Postoperative pulmonary vascular growth in patients with congenital diaphragmatic hernia.

BACKGROUND: Postoperative pulmonary growth in congenital diaphragmatic hernias (CDH) remains unclear. We investigated postoperative pulmonary vascular growth using serial lung perfusion scintigraphy in patients with CDH. METHODS: Neonates with left CDH who underwent surgery and postoperative lung perfusion scintigraphy at our institution between 2001 and 2020 were included. Patient demographics, clinical courses, and lung scintigraphy data were retrospectively analyzed by reviewing medical records. RESULTS: Twenty-one patients with CDH were included. Of these, 10 underwent serial lung scintigraphy. The ipsilateral perfusion rate and median age on the 1st and serial lung scintigraphy were 32% (34 days) and 33% (3.6 years), respectively. Gestational age at prenatal diagnosis (p = 0.02), alveolar-arterial oxygen difference (A-aDO2) at birth (p = 0.007), and preoperative nitric oxide (NO) use (p = 0.014) significantly correlated with the 1st lung scintigraphy. No other variables, including operative approach, were significantly correlated with the 1st or serial scintigraphy findings. All patients improved lung perfusion with serial studies [Difference: + 7.0 (4.3-13.25) %, p = 0.001, paired t-test]. This improvement was not significantly correlated with preoperative A-aDO2 (p = 0.96), NO use (p = 0.28), or liver up (p = 0.90). The difference was significantly larger in patients who underwent thoracoscopic repair than in those who underwent open abdominal repair [+ 10.6 (5.0-17.1) % vs. + 4.25 (1.2-7.9) %, p = 0.042]. CONCLUSION: Our study indicated a postoperative improvement in ipsilateral lung vascular growth, which is possibly enhanced by a minimally invasive approach, in patients with CDH.

A survey of physical and occupational therapists' views on lumbar loading movements.

[Purpose] To identify the lumbar loading movements necessary in clinical practice. [Participants and Methods] A questionnaire survey was conducted among physical and occupational therapists in Japan. There were no exclusion criteria regarding the number of years of experience, age, or field of employment. The participants were randomly selected and administered the questionnaire. They were asked to list and rank the lumbar loadings they considered necessary. [Results] A total of 739 respondents participated in the survey. The results of this nationwide survey indicated that the lifting movement of heavy objects in the trunk flexion position was the most common movement (for 354 participants). [Conclusion] The main loading movements of the lumbar spine were reported to be heavy lifting movements (in the trunk flexion position) and trunk rotation movements. As perspectives, we aim to conduct an analytical study of some of lumbar spine loading movements outlined in this study, using a musculoskeletal simulator and electromyography.

Adding a Model-free Diffusion MRI Marker to BI-RADS Assessment Improves Specificity for Diagnosing Breast Lesions.

Background The apparent diffusion coefficient (ADC) is a commonly used quantitative diffusion-weighted (DW) imaging marker in breast lesion assessment; however, reported ADC values to distinguish malignant and benign lesions show wide variability. Purpose To investigate the diagnostic performance of a tissue signature index (S-index) as a model-free diffusion marker to differentiate malignant and benign breast lesions. Materials and Methods This was a single-institution retrospective study of patients who underwent breast MRI from April 2017 to September 2018. Dynamic contrast-enhanced (DCE) MRI and DW imaging were performed with a 3-T MRI system. For DW imaging, three b values (0, 200, and 1500 sec/mm2) were used for Breast Imaging Reporting and Data Systems (BI-RADS) scoring and to calculate the S-index and a shifted ADC. The diagnostic performances of S-index, shifted ADC, and BI-RADS scoring were evaluated by using receiver operating coefficient analysis. Results The study involved 99 women (mean age, 54 years ± 14 [standard deviation]) with 69 malignant and 38 benign lesions. The S-index was higher for malignant lesions (mean, 75.9 ± 17.4) than for benign lesions (mean, 31.6 ± 21.0; P < .001). Overall diagnostic performance was identical for S-index and shifted ADC (area under the receiver operating characteristic curve [AUC], 0.95; 95% confidence interval [CI]: 0.91, 0.99) and slightly higher than for BI-RADS (AUC, 0.91; 95% CI: 0.87, 0.96; P = .22). The AUC of S-index combined with BI-RADS reached 0.98 (95% CI: 0.96, 1.00), higher than for BI-RADS alone (P < .001), yielding high sensitivity (65 of 69 [94%]; 95% CI: 85%, 98%) and specificity (36 of 38 [95%]; 95% CI: 81%, 99%). Significant differences were identified with the S-index for progesterone receptor and human epidermal growth factor receptor type 2 status (P = .003 and P < .001, respectively). Conclusion The signature index has the potential to enable classification of breast lesion types with high accuracy, especially in combination with dynamic contrast-enhanced MRI and correlates with histologic prognostic factors in invasive breast cancer. © RSNA, 2019 Online supplemental material is available for this article.

