the amount of proteinuria. Regarding the treatment of HSPN, there were certain commonalities among the treatment protocols, they eventually differed depending on the institutions involved. CONCLUSIONS: The incidence of biopsy-proven HSPN was 1.32 cases/100,000 children per year in Japan. The male-to-female ratio and date of diagnosis of HSPN were similar to those in previous studies. The kidney biopsy criteria and treatment protocols for HSPN varied among institutions. Further studies are warranted to establish an optimal treatment policy based on the prognosis.

Perinatal factors contributing to chronic kidney disease in a cohort of Japanese children with very low birth weight.

BACKGROUND: Developmental programming of chronic kidney disease (CKD) in young adults is linked to preterm birth and intrauterine growth restriction (IUGR). Which confers a higher risk of progression to chronic kidney damage in children with very low birth weight (VLBW; born weighing < 1500 g): prematurity or IUGR? METHODS: This is a national historical cohort study of children with VLBW cared for in perinatal medical centers in Japan. Predictive factors included three latent variables (prematurity, IUGR, stress during neonatal period) and eight observed variables (gestational age, birth weight Z-score, maternal age, duration of treatment with antibiotics and diuretics, maternal smoking, late-onset circulatory collapse, kidney dysfunction) during the perinatal period. The primary endpoint was estimated glomerular filtration rate (eGFR) at age ≥ 3 years. A structural equation model was used to examine the pathologic constitution. RESULTS: The 446 children with VLBW included 253 boys and 193 girls, of mean age 5.8 ± 2.6 years and mean eGFR 111.7 ml/min/1.73 m2 at last encounter. Pathway analyses showed intrauterine malnutrition (ß = 0.85) contributed more to chronic kidney damage than stress during the neonatal period (ß = - 0.19) and prematurity (ß = 0.12), and kidney dysfunction and late-onset circulatory collapse were important observed variables in stress during the neonatal period. CONCLUSIONS: IUGR was more harmful to future kidneys of VLBW neonates. Neonatal kidney dysfunction and late-onset circulatory collapse were important risk factors for subsequent CKD development. This emphasizes the need for obstetricians to monitor for fetal growth restriction and neonatologists to minimize neonatal stress to prevent CKD in later life.

A cross-sectional nationwide survey of congenital and infantile nephrotic syndrome in Japan.

BACKGROUND: Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) cause substantial morbidity and mortality. In Japan, there is a lack of knowledge regarding the characteristics of CNS and INS. This study aimed to clarify the characteristics of CNS and INS in Japan. METHODS: This cross-sectional nationwide survey obtained data from 44 institutions in Japan managing 92 patients with CNS or INS, by means of two survey questionnaires sent by postal mail. Patients aged < 16 years by 1 April 2015, with a diagnosis of CNS or INS, were included in this study. The primary outcome was end-stage kidney disease. RESULTS: A total of 83 patients with CNS or INS were analyzed. The most frequent disease type was non-Finnish (60.2%); 33 patients (39.8%) had Finnish type. Among those with non-Finnish-type disease, 26 had no syndrome and 24 had a syndrome, of which the most frequent was Denys-Drash syndrome (70.8%). Patients with non-Finnish-type disease with syndrome showed the earliest progression to end-stage kidney disease compared with the other two groups, whereas patients with non-Finnish-type disease without syndrome progressed more slowly compared with the other two groups. In the Finnish-type group, the disease was diagnosed the earliest; a large placenta was reported more frequently; genetic testing was more frequently performed (93.8%); mental retardation was the most frequent extra-renal symptom (21.2%); and thrombosis and infection were more frequent compared with the other groups. Patients with non-Finnish-type disease with syndrome had a higher frequency of positive extra-renal symptoms (79.2%), the most common being urogenital symptoms (54.2%). Treatment with steroids and immunosuppressants was more frequent among patients with non-Finnish-type disease without syndrome. Two patients with non-Finnish-type disease without syndrome achieved complete remission. In all groups, unilateral nephrectomy was performed more often than bilateral nephrectomy and peritoneal dialysis was the most common renal replacement therapy. CONCLUSIONS: The present epidemiological survey sheds light on the characteristics of children with CNS and INS in Japan. A high proportion of patients underwent genetic examination, and patient management was in accord with current treatment recommendations and practices. TRIAL REGISTRATION: Not applicable.

