Sunday, November 8, 2020

Effects of Yinzhihuang Granules on Serum Liver Enzymes in Jaundice Patients: A Real-World Study Based on HIS Data

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Objective. Our aim was to analyze the influence of Yinzhihuang granules on serum liver enzymes in jaundice patients and to provide real-world evidence for the efficacy evaluation of Yinzhihuang granules in treating jaundice. Methods. We constructed a data warehouse which integrates real-world electronic medical records from the hospital information system of multiple 3A hospitals in China and used a descriptive statistical method to analyze the changes in the serum liver enzymes of the jaundice patients treated with Yinzhihuang granules and then used Wilcoxon signed-rank to test the changes in the indicators caused by the treatment. Results. After being treated with Yinzhihuang granules, the jaundice patients had a decrease in the average serum levels of total bilirubin, indirect bilirubin, aspartate amino transferase, glutamyl transpeptidase, and alkaline phosphatase, and the differences were statistically significant () but had no significant changes in the average serum levels of direct bilirubin and alanine aminotransferase ().Conclusion. The data analysis on the real-world electronic medical records demonstrate that Yinzhihuang granules help to reduce jaundice patients' serum levels of total bilirubin, indirect bilirubin, aspartate aminotransferase, glutamyl transpeptidase, and alkaline phosphatase, but there is no evidence that Yinzhihuang granules help to reduce the jaundice patients' serum levels of direct bilirubin and alanine aminotransferase.
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Acoustic Trauma Increases Ribbon Number and Size in Outer Hair Cells of the Mouse Cochlea

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Abstract

Outer hair cells (OHCs) in the mouse cochlea are contacted by up to three type II afferent boutons. On average, only half of these are postsynaptic to presynaptic ribbons. Mice of both sexes were subjected to acoustic trauma that produced a threshold shift of 44.2 ± 9.1 dB 7 days after exposure. Ribbon synapses of OHCs were quantified in post-trauma and littermate controls using immunolabeling of CtBP2. Visualization with virtual reality was used to determine 3-D cytoplasmic localization of CtBP2 puncta to the synaptic pole of OHCs. Acoustic trauma was associated with a statistically significant increase in the number of synaptic ribbons per OHC. Serial section TEM was carried out on similarly treated mice. This also showed a significant increase in the number of ribbons in post-trauma OHCs, as well as a significant increase in ribbon volume compared to ribbons in control OHCs. An increase in OHC ribbon synapses after acoustic trauma is a nov el observation that has implications for OHC:type II afferent signaling. A mathematical model showed that the observed increase in OHC ribbons considered alone could produce a significant increase in action potentials among type II afferent neurons during strong acoustic stimulation.

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ChAdOx1 nCoV-19 vaccine for SARS-CoV-2

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The ChAdOx1 nCoV-19 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), described by Pedro Folegatti and colleagues,1 was an important milestone in vaccine development to contain the ongoing pandemic. The vaccine is one of several SARS-CoV-2 vaccines that have entered the human trial phase, and the phase 1/2 trial showed encouraging results. This trial has focused on the most relevant clinical outcomes of safety, reactogenicity, and immunogenicity of the vaccine. The recruited participants (ie, healthy adults aged 18–55 years who were negative for SARS-CoV-2) were randomly assigned to receive either the vaccine (ie, ChAdOx1 nCoV-19 at a dose of 5 × 104 viral particles) or an active control (ie, a meningococcal conjugate vaccine; MenACWY) as a single intramuscular injection.
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Early triple antiviral therapy for COVID-19

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In the trial led by Ivan Hung and colleagues,1 adults admitted to hospital with COVID-19 received two antiviral treatment combinations. In the combination group, 52 (60%) of 86 patients received interferon beta-1b (most patients received one to two doses), lopinavir–ritonavir, and ribavirin, based on the time elapsed from symptom onset to the start of study treatment (median 5 days [IQR 4–7]). However, 34 (40%) patients had interferon beta-1b omitted due to concerns of proinflammatory side-effects in patients who started treatment 7 days or more after symptom onset.
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PWD/Ph-encoded genetic variants modulate the cellular Wnt/{beta}-Catenin response to suppress ApcMin-triggered intestinal tumor formation