Diagnostic performance of initial enhancement analysis using ultra-fast dynamic contrast-enhanced MRI for breast lesions.

OBJECTIVES: To assess the diagnostic value and contribution to BI-RADS categorisation of initial enhancement on ultra-fast DCE-MRI for differentiating malignant and benign breast lesions. METHODS: The institutional review board approved this study, and written informed consent was obtained from each participant. Both ultra-fast DCE-MRI for initial enhancement analysis and conventional MRI were performed on 200 subjects with a total of 215 lesions (147 malignant and 68 benign). BI-RADS categorisation of enhancing lesions was performed using the conventional MRI. Two initial enhancement measures, time to enhancement (TTE) and maximum slope (MS), were derived from the ultra-fast DCE-MRI. Diagnostic performance and the additional diagnostic value of adding TTE and MS to BI-RADS were evaluated. RESULTS: Both TTE and MS showed significant differences between malignant and benign breast lesions in masses (TTE, p <.001; MS, p = .006) and non-mass enhancement (NME) (TTE, p <.001; MS, p <.001). For masses, the AUC of TTE+MS combined with BI-RADS (0.864) was better than BI-RADS alone (0.823, p = .065). For NME, the AUC of TTE+MS combined with BI-RADS (0.923) was significantly larger than BI-RADS alone (0.865, p = .036), and diagnostic specificity improved by 40.9% (p = .005), without a significant decrease in the sensitivity (p = .083). CONCLUSION: Initial enhancement analysis using ultra-fast DCE-MRI is especially useful for increasing the diagnostic performance of NME in breast MRI. KEY POINTS: • Ultra-fast dynamic MRI effectively differentiates benign from malignant breast lesions. • Ultra-fast dynamic MRI contributes to BI-RADS categorisation in non-mass enhancement. • Management of non-mass breast lesions becomes more appropriate.

Aberrant myelination in patients with Sturge-Weber syndrome analyzed using synthetic quantitative magnetic resonance imaging.

PURPOSE: Accelerated myelination in the affected hemisphere has been demonstrated previously in patients with Sturge-Weber syndrome (SWS). This prospective study investigated myelin-related changes in patients with unilateral SWS using synthetic quantitative magnetic resonance imaging (qMRI). METHODS: Fourteen children with unilateral SWS were categorized according to age, i.e., ≤ 2 years (group A, n = 5, mean age 1.1 years, 3 males) and > 2 years (group B, n = 9, mean age 3.9 years, 4 males). All children underwent two-dimensional synthetic qMRI. The myelin volume in the cerebral hemisphere and white matter (WM) myelin volume fraction (MVF), proton density (PD), R1 and R2 relaxation rates ipsilateral to the leptomeningeal enhancement, and/or a port-wine birthmark were compared with the corresponding values in the contralateral hemisphere. RESULTS: In group A, 3 patients had a higher myelin volume in the ipsilateral hemisphere and a higher MVF, R1, and R2 and lower PD in the ipsilateral WM than on the contralateral side; the findings were the opposite in the remaining two patients. All patients in group B had a significantly lower myelin volume in the ipsilateral hemisphere (P < 0.05) and a lower MVF and R1 and higher PD in the ipsilateral WM than on the contralateral side (P < 0.0125). CONCLUSION: Higher estimated myelin was observed on the ipsilateral side in some patients aged ≤ 2 years and lower myelin on the ipsilateral side in all older patients. Synthetic qMRI might be useful for showing myelin-related abnormalities in SWS.

Sporadic PCDH18 somatic mutations in EpCAM-positive hepatocellular carcinoma.