Factors affecting enrollment in randomized controlled trials conducted for patients with metastatic breast cancer.

BACKGROUND: It is critical to obtain informed consent from eligible patients to complete clinical trials. We investigated the factors that affect the participation rates of eligible patients. PATIENTS AND METHODS: Patients with metastatic breast cancer who were eligible for SELECT BC or SELECT BC-CONFIRM trials, randomized controlled trials conducted for patients with chemotherapy-naive metastatic breast cancer were recruited to prospective studies, SELECT BC-FEEL and SELECT BC-FEEL II, respectively. SELECT BC FEEL and SELECT BC-FEEL II were conducted to identify the factors affecting the rates at which informed consent was obtained, using a self-administered questionnaire we developed. RESULTS: In total, 232 patients participated in the studies. The patients who agreed to take part in the randomized trials were more likely than the refusers to answer that they decided to participate because: 'My doctor wanted me to participate in this trial' (P = 0.00000), ' My family or friends wanted me to participate in this trial' (P = 0.00000), 'Both treatment regimens used in the trial are suitable to me' (P = 0.00383), 'I know that the trial is conducted to determine which is a better treatment' (P = 0.01196), and ' I think that my participation in the trial will contribute to the benefit to future patients with the same disease' (P = 0.00756). CONCLUSIONS: To enhance the consent rate in randomized trials of metastatic breast cancer patients, concepts of the trials must be considered important and acceptable not only by patients but also by doctors and their families.

Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: A protocol for a randomized phase 2 trial.

Although cisplatin is one of the most effective agents against various pediatric cancers, it is sometimes difficult to manage due to its dose-limiting nephrotoxicity. Magnesium sulfate (Mg) showed a kidney-protective effect against cisplatin-induced nephrotoxicity (CIN) by regulating renal platinum accumulation both in vitro and in vivo, and the body of clinical data demonstrating the efficacy of this drug in adult cancer patients is increasing.In this open, multicenter, phase-2, randomized trial, patients under age 18 years who are scheduled to receive cisplatin-containing chemotherapy will be enrolled and randomly allocated either to an Mg supplementation arm in even-numbered chemotherapy courses (arm AB) or to another arm in odd-numbered courses (arm BA), with a 1:1 allocation. Analysis objects will be reconstructed into two groups depending on whether the chemotherapy course has Mg supplementation (group B) or not (group A). The primary endpoint is the proportion of chemotherapy courses resulting in elevated serum creatinine equal to or greater than 50% of the prechemotherapy value. For the secondary endpoints, various parameters for measuring kidney function, such as serum cystatin-C, B2M, L-FABP, NGAL, and urinary NAG in the two groups will be compared. A sample size based on alpha = 5% and 80% power requires at least 40 samples per group (ideally, 60 samples per group).If Mg demonstrates efficacy, a phase-3 study to confirm the prophylactic effect of Mg supplementation in both acute and chronic CIN will be developed using novel and better biomarkers. TRIAL REGISTRATION: UMIN-CTR (http://www.umin.ac.jp/icdr/index.html) Identifier UMIN000029215.

The North Wind and the Sun: Pediatric Antimicrobial Stewardship Program Combining Restrictive and Persuasive Approaches in Hematology-Oncology Ward and Hematopoietic Stem Cell Transplant Unit.

