Clinical outcomes and medical management of achondroplasia in Japanese children: A retrospective medical record review of clinical data.

Achondroplasia (ACH) is a rare, autosomal dominant skeletal dysplasia characterized by short stature, characteristic facial configuration, and trident hands. Before vosoritide approval in Japan, patients with ACH could start growth hormone (GH) treatment at age 3 years. However, ACH and its treatment in young Japanese children have not been studied. This retrospective, longitudinal, medical records-based cohort study (before vosoritide approval) summarized symptoms, complications, monitoring, surgery/interventions, and height with/without GH in Japanese patients with ACH <5 years. Complications were observed in 89.2% of all 37 patients; 75.7% required surgery or intervention. All patients were monitored by magnetic resonance imaging; 73.0% had foramen magnum stenosis, while 54.1% had Achondroplasia Foramen Magnum Score 3 or 4. Of 28 GH-treated patients, 22 initiating at age 3 years were generally taller after 12 months versus 9 non-GH-treated patients. Mean annual growth velocity significantly increased from age 2 to 3 versus 3 to 4 years in GH-treated patients (4.37 vs. 7.23 cm/year; p = 0.0014), but not in non-GH-treated patients (4.94 vs. 4.20 cm/year). The mean height at age 4 years with/without GH was 83.6/79.8 cm. These results improve our understanding of young patients with ACH in Japan and confirm that early diagnosis of ACH and monitoring of complications help facilitate appropriate interventions.

Risk Factors and the Prevention of Weight Gain During Induction Chemotherapy in Children With Acute Lymphoblastic Leukemia.

Weight gain is often observed in children with acute lymphoblastic leukemia (ALL) who undergo chemotherapy including steroids. An increase in body mass index (BMI)-standard deviation score (SDS) during induction therapy is reported as a risk factor for obesity after treatment. However, risk factors of an increase in BMI-SDS during induction therapy are not known. Ninety-six patients with ALL who were treated at our hospital between 1996 January and September 2013 were analyzed retrospectively. Daily body weight measurement was initiated in July 2005 in an attempt to control weight. Fifty-four patients were boys and 42 were girls. The median age at onset was 5.1 years (0.5-16.6 y), and 7.3% of patients were overweight/obese at onset. BMI-SDS increased +0.1% (-3.3% to +3.2%) during induction therapy. BMI-SDS increased by 1 and 2 or more SDs in 20% and 3% of patients, respectively. In multivariate analysis, non-high-risk treatment and earlier treatment start date (before daily body weight measurement) were independent risk factors. Ten percent of patients were overweight/obese at 3 years after completion therapy, and high BMI-SDS after induction therapy was a risk factor. Daily body weight measurement might prevent excess weight gain during induction therapy, resulting in patients maintaining a healthy weight after ALL treatment.

[Exposure Dose Reduction for Radiologists with Combination of Angular Beam Modulation and Radiation Protection Drape in CT Fluoroscopy: A Phantom Study].

PURPOSE: To assess the dose reduction of radiologists by using angular beam modulation (ABM) and radiation protection drape during computed tomography (CT) fluoroscopy. MATERIALS AND METHODS: The phantom was set on the lower that is 15 cm from the isocenter position. We measured the radiation exposure around the phantom with radiophotoluminescence glass dosimeters. The space radiation dose rate was measured with an ionization chamber dosimeter in the CT room. RESULTS: The dose rate of finger radiation exposure was 67% at assumed assist tool position with ABM. And the dose rate of finger radiation exposure with the combination of ABM and radiation protection drape was 33%. The space dose rate of exposure with the combination of ABM and radiation protection drape was 49% at 150 cm. CONCLUSION: The combination of ABM and radiation protection drape can reduce finger radiation exposure at assumed assist tool position. The space dose rate of the standing position of radiologists can get a clear dose of radiation reduction by the combination of both.

DIC Complicating APL Successfully Treated With Recombinant Thrombomodulin Alfa.

