Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia.

BACKGROUND: Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels. RESULTS: Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels. CONCLUSIONS: In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA. (Funded by the National Natural Science Foundation of China and the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine; ClinicalTrials.gov number, NCT02707484.).

ZBTB20 is essential for cochlear maturation and hearing in mice.

The mammalian cochlear epithelium undergoes substantial remodeling and maturation before the onset of hearing. However, very little is known about the transcriptional network governing cochlear late-stage maturation and particularly the differentiation of its lateral nonsensory region. Here, we establish ZBTB20 as an essential transcription factor required for cochlear terminal differentiation and maturation and hearing. ZBTB20 is abundantly expressed in the developing and mature cochlear nonsensory epithelial cells, with transient expression in immature hair cells and spiral ganglion neurons. Otocyst-specific deletion of Zbtb20 causes profound deafness with reduced endolymph potential in mice. The subtypes of cochlear epithelial cells are normally generated, but their postnatal development is arrested in the absence of ZBTB20, as manifested by an immature appearance of the organ of Corti, malformation of tectorial membrane (TM), a flattened spiral prominence (SP), and a lack of identifiable Boettcher cells. Furthermore, these defects are related with a failure in the terminal differentiation of the nonsensory epithelium covering the outer border Claudius cells, outer sulcus root cells, and SP epithelial cells. Transcriptome analysis shows that ZBTB20 regulates genes encoding for TM proteins in the greater epithelial ridge, and those preferentially expressed in root cells and SP epithelium. Our results point to ZBTB20 as an essential regulator for postnatal cochlear maturation and particularly for the terminal differentiation of cochlear lateral nonsensory domain.

Passive Focusing of Single Cells Using Microwell Arrays for High-Accuracy Image-Activated Sorting.

Sorting single cells from a population was of critical importance in areas such as cell line development and cell therapy. Image-based sorting is becoming a promising technique for the nonlabeling isolation of cells due to the capability of providing the details of cell morphology. This study reported the focusing of cells using microwell arrays and the following automatic size sorting based on the real-time recognition of cells. The simulation first demonstrated the converged streamlines to the symmetrical plane contributed to the focusing effect. Then, the influence of connecting microchannel, flowing length, particle size, and the sample flow rate on the focusing effect was experimentally analyzed. Both microspheres and cells could be aligned in a straight line at the Reynolds number (Re) of 0.027-0.187 and 0.027-0.08, respectively. The connecting channel was proved to drastically improve the focusing performance. Afterward, a tapered microwell array was utilized to focus sphere/cell spreading in a wide channel to a straight line. Finally, a custom algorithm was employed to identify and sort the size of microspheres/K562 cells with a throughput of 1 event/s and an accuracy of 97.8/97.1%. The proposed technique aligned cells to a straight line at low Reynolds numbers and greatly facilitated the image-activated sorting without the need for a high-speed camera or flow control components with high frequency. Therefore, it is of enormous application potential in the field of nonlabeled separation of single cells.

The gut microbiota participates in the effect of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C): a multicenter, prospective, pre-post study.

BACKGROUND: Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy. METHODS: IBS-C patients were administered a daily linaclotide dose of 290 µg over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations. RESULTS: Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the Blautia genus, and the abundance of Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients. CONCLUSION: The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).

A new artificial intelligence system for both stomach and small bowel capsule endoscopy.