BACKGROUND: The Japanese government's goal for the reduction of antimicrobial consumption is two-thirds of the 2013 rate by 2020. While the antimicrobial stewardship programs (ASPs) are essential in health care facilities, ASP data on pediatric hematology-oncology and hematopoietic stem cell transplant (HSCT) patients are limited. Our aim was to evaluate the impact of restrictive and persuasive ASP on immunocompromised children. METHODS: The ASP for hematology-oncology and HSCT patients at Tokyo Metropolitan Children's Medical Center was assessed. Phase 1 was a postprescriptive review of carbapenem conducted between April 2010 and September 2011. Phase 2 consisted of the preauthorization of carbapenem, prospective audit with feedback, a weekly luncheon meeting among physicians, consensus on febrile neutropenia management, and implementation of viral molecular diagnostics between October 2011 and September 2015. Both phases were compared for day-of-therapy per 1,000 patient-days, cost of intravenous antimicrobial agents, average hospitalization duration, all-cause mortality, infection-related mortality at 30 days, and appropriateness of empirical treatment of bacteremia. RESULTS: The ASP did not differ from phase 1 to phase 2 in terms of average hospitalization length, mortality rate, or appropriateness of empirical treatment for bacteremia. Day-of-therapies of cefepime, piperacillin/tazobactam, meropenem, vancomycin, liposomal amphotericin B, and fosfluconazole decreased by 20%, 45%, 57%, 38%, 85% and 44%, respectively (P < 0.05). The total cost of antibiotic and antifungal agents decreased by 27%, for a savings of $59,905 USD annually. CONCLUSION: Restrictive and persuasive ASP in the hematology-oncology ward and the HSCT unit safely decreased the use of antibacterial and antifungal agents.

Randomized Comparison of Subcuticular Sutures Versus Staples for Skin Closure After Open Abdominal Surgery: a Multicenter Open-Label Randomized Controlled Trial.

BACKGROUND: The incisional surgical site infection (SSI) is an extremely common complication following open abdominal surgery and imposes a considerable treatment and cost burden. METHOD: We conducted a multicenter open-label randomized controlled trial at three Tokyo Metropolitan medical institutions. We enrolled adult patients who underwent either an elective or an emergency open laparotomy. Eligible patients were allocated preoperatively to undergo wound closure with either subcuticular sutures or staples. A central Web-based randomization tool was used to assign participants randomly by a permuted block sequence with a 1:1 allocation ratio and a block size of 4 before mass closure to each group. The primary endpoint was the occurrence of a superficial SSI within 30 days after surgery in accordance with the Centers for Disease Control and Prevention criteria. This trial was registered with UMIN-CTR as UMIN 000004836 ( http://www.umin.ac.jp/ctr ). RESULTS: Between September 1, 2010 and August 31, 2015, 401 patients were enrolled and randomly assigned to either group. One hundred and ninety-nine patients were allocated to the subcuticular suture and 202 patients to the staple groups (hereafter the "suture" and "staple" group, respectively). Three hundred and ninety-nine were eligible for the primary endpoint. Superficial SSIs occurred in 25 of 198 suture patients and in 27 of 201 staple patients. Overall, the rate of superficial SSIs did not differ significantly between the suture and staple groups. CONCLUSION: Subcuticular sutures did not increase the occurrence of superficial SSIs following open laparotomies mainly consisting of clean-contaminated surgical procedures. The applicability of the wound closure material and method is likely to depend on individual circumstances of the patient and surgical procedure.

Assessment of kidney function in children by enzymatic determination of 2- or 24-h creatinine clearance: comparison with inulin clearance.

BACKGROUND: Although renal inulin clearance (Cin) is the gold standard for evaluation of kidney function, it cannot be measured easily. Therefore, creatinine clearance (Ccr) is often used clinically to evaluate kidney function. Enzymatically measured Ccr was recently found to be much higher than Cin because of the tubular secretion of creatinine (Cr). This study compared three measures of renal clearance, inulin, 2-h Ccr, and 24-h Ccr, in children. METHODS: Kidney function was evaluated in 76 children (51 males and 25 females) aged 1 month to 18 years with chronic kidney disease (CKD) by three renal clearance methods at almost the same time. RESULTS: Correlations between each pair of three renal clearance measurements were determined. Approximate glomerular filtration rate (GFR) was equal to 62 % of 2-h Ccr or 76 % of 24-h Ccr. CONCLUSION: Cr secretion by renal tubules was approximately 50 % of the GFR. In this study, we indicate that the measurements of 2-h Ccr or 24-h Ccr do not show true GFR but we could infer approximate GFR from the values. The use of 2- or 24-h Ccr might contribute to the treatment of pediatric CKD patients.