An 8-year-old boy developed anorexia, fatigue, and fever. Laboratory examination revealed a high white blood cell (WBC) count of 145×10/µL with 97.5% abnormal promyelocytic cells that contained Auer bodies. Faggot cells were seen. He was diagnosed with acute promyelocytic leukemia. Later, a chromosome analysis showed 46,XY,t(15;17)(q22;q12). Promyelocytic Leukemia-retinoic acid receptor α-fused gene and chimeric mRNA were confirmed by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction, respectively. He was complicated with disseminated intravascular coagulation (DIC) and his fibrin and fibrinogen degradation product at the onset was 37.6 µg/mL. Human recombinant thrombomodulin (rTM) was started for DIC. After dexamethasone was administered at a dose of 8 mg/m to prevent all-trans retinoic acid syndrome on day 1, all-trans retinoic acid was started at a dose of 45 mg/m on day 4. Cytarabine (100 mg/m/d) and daunorubicin (45 mg/m/d) were started on day 9. The WBC count gradually increased to 270×10/µL on day 8, and then decreased beginning on day 9. DIC improved after the initiation of chemotherapy and only minor petechia was noted. DIC did not become worse even after rTM was stopped on day 8. The risk of DIC and bleeding is high in the early stage of treatment for acute promyelocytic leukemia, especially in patients with a high WBC count. In our patient, rTM may have prevented fatal DIC and made it possible to safely administer induction chemotherapy.

Phenotypes of children with 20q13.3 microdeletion affecting KCNQ2 and CHRNA4.

In order to clarify the phenotypes of 20q13.33 microdeletion, clinical manifestations and genetic findings from four patients are discussed in relation to chromosomal microdeletions at 20q13.33. All patients had epileptic seizures mostly beginning within the neonatal period and disappearing by 4 months of age, similar to epilepsy phenotypes of benign familial neonatal seizures. We performed array comparative, genomic hybridization analysis in order to investigate the chromosomal aberration. Developmental outcome was good in two patients with deletion restricted to three genes (CHRNA4, KCNQ2, and COL20A1), whereas delay in developmental milestones was observed in the other two with a wider range of deletion. Information obtained from array comparative genomic hybridization may be useful to predict seizure and developmental outcome, however, there is no distinctive pattern of abnormalities that would arouse clinical suspicion of a 20q13.33 microdeletion. Deletion of KCNQ2 and CHRNA4 does not appear to affect seizure phenotype. Molecular cytogenetic techniques, such as array comparative genomic hybridization, will be necessary to clarify the relationship between phenotypes and individual genes within this region.

Adiposity and clinical outcomes in East Asian patients with heart failure and preserved ejection fraction.

Background: Despite the obesity paradox, visceral adiposity is associated with poor clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). However, it remains unclear whether a relationship between visceral fat and clinical outcomes exists in Asian patients with HFpEF, in whom obesity is rare. Methods: Visceral and subcutaneous adipose tissue (VAT and SAT) volume and area were measured using computed tomography (CT) in 196 HFpEF patients. The primary endpoint was a composite of all-cause mortality or HF hospitalization. Results: Participants had a normal body mass index (BMI) (22.5 ± 4.4 kg/m2), and obesity (BMI > 30 kg/m2) was rare (4.6 %). The primary outcome was observed in 64 patients during a median follow-up of 11.6 months. Lower VAT and SAT volumes were associated with underweight and malnutrition. Composite outcomes increased as body weight, BMI, and height-indexed SAT volume and area decreased. Lower height-indexed VAT volume and area were also associated with the outcomes. The height-indexed SAT area provided independent and incremental prognostic value over age, BMI, blood pressure, and creatinine and albumin levels. Conclusions: In lean East Asian patients with HFpEF, a lower VAT volume was associated with poorer clinical outcomes. CT-based assessments of adiposity may provide incremental prognostic value over simple anthropometric indices in lean HFpEF patients.