BACKGROUND AND AIMS: Despite the benefits of artificial intelligence (AI) in small bowel (SB) capsule endoscopy (CE) image reading, information on its application in the stomach and SB CE is lacking. METHODS: In this multicenter, retrospective diagnostic study, gastric imaging data were added to the deep learning (DL)-based SmartScan (SS), which has been described previously. A total of 1,069 magnetically controlled gastrointestinal (GI) CE examinations (comprising 2,672,542 gastric images) were used in the training phase for recognizing gastric pathologies, producing a new AI algorithm named SS Plus. 342 fully automated, magnetically controlled CE (FAMCE) examinations were included in the validation phase. The performance of both senior and junior endoscopists with both the SS Plus-Assisted Reading (SSP-AR) and conventional reading (CR) modes was assessed. RESULTS: SS Plus was designed to recognize 5 types of gastric lesions and 17 types of SB lesions. SS Plus reduced the number of CE images required for review to 873.90 (1000) (median, IQR 814.50-1,000) versus 44,322.73 (42,393) (median, IQR 31,722.75-54,971.25) for CR. Furthermore, with SSP-AR, endoscopists took 9.54 min (8.51) (median, IQR 6.05-13.13) to complete the CE video reading. In the 342 CE videos, SS Plus identified 411 gastric and 422 SB lesions, whereas 400 gastric and 368 intestinal lesions were detected with CR. Moreover, junior endoscopists remarkably improved their CE image reading ability with SSP-AR. CONCLUSIONS: Our study shows that the newly upgraded DL-based algorithm SS Plus can detect GI lesions and help improve the diagnostic performance of junior endoscopists in interpreting CE videos.

Lactobacillus rhamnosus GG ameliorates triptolide-induced liver injury through modulation of the bile acid-FXR axis.

Triptolide (TP) is the principal bioactive compound of Tripterygium wilfordii with significant anti-tumor, anti-inflammatory and immunosuppressive activities. However, its severe hepatotoxicity greatly limits its clinical use. The underlying mechanism of TP-induced liver damage is still poorly understood. Here, we estimate the role of the gut microbiota in TP hepatotoxicity and investigate the bile acid metabolism mechanisms involved. The results of the antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) experiment demonstrate the involvement of intestinal flora in TP hepatotoxicity. Moreover, TP treatment significantly perturbed gut microbial composition and reduced the relative abundances of Lactobacillus rhamnosus GG (LGG). Supplementation with LGG reversed TP-induced hepatotoxicity by increasing bile salt hydrolase (BSH) activity and reducing the increased conjugated bile acids (BA). LGG supplementation upregulates hepatic FXR expression and inhibits NLRP3 inflammasome activation in TP-treated mice. In summary, this study found that gut microbiota is involved in TP hepatotoxicity. LGG supplementation protects mice against TP-induced liver damage. The underlying mechanism was associated with the gut microbiota-BA-FXR axis. Therefore, LGG holds the potential to prevent and treat TP hepatotoxicity in the clinic.

Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents.

Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9-guide RNA-lipid complexes targeting the Tmc1Bth allele into the cochlea of neonatal Tmc1Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected Tmc1Bth/+ mice. These findings suggest that protein-RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.

Effects of Bone Transport Combined with Drug-loaded Calcium Sulfate on Expression of Inflammatory Factors and VEGF in Rats with Infectious Bone Defects.

Background: Infectious bone defect refers to severe bone tissue damage caused by skeletal infection, often resulting in impaired skeletal function and intense inflammatory responses. Treating infectious bone defects is a challenging task, as conventional treatment methods often fail to completely eliminate the infection focus and may easily lead to inflammatory responses in the bone defect area. Objective: To examine the impacts of bone transport (BT) in conjunction with drug-loaded calcium sulfate (DLCS) on the expression of inflammatory factors and vascular endothelial growth factor (VEGF) in rats with infectious bone defects. Methods: A total of 40 rats were randomly allocated to 4 groups-the sham, model, BT, and BT + DLCS groups-with 10 rats in each group. Interleukin 10 (IL-10), tumor necrosis factor (TNF), nuclear factor-κB (NF-κB), insulinlike growth factor 1 (IGF 1), and recombinant human basic fibroblast growth factor (rhbFGF) concentrations in serum were measured using enzyme-linked immunosorbent assay. In bone tissue, histopathological changes in defective bone were assessed through hematoxylin-eosin staining, CD34 expression was examined by immunohistochemistry, and VEGF expression was examined by Western blot. Results: In comparison with the sham group, the model group had significant increases in serum IL-10, TNF, and NF-κB concentrations as well as notable decreases in IGF-1 and rhbFGF serum concentrations and CD34 and VEGF expression in the bone tissue (P < .05). In contrast to the model group, both the BT and BT + DLCS groups had significant reductions in serum concentrations of IL-10, TNF, and NF-κB. Additionally, the BT and BT + DLCS groups had significant increases in serum concentrations of IGF-1 and rhbFGF as well as expression of CD34 and VEGF in the bone tissue (P < .05). The BT + DLCS group had significantly lower serum concentrations of IL-10, TNF, and NF-κB compared with the BT group. Furthermore, the BT + DLCS group had significantly elevated serum concentrations of IGF-1 and rhbFGF as well as increased expression of CD34 and VEGF in the bone tissue compared with the BT group (P < .05). Conclusion: The promotion of infected bone defect healing in rats through the combination of BT and DLCS may be attributed to the suppression of inflammatory responses and the elevation of VEGF expression to facilitate vascular regeneration.