BACKGROUND: The relationship between specific genome alterations and hepatocellular carcinoma (HCC) cancer stem cells (CSCs) remains unclear. In this study, we evaluated the relationship between somatic mutations and epithelial cell adhesion molecule positive (EpCAM+) CSCs. METHODS: Two patient-derived HCC samples (HCC1 and HCC2) were sorted by EpCAM expression and analyzed by whole exome sequence. We measured PCDH18 expression level in eight HCC cell lines as well as HCC1 and HCC2 by real-time quantitative RT-PCR. We validated the identified gene mutations in 57 paired of HCC and matched non-cancerous liver tissues by Sanger sequence. RESULTS: Whole exome sequencing on the sorted EpCAM+ and EpCAM- HCC1 and HCC2 cells revealed 19,263 nonsynonymous mutations in the cording region. We selected mutations that potentially impair the function of the encoded protein. Ultimately, 60 mutations including 13 novel nonsense and frameshift mutations were identified. Among them, PCDH18 mutation was more frequently detected in sorted EpCAM+ cells than in EpCAM- cells in HCC1 by whole exome sequences. However, we could not confirm the difference of PCDH18 mutation frequency between sorted EpCAM+ and EpCAM- cells by Sanger sequencing, indicating that PCDH18 mutation could not explain intracellular heterogeneity. In contrast, we found novel PCDH18 mutations, including c.2556_2557delTG, c.1474C>G, c.2337A>G, and c.2976G>T, were detected in HCC1 and 3/57 (5.3%) additional HCC surgical specimens. All four HCCs with PCDH18 mutations were EpCAM-positive, suggesting that PCDH18 somatic mutations might explain the intertumor heterogeneity of HCCs in terms of the expression status of EpCAM. Furthermore, EpCAM-positive cell lines (Huh1, Huh7, HepG2, and Hep3B) had lower PCDH18 expression than EpCAM-negative cell lines (PLC/PRL/5, HLE, HLF, and SK-Hep-1), and PCDH18 knockdown in HCC2 cells slightly enhanced cell proliferation. CONCLUSIONS: Our data suggest that PCDH18 is functionally suppressed in a subset of EpCAM-positive HCCs through somatic mutations, and may play a role in the development of EpCAM-positive HCCs.

Alveolar macrophage-derived microvesicles mediate acute lung injury.

BACKGROUND: Microvesicles (MVs) are important mediators of intercellular communication, packaging a variety of molecular cargo. They have been implicated in the pathophysiology of various inflammatory diseases; yet, their role in acute lung injury (ALI) remains unknown. OBJECTIVES: We aimed to identify the biological activity and functional role of intra-alveolar MVs in ALI. METHODS: Lipopolysaccharide (LPS) was instilled intratracheally into C57BL/6 mice, and MV populations in bronchoalveolar lavage fluid (BALF) were evaluated. BALF MVs were isolated 1 hour post LPS, assessed for cytokine content and incubated with murine lung epithelial (MLE-12) cells. In separate experiments, primary alveolar macrophage-derived MVs were incubated with MLE-12 cells or instilled intratracheally into mice. RESULTS: Alveolar macrophages and epithelial cells rapidly released MVs into the alveoli following LPS. At 1 hour, the dominant population was alveolar macrophage-derived, and these MVs carried substantive amounts of tumour necrosis factor (TNF) but minimal amounts of IL-1ß/IL-6. Incubation of these mixed MVs with MLE-12 cells induced epithelial intercellular adhesion molecule-1 (ICAM-1) expression and keratinocyte-derived cytokine release compared with MVs from untreated mice (p<0.001). MVs released in vitro from LPS-primed alveolar macrophages caused similar increases in MLE-12 ICAM-1 expression, which was mediated by TNF. When instilled intratracheally into mice, these MVs induced increases in BALF neutrophils, protein and epithelial cell ICAM-1 expression (p<0.05). CONCLUSIONS: We demonstrate, for the first time, the sequential production of MVs from different intra-alveolar precursor cells during the early phase of ALI. Our findings suggest that alveolar macrophage-derived MVs, which carry biologically active TNF, may play an important role in initiating ALI.