Predictive value of prostate calcification for future cancer occurrence: a retrospective long-term follow-up cohort study.

OBJECTIVE: Although prostate calcification is often identified on pelvic CT images, calcification itself is usually not considered clinically significant. A recent histological study proposed an association between prostate calcification and prostate cancer occurrence. Our aim was to determine the predictive value of prostate calcifications for future prostate cancer occurrence. METHODS: We retrospectively analysed male patients (≥50 years old) without prior prostate cancer history, who underwent unenhanced pelvic CT between April 2010 and March 2011, and followed-up until December 2021. Cox proportional hazards models were used to assess prostate cancer risk with prostate calcification (defined as a high-density area larger than 3 mm with CT attenuation values ≥ 130 HU), controlling for age, body mass index (BMI), hypertension and diabetes mellitus. RESULTS: A total of 636 male patients (mean age, 68 years ± 9 [standard deviation]) were evaluated. At the end of follow-up, prostate cancer had been more frequently diagnosed in patients with prostate calcification than those without prostate calcification (6.5% vs 2.6%). Multivariate analysis revealed that prostate calcification on CT was a significant predictor of future prostate cancer occurrence (hazard ratio [HR], 2.7; 95% CI: 1.20, 5.91; p = 0.016). No statistical differences were observed in any other factors. CONCLUSION: Prostate calcification may be a significant predictor of future prostate cancer occurrence, and may be used for risk stratification and to guide screening protocols. ADVANCES IN KNOWLEDGE: Presence of prostate calcification on unenhanced CT scan was associated with increased incidence of prostate cancer occurrence on long term follow-up.

Pathophysiologic Contributions of Visceral Adiposity to Left Ventricular Diastolic Dysfunction.

BACKGROUND: Visceral fat produces inflammatory cytokines and may play a major role in heart failure with preserved ejection fraction (HFpEF). However, little data exist regarding how qualitative and quantitative abnormalities of visceral fat would contribute to left ventricular diastolic dysfunction (LVDD). METHODS: We studied 77 participants who underwent open abdominal surgery for intra-abdominal tumors (LVDD, n = 44; controls without LVDD, n = 33). Visceral fat samples were obtained during the surgery, and mRNA levels of inflammatory cytokines were measured. Visceral and subcutaneous fat areas were measured using abdominal computed tomography. RESULTS: Patients with significant LVDD had greater LV remodeling and worse LVDD than controls. While body weight, body mass index, and subcutaneous fat area were similar in patients with LVDD and controls, the visceral fat area was larger in patients with LVDD than in controls. The visceral fat area was correlated with BNP levels, LV mass index, mitral e' velocity, and E/e' ratio. There were no significant differences in the mRNA expressions of visceral adipose tissue cytokines (IL-2, -6, -8, and -1ß, TNFα, CRP, TGFß, IFNγ, leptin, and adiponectin) between the groups. CONCLUSIONS: Our data may suggest the pathophysiological contribution of visceral adiposity to LVDD.

Pathogenic variants of the GNAS gene introduce an abnormal amino acid sequence in the ß6 strand/α5 helix of Gsα, causing pseudohypoparathyroidism type 1A and pseudopseudohypoparathyroidism in two unrelated Japanese families.

Pseudohypoparathyroidism 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP) are caused by loss-of-function variants of GNAS, which encodes Gsα. We present two unrelated Japanese families with PHP1A and PPHP harboring unreported pathogenic variants of GNAS (c.1141delG, p.Asp381Thrfs*23 and c.1117delC, p.Arg373Alafs*31). These variants introduce abnormal amino acids in the ß6 strand/α5 helix of Gsα, which interact with G protein coupling receptor (GPCR). We conclude that these variants alter the association of Gsα with GPCR and cause PHP1A or PPHP.

Effect of type 2 diabetes on Gd-EOB-DTPA uptake into liver parenchyma: replication study in human subjects.