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Genetic predisposition affects the penetrance of tumor-initiating mutations, such as APC mutations that stabilize β-Catenin and cause intestinal tumors in mice and humans. However, the mechanisms involved in genetically predisposed penetrance are not well understood. Here we analyzed tumor multiplicity and gene expression in tumor-prone ApcMin/+ mice on highly variant C57BL/6J and PWD/Ph genetic backgrounds. (C57BL/6J x PWD/Ph) F1 APCMin offspring mice were largely free of intestinal adenoma, and several consomic strains carrying single PWD/Ph chromosomes on the C57BL/6J genetic background displayed reduced adenoma numbers. Multiple dosage-dependent modifier loci on PWD/Ph chromosome 5 each contributed to tumor suppression. Activation of β-Catenin-driven and stem cell-specific gene expression in the presence of ApcMin or following APC loss remained moderate in intestines carrying PWD/Ph chromosome 5, suggesting that PWD/Ph variants restrict adenoma initiation by controlling s tem cell homeostasis. Gene expression of modifier candidates and DNA methylation on chromosome 5 were predominantly cis-controlled and largely reflected parental patterns, providing a genetic basis for inheritance of tumor susceptibility. Human SNP variants of several modifier candidates were depleted in colorectal cancer genomes suggesting that similar mechanisms may also affect the penetrance of cancer driver mutations in humans. Overall, our analysis highlights the strong impact that multiple genetic variants acting in networks can exert on tumor development.
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Cholangiocarcinoma Evaluation via Imaging and Artificial Intelligence.

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Via Oncology
Authors: Yang CM, Shu J Abstract BACKGROUND: Cholangiocarcinoma (CCA) is a relatively rare malignant biliary system tumor, and yet it represents the second most common primary hepatic neoplasm, following hepatocellular carcinoma. Regardless of the type, location, or etiology, the survival prognosis of these tumors remains poor. The only method of cure for CCA is complete surgical resection, but part of patients with complete resection are still subject to local recurrence or distant metastasis. SUMMARY: Over the last several decades, our understanding of the molecular biology of CCA has increased tremendously, diagnostic and evaluative techniques have evolved, and novel therapeutic approaches have been established. Key Messages: This review provides an overview of preoperative ...
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Magnetic resonance imaging features of intra-articular tenosynovial giant cell tumor in children

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Abstract

Background

Magnetic resonance imaging (MRI) plays a critical role in disease characterization of intra-articular tenosynovial giant cell tumor.

Objective

To characterize the MRI features of intra-articular tenosynovial giant cell tumor in children with respect to disease subtype and anatomical location.

Materials and methods

This retrospective study included children with tenosynovial giant cell tumor who underwent preoperative MRI between January 2006 and May 2020. Two radiologists reviewed each examination to determine disease subtype, signal intensities and the presence of an effusion, osseous changes, chondromalacia, juxtacapsular disease and concomitant joint involvement. Fisher exact, Mann-Whitney U, and Kruskal-Wallis H tests were used to compare findings between subtypes and locations.

Results

Twenty-four children (16 girls, 8 boys; mean age: 13.1±3.8 years) with 19 knee and 5 ankle-hindfoot tenosynovial giant cell tumor had either diffuse (n=15) or localized (n=9) disease. An effusion (P=0.004) was significantly more common with diffuse than localized disease. There was no significant difference in MRI signal (P-range: 0.09–1) or other imaging findings (P-range: 0.12–0.67) between subtypes. Children with knee involvement were significantly more likely to present with diffuse disease while those with ankle-hindfoot involvement all presented with focal disease (P=0.004). Juxtacapsular (n=4) and concomitant proximal tibiofibular joint involvement (n=5) were observed with diffuse disease in the knee. Erosions (P=0.01) were significantly more common in the ankle than in the knee.

Conclusion

In our study, diffuse tenosynovial giant cell tumor was more common than localized disease, particularly in the knee where juxtacapsular and concomitant proximal tibiofibular joint disease can occur.

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Normal anterior-posterior diameters of the spinal cord and spinal canal in healthy term newborns on sonography

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Abstract

Background

There are no published normal values for spinal cord and canal diameters in newborns. Spinal cord and spinal canal diameters are assessed subjectively by radiologists without any objective values for the upper limit of normal.