Defeating EpCAM(+) liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma is composed of a subset of cells with enhanced tumorigenicity and chemoresistance that are called cancer stem (or stem-like) cells. We explored the role of chromodomain-helicase-DNA-binding protein 4, which is encoded by the CHD4 gene and is known to epigenetically control gene regulation and DNA damage responses in EpCAM(+) liver cancer stem cells. METHODS: Gene and protein expression profiles were determined by microarray and immunohistochemistry in 245 and 144 hepatocellular carcinoma patients, respectively. The relationship between gene/protein expression and prognosis was examined. The functional role of CHD4 was evaluated in primary hepatocellular carcinoma cells and in cell lines in vitro and in vivo. RESULTS: CHD4 was abundantly expressed in EpCAM(+) hepatocellular carcinoma with expression of hepatic stem cell markers and poor prognosis in two independent cohorts. In cell lines, CHD4 knockdown increased chemosensitivity and CHD4 overexpression induced epirubicin chemoresistance. To inhibit the functions of CHD4 that are mediated through histone deacetylase and poly (ADP-ribose) polymerase, we evaluated the effect of the histone deacetylase inhibitor suberohydroxamic acid and the poly (ADP-ribose) polymerase inhibitor AG-014699. Treatment with either suberohydroxamic acid or AG-014699 reduced the number of EpCAM(+) liver cancer stem cells in vitro, and suberohydroxamic acid and AG-014699 in combination successfully inhibited tumor growth in a mouse xenograft model. CONCLUSIONS: CHD4 plays a pivotal role in chemoresistance and the maintenance of stemness in liver cancer stem cells and is therefore a good target for the eradication of hepatocellular carcinoma.

Analysis of normal-appearing white matter of multiple sclerosis by tensor-based two-compartment model of water diffusion.

OBJECTIVES: To compare the significance of the two-compartment model, considering diffusional anisotropy with conventional diffusion analyzing methods regarding the detection of occult changes in normal-appearing white matter (NAWM) of multiple sclerosis (MS). METHODS: Diffusion-weighted images (nine b-values with six directions) were acquired from 12 healthy female volunteers (22-52 years old, median 33 years) and 13 female MS patients (24-48 years old, median 37 years). Diffusion parameters based on the two-compartment model of water diffusion considering diffusional anisotropy was calculated by a proposed method. Other parameters including diffusion tensor imaging and conventional apparent diffusion coefficient (ADC) were also obtained. They were compared statistically between the control and MS groups. RESULTS: Diffusion of the slow diffusion compartment in the radial direction of neuron fibers was elevated in MS patients (0.121 × 10(-3) mm2/s) in comparison to control (0.100 × 10(-3) mm(2)/s), the difference being significant (P = 0.001). The difference between the groups was not significant in other comparisons, including conventional ADC and fractional anisotropy (FA) of diffusion tensor imaging. CONCLUSION: The proposed method was applicable to clinically acceptable small data. The parameters obtained by this method improved the detectability of occult changes in NAWM compared to the conventional methods. KEY POINTS: • Water diffusion was compared between the controls and multiple sclerosis patients. • A two-compartment model, considering diffusional anisotropy was selected for water diffusion analysis. • Axial and radial diffusion of fast and slow diffusion components were evaluated. • A new method was developed to obtain the metrics stably. • The metrics indicated high detectability of slight differences between the groups.

The transcription factor SALL4 regulates stemness of EpCAM-positive hepatocellular carcinoma.

BACKGROUND & AIMS: Recent evidence suggests that hepatocellular carcinoma can be classified into certain molecular subtypes with distinct prognoses based on the stem/maturational status of the tumor. We investigated the transcription program deregulated in hepatocellular carcinomas with stem cell features. METHODS: Gene and protein expression profiles were obtained from 238 (analyzed by microarray), 144 (analyzed by immunohistochemistry), and 61 (analyzed by qRT-PCR) hepatocellular carcinoma cases. Activation/suppression of an identified transcription factor was used to evaluate its role in cell lines. The relationship of the transcription factor and prognosis was statistically examined. RESULTS: The transcription factor SALL4, known to regulate stemness in embryonic and hematopoietic stem cells, was found to be activated in a hepatocellular carcinoma subtype with stem cell features. SALL4-positive hepatocellular carcinoma patients were associated with high values of serum alpha fetoprotein, high frequency of hepatitis B virus infection, and poor prognosis after surgery compared with SALL4-negative patients. Activation of SALL4 enhanced spheroid formation and invasion capacities, key characteristics of cancer stem cells, and up-regulated the hepatic stem cell markers KRT19, EPCAM, and CD44 in cell lines. Knockdown of SALL4 resulted in the down-regulation of these stem cell markers, together with attenuation of the invasion capacity. The SALL4 expression status was associated with histone deacetylase activity in cell lines, and the histone deacetylase inhibitor successfully suppressed proliferation of SALL4-positive hepatocellular carcinoma cells. CONCLUSIONS: SALL4 is a valuable biomarker and therapeutic target for the diagnosis and treatment of hepatocellular carcinoma with stem cell features.

