Neurodevelopmental outcome after antenatal therapy for fetal supraventricular tachyarrhythmia: 3-year follow-up of multicenter trial.

OBJECTIVES: Although many studies have supported the efficacy of transplacental treatment for fetal supraventricular tachyarrhythmia, the long-term neurodevelopmental outcome after antenatal antiarrhythmic treatment is not well understood. The aim of this study was to investigate the prognosis and neurodevelopmental outcome at 36 months of corrected age and the incidence of tachyarrhythmia after birth, following protocol-defined antenatal therapy for fetal supraventricular tachyarrhythmia. METHODS: This was a 3-year follow-up study of a multicenter trial that evaluated the efficacy and safety of protocol-defined transplacental treatment for fetal supraventricular tachycardia (SVT) and atrial flutter (AFL). The primary endpoints were mortality and neurodevelopmental impairment (NDI) at 36 months of corrected age. NDI was defined as any of the following outcomes: cerebral palsy, bilateral blindness, bilateral deafness or neurodevelopmental delay. Neurodevelopmental delay was evaluated using appropriate developmental quotient scales, mainly the Kyoto Scale of Psychological Development, or examination by pediatric neurologists. The detection rate of tachyarrhythmia at birth and at 18 and 36 months of corrected age was also evaluated as the secondary endpoint. In addition, the association of NDI at 36 months with perinatal and postnatal factors was analyzed. RESULTS: Of 50 patients enrolled in the original trial, one withdrew consent and in two there was fetal death, leaving 47 patients available for enrollment in this follow-up study. Of these, 45 cases were available for analysis after two infants were lost to follow-up. The mortality rate was 2.2% (1/45) during a median follow-up of 3.2 (range, 2.1-9.4) years. The infant died at the age of 2.1 years. Another infant had missing neurodevelopmental assessment data. In the remaining 43 infants, at 36 months of corrected age, NDI was detected in 9.3% (4/43) overall and in two of three (66.7%) cases with fetal hydrops with subcutaneous edema. Cerebral palsy was noted in two infants with severe subcutaneous edema or ascites at an early gestational age. Neurodevelopmental delay was found in two infants with severe congenital abnormalities (one with tuberous sclerosis and the other with heterotaxy syndrome). Tachyarrhythmia was present in 31.9% (15/47) cases in the neonatal period and decreased to 8.9% (4/45) and 4.5% (2/44) at 18 and 36 months of corrected age, respectively. The median ventricular rate at diagnosis was significantly higher in infants with NDI compared to those without (265 vs 229 bpm; P = 0.003). In infants with NDI, compared to those without, fetal hydrops with subcutaneous edema at diagnosis was more common (50.0% vs 2.6%; P = 0.019) and the duration of fetal effusion was longer (median, 10.5 vs 0 days; P = 0.013). Postnatal arrhythmia and physical development abnormalities were not associated with NDI. CONCLUSIONS: This multicenter 3-year follow-up study is the first to demonstrate the long-term mortality and morbidity of infants born following protocol-defined transplacental treatment for fetal SVT and AFL. NDI was associated with the presence of fetal hydrops with subcutaneous edema at diagnosis and longer duration of fetal effusion. Neurodevelopmental delay was detected only in infants with severe congenital abnormalities. Therefore, in infants that have undergone antenatal treatment for fetal tachyarrhythmia and in which there are no comorbidities, the risk of NDI is low. However, in those with fetal hydrops with subcutaneous edema and/or associated severe congenital abnormalities, the risk for long-term neurologic morbidity might be considered somewhat increased. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Utility of synthetic MRI in predicting pathological complete response of various breast cancer subtypes prior to neoadjuvant chemotherapy.