Objective

To determine normal values for anteroposterior (AP) diameters of the spinal cord and spinal canal on sonography in healthy term newborns.

Materials and methods

We performed ultrasound of the entire spine on 37 healthy newborns (23 male, 14 female). The AP diameters of the spinal canal and spinal cord were measured at representative levels of the cervical (C4, C5, C6), thoracic (T5, T6, T7, T8) and lumbar spine (lumbar enlargement and above and below the lumbar enlargement level). Statistical analysis was performed to determine the mean and standard deviation of the spinal canal and spinal cord AP diameter at each aforementioned vertebral level, and their correlations with birth weight, length and head circumference.

Results

The mean AP spinal cord diameter was 4.1±0.5 mm at the cervical level, 3.3±0.3 mm at the thoracic level and 4.4±0.6 mm at the lumbar level. The mean AP spinal canal diameter was 7.7±0.7 mm at the cervical level, 6.2±0.8 mm at the thoracic level, and 8.4±0.7 mm at the lumbar level.

Conclusion

In this prospective study, we have determined normal values for AP diameters of the spinal cord and spinal canal on sonography in healthy newborns at representative cervical, thoracic and lumbar levels. This data may assist in evaluating the neonatal spine in clinical situations such as suspected spinal cord injury.

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Non‐Conventional Dysplasia in Inflammatory Bowel Disease is More Frequently Associated with Advanced Neoplasia and Aneuploidy than Conventional Dysplasia

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Abstract

Aims

Several different non‐conventional morphologic patterns of epithelial dysplasia have been recently described in inflammatory bowel disease (IBD), but there is limited information regarding their clinicopathologic and molecular features as well as potential risk for high‐grade dysplasia (HGD) or colorectal cancer (CRC) compared with conventional dysplasia developing in IBD.

Methods and Results

A total of 317 dysplastic lesions from 168 IBD patients were analyzed. All lesions were re‐reviewed and subtyped as either conventional (including tubular adenoma‐like [n = 183] and tubulovillous/villous adenoma‐like [n = 56]) or non‐conventional dysplasia (including dysplasia with increased Paneth cell differentiation [DPD, n = 40], crypt cell dysplasia [CCD, n = 14], goblet cell deficient [GCD, n = 10], hypermucinous [n = 7], sessile serrated lesion [SSL]‐like [n = 4], and traditional serrated adenoma [TSA]‐like [n = 3]). DNA flow cytometry was performed on 70 low‐grade conventional (n = 24) and non‐conventional (n = 46) dysplastic biopsies to determine their malignant potential and molecular pathways to HGD or CRC. Eleven sporadic tubular adenomas with low‐grade dysplasia (LGD) were utilized as controls. Seventy‐eight non‐conventional dysplastic lesions were identified in 56 (33%) of the 168 patients, whereas 239 conventional dysplastic lesions were identi fied in 149 (89%) patients. Although both non‐conventional and conventional dysplasias were most often graded as LGD at diagnosis (83% and 84%, respectively), non‐conventional dysplasia (38%) was more likely to develop HGD or CRC in the same colonic segment than conventional dysplasia (19%) on follow‐up (p = < 0.001). Almost half (46%) of non‐conventional dysplastic samples showed aneuploidy, whereas only 8% of conventional dysplasia (p = 0.002) and 9% of sporadic tubular adenomas (p = 0.037) did. Also, non‐conventional dysplasia more frequently presented as a flat/invisible lesion (41%) compared with conventional dysplasia (18%) (p < 0.001). Among the non‐conventional subtypes (n = 78), DPD was the most common (n = 40; 51%), followed by CCD (n = 14; 18%), GCD (n = 10; 13%), hypermucinous (n = 7; 9%), SSL‐like (n = 4; 5%), and TSA‐like (n = 3; 4%) variants. Hypermucinous dysplasia (mean: 2.1 cm) was significantly larger than DPD, SSL‐like, TSA‐like, and GCD variants (mean: 1.0, 1.2, 1.2, and 1.9 cm, respectively) (p = 0.037). HGD or CRC was more likely to be associated with CCD (n = 13; 93%), hypermucinous (n = 4; 57%), GCD (n = 4; 40%), and SSL‐like (n = 3; 75%) variants than DPD (n = 6; 15%) and TSA‐like dysplasia (n = 0; 0%) (p = < 0.001). Furthermore, the rate of aneuploidy was significantly higher in CCD (100%), hypermucinous (80%), and GCD (25%) variants than in DPD (12%), SSL‐like dysplasia (0%), and TSA‐like dysplasia (0%) (p < 0.001).