Changes of gut microbiota and short chain fatty acids in patients with Peutz-Jeghers syndrome.

Peutz-Jeghers Syndromeis a rare autosomal dominant genetic disease characterized by gastrointestinal hamartomatous polyps and skin and mucous membrane pigmentation. The pathogenesis of PJS remains unclear; however, it may be associated with mutations in the STK11 gene, and there is currently no effective treatment available. The gut microbiota plays an important role in maintaining intestinal homeostasis in the human body, and an increasing number of studies have reported a relationship between gut microbiota and human health and disease. However, relatively few studies have been conducted on the gut microbiota characteristics of patients with PJS. In this study, we analyzed the characteristics of the gut microbiota of 79 patients with PJS using 16 S sequencing and measured the levels of short-chain fatty acids in the intestines. The results showed dysbiosis in the gut microbiota of patients with PJS, and decreased synthesis of short-chain fatty acids. Bacteroides was positively correlated with maximum polyp length, while Agathobacter was negatively correlated with age of onset. In addition, acetic acid, propionic acid, and butyric acid were positively correlated with the age of onset but negatively correlated with the number of polyps. Furthermore, the butyric acid level was negatively correlated with the frequency of endoscopic surgeries. In contrast, we compared the gut microbiota of STK11-positive and STK11-negative patients with PJS for the first time, but 16 S sequencing analysis revealed no significant differences. Finally, we established a random forest prediction model based on the gut microbiota characteristics of patients to provide a basis for the targeted diagnosis and treatment of PJS in the future.

Roles of Activated Carbon in UV/Chlorine/Activated Carbon-TiO2 Process for Micropollutant Abatement and DBP Control.

The ultraviolet (UV)/chlorine process has attracted increasing attention for micropollutant abatement. However, the limited hydroxyl radical (HO•) generation and the formation of undesired disinfection byproducts (DBPs) are the two major issues in this process. This study investigated the roles of activated carbon (AC) in the UV/chlorine/AC-TiO2 process for micropollutant abatement and DBP control. The degradation rate constant of metronidazole by UV/chlorine/AC-TiO2 was 3.44, 2.45, and 1.58 times higher than those by UV/AC-TiO2, UV/chlorine, and UV/chlorine/TiO2, respectively. AC acted as an electron conductor and dissolved oxygen (DO) adsorbent, resulting in the steady-state concentration of HO• that was ∼2.5 times that of UV/chlorine. Compared with UV/chlorine, the formation of total organic chlorine (TOCl) and known DBPs in UV/chlorine/AC-TiO2 was reduced by 62.3 and 75.7%, respectively. DBP could be controlled via adsorption on AC, and the increased HO• and decreased chlorine radical (Cl•) and chlorine exposure reduced DBP formation. UV/chlorine/AC-TiO2 efficiently abated 16 structurally different micropollutants under environmentally relevant conditions owing to the enhanced generation of HO•. This study provides a new strategy for designing catalysts with photocatalytic and adsorption properties for UV/chlorine to promote micropollutant abatement and DBP control.