AIM: To evaluate the usefulness of synthetic magnetic resonance imaging (MRI) performed before the initiation of neoadjuvant chemotherapy (NAC) in predicting whether breast cancers can achieve a pathological complete response (pCR) after the completion of NAC. MATERIALS AND METHODS: This retrospective study investigated 37 consecutive patients with 39 breast cancers (pCR: 14, and non-pCR: 25) who underwent dynamic contrast-enhanced (DCE)-MRI and synthetic MRI before the initiation of NAC. Using synthetic MRI images, quantitative values (T1 and T2 relaxation times, proton density [PD] and their standard deviations [SD]) were obtained in breast lesions, before (Pre-T1, Pre-T2, Pre-PD, SD of Pre-T1, SD of Pre-T2, SD of Pre-PD) and after (Gd-T1, Gd-T2, Gd-PD, SD of Gd-T1, SD of Gd-T2, SD of Gd-PD) contrast agent injection. The aforementioned quantitative values and several morphological features that were identified on DCE-MRI were compared between pCR and non-pCR. RESULTS: Multivariate analyses revealed that the SD of Pre-T2 (p=0.038) was significant and was an independent predictor of pCR, with an area under the receiver operating characteristics curve of 0.829. The sensitivity, specificity, and accuracy of the SD of Pre-T2 with an optimal cut-off value of 11.5 were 71.4%, 80%, and 76.3%, respectively. CONCLUSIONS: The SD of Pre-T2 obtained from synthetic MRI was used successfully to predict those breast cancers that would achieve a pCR after the completion of NAC; however, these results are preliminary and need to be verified by further studies.

Assessment of Heating on Titanium Alloy Cerebral Aneurysm Clips during 7T MRI.

BACKGROUND AND PURPOSE: Patients with cerebral aneurysms often undergo MR imaging after microsurgical clipping. Ultra-high-field MR imaging at 7T may provide high diagnostic capability in such clinical situations. However, titanium alloy clips have safety issues such as adverse interactions with static magnetic fields and radiofrequency-induced heating during 7T MR imaging. The purpose of this study was to quantitatively assess temperature increases on various types of titanium alloy aneurysm clips during 7T MR imaging. MATERIALS AND METHODS: Five types of titanium alloy aneurysm clips were tested, including combinations of short, long, straight, angled, and fenestrated types. Each clip was set in a phantom filled with gelled saline mixed with polyacrylic acid and underwent 7T MR imaging with 3D T1WI with a spoiled gradient recalled acquisition in the steady-state technique. Temperature was chronologically measured at the tips of the clip blade and head, angled part of the clip, and 5 mm from the tip of the clip head using MR imaging-compatible fiber-optic thermometers. RESULTS: Temperature increases at all locations for right-angled and short straight clips were <1°C. Temperature increases at the angled part for the 45° angled clip and the tip of the clip head for the straight fenestrated clip were >1°C. Temperature increases at all locations for the long straight clip were >2°C. CONCLUSIONS: Temperature increases on the right-angled and short straight clips remained below the regulatory limit during 7T MR imaging, but temperature increases on the 45° angled, straight fenestrated, and long straight clips exceeded this limit.

Diagnostic Accuracy of Screening Arterial Spin-Labeling MRI Using Hadamard Encoding for the Detection of Reduced CBF in Adult Patients with Ischemic Moyamoya Disease.

BACKGROUND AND PURPOSE: Adult patients with ischemic Moyamoya disease are advised to undergo selective revascularization surgery based on cerebral hemodynamics. The purpose of this study was to determine the diagnostic accuracy of arterial spin-labeling MR imaging using Hadamard-encoded multiple postlabeling delays for the detection of reduced CBF in such patients. MATERIALS AND METHODS: Thirty-seven patients underwent brain perfusion SPECT and pseudocontinuous arterial spin-labeling MR imaging using standard postlabeling delay (1525 ms) and Hadamard-encoded multiple postlabeling delays. For Hadamard-encoded multiple postlabeling delays, based on data obtained from the 7 sub-boluses with combinations of different labeling durations and postlabeling delays, CBF corrected by the arterial transit time was calculated on a voxel-by-voxel basis. Using a 3D stereotaxic template, we automatically placed ROIs in the ipsilateral cerebellar hemisphere and 5 MCA territories in the symptomatic cerebral hemisphere; then, the ratio of the MCA to cerebellar ROI was calculated. RESULTS: The area under the receiver operating characteristic curve for detecting reduced SPECT-CBF ratios (<0.686) was significantly greater for the Hadamard-encoded multiple postlabeling delays-CBF ratios (0.885) than for the standard postlabeling delay-CBF ratios (0.786) (P = .001). The sensitivity and negative predictive value for the Hadamard-encoded multiple postlabeling delays-CBF ratios were 100% (95% confidence interval, 100%-100%) and significantly higher than the sensitivity (95% CI, 44%-80%) and negative predictive value (95% CI, 88%-97%) for the standard postlabeling delay-CBF ratio, respectively. CONCLUSIONS: ASL MR imaging using Hadamard-encoded multiple postlabeling delays may be applicable as a screening tool because it can detect reduced CBF on brain perfusion SPECT with 100% sensitivity and a 100% negative predictive value in adult patients with ischemic Moyamoya disease.

