Aim
We aimed to examine the relationship between the Wisteria floribunda agglutinin positive Mac‐2‐binding protein (WFA+‐M2BP) level and high‐sensitivity C‐reactive protein (hCRP) concentration and ...liver histological findings for patients with autoimmune hepatitis (AIH).
Methods
A total of 84 AIH patients (median age, 64 years) were analyzed. We examined the effect of pretreatment WFA+‐M2BP level and hCRP concentration on histological findings of liver fibrosis and liver inflammation activity comparing with other laboratory markers. Receiver–operator curve (ROC) analysis was performed for calculating the area under the ROC (AUROC).
Results
The median WFA+‐M2BP values in each fibrosis stage were: 1.5 cut‐off index (COI) in F1, 2.1 in F2, 3.3 in F3 and 9.8 in F4 (P < 0.001). The median WFA+‐M2BP values in each liver inflammation stage were: 1.6 COI in A1, 2.5 in A2 and 5.4 in A3 (P < 0.001). For predicting liver cirrhosis (F4), WFA+‐M2BP yielded the highest AUROC (0.853). For predicting advanced liver fibrosis (F3 or F4), WFA+‐M2BP, FIB‐4 index and hyaluronic acid yielded the highest AUROC (0.747). For predicting severe liver inflammation activity (A3), WFA+‐M2BP yielded the highest AUROC (0.739). The hCRP concentration in patients with A3 (median, 2230 ng/mL) was significantly higher than that in patients with A1 or A2 (median, 854.5 ng/mL) (P < 0.01). WFA+‐M2BP level significantly correlated with hCRP concentration (rs = 0.461, P < 0.001).
Conclusion
WFA+‐M2BP can be a useful marker for assessing liver histological findings in AIH patients and it correlated well with hCRP concentration.
Aim
Transient elastography (TE) is the gold standard for measurement of liver stiffness. The usefulness of shear wave elastographies (SWE) is well accepted. However, the measurement values cannot be ...equivalently compared because cut‐off values for the diagnosis of liver fibrosis are different among those devices.
We aimed to clarify correlations, to generate the regression equations between TE and SWEs, and to compare the diagnostic ability of each device to diagnose liver fibrosis.
Methods
A total of 109 patients with chronic liver disease who underwent liver biopsy and same‐day evaluation of liver stiffness using six ultrasound devices were analyzed. The diagnostic ability of liver stiffness from each ultrasound device and correlations between TE and each SWE were analyzed.
Results
Liver stiffness measured by all six ultrasound devices increased significantly as liver fibrosis stage advanced (P < 0.001). Receiver operating characteristic (ROC) curve analysis for predicting significant fibrosis (≥F2) and cirrhosis yielded area under the ROC curve (AUROC) values based on TE of 0.830 (95% confidence interval CI, 0.755–0.905) and 0.959 (95% CI, 0.924–0.995), respectively. The AUROCs for predicting significant fibrosis (≥F2) and cirrhosis (F4) based on SWE from all five ultrasound devices were over 0.8 and 0.9, respectively. Furthermore, the correlation coefficients between TE values and SWE values from five ultrasound devices were all over 0.8, indicating a strong relationship.
Conclusion
Our study showed strong correlations between TE and SWEs with high correlation coefficients. The regression equations between TE and SWEs demonstrated the ability to compare the measurement values in each device equivalently.