Prognostic factor analysis in patients with early-stage nasopharyngeal carcinoma in the USA.

Aim: To evaluate independent risk factors specific for early-stage nasopharyngeal carcinoma (NPC). Methods: A total of 566 patients with early-stage NPC from 2004 to 2019 were identified using the Surveillance, Epidemiology and End Results database. Results: Older ages (70-79 and >80 years) were independent risk factors, with hazard ratios of 1.961 and 5.011, respectively. The hazard ratio for early-stage NPC in Asian and Pacific Islander residents (0.475) was lower than that for White residents. A tumor size <3 cm was a protective factor for overall and cancer-specific survival in the current study. Conclusion: In patients with early-stage NPC, age >70 years, race and tumor size were independent prognosticators for cancer-specific survival.

Surgical management of endolymphatic sac tumor: classification, outcomes and strategy. A single institution's experience.

PURPOSE: To review the resections of endolymphatic sac tumor (ELST) and describe our experience in the surgical management of ELST. METHODS: Retrospective investigation of consecutive patients who underwent resection of ELSTs at our hospital between 1999 and 2019. The symptoms, diagnosis, surgical findings, and outcomes were analyzed to develop a tumor staging system and corresponding surgical strategy. RESULTS: Retrospective review revealed the surgical treatment of 22 ELSTs. Based on intraoperative findings of tumor extent and size, ELSTs were classified into two types. Type-I (n = 6) referred to the small tumors that were locally confined with limited invasion of semicircular canals and dura; type-II (n = 16) referred to the large tumors that presented extensive erosion of at least one anatomic structure apart from the semicircular canals and the dura around endolymphatic sac. In this case series, Type-I ELST is amenable to resection through a transmastoidal approach, and subtotal petrosectomy is appropriate for the resection of type-II ELST. Sensorineural hearing loss (SNHL) is the most commonly preoperative symptom in both two types of cases. Five type-II ELSTs experienced recurrence and underwent reoperation, whereas all type-I ELSTs did not. CONCLUSION: ELST usually results in SNHL (95%) at the time of diagnosis. The surgical strategy and prognosis of ELST resections are different between type-I and type-II: type-I ELST is amenable to transmastoidal approach with the preservation of facial nerve, whereas type-II ELST increase the surgical difficulty and the risk of recurrence, and subtotal petrosectomy is the basic requirement for the resection of type-II ELST.

[Latest Findings on the Effect of Gastrointestinal Microecology Remodeling of Tumor Microenvironment on Tumor Stemness].

Gastrointestinal microecology (GM) system is composed of normal gut microbiota and its living environment. The impact of GM on human health and many diseases has been widely studied. The impact of GM system on tumors is mainly reflected in the remodeling of the tumor microenvironment (TME). TME, a special microenvironment that tumors live in, can regulate the characteristics of tumor cells and affect the occurrence and development of tumors through intercellular contact and the secretion of cytokines. At present, cancer stem cell (CSC) model is considered an important theory that explains the origin and malignant progression of tumors. The formation and proliferation of CSC usually represent increased tumor invasion, metastasis, and chemotherapy resistance, resulting in poor clinical prognosis in patients. Therefore, it is important to study the role and mechanism through which GM system affects the acquisition of CSC characteristics through remodeling TME, thereby affecting tumor invasion, metastasis, and chemotherapy resistance. Studies on this topic are of great significance for clinical understanding of tumor malignant progression and improving tumor treatment outcomes. However, due to the low content of single bacteria in the gastrointestinal model, high heterogeneity, and difficulty in tracing distant metastasis, there are still great limitations in the previous research. Herein, we reviewed the research progress in the effect of GM remodeling of TME on the acquisition of tumor stemness, tumor invasion and metastasis, and the resistance to chemotherapy.

Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification.