Evaluation of flexible ureteroscope with an omni-directional bending tip, using a JOYSTICK unit (URF-Y0016): an ex-vivo study.

PURPOSE: To compare the range of reach of our newly designed omni-directional ureteroscope (URF-Y0016), compared to the commonly used URF-P6, FlexX2s, and LithoVue™ scopes, in the upper, middle, and lower calyces in an ex-vivo pyelocaliceal model. METHODS: We fabricated a three-dimensional pyelocaliceal model of the upper, middle, and lower pole calyces using urethane and acrylic resin. The inner surface of the dome of each calyx was engraved with reference lines along eight directions, set at 10° of latitude from the top to the base of the dome, and at angles of 0-90°, to precisely determine the range of reach of each scope. The main feature of the URF-Y0016 scope is the omni-directional bending of the tip of the flexible ureteroscope, with the control of these four directions integrated into a handgun-type control unit with a joystick. The range of reach within each calyx was measured by four expert surgeons. RESULTS: The URF-Y0016 scope provided a greater range of reach along all directions in the lower pole calyx compared to URF-P6, FlexX2s, and LithoVue™ scopes (p < 0.001), particularly along the anterior-posterior direction in the lower lobe calyx. However, the URF-Y0016 scope did not influence the improvement of reach range in the upper and middle pole calyx compared to URF-P6, FlexX2s, and LithoVue™ scopes (p = 0.08, p = 0.296). CONCLUSION: The novel design of the URF-Y0016 could improve treatment outcomes for calyceal stones in the lower pole in practice.

Safety and feasibility of minimally invasive esophagectomy for elderly esophageal cancer patients.

The number of elderly patients with esophageal cancer has increased in recent years. The use of thoracoscopic esophagectomy has also increased, and its minimal invasiveness is believed to contribute to postoperative outcomes. However, the short- and long-term outcomes in elderly patients remain unclear. This study aimed to elucidate the safety and feasibility of minimally invasive esophagectomy in elderly patients. This retrospective study included 207 patients who underwent radical thoracoscopic esophagectomy for thoracic esophageal squamous cell carcinoma at Kobe University Hospital between 2005 and 2014. Patients were divided into non-elderly (<75 years) and elderly (≥75 years) groups. A propensity score matching analysis was performed for sex and clinical T and N stage, with a total of 29 matched pairs. General preoperative data, surgical procedures, intraoperative data, postoperative complications, in-hospital death, cancer-specific survival, and overall survival were compared between groups. The elderly group was characterized by lower preoperative serum albumin levels and higher American Society of Anesthesiologists grade. Intraoperative data and postoperative complications did not differ between the groups. The in-hospital death rate was 4% in the elderly group, which did not significantly differ from the non-elderly group. Cancer-specific survival was similar between the two groups. Although overall survival tended to be poor in the elderly group, it was not significantly worse than that of the non-elderly group. In conclusion, the short- and long-term outcomes of minimally invasive esophagectomy in elderly versus non-elderly patients were acceptable. Minimally invasive esophagectomy is a safe and feasible modality for elderly patients with appropriate indications.

CD49d and CD49e induce cell adhesion-mediated drug resistance through the nuclear factor-κB pathway in Burkitt lymphoma.