BACKGROUND Pleuroparenchymal fibroelastosis (PPFE) is a rare form of interstitial pneumonia and sometimes coexists with a histologic usual interstitial pneumonia (UIP) pattern. This study aimed to ...describe the distinct clinical features of PPFE with UIP pattern compared with idiopathic pulmonary fibrosis (IPF). METHODS We conducted a retrospective review of the medical records of 110 consecutive patients with IPF with a histologic UIP pattern on surgical lung biopsy specimen. Patients meeting radiologic criteria for the diagnosis of PPFE based on high-resolution CT scan and with a histologic UIP pattern were included. RESULTS Nine of eleven patients meeting radiologic criteria for the diagnosis of PPFE were histologically confirmed as having PPFE with UIP pattern. The PPFE with UIP pattern group showed a significantly higher residual volume (1.8 L vs 1.3 L, P < .01), higher Paco2 (44.6 mm Hg vs 41.7 mm Hg, P = .04), and higher complication rate of pneumothorax and pneumomediastinum than the 99 patients with IPF/UIP. The ratio of anteroposterior to transthoracic diameter in patients with PPFE with UIP pattern was significantly lower than that in patients with IPF/UIP ( P = .04). Survival time tended to be shorter in patients with PPFE with UIP pattern. CONCLUSIONS The results support the view that PPFE with UIP pattern is a disease entity distinct from IPF/UIP and may well be classified as PPFE.
Atypical phenotype of an imprinting disease can develop with a recessive homozygous variant due to uniparental isodisomy. We present a girl with severe intellectual disability, developmental delay, ...distinctive facial features, and other neuropsychiatric features. Trio whole exome sequencing revealed a novel homozygous frameshift variant in AP4E1 NM_007347.5:c.2412dupT:p.(Gly805Trpfs*8) and uniparental isodisomy of chromosome 15 iUPD(15). Single nucleotide polymorphism mapping analysis of exome data showed that the homozygous AP4E1 variant was derived from her heterozygous carrier father and unmasked by paternal iUPD(15). Brain magnetic resonance imaging confirmed the brain abnormalities characteristic of AP4 deficiency including the dilated ventricles and hypointensity in the globus pallidus in susceptibility-weighted imaging. This is the first case report of a combination of AP4E1 deficiency and Angelman syndrome. Our patient indicates that whole exome sequencing could uncover an atypical phenotype caused by multiple genetic factors including the uniparental isodisomy.
Size exclusion chromatography (SEC) with a multiangle light scattering (MALS) detector is widely used as standard molecular characterization equipment. The interdetector delay volume (IDV) between ...the MALS and differential refractometer (RI) detectors is an essential instrumental parameter that affects reliability and accuracy. However, a reliable and accurate determination method has not been established to date. This paper presents a method for determining the IDV value. SEC-MALS elution behavior has been thoroughly studied for polystyrene (PSt) standards with weight average molar mass (Mw) ranging from 1.02 × 104 to 109 × 104 g mol−1, ethylbenzene, and bovine serum albumin at different flow rates (U) ranging from 0.1 to 1.0 cm3 min−1 and at different particle sizes (dp) of the porous packing gels ranging from 5 to 30 μm. The apparent IDV values, IDVapp, estimated by superimposing the RI signal on the MALS signal, varied considerably with U, dp, and Mw because of band broadening and turbulence. The heights equivalent to a theoretical plate, H, were estimated for the MALS chromatogram (HMALS) and RI chromatogram (HRI), and they were rationalized as a function of U, Mw, and dp. The IDVapp functions HMALS and ΔH = HMALS − HRI corresponded to the band broadening occurring in SEC columns and the disturbance effects in the connecting tube between the MALS and RI detectors and in both cells, respectively. A reliable IDV was obtained when both the HMALS and ΔH values were minimized, i.e., U → 0 and Mw → 0. The IDV value determined at U = 0 and Mw = 0 was 24% lower than resulting from the currently recommended method. A SEC-MALS setup with the correct IDV value enables one to estimate more accurately not only the Mw and z-average root-mean-square radius of gyration but also the number average molar mass (Mn) and differential weight distribution function for PSts having narrow and broad molar mass distributions.The interdetector delay volumes (IDV) for multiangle light scattering (MALS) and differential refractometer detectors are essential instrumental parameters affecting reliability and accuracy. However, a reliable and accurate determination method has not yet been established. The paper proposes a method for determining the IDV value. An SEC-MALS setup with the correct IDV value provides more accurate estimates of not only the weight average molar mass and z-average mean-square radius of gyration but also the number average molar mass and differential weight distribution function for polymer samples having narrow and broad molar mass distributions.