BACKGROUND: Gastric cancer (GC) is one of the most pernicious tumors that seriously harm human healthcare. GC metastasis is one of the prime cause of failed cancer treatment, but correlation between N6-methyladenosine (m6A) and GC metastasis was less reported. METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) of GC tissues was conducted. Quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry (IHC) were taken to determine the expression of ALKBH5 in GC tissues and cell lines. RNA-seq together with MeRIP-qRT-PCR was used to screen the target gene of ALKBH5. RNA pulldown, mass spectrometry and RNA immunoprecipitation (RIP) were used to search the "reader" protein of target gene. The mechanism was also validated via a tail vein injection method for lung metastasis model. RESULTS: Decreased expression of ALKBH5 was detected in GC samples, and it was correlated with clinical tumor distal metastasis and lymph node metastasis. ALKBH5 interference promoted metastasis of GC cells and this effect was closely related to the demethylase activity of ALKBH5. PKMYT1, as a downstream target of ALKBH5, promoted invasion and migration in GC. Caused by ALKBH5 knockdown or its demethylase activity mutation, upregulated expression of PKMYT1 indicated that ALKBH5 modulates expression of PKMYT1 in an m6A-dependent manner. IGF2BP3 helped stabilize the mRNA stability of PKMYT1 via its m6A modification site. CONCLUSIONS: This study established an ALKBH5-PKMYT1-IGF2BP3 regulation system in metastasis, representing a new therapeutic target for GC metastasis.

Lithium carbonate alleviates colon inflammation through modulating gut microbiota and Treg cells in a GPR43-dependent manner.

BACKGROUND: Recent evidence suggests that neuropsychiatric stabilizers have a place in resolving gastrointestinal disorders. Lithium carbonate (LC) is one of the most commonly used drugs for bipolar disorder clinically. Here, we estimate the therapeutic function of LC against colitis and investigate the mechanism of intestinal flora and metabolism modulation. METHODS: A colitis model was constructed by continuously administering 2.5% dextran sodium sulfate (DSS) solution daily for 7 days. Analysis of gut microbiota was carried out by 16S rRNA gene high-throughput sequencing. Spectrum antibiotic cocktail (ABX) and faecal microbiota transplantation (FMT) were employed to evaluate the protective effect of intestinal flora. Colonic Treg cells and related immune responses were detected by flow cytometry. RESULTS: LC treatment significantly alleviated colon inflammation by regulating gut microbial diversity and altering flora composition. Notably, LC treatment upregulated short-chain fatty acid (SCFA)-producing bacteria, especially Akkermansia muciniphila (A. muciniphila), and transformed metabolite SCFA profiles. LC activated anti-inflammatory Treg cell responses in colonic lamina propria (LP) in a G-protein coupled receptor 43 (GPR43)-dependent mechanism. ABX, FMT and single bacteria gavage experiments were conducted to confirm the above mechanism. CONCLUSIONS: As an intestinal microbiome and metabolite modulator, LC alleviates colon inflammation in a GPR43-dependent manner through activating Treg cell responses. Therefore, the therapeutic strategy of the microbiome-metabolite-immune axis, as observed in the A. muciniphila-SCFA-Treg cell axis in our study, might provide a new direction for the treatment of IBD.

Effectiveness of Vitamin C Solution in Reducing Adverse Reactions Caused by Painless Lugol Chromoendoscopy: A Multicenter Randomized Controlled Trial.