PURPOSE: Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is a contrast agent for magnetic resonance imaging (MRI), which specifically taken up by hepatocytes through organic anion-transporting polypeptides (OATPs). Previous research in mice has shown that type 2 diabetes is associated with reduced uptake of Gd-EOB-DTPA into the liver parenchyma, reflecting reduced expression of OATP. Since considerable differences in OATP expression exist between mice and humans, human studies are necessary to clarify the effect of diabetes to Gd-EOB-DTPA uptake. The purpose of this study was to validate the effect of diabetes to Gd-EOB-DTPA liver uptake by a confirmatory study in humans. METHODS: Patients who underwent Gd-EOB-DTPA-enhanced MRI were retrospectively reviewed and divided into two groups: severe or uncontrolled diabetic group (patients with insulin therapy and/or HbA1c ≥ 8.4%) and the control group. Liver-to-spleen ratio (LSR) and relative enhancement of the liver (REL) were calculated to represent Gd-EOB-DTPA liver uptake. RESULTS: A total of 94 patients fulfilled the criteria. The severe or uncontrolled diabetic group (n = 15) showed significantly lower LSR (1.74 ± 0.26 vs. 1.98 ± 0.31, p = 0.007) and REL (0.69 ± 0.23 vs. 0.87 ± 0.31, p = 0.005), compared to the control group (n = 79). CONCLUSION: Our study revealed decreased uptake of Gd-EOB-DTPA into liver parenchyma in the severe or uncontrolled diabetic patients. Further studies to determine the impact of the reduced liver enhancement on clinical diagnostic practice will be needed.

Post-contrast Acute Kidney Injury Following Emergency Transcatheter Arterial Embolization for Uncontrollable Postpartum Hemorrhage.

The aim of this study was to investigate the incidence of post-contrast acute kidney injury (PC-AKI) in patients with uncontrollable postpartum hemorrhage undergoing emergency transcatheter arterial embolization (TAE). Data collected included patient characteristics, serum creatinine (SCr) level before and after TAE, iodine quantity of contrast media, time between computed tomography and TAE, diabetes mellitus, hemorrhage volume, and blood transfusion volume. For the diagnosis of PC-AKI, the criteria of the European Society of Urogenital Radiology Guidelines (version 10.0) were used. A total of 71 TAE procedures were performed over a 5-year period, and 47 patients met the inclusion criteria. Preprocedural renal function and change of SCr were positively correlated (P < .001), although no patients met the PC-AKI criteria and none showed renal impairment on the follow-up examination (95% upper confidence limit = 6.2%). Total iodine quantity was not correlated with SCr change. Postpartum hemorrhage was finally controlled in all 47 patients, and they were subsequently discharged. In conclusion, emergency TAE for patients with uncontrollable postpartum hemorrhage was a safe and effective procedure, not only in terms of bleeding-related and other outcomes but also with respect to the risk of PC-AKI.

Patients' radiation dose in computed tomography-fluoroscopy-guided percutaneous cryoablation for small renal tumors.

PURPOSE: This study aimed to evaluate patients' radiation dose in computed tomography (CT)-fluoroscopy-guided cryoablation for small renal tumors and assess the possible factors affecting it. METHODS: In our institution, cryoablation was performed in 152 patients between 2013 and 2020. Procedures that were not for renal tumors and did not have radiation dose records and detailed information were excluded from the analysis. The size-specific dose estimates (SSDE), volume CT dose index (CTDIvol), dose-length product (DLP), and entrance skin dose (ESD) were evaluated for both spiral scan and CT-fluoroscopy. The effects of the number of cryoneedle punctures; combined use of hydro- and/or pneumodissection procedures; patients' characteristics, such as body-mass index (BMI); and the tumor-related factors, such as tumor location, were determined by the univariate and multivariate analyses. RESULTS: In the 72 included procedures, the median SSDE was 658 mGy and the median CTDIvol was 456 mGy. The median percentage dose of CT-fluoroscopy to the total procedure dose was estimated as 89.8% (591/658 mGy) with SSDE and 41.4% (611/1,475 mGy cm) with DLP. The combined use of hydro- and/or pneumodissection and number of cryoneedle punctures were significantly associated with the total ESD, and the maximum total ESD was 863 mGy in our cases. CONCLUSIONS: Using SSDE as an index, 89.8% of patients' radiation dose was attributed to CT-fluoroscopy, and ESD for the total procedure did not exceed 1 Gy. The increased number of cryoneedle punctures and combined use of hydro- and/or pneumodissection increased the total ESD.