P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma.

Cancer vaccine therapy is one of the most attractive therapies as a new treatment procedure for pancreatic adenocarcinoma. Recent technical advances have enabled the identification of cytotoxic T lymphocyte (CTL) epitopes in various tumor-associated antigens (TAAs). However, little is known about which TAA and its epitope are the most immunogenic and useful for a cancer vaccine for pancreatic adenocarcinoma. We examined the expression of 17 kinds of TAA in 9 pancreatic cancer cell lines and 12 pancreatic cancer tissues. CTL responses to 23 epitopes derived from these TAAs were analyzed using enzyme-linked immunospot (ELISPOT), CTL, and tetramer assays in 41 patients, and factors affecting the immune responses were investigated. All TAAs were frequently expressed in pancreatic adenocarcinoma cells, except for adenocarcinoma antigens recognized by T cells 1, melanoma-associated antigen (MAGE)-A1, and MAGE-A3. Among the epitopes recognized by CTLs in more than two patients in the ELISPOT assay, 6 epitopes derived from 5 TAAs, namely, MAGE-A3, p53, human telomerase reverse transcriptase (hTERT), Wilms tumor (WT)-1, and vascular endothelial growth factor receptor (VEGFR)2, could induce specific CTLs that showed cytotoxicity against pancreatic cancer cell lines. The frequency of lymphocyte subsets correlated well with TAA-specific immune response. Overall survival was significantly longer in patients with TAA-specific CTL responses than in those without. P53, hTERT, WT-1, and VEGFR2 were shown to be attractive targets for immunotherapy in patients with pancreatic adenocarcinoma, and the induction of TAA-specific CTLs may improve the prognosis of these patients.

Virus specific cell-mediated immunity may play a role in controlling reactivated human herpesvirus 6B in patients under measles induced immunosuppression.

For a better understanding of the cellular immune responses to reactivated HHV 6B the lymphoproliferative response to human herpesvirus 6B (HHV 6B) antigen was measured in three consecutive specimens obtained biweekly from 22 young children and infants suffering from acute measles, and in 19 influenza patients and nine healthy control subjects. HHV 6B DNA in peripheral blood mononuclear cells (PBMCs) was detected in 18 of 22 subjects with measles, but not in the influenza patients or the healthy population. A novel reactivation profile of HHV 6B was found in patients with measles in the milder form of immunosuppression than in patients with organ transplantation. HHV 6B specific lymphoproliferation activities increased correspondingly with reactivation of HHV 6B assessed by detecting HHV 6B DNA in PBMCs in patients with measles, but no significant change in either the antibody response to HHV 6B or DNAemia occurred in serial specimens obtained either from patients with influenza or healthy subjects. This novel form of HHV 6B reactivation without antibody response was observed in patients with measles. The dynamic fluctuations in lymphoproliferative responses in measles may represent the balance between HHV 6B reactivation and its suppression by the host immune system.

A preliminary diffusional kurtosis imaging study of Parkinson disease: comparison with conventional diffusion tensor imaging.

INTRODUCTION: Diffusional kurtosis imaging (DKI) is a more sensitive technique than conventional diffusion tensor imaging (DTI) for assessing tissue microstructure. In particular, it quantifies the microstructural integrity of white matter, even in the presence of crossing fibers. The aim of this preliminary study was to compare how DKI and DTI show white matter alterations in Parkinson disease (PD). METHODS: DKI scans were obtained with a 3-T magnetic resonance imager from 12 patients with PD and 10 healthy controls matched by age and sex. Tract-based spatial statistics were used to compare the mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA) maps of the PD patient group and the control group. In addition, a region-of-interest analysis was performed for the area of the posterior corona radiata and superior longitudinal fasciculus (SLF) fiber crossing. RESULTS: FA values in the frontal white matter were significantly lower in PD patients than in healthy controls. Reductions in MK occurred more extensively throughout the brain: in addition to frontal white matter, MK was lower in the parietal, occipital, and right temporal white matter. The MK value of the area of the posterior corona radiata and SLF fiber crossing was also lower in the PD group. CONCLUSION: DKI detects changes in the cerebral white matter of PD patients more sensitively than conventional DTI. In addition, DKI is useful for evaluating crossing fibers. By providing a sensitive index of brain pathology in PD, DKI may enable improved monitoring of disease progression.