GOAL: The purpose of this study was to evaluate the effectiveness of vitamin C solution (VCS) in reducing adverse reactions caused by painless Lugol chromoendoscopy. BACKGROUND: Lugol chromoendoscopy is an effective method for screening superficial esophageal squamous cell carcinoma, although Lugol iodine solution (LIS) causes mucosal irritation. STUDY: In 4 hospitals in China, patients were randomized and divided into a distilled water (DW) group, an sodium thiosulfate solution (STS) group and a VCS group. Patients' esophageal mucosal surfaces were stained with either 1.2% or 0.5% LIS and then sprayed with DW, STS, or VCS at various concentrations. For the current randomized study, 1610 patients were enrolled in the 1.2% LIS group and 1355 patients were enrolled in the 0.5% LIS group. In addition, 150 patients were enrolled to assess the discoloration effect. The primary outcome for evaluation was the incidence of acute or late adverse reactions after Lugol iodine staining. The secondary outcome for evaluation was the discoloration effect on esophageal iodine-stained mucosa. RESULTS: VCS significantly reduced the occurrence of acute adverse reactions due to staining from 1.2% LIS. The effect of VCS was similar to that of STS but better than that of DW ( P <0.05). Regarding 0.5% LIS staining, VCS reduced the incidence of acute adverse reactions and heartburn within 1 week ( P <0.05). Both VCS and STS had similar effects. In addition, compared with spraying NS, VCS caused rapid decolorization of iodine-stained esophageal mucosa. After 120 seconds of deiodination, the color of the esophageal mucosa faded by 90%, which is similar to the results seen in the STS group. This contrasts with the results seen in the DW group, which showed fading by only 50.97% ( P <0.05). CONCLUSION: VCS can effectively reduce adverse reactions caused by different concentrations of LIS, indicating its important clinical application in the screening of superficial esophageal squamous cell carcinoma.

Leveraging Continuous Vital Sign Measurements for Real-Time Assessment of Autonomic Nervous System Dysfunction After Brain Injury: A Narrative Review of Current and Future Applications.

Subtle and profound changes in autonomic nervous system (ANS) function affecting sympathetic and parasympathetic homeostasis occur as a result of critical illness. Changes in ANS function are particularly salient in neurocritical illness, when direct structural and functional perturbations to autonomic network pathways occur and may herald impending clinical deterioration or intervenable evolving mechanisms of secondary injury. Sympathetic and parasympathetic balance can be measured quantitatively at the bedside using multiple methods, most readily by extracting data from electrocardiographic or photoplethysmography waveforms. Work from our group and others has demonstrated that data-analytic techniques can identify quantitative physiologic changes that precede clinical detection of meaningful events, and therefore may provide an important window for time-sensitive therapies. Here, we review data-analytic approaches to measuring ANS dysfunction from routine bedside physiologic data streams and integrating this data into multimodal machine learning-based model development to better understand phenotypical expression of pathophysiologic mechanisms and perhaps even serve as early detection signals. Attention will be given to examples from our work in acute traumatic brain injury on detection and monitoring of paroxysmal sympathetic hyperactivity and prediction of neurologic deterioration, and in large hemispheric infarction on prediction of malignant cerebral edema. We also discuss future clinical applications and data-analytic challenges and future directions.

Self-Directed Neurofeedback Treatment for Subjective Tinnitus Patients Evaluated by Multimodal Functional Imaging.

Neurofeedback (NFB) is a relatively novel approach to the treatment of tinnitus, and prior studies have demonstrated that the increases in alpha activity rather than reduced delta power seem to drive these NFB-related improvements in tinnitus symptoms. The present study was therefore designed to explore whether the implementation of an alpha training protocol with a portable neurofeedback apparatus would achieve improvements in tinnitus patient symptoms. In this study, 38 tinnitus patients underwent NFB training while 18 were enrolled in a control group. The study was single-blinded such that only participants were not aware of their group assignments. Those in the NFB group underwent 15 NFB training sessions over 5 weeks, in addition to pre- and posttraining tests including the Tinnitus Handicap Inventory (THI), Tinnitus Handicap Questionnaire (THQ), visual analog scales (VAS), electroencephalography (EEG), and functional magnetic resonance imaging (fMRI). Our result find that when the THI, THQ, and VAS scores of patients in the two groups were assessed after a 5-week training period, these scores were unchanged in control patients whereas they had significantly improved in the NFB group patients. EEG analyses revealed that the alpha band was increased in the occipital lobe following NFB treatment, while fMRI indicated an increase in regional homogeneity (ReHo) in the right frontal lobe of patients in the NFB group after treatment that was negatively correlated with THI and VAS scores. The results of this analysis indicate that alpha NFB training can be effectively used to reduce tinnitus-related distress and sound perception in patients.