Reference glomerular filtration rate levels in Japanese children: using the creatinine and cystatin C based estimated glomerular filtration rate.

BACKGROUND: The present study was performed to determine the reference values of glomerular filtration rate (GFR) in children by age using the new eGFR equations derived from serum creatinine (Cr) and cystatine C (cysC). METHODS: A total of 1137 children (509 males and 628 females) between the ages of 3 months and 16 years presenting at our facilities between 2008 and 2009 without diseases affecting the renal function were included in this study as in our previous reports for reference values of serum Cr and cysC. We calculated eGFR with the Cr based equation in children aged 2-16 years, and with the cysC based equation in those aged 3-23 months, and determined the reference values of GFR in Japanese children by each age group. RESULTS: We reviewed the median, 2.5 and 97.5 percentile of GFR reference value in each age group. The medians of reference GFRs are 91.7, 98.5, 106.3, and 113.1 mL/min/1.73 m(2) in children aged 3-5, 6-11, 12-17, and 18 months-16 years, respectively. CONCLUSION: We determined the normal reference values of GFR in children. It is important for pediatricians who examine pediatric chronic kidney disease patients to know the values of normal renal function.

Attitudes toward cervical cancer screening among women receiving human papillomavirus vaccination in a university-hospital-based community: interim 2-year follow-up results.

AIM: This study investigated the status of cervical cancer screening among women in a university hospital-based community who received catch-up human papillomavirus (HPV) vaccinations as a basic element of our community-based cervical cancer prevention advocacy. METHODS: Self-administered questionnaires were distributed to 173 women working or studying in the community at their first HPV vaccination in 2010, at the third vaccination, and 2 years later. Their demographics and attitudes toward the Pap test were analyzed. RESULTS: The median age of the participants was 27.5 years and 88.2% were sexually active. Before the first vaccination, 38.5% (57/148) of the screening targets had never had a Pap test. Among the women who completed the third vaccination, Pap test experiences within the recent 2 years increased from 45.3% (63/139) at the first vaccination to 71.2% (99/137) at the third vaccination, and 67.5% (54/80) 2 years later. In 45.3% of the screening targets who had never had a Pap test at the time of their first HPV vaccination, their first Pap test was followed by their vaccination. CONCLUSIONS: Having biennial Pap tests in accordance with the Japanese national cancer screening guideline was shown to be difficult even for the women in the medical community; however, education about the Pap test and the efficacy of HPV vaccination in providing opportunistic screening encouraged them to have their first or suspended Pap test. Our interim data suggest the need for urgently changing the cervical cancer prevention strategy for young adult women who are excluded from the national HPV vaccine program.

Cystatin C-based equation for estimating glomerular filtration rate in Japanese children and adolescents.

BACKGROUND: Renal inulin clearance is the gold standard for evaluation of kidney function, but is compromised by problems of collecting urine samples in children, especially those <6 years or with a bladder dysfunction. Therefore, we should utilize the serum cystatin C (cysC)-based estimated glomerular filtration rate (eGFR) for measuring serum cysC. The purpose of the present study is to determine the applicability of the new serum cysC-based eGFR in Japanese children and adolescents, including infants with chronic kidney disease (CKD), for evaluation of renal function. METHODS: Inulin clearance and standardized serum cysC level determined by the colloidal gold immunoassay were measured in 135 pediatric CKD patients between the ages of 1 month and 18 years with no underlying disease that affects renal function except CKD, to determine serum cysC-based eGFR in Japanese children and adolescents. RESULTS: We showed the inulin clearance by expression of 1/serum cysC in pediatric CKD patients, which resulted in the equation: inulin GFR (mL/min/1.73 m(2)) = 104.1 × 1/serum cysC (mg/L) - 7.80. We also validated the cysC-based eGFR formula for Japanese adults. eGFR values obtained with the adult formula significantly underestimated GFR by approximately 8 % in children with CKD. CONCLUSION: We determined the new cysC-based eGFR formula is useful for clinical screening of renal function in Japanese children and adolescents, including infants.

Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy.

High-dose methotrexate therapy (HD-MTX) has been well established for the treatment of childhood acute lymphoblastic leukemia (ALL). The aims of this study were to investigate whether clinical and pharmacogenetic factors influence plasma MTX concentration and renal dysfunction in patients treated with HD-MTX. In a total of 127 courses of HD-MTX in 51 patients with childhood ALL, influence of clinical and pharmacogenetic factors on plasma MTX concentration and HD-MTX-related renal dysfunction was evaluated. Clinical factors included age, gender, duration of HD-MTX continuous-infusion and duration of pre-hydration before HD-MTX. Pharmacogenetic factors included 5 gene polymorphisms within the MTX pathway genes, namely, SLC19A1, MTHFR, ABCC2 and ABCG2. Short duration of pre-hydration before HD-MTX is the most important risk factor for prolonged high MTX concentration (p < 0.001, OR 6.40, 95 % CI 2.39-17.16) and renal dysfunction (p = 0.013, OR 3.15, 95 % CI 1.27-7.80). The T allele at MTHFR C677T was the risk factor for prolonged high MTX concentration (p = 0.009, OR 5.54, 95 % CI 1.54-19.85), but not for renal dysfunction. We found the influence of MTHFR C677T polymorphism on prolonged high MTX concentration. We reconfirmed the importance of adequate pre-hydration before HD-MTX to prevent prolonged high MTX concentration and MTX-related renal dysfunction.

Analysis of gender differences in genetic risk: association of TNFAIP3 polymorphism with male childhood-onset systemic lupus erythematosus in the Japanese population.

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic multisystem autoimmune disorder influenced by genetic background and environmental factors. Our aim here was to replicate findings of associations between 7 of the implicated single nucleotide polymorphisms (SNPs) in IRF5, BLK, STAT4, TNFAIP3, SPP1, TNIP1 and ETS1 genes with susceptibility to childhood-onset SLE in the Japanese population. In particular, we focused on gender differences in allelic frequencies. METHODOLOGY/PRINCIPAL FINDINGS: The 7 SNPs were genotyped using TaqMan assays in 75 patients with childhood-onset SLE and in 190 healthy controls. The relationship between the cumulative number of risk alleles and SLE manifestations was explored in childhood-onset SLE. Logistic regression was used to test the effect of each polymorphism on susceptibility to SLE, and Wilcoxon rank sum testing was used for comparison of total risk alleles. Data on rs7574865 in the STAT4 gene and rs9138 in SPP1 were replicated for associations with SLE when comparing cases and controls (corrected P values ranging from 0.0043 to 0.027). The rs2230926 allele of TNFAIP3 was associated with susceptibility to SLE in males, but after Bonferroni correction there were no significant associations with any of the other four SNPs in IRF5, BLK, TNIP1 and ETS1 genes. The cumulative number of risk alleles was significantly increased in childhood-onset SLE relative to healthy controls (P = 0.0000041). Male SLE patients had a slightly but significantly higher frequency of the TNFAIP3 (rs2230926G) risk allele than female patients (odds ratio [OR] = 4.05, 95% confidence interval [95%CI] = 1.46-11.2 P<0.05). CONCLUSIONS: Associations of polymorphisms in STAT4 and SPP1 with childhood-onset SLE were confirmed in a Japanese population. Although these are preliminary results for a limited number of cases, TNFAIP3 rs2230926G may be an important predictor of disease onset in males. We also replicated findings that the cumulative number of risk alleles was significantly increased in childhood-onset SLE.