Burkitt lymphoma (BL) is a highly aggressive form of non-Hodgkin's B-cell lymphoma. Currently, multi-agent chemotherapy regimens are being used to significantly improve cure rates and achieve complete remissions in BL patients. However, drug resistance can often occur within 6 months in BL patients, contributing to poor prognosis. Mounting evidence suggests that cell adhesion-mediated drug resistance (CAM-DR), caused by the interaction between the bone marrow microenvironment and tumour cells may play an important role in drug resistance to chemotherapy. However, the molecular mechanism underlying CAM-DR in BL has not been identified yet. In this study, we investigated the molecular mechanism responsible for CAM-DR in BL cells. We also examined the therapeutic targets of CAM-DR in BL cells and found CD49d and CD49e to be the important adhesion molecules involved. However, CD49a, CD49b, CD11a, CD29, CD18, and CD61 were not found to be associated with CAM-DR in BL cells. Furthermore, we clarified that CD49d- and CD49e-mediated CAM-DR could be attributed to an increase in the expression of B cell leukemia-xL (Bcl-xL) and survivin proteins, and a decrease in the expression of Bcl-2 associated X (Bax), Bcl-2 interacting mediator (Bim) and p53 upregulated modulator of apoptosis (PUMA) proteins via nuclear factor kappaB (NF-κB) activation. In addition, bortezomib was found to overcome CAM-DR in BL cells by inhibiting NF-κB. Thus, bortezomib may have potential clinical applications in the treatment of CD49d- and CD49e-mediated CAM-DR in BL patients.

A randomized, open-label, controlled trial of monthly oral minodronate or semiannual subcutaneous injection of denosumab for bone loss by androgen deprivation in Asian men with prostate cancer: the PRevention of Osteopenia with Minodronate And DEnosumab (PROMADE) study.

There is still a lack of evidence that minodronate or denosumab prevents bone loss due to androgen deprivation therapy (ADT) in non-Western patients. This study showed that both drugs significantly improved lumbar spine and total hip bone mineral density in Asian men with prostate cancer who received ADT. INTRODUCTION: To evaluate whether monthly oral minodronate or semiannual subcutaneous injection of denosumab improves bone mineral density (BMD) in Asian men with prostate cancer (PCa) receiving ADT. METHODS: A multicenter, open-label, randomized, controlled study including patients with hormone-sensitive PCa without bone metastasis receiving ADT was performed. Patients were randomized (1:1:1) to minodronate, denosumab, or no agent control groups. The primary end point was the mean percentage change in BMD at the lumbar spine at 12 months. Secondary end points were the mean percentage change in BMD at the femoral neck and total hip and changes in bone turnover markers. Statistical comparison was performed using analysis of covariance. RESULTS: Of the 147 subjects enrolled in this study, 102 were randomly assigned into the minodronate (n = 36), denosumab (n = 36), and control (n = 30) groups. The percentage change in BMD at the lumbar spine was significantly improved in the minodronate (2.5%, p < 0.05) and denosumab groups (4.0%, p < 0.01) compared with that in the control group (- 0.1%). Denosumab increased BMD at the femoral neck and total hip at 12 months, whereas minodronate only increased BMD at the total hip compared with controls (all p < 0.05). The percentage change in bone turnover markers at 12 months was significantly lower in the minodronate and denosumab groups compared with that in the control group (both p < 0.01). CONCLUSION: Minodronate or denosumab can be used for preventing bone loss related to ADT in Asian patients with PCa.

Effects of Wolbachia/Cardinium Infection on the Mitochondrial Phylogeny of Oligonychus castaneae (Acari: Tetranychidae).