Conclusions

Non‐conventional morphologic patterns of dysplasia are not uncommon in IBD, detected in 33% of the patients. The higher frequencies of advanced neoplasia (HGD or CRC) and aneuploidy in non‐conventional dysplasia, in particular CCD, hypermucinous, and GCD variants, suggest that they may have a higher malignant potential than conventional dysplasia or sporadic tubular adenoma, and thus, need complete removal and/or careful follow‐up. Greater than 40% of non‐conventional dysplasia presented as a flat/invisible lesion, suggesting that IBD patients may benefit from random biopsy sampling in addition to targeted biopsies. The majority of non‐conventional subtypes appear to develop via the chromosomal instability pathway, whereas an alternative serrated pathway may be responsible for the development of at least a subset of SSL‐like and TSA‐like dysplasias.

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Primary mucinous ovarian neoplasms rarely exhibit a germ cell histogenesis

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Abstract

Recently, genetic analyses of primary mucinous ovarian tumours (MOT) have considerably enhanced our understanding of the biology of such neoplasms, supporting a progressive model of carcinogenesis from benign/borderline tumours to carcinomas. Nevertheless, the histogenesis of these neoplasms remains a subject of discussion and several cell types of origin have been proposed; a proportion of these tumours are associated with Brenner (transitional cell) tumours, therefore some are believed to be derived from metaplastic mucinous epithelium lining cystic transitional cell nests (Walthard rests).

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Inclusion of multiple high‐risk histopathological criteria improves the prediction of adjuvant chemotherapy efficacy in lung adenocarcinoma

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Abstract

Aims

The decision to consider adjuvant chemotherapy (AC) for non‐small cell lung cancer is currently governed by clinical stage. This study aims to assess other routinely collected pathological variables related to metastasis and survival for their ability to predict the efficacy of AC in lung adenocarcinoma.

Methods and Results

A retrospective single‐centre series of 620 resected lung non‐mucinous adenocarcinoma cases from 2005‐2015 was used. Digital images of all slides were subjected to central review, and data on tumour histopathology, AC treatment and patient survival were compiled. A statistical case matching approach was used to counter selection bias. Several high‐risk pathological criteria predict both pathological nodal involvement and early death: positive vascular invasion status (VI+) (HR=2.10 P<0.001), positive visceral pleural invasion status (VPI+) (HR=2.16 P<0.001), and solid/micropapillary‐predominant WHO tumour type (SPA/MPPA) (HR=3.29 P<0.001). Crucially, these criteria also identify patient groups benefiting from AC (VI+ HR=0.69 P=0.167, VPI+ HR=0.44 P=0.004, SPA/MPPA HR=0.36 P=0.006). Cases showing VI+/VPI+/SPA/MPPA histology in the absence of AC stage criteria were common (170 of 620 total), and 8 had actually received AC. This group showed much better outcomes th an equivalent untreated cases in matched analysis (3‐year OS 100.0% vs 31.3%). Inclusion of patients with VI+/VPI+/SPA/MPPA histology would increase AC‐eligible patients from 51.0% to 84.0% of non‐mucinous tumours in our cohort.

Conclusions

Our data provide preliminary evidence that the consideration of AC in patients with additional high‐risk pathological indicators may significantly improve outcomes in operable lung adenocarcinoma, and that AC may be currently underused.

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Preoperative underweight is associated with adverse postoperative events in patients undergoing microvascular reconstruction surgery for oral and maxillofacial cancer

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We aimed to describe the prevalence of postoperative complications and evaluate its relationship with underweight, obesity, preoperative nutritional status, and systemic inflammation status in patients undergoing microvascular reconstruction for oral and maxillofacial cancer. Patients who were ≥20 years old and underwent microvascular reconstruction surgery between January 2009 to June 2019 were investigated. Patient demographics including body mass index, prognostic nutritional status, and neutrophil-lymphocyte ratio were collected. (Source: International Journal of Oral and Maxillofacial Surgery)
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