Efficacy of fusion imaging combining sonography and hepatobiliary phase MRI with Gd-EOB-DTPA to detect small hepatocellular carcinoma.

OBJECTIVE: We evaluated the efficacy of fusion imaging that fuses conventional sonography images with hepatobiliary phase contrast-enhanced MR images obtained with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) as the reference image for the detection of hepatocellular carcinomas (HCCs). SUBJECTS AND METHODS: Eighty-seven HCCs with a maximum diameter of between 1 and 3 cm at the time of diagnosis were enrolled in this prospective study. We compared the detection rates of HCCs using three sonography modalities: conventional sonography, late phase of contrast-enhanced sonography with Sonazoid, and fusion imaging combining conventional sonography and the hepatobiliary phase of contrast-enhanced MRI with Gd-EOB-DTPA as the reference image. The comparisons were made using the McNemar test. RESULTS: The detection rate of HCCs using fusion imaging (98%, 85/87) was significantly higher than the detection rates using conventional sonography (76%, 66/87) and contrast-enhanced sonography (83%, 72/87) (p<0.01, for both). For small HCCs (maximum diameter, 1-2 cm), the detection rate using fusion imaging (97%, 59/61) was also significantly higher than those using conventional sonography (66%, 40/61) and contrast-enhanced sonography (80%, 49/61) (p<0.01, for both). The detection rate for atypical HCCs was also significantly higher using fusion imaging (95%, 18/19) than using conventional sonography (53%, 10/19) and contrast-enhanced sonography (26%, 5/19) (p<0.01, for both). CONCLUSION: Fusion imaging combining conventional sonography and the hepatobiliary phase of contrast-enhanced MRI with Gd-EOB-DTPA is more sensitive than conventional sonography or contrast-enhanced sonography for detecting HCCs, especially small or atypical HCCs.

Association of IRF5 polymorphisms with susceptibility to hemophagocytic lymphohistiocytosis in children.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome and has a varied genetic background. The polymorphism of interferon regulatory factor 5 gene (IRF5) was reported to be associated with susceptibility to macrophage activation syndrome. IRF5 acts as a master transcription factor in the activation of pro-inflammatory cytokines. We assessed associations of IRF5 gene polymorphisms with susceptibility to secondary HLH. METHODS: Three IRF5 single nucleotide polymorphisms (rs729302, rs2004640, and rs2280714) were genotyped using TaqMan assays in 82 secondary HLH patients and 188 control subjects. RESULTS: There was a significant association of the GT/TT genotype at rs2004640 with secondary HLH susceptibility (p < 0.01). The IRF5 haplotype (rs729302 A, rs2004640 T, and rs2280714 T) was associated with secondary HLH susceptibility (p < 0.01). CONCLUSIONS: These findings indicate that IRF5 is a genetic factor influencing the susceptibility to secondary HLH and that the IRF5-associated immune response contributes to the pathogenesis of HLH.

New clinical diagnostic criteria for eosinophilic chronic rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis is a heterogeneous disease. Most cases of chronic rhinosinusitis with nasal polyp(s) (CRSwNP) in Western countries show a strong tendency for recurrence after surgery and pronounced eosinophil infiltration in the nasal polyps. The prevalence of CRSwNP with pronounced eosinophilic inflammation is steadily increasing and is classified as eosinophilic chronic rhinosinusitis (ECRS) in Japan. However, less than 50% of CRSwNP patients in Japan and East Asia show such features. Since the treatment strategy of ECRS differs from that of non-ECRS, clinical diagnostic criteria that distinguish ECRS from non-ECRS are needed. METHODS: A total of 124 patients with CRSwNP patients who underwent endonasal sinus surgery were classified as ECRS or non-ECRS according to their clinical characteristics and the clinical features of the two groups were compared. Computed tomography (CT) images of the sinuses were graded according to the Lund-Mackay system. We also graded CT images of the olfactory cleft. Blood examination findings, sinus CT images and asthma complications were analyzed by multivariate logistic regression. Clinical findings that were significantly different between ECRS and non-ECRS were analyzed by receiver operating characteristic curves to determine optimal predictors of ECRS. RESULTS: Blood eosinophilia, asthma complications and CT image scores were significantly different between ECRS and non-ECRS. In particular, increased blood eosinophil percentage and CT image scores for the posterior ethmoid and the olfactory cleft showed good accuracy as predictors of ECRS. A combination of the cut-off values for three predictors (increased blood eosinophil percentage above the normal range, olfactory cleft score ≥1 and posterior ethmoid score ≥1) indicated high accurate diagnostic ability (sensitivity, 84.6%; specificity, 92.3%). CONCLUSION: A set of three clinical findings can differentiate ECRS from non-ECRS with high accuracy, even when these findings are assessed in regular outpatient clinics.