Efficacy and safety of a treatment in patients with locoregionally advanced nasopharyngeal carcinoma (LANC) involving carotid artery invasion.

PURPOSE: Locally advanced nasopharyngeal carcinoma (LANC) often invades the parapharyngeal space and internal carotid artery. Are patients with LANC invading carotid artery are at risk of massive neck hemorrhage after radiotherapy? METHODS: This retrospective study included 130 LANC patients with carotid artery invasion admitted to our hospital between January 2012 and September 2019. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) ± epidermal growth factor receptor (EGFR) inhibitor. Univariate and multivariate analysis of risk factors were conducted for the prognosis and the occurrence of massive neck hemorrhage of LANC patients with carotid artery invasion. OUTCOMES: The 5-year progression-free survival (PFS), distant metastasis-free survival (DMFS), local nodal recurrence-free survival (LNRFS), local recurrence-free survival (LRFS), nodal recurrence-free survival (NRFS) and overall survival (OS) of the 130 patients were 75.2%, 76.8%, 90.0%, 93.9%, 95.8% and 87.2%, respectively. The incidence of fatal bleeding after radiotherapy was 2.3% (3/130). The primary site of the three cases were all the pharyngeal recess, with more than 270° carotid artery invasion, suffering nasopharyngeal necrosis after radiotherapy (2 of which were diabetics and 1 received re-radiation after recurrence). Univariate analysis showed that clinical stage was negatively correlated with DMFS and PFS (P < 0.05). The induction chemotherapy TP regimen, platinum-based concurrent chemotherapy and EGFR inhibitors (Nituzumab/Cetuximab) significantly improved PFS and DMFS (P < 0.05). Patients with hemoglobin levels > 110 g/L had significantly inferior PFS, DMFS and OS than those with hemoglobin levels ≤ 110 g/L (P < 0.05). Multivariate analysis showed that the EGFR inhibitor was an independent risk factor for PFS and DMFS, while the lowest hemoglobin level was an independent risk factor for OS. CONCLUSIONS: In LANC patients whose carotid artery invasion was < 270°, induction chemotherapy (IC) followed by helical tomotherapy (HT) and concurrent chemoradiotherapy (CCRT) with EGFR (epidermal growth factor receptor) inhibitor had mild and tolerable side effects, better PFS and DMFS, with no massive hemorrhage. In patients whose primary tumor was pharyngeal recess with carotid artery invasion ≥ 270°, poorly controlled diabetes or re-radiotherapy led to a higher risk of massive hemorrhage after radiotherapy.

Petrous bone cholesteatoma: our experience of 20 years and management of two giant cases affecting rhinopharynx.

PURPOSE: To demonstrate our experience in the treatment of petrous bone cholesteatoma (PBC). METHODS: Data of PBC patients in our hospital from January 2000 to December 2019 were collected. Surgical approaches and facial function were mainly discussed and compared with the literature. The management of 2 giant PBC cases affecting rhinopharynx has been demonstrated. RESULTS: The supralabyrinthine type was the most frequent type followed by the massive type. There were 5 cases with cholesteatoma extending into the clivus (2 cases), sphenoid (1 case) and rhinopharynx (2 cases). The translabyrinthine approach (40%) was our most frequently used approach followed by the middle fossa approach (36%) and the transmastoid approach (11%). There were 10 cases managed with the assistance of endoscope, including 3 cases with cholesteatoma extending into clivus, sphenoid and rhinopharynx separately. Obliteration of the cavity was performed in 70.3% (135/192) cases; 3 of them recurred. For the 2 giant PBC cases affecting rhinopharynx, traditional microscopic surgery assisted with transnasal endoscope was performed. The reduced exposure was beneficial for postoperative recovery, and the approach in the nasal cavity provided a permanent drainage for postoperative examination. CONCLUSION: Otologic endoscope combined with traditional microscopic surgery could reduce the exposure in surgery. For extremely extended cases of PBC, supplementary transnasal endoscopic approach deserves to be considered for the traditional temporal bone approach.