A wide range of invertebrates harbor intracellular endosymbiotic bacteria. Within these endosymbionts, Wolbachia and Cardinium, have been attracting particular attention because these bacteria frequently affect the genetic structure and genetic diversity of their hosts. They cause various reproductive alterations such as cytoplasmic incompatibility, parthenogenesis induction, male-killing, and feminization. Through these alterations, they also affect the maternally inherited organelles of their hosts. Mitochondrial DNA (mtDNA) can be used for molecular phylogenetic analysis of invertebrates. However, in Wolbachia- or Cardinium-infected invertebrates, phylogenetic trees based on mtDNA are often inconsistent with those based on nuclear DNA. In the present study, we determined the Wolbachia/Cardinium infection status of 45 populations of the mite, Oligonychus castaneae Ehara & Gotoh (Acari: Tetranychidae), collected throughout Japan. Then, we compared phylogenetic trees of O. castaneae based on both the cytochrome c oxidase subunit I (COI) gene of mtDNA and the 28S rRNA gene of nuclear DNA to clarify the effects of Wolbachia and/or Cardinium infection. We found 106 Wolbachia-infected individuals and 250 Cardinium-infected individuals in a total of 450 individuals, indicating an infection rate of 79%. No double-infected individuals were observed. In the 28S tree, almost all populations formed a single group. In the COI tree, O. castaneae formed four separate groups that more closely followed Wolbachia/Cardinium infection than geographic distribution. These results strongly suggest that the endosymbionts affected mitochondrial variation of O. castaneae.

Factors Related to Osteosarcopenia in Kidney Transplant Recipients.

INTRODUCTION: Sarcopenia and osteopenia are highly prevalent in older patients, and are associated with a high risk for falls, fractures, and further functional decline. However, related factors in kidney transplant recipients suffering from osteosarcopenia, the combination of sarcopenia and osteopenia, remain unknown. MATERIAL AND METHODS: Fifty-eight transplant recipients (42 men and 16 women), with a mean age of 46.6 ± 12.7 years, were enrolled in this study. Sarcopenia was diagnosed according to the criteria of the Asia Working Group for Sarcopenia. Osteopenia was diagnosed according to World Health Organization criteria using bone mineral density (BMD) of the lumbar spine. Patients who met the diagnostic criteria of both diseases were defined as having osteosarcopenia. RESULTS: Ten patients had osteosarcopenia. According to univariate analyses, there were significant differences between osteosarcopenia group and non osteosarcopenia group in age (P = .002), duration of dialysis (P = .013), vitamin D levels (P = .002), and MET (P = .007). There was a significant positive correlation between vitamin D level and MET (r = .464; P < .001). The results of the multivariate analysis indicated that only MET was a relevant factor in osteosarcopenia. CONCLUSION: Duration of dialysis, low vitamin D levels, and physical activity after kidney transplantation were related to osteosarcopenia. These results suggested that osteosarcopenia in kidney transplant recipients is a carryover from the dialysis period.

Pathotyping of Escherichia coli isolated from community toilet wastewater and stored drinking water in a slum in Bangladesh.

This study investigated the occurrence of Escherichia coli pathotypes in sanitary wastewater and drinking water in a Bangladeshi urban slum and the potential associations between these sources. We examined 621 E. coli isolates from sanitary wastewater and stored drinking water by multiplex PCR and dual-index sequencing, classifying them into eight pathotypes based on 14 virulence genes and additionally evaluating the possession of the human-specific E. coli genetic biomarker H8. The proportions of pathogenic E. coli were significantly different (P < 0·001) between wastewater (18·6%) and drinking water (1·7%). StIb-positive enterotoxigenic E. coli (ETEC) were predominant in wastewater, indicating that people in the site carried ETEC. In contrast, no ETEC was present in drinking water and the proportion of H8-positive isolates was significantly smaller (7·8%) than that in wastewater (16·3%) (P = 0·001). Our findings indicate that sanitary wastewater from the slum was heavily contaminated with pathogenic E. coli, posing a great health risk. Furthermore, E. coli contamination of drinking water could be derived from not only human but also other sources. SIGNIFICANCE AND IMPACT OF THE STUDY: Sanitary wastewater from an urban slum was heavily contaminated with pathogenic Escherichia coli. It is worth noting a great health risk of accidental exposure to pathogenically contaminated wastewater improperly discharged in and around urban slums. The distinct difference in pathotypes between wastewater and drinking water and the significantly smaller positive proportion of the human-specific E. coli genetic biomarker (H8) in drinking water indicate that drinking water contamination could be derived from not only human but also other sources. This highlights that pathotyping in association with the H8 marker provides an indication of pathogen contamination sources of environmental transmission media.