The prognosis of elderly individuals with idiopathic pulmonary fibrosis (IPF) remains poor. Fibroblastic foci, in which aggregates of proliferating fibroblasts and myofibroblasts are involved, are ...the pathological hallmark lesions in IPF to represent focal areas of active fibrogenesis. Fibroblast heterogeneity in fibrotic lesions hampers the discovery of the pathogenesis of pulmonary fibrosis. Therefore, to determine the pathogenesis of IPF, identification of functional fibroblasts is warranted. The aim of this study was to determine the role of fibroblasts positive for meflin, identified as a potential marker for mesenchymal stromal cells, during the development of pulmonary fibrosis.We characterised meflin-positive cells in a single-cell atlas established by single-cell RNA sequencing (scRNA-seq)-based profiling of 243 472 cells from 32 IPF lungs and 29 normal lung samples. We determined the role of fibroblasts positive for meflin using bleomycin (BLM)-induced pulmonary fibrosis.scRNA-seq combined with
RNA hybridisation identified proliferating fibroblasts positive for meflin in fibroblastic foci, not dense fibrosis, of fibrotic lungs in IPF patients. A BLM-induced lung fibrosis model for meflin-deficient mice showed that fibroblasts positive for meflin had anti-fibrotic properties to prevent pulmonary fibrosis. Although transforming growth factor-β-induced fibrogenesis and cell senescence with the senescence-associated secretory phenotype were exacerbated in fibroblasts
the repression or lack of meflin, these were inhibited in meflin-deficient fibroblasts with meflin reconstitution.These findings provide evidence to show the biological importance of meflin expression on fibroblasts and myofibroblasts in the active fibrotic region of pulmonary fibrosis.
Background
Oral care using chlorhexidine has been considered useful in reducing the incidence of ventilator‐associated pneumonia (VAP) in adult patients. However, no study has proved the effect of ...oral care in reducing the incidence of VAP in preterm infants.
Objectives
To investigate the efficacy of oral care using a sponge brush moistened with sterile water in reducing the bacterial load in the oral cavity and the incidence of early‐onset VAP in preterm infants
Methods
The bacterial number in the oral cavity was evaluated on‐site with the dielectrophoretic impedance measurement system. Bacterial numbers before and after oral care were investigated prospectively. Then, the incidence of early‐onset VAP was compared retrospectively between infants who received oral care before re‐intubation and those who did not.
Results
The mean bacterial number (cfu/ml) in the oral cavity in infants managed with endotracheal intubation (n = 23), continuous positive airway pressure (n = 38), and high‐flow nasal cannula (n = 22) significantly reduced (p < .01) after versus before oral care (4.46 × 107 vs. 1.25 × 106; 1.32 × 107 vs. 6.82 × 105; and 1.68 × 107 vs. 6.50 × 105). The incidence rate of early‐onset VAP after re‐intubation was 51% (20/39) in patients who did not receive oral care. Then, it significantly decreased to 21% (7/33; p = .009) after receiving oral care.
Conclusion
Oral care with sterile water may be effective in reducing the bacterial load in the oral cavity and the incidence of early‐onset VAP in preterm infants.
A loss-of-function mutation of SET causes nonsyndromic intellectual disability, often associated with mild facial dysmorphic features, including plagiocephaly, facial asymmetry, broad and high ...forehead, a wide mouth, and a prominent mandible. We report a male individual with a 2.0 Mb deletion within 9q34.11, involving SET and SPTAN1, but not STXBP1. Among the genes with a high probability of being loss-of-function intolerant in the deletion interval, only SPTAN1 and SET had haploinsufficiency score (%HI) <10, indicating a high likelihood of haploinsufficiency. Pathogenic variants in SPTAN1 are responsible for early-onset epileptic encephalopathy by exerting a dominant-negative effect. However, whether haploinsufficiency of SPTAN1 alone also causes the severe phenotype remained unknown. SET is a regulator of cell differentiation in early human development and a component of the inhibitor of histone acetyltransferases complex. Therefore, combining the previously reported patients, our patient delineated the phenotypic spectrum of SET-related nonsyndromic intellectual disability with mild facial dysmorphism.
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