Correlation between the spread of IMP-producing bacteria and the promoter strength of blaIMP genes.

The first report of transmissible carbapenem resistance encoded by blaIMP-1 was discovered in Pseudomonas aeruginosa GN17203 in 1988, and blaIMP-1 has since been detected in other bacteria, including Enterobacterales. Currently, many variants of blaIMPs exist, and point mutations in the blaIMP promoter have been shown to alter promoter strength. For example, the promoter (Pc) of blaIMP-1, first reported in P. aeruginosa GN17203, was a weak promoter (PcW) with low-level expression intensity. This study investigates whether point mutations in the promoter region have helped to create strong promoters under antimicrobial selection pressure. Using bioinformatic approaches, we retrieved 115 blaIMPs from 14,529 genome data of Pseudomonadota and performed multiple alignment analyses. The results of promoter analysis of the 115 retrieved blaIMPs showed that most of them used the Pc located in class 1 integrons (n = 112, 97.4%). The promoter analysis by year revealed that the blaIMP population with the strong promoter, PcS, was transient. In contrast, the PcW-TG population, which had acquired a TGn-extended -10 motif in PcW and had an intermediate promoter strength, gradually spread throughout the world. An inverse correlation between Pc promoter strength and Intl1 integrase excision efficiency has been reported previously [1]. Because of this trade-off, it is unlikely that blaIMPs with strong promoters will increase rapidly, but the possibility that promoter strength will increase with the use of other integrons cannot be ruled out. Monitoring of the blaIMP genes, including promoter analysis, is necessary for global surveillance of carbapenem-resistant bacteria.

Impact of Portal Flow on the Prognosis of Children With Congenital Portosystemic Shunt: A Multicentric Observation Study in Japan.

BACKGROUND: Although congenital portosystemic shunts (CPSSs) are increasingly being recognized, the optimal treatment strategies and natural prognosis remain unclear, as individual CPSSs show different phenotypes. METHODS: The medical records of 122 patients who were diagnosed with CPSSs at 15 participating hospitals in Japan between 2000 and 2019 were collected for a retrospective analysis based on the state of portal vein (PV) visualization on imaging. RESULTS: Among the 122 patients, 75 (61.5%) showed PV on imaging. The median age at the diagnosis was 5 months. The main complications related to CPSS were hyperammonemia (85.2%), liver masses (25.4%), hepatopulmonary shunts (13.9%), and pulmonary hypertension (11.5%). The prevalence of complications was significantly higher in patients without PV visualization than in those with PV visualization (P < 0.001). Overall, 91 patients (74.6%) received treatment, including shunt closure by surgery or interventional radiology (n = 82) and liver transplantation (LT) or liver resection (n = 9). Over the past 20 years, there has been a decrease in the number of patients undergoing LT. Although most patients showed improvement or reduced progression of symptoms, liver masses and pulmonary hypertension were less likely to improve after shunt closure. Complications related to shunt closure were more likely to occur in patients without PV visualization (P = 0.001). In 25 patients (20.5%) without treatment, those without PV visualization were significantly more likely to develop complications related to CPSS than those with PV visualization (P = 0.011). CONCLUSION: Patients without PV visualization develop CPSS-related complications and, early treatment using prophylactic approaches should be considered, even if they are asymptomatic. LEVEL OF EVIDENCE: Level III.

Fetal lung interstitial tumor: the first Japanese case report and a comparison with fetal lung tissue and congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3.

Fetal lung interstitial tumor, a newly recognized lung lesion in infants, was first reported in 2010. Here, we report the first Japanese case of fetal lung interstitial tumor which was originally diagnosed as atypical congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3. A 7-day-old girl was referred to our hospital with respiratory distress and a left lung mass and she subsequently underwent left lower lobectomy. The specimen showed a 5 cm solid mass with a fibrous capsule. Histological examination revealed immature airspaces and interstitium, containing bronchioles and cartilage. The epithelial and interstitial cells contained abundant glycogen granules. Immunohistochemistry showed nuclear/cytoplasmic expression of ß-catenin in the epithelial and interstitial cells. ß-catenin gene mutations and trisomy 8 were not detected, so a neoplastic origin could not be confirmed. The histological findings were partly consistent with normal fetal lung at the canalicular stage, pulmonary interstitial glycogenosis, and congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3. In this report, we compare the above conditions and discuss the pathogenesis of fetal lung interstitial tumor.