Metallic phase in stoichiometric CeOBiS2 revealed by space-resolved ARPES.

Recently CeOBiS2 system without any fluorine doping is found to show superconductivity posing question on its origin. Using space resolved ARPES we have found a metallic phase embedded in the morphological defects and at the sample edges of stoichiometric CeOBiS2. While bulk of the sample is semiconducting, the embedded metallic phase is characterized by the usual electron pocket at X point, similar to the Fermi surface of doped BiS2-based superconductors. Typical size of the observed metallic domain is larger than the superconducting correlation length of the system suggesting that the observed superconductivity in undoped CeOBiS2 might be due to this embedded metallic phase at the defects. The results also suggest a possible way to develop new systems by manipulation of the defects in these chalcogenides with structural instability.

Dual Energy X-ray Absorptiometry and Bioimpedance Analysis are Clinically Useful for Measuring Muscle Mass in Kidney Transplant Recipients With Sarcopenia.

PURPOSE: Computed tomography (CT) is considered the gold standard method for the diagnosis and characterization of sarcopenia. The aim of the present study was to determine the correlation between the volume of psoas muscle measured using CT and the measurement of muscle mass with dual energy X-ray absorptiometry (DXA) and bioimpedance analysis (BIA) in kidney transplant recipients. METHODS: Fifty-eight recipients (42 males and 16 females) were enrolled. Diagnostic criteria for sarcopenia were according to those of the Asia Working Group for Sarcopenia. The volume of psoas muscle was extracted using image recognition software from three-dimensional CT images. RESULTS: The volume of psoas muscle was 227.2 ± 61.3 mL in Group 1 (sarcopenia), 283.9 ± 75.3 mL in Group 2 (presarcopenia), and 363.7 ± 138.0 mL in Group 3 (without sarcopenia). Muscle mass measured using DXA was 15.80 ± 3.19 kg in Group 1, 16.36 ± 2.49 kg in Group 2, and 21.21 ± 4.14 kg in Group 3. Additionally, muscle mass assessed using BIA was 17.22 ± 4.11 kg in Group 1, 17.86 ± 3.30 kg in Group 2, and 21.48 ± 5.39 kg in Group 3. There were significant differences in the mean volume of psoas muscle between the 3 groups. There was a significant positive correlation between the volume of psoas muscle and the muscle mass assessed using DXA (r = 0.797; P < .001) and BIA (r = 0.761; P < .001). Furthermore, there was a significant positive correlation between DXA and BIA (r = 0.900; P < .001). CONCLUSIONS: It was suggested that estimating muscle mass using DXA and BIA is a preferred method for diagnosis of sarcopenia in kidney transplant recipients.

Evidence for Spin Singlet Pairing with Strong Uniaxial Anisotropy in URu_{2}Si_{2} Using Nuclear Magnetic Resonance.

In order to identify the spin contribution to superconducting pairing compatible with the so-called "hidden order", ^{29}Si nuclear magnetic resonance measurements have been performed using a high-quality single crystal of URu_{2}Si_{2}. A clear reduction of the ^{29}Si Knight shift in the superconducting state has been observed under a magnetic field applied along the crystalline c axis, corresponding to the magnetic easy axis. These results provide direct evidence for the formation of spin-singlet Cooper pairs. Consequently, results indicating a very tiny change of the in-plane Knight shift reported previously demonstrate extreme uniaxial anisotropy for the spin susceptibility in the hidden order state.

Elastic modulus estimation based on local displacement observation of elastic body.

A method is proposed that provides estimates of the spatial variation of elastic moduli using local displacements of the elastic body. A central issue of elastography imaging has been the limited area of measurement. With the proposed method, stiffness parameter estimations are considered as minimization problems using finite-element models. The sparseness of the gradient of tissue elasticity is also exploited to improve estimation accuracy. Simulation experiments show that based on a 5% area of observation of a simple plate model with non-uniform elasticity the spatial variation of Young's modulus is reconstructed to within 5% accuracy. This result suggests that the proposed framework significantly extends the area of estimation overcoming the limitations of conventional elastography techniques.