Rectal content and intrafractional prostate gland motion assessed by magnetic resonance imaging.

We evaluated the interrelationship between rectal content and intrafraction motion of the prostate. Forty seven prostate cancer patients instructed to remove their rectal gas were imaged by planning CT and MRI before radiotherapy (RT) and during RT. The total scan time was comparable to our cone-beam CT scanning and treatment times. Rectal content was qualitatively assessed into four different categories by T2-weighted axial MRI: empty (Group E), gas (Group G), combination of gas and feces (Group C), and feces (Group F). Eleven anatomic points of interest (POI) were determined on subsequent sagittal cine-MRI slices. The incidence of displacement of more than 3 mm for more than 10% of time (> 10% time over 3 mm) at least in one of the prostate POIs in Group E was 6.3%, Group G 40.9%, Group C 6.3%, and Group F 0%, respectively. Except for Group G, the mean probability of > 3 mm displacement was < 3%. More than 10% time over 3 mm displacement of the superior prostate in the AP direction (SAP) was noted in only Group G patients and was 45.5% before RT and 18.2% during RT. Only Group G patients were significantly related to both the mean of means and the mean of maxs of prostate displacement of SAP by multivariate analysis. Group G patients were also significantly related to the mean of the standard deviation of rectum width of superior rectum and mid-rectum by multivariate analysis. Patients with rectal gas only were significantly related to prostate displacement and rectal movement.

Preoperative inner segment/outer segment junction in spectral-domain optical coherence tomography as a prognostic factor in epiretinal membrane surgery.

PURPOSE: To evaluate the macular structure on spectral-domain optical coherence tomographic (SD-OCT) images to predict the outcome of surgery for idiopathic epiretinal membrane. METHODS: Forty-five eyes of 45 consecutive patients with idiopathic epiretinal membrane who had a preoperative visual acuity of ≤ 20/32 and were scheduled to undergo a transconjunctival 25-gauge vitrectomy were involved in this prospective cohort study. The best-corrected visual acuity (BCVA) and SD-OCT images of the fovea were examined before the surgery and at 3, 6, and 12 months after the surgery. Associations between the visual acuity parameters and the preoperative SD-OCT features, including the morphology of the photoreceptor inner segment/outer segment junction, macular thickness, presence/absence of retinal cysts, and presence/absence of a macular pseudohole, were investigated as predictors of the outcome of the surgery. The main outcome measures were the association between the macular microstructure on preoperative SD-OCT images and the visual acuity parameters, such as the BCVA, at 12 months after the surgery (postoperative BCVA) and the difference between the preoperative visual acuity and the postoperative BCVA. RESULTS: A total of 45 patients were enrolled in this study. The postoperative visual acuity was significantly better for the eyes with an intact inner segment/outer segment junction on the preoperative SD-OCT images than for those with an irregular or a disrupted inner segment/outer segment junction on the images (P < 0.001). Better preoperative visual acuity was associated with better visual acuity at 12 months and a lesser degree of improvement in the visual acuity (P < 0.001, respectively). CONCLUSION: The presence of an intact inner segment/outer segment junction on the preoperative SD-OCT images was found to be an important predictor of better visual recovery and better postoperative BCVA after epiretinal membrane surgery.