A case of Hirschsprung's disease with segmental dilatation of the colon.

BACKGROUND: Segmental dilatation of the colon (SDC) is a rare disease that is characterized by an abrupt segment of dilated colon between regions of normal-sized colon. We herein report a case of SDC associated with Hirschsprung's disease (HD). CASE PRESENTATION: The patient developed abdominal distension soon after birth, and enema examination showed localized intestinal dilatation from the descending colon to the sigmoid colon with significant caliber changes on both the oral and anal sides of the dilated colon. The findings of the rectal mucosal biopsy were consistent with HD. We considered this case to be a combination of HD and SDC and performed laparoscopic-assisted Soave pull-through with resection of the dilated colon when the patient was 7 months old. Resected specimens showed steep caliber changes on the oral and anal sides of the dilated colon. In the pathological examination, no ganglion cells were found in the submucosa on the anal side of the dilated colon. Based on the above findings, we finally made the diagnosis of HD with SDC. CONCLUSION: In HD with a characteristic dilated colon, the possibility of SDC should be considered.

Physical compatibility of remimazolam with opioid analgesics, sedatives, and muscle relaxants during simulated Y-site administration.

PURPOSE: There is a lack of information on the compatibility of remimazolam with opioid analgesics, muscle relaxants, and other sedatives. This study aimed to evaluate the physical compatibility of remimazolam with these drug classes. METHODS: Remimazolam was combined with 1 or 2 target drugs (remifentanil, fentanyl, rocuronium, vecuronium, dexmedetomidine, and midazolam). Ten physical compatibility tests were conducted, including four 3-drug compatibility tests. Remimazolam was dissolved in 0.9% sodium chloride injection to a final concentration of 5 mg/mL. Other medications were diluted in 0.9% sodium chloride injection to obtain clinically relevant concentrations. Compatibility tests were conducted with 3 test solutions, wherein remimazolam and the target drugs were compounded at equal volume ratios (1:1 or 1:1:1). Visual appearance was assessed and testing of Tyndall effect, turbidity, and pH was performed immediately after mixing and then again 1 hour and 4 hours after mixing. Appearance and turbidity were evaluated by comparison with the control solution of each target drug diluted with 0.9% sodium chloride injection to the same concentration as the test solution. RESULTS: All drugs tested were determined to be compatible with remimazolam. The drug combination with the highest change of turbidity was remimazolam and vecuronium (a mean increase of 0.16 NTU relative to the remimazolam control solution), 4 hours after mixing. The combination with the highest pH was remimazolam, fentanyl, and vecuronium (mean [SD], 3.76 [0.01]), 4 hours after mixing. The combination of remimazolam and fentanyl showed a larger change in pH at 4 hours after mixing (a mean increase of 2.6%) than immediately after mixing. CONCLUSION: Remifentanil, fentanyl, rocuronium, vecuronium, dexmedetomidine, and midazolam are physically compatible with remimazolam during simulated Y-site administration.

Complement C5a exhibits anxiolytic-like activity via the prostaglandin D2-DP1 receptor system coupled to adenosine A2A and GABAA receptors.

We have recently found that central PGD(2) exhibits anxiolytic-like activity. Here we show that complement C5a exhibits anxiolytic-like activity via the PGD(2) system. Centrally administered C5a had anxiolytic-like activity at a dose of 0.3 pmol/mouse in the elevated plus-maze test in mice. C5a-induced anxiolytic-like activity was inhibited by indomethacin, a cyclooxygenase inhibitor, or BWA868C, an antagonist of DP(1) receptor for PGD(2), respectively. The anxiolytic effect of C5a was also blocked by SCH58261 or bicuculline, antagonists of adenosine A(2A) and GABA(A) receptors, respectively, which were activated downstream of PGD(2)-DP(1) receptor. These results suggest that C5a exhibits anxiolytic-like activity via the PGD(2)-DP(1) receptor system coupled to the activation of adenosine A(2A) and GABA(A) receptors.