Radiation Exposure of Interventional Radiologists during Computed Tomography Fluoroscopy-Guided Percutaneous Cryoablation.

Purpose: The principal aim of this study was to evaluate radiation exposure of interventionalists during computed tomography (CT) fluoroscopy-guided percutaneous cryoablation (PCA) using radiophotoluminescent glass dosimeters (RPLDs). The radioprotective effects of safety glasses and lead apron were also evaluated. Materials and Methods: Radiation exposure of interventionalists during 46 CT fluoroscopy-guided PCA procedures was evaluated. Entrance surface dose (ESD) was measured using RPLDs on multiple sites: five sites, representing eye lens exposure; five sites, representing body exposure; and four sites, representing skin exposure. The ESD values on multiple sites were compared between different PCA procedures (renal, liver, and bone). Results: The mean ESD on the X-ray-side hand exhibited the highest value (358.8 µGy). Regarding evaluation sites representing exposure to the eye lens, the highest ESD inside the radiation protective glasses was detected on the X-ray-side cheek (167.1 µGy). Most ESD values among multiple sites (10/14) were linearly correlated with CT fluoroscopy time. Among them, the ESD values measured during renal and liver PCA were relatively higher than those measured during bone PCA, especially on the chest area outside the lead apron, and on the X-ray tube-side elbow and hand during renal and bone PCA. Radioprotective effects of safety glasses and lead apron ranged from 44.6 to 50.6% and from 30.2 to 79.6%, respectively, on each evaluation site. Conclusion: The site with the highest radiation exposure on interventionalists during CT fluoroscopy-guided PCA was the X-ray tube-side hand. Radiation exposure of interventionalists was at acceptable levels and consistent with the recommended dose limits.

The effect of abolishing instructions to fast prior to contrast-enhanced CT on the incidence of acute adverse reactions.

OBJECTIVES: To evaluate the effect of abolishing instructions to fast prior to contrast-enhanced CT on acute adverse reactions (AARs). METHODS: In our institution, we instructed patients to fast one meal before contrast-enhanced CT examinations. However, we abolished these instructions at the end of March 2019, and solid food intake was not restricted before contrast-enhanced CT after this date. The differences in the incidence of AARs before (December 2015-November 2018, n = 43,927) and after (April 2019-March 2020, n = 14,676) abolishing instructions to fast were compared. We allowed 4 months (December 2018-March 2019) for this policy change to fully permeate the CT referrals. The medical records of patients who vomited were retrospectively reviewed by one of the authors for notations of aspiration or aspiration pneumonia attributable to vomiting. RESULTS: The overall incidence of AARs before (1.60%, n = 705) and after abolition (1.40%, n = 205) did not change significantly. As the chemotoxic reactions, the incidence of nausea decreased significantly (0.31 to 0.18%, p = 0.006). The incidence of vomiting did not change (0.12 to 0.16%), and there were no cases of aspiration pneumonia attributable to vomiting during the study period. The incidence of severe hypersensitivity/allergy-like reactions did not change (0.06 to 0.05%). CONCLUSIONS: Abolishing instructions to fast decreased the incidence of nausea, but did not affect the incidence of vomiting. No cases of aspiration pneumonia attributable to vomiting were found. Our study confirmed that fasting is not required prior to contrast-enhanced CT.