Extraction of terminal ileal lipomas to cecum can facilitate endoscopic resection: A case series with video.

Large ileal lipomas over 2 cm can cause symptoms, that may require a resection. Due to the narrow lumen and thin walls of the ileum, endoscopic treatments can have a high risk of adverse events and require technical expertise, thus surgical resection is currently the mainstay of treatment. To overcome the technical challenges, we developed a novel method to endoscopically resect terminal ileal lipomas. The technique involves extracting the lesion into the cecum, which creates sufficient space to maneuver, and a better field of view. The lipoma is resected with endoscopic mucosal resection or endoscopic submucosal dissection. The appearance of the lipoma protruding out of the ileocecal valve resembles that of a tongue sticking out of the mouth, thus we named this the "tongue out technique". To assess the technical feasibility of this method, we retrospectively analyzed seven cases of terminal ileal lipoma that were endoscopically resected using the "tongue out technique" at NTT Medical Center Tokyo between January 2017 and October 2023. Technical success was 100% and en bloc resection was achieved in all cases. The median size was 31 (14-55) mm. Three cases were resected with endoscopic mucosal resection while endoscopic submucosal dissection was performed on the other four cases. There was one case of delayed post-endoscopic mucosal resection bleeding, which was caused by clip dislodgement. There were no perforations. No recurrence of the lipoma or associated symptoms have been observed. This new technique can allow more ileal lipomas to be treated with minimally invasive and organ-preserving endoscopic procedures.

Safety and efficacy of low-power pure-cut hot snare polypectomy for small nonpedunculated colorectal polyps compared with conventional resection methods: A propensity score matching analysis.

Objectives: Cold snare polypectomy (CSP) is widely performed for small colorectal polyps. However, small colorectal polyps sometimes include high-grade adenomas or carcinomas that require endoscopic resection with electrocautery. This study aimed to evaluate the efficacy and safety of a novel resection technique, hot snare polypectomy with low-power pure-cut current (LPPC-HSP) for small colorectal polyps, compared with CSP and conventional endoscopic mucosal resection (EMR). Methods: Records of patients who underwent CSP, EMR, or LPPC-HSP for nonpedunculated colorectal polyps less than 10 mm between April 2021 and March 2022 were retrospectively evaluated. We analyzed and compared the treatment outcomes of CSP and EMR with those of LPPC-HSP using propensity score matching. Results: After propensity score matching of 396 pairs, an analysis of CSP and LPPC-HSP indicated that LPPC-HSP had a significantly higher R0 resection rate (84% vs. 68%; p < 0.01). Delayed bleeding was observed in only two cases treated with CSP before matching. Perforation was not observed with either treatment. After propensity score matching of 176 pairs, an analysis of EMR and LPPC-HSP indicated that their en bloc and R0 resection rates were not significantly different (99.4% vs. 100%, p = 1.00; 79% vs. 81%, p = 0.79). Delayed bleeding and perforation were not observed with either treatment. Conclusions: The safety of LPPC-HSP was comparable to that of CSP. The treatment outcomes of LPPC-HSP were comparable to those of conventional EMR for small polyps. These results suggest that this technique is a safe and effective treatment for nonpedunculated polyps less than 10 mm.

Gel immersion endoscopic mucosal resection for small gastric neoplastic lesions: A pilot study.

Gastric endoscopic mucosal resection is challenging due to the slippery mucosa, abundant blood vessels, and the presence of mucus. We developed gel immersion endoscopy to secure the visual field, even in a blood-filled gastrointestinal lumen in 2016. Clear gel with appropriate viscosity, instead of water, can prevent rapid mixture with blood and facilitate identification of the culprit vessel. We further optimized the gel for endoscopic treatment, and the resultant product, Viscoclear (Otsuka Pharmaceutical Factory) was first released in Japan in 2020. The viscosity of this gel has been optimized to maximize endoscopic visibility without compromising the ease of its irrigation. The aim of this study is to clarify the effectiveness of gel immersion endoscopic mucosal resection for small-sized early gastric neoplasms. Seven lesions in seven patients were treated by gel immersion endoscopic mucosal resection. The size of all lesions was under 10 mm. The median procedure time was 4.5 min. Intraoperative bleeding occurred in four of seven lesions immediately after snare resection and was easily controlled by endoscopic hemostatic forceps during the gel immersion endoscopy. The R0 resection rate was 100%. In conclusion, gel immersion endoscopic mucosal resection may be a straightforward, rapid, and safe technique for resecting superficial gastric neoplasms <10 mm in diameter.

Biological evaluation of curdlan sulfate-based nanoparticles in trained immunity enhancement: In vitro and in vivo approaches.

OBJECTIVES: Recently, more and more evidences suggest that ß-glucans can induce trained immunity and non-specific protections against pathogens. However, most of the reports evaluated the immunological activities of ß-glucans through injection route but no nasal inhalation. In this study, the effects of curdlan sulfate-based nanoparticles, CS/O-HTCC on trained immunity through intranasal administration were evaluated. METHODS: Macrophages were treated with CS/O-HTCC and the metabolisms of the macrophages were detected. Mice were intranasal administered with CS/O-HTCC for 3 times with a 14 days interval, then the antitumor or infection prevention effects were assessed. RESULTS: In vitro, CS/O-HTCC enhanced the macrophage metabolism significantly through upregulating glycolysis (26.1 ±â€¯4.3 mpH/min) and oxidative phosphorylation (36.0 ±â€¯9.0 pmol/min) compared with that of negative group (7.5 ±â€¯2.3 mpH/min and 19.5 ±â€¯4.9 pmol/min). In vivo, CS/O-HTCC inhibited lung metastasis of B16F10 tumor cells and improved the survival time (26.5 days) of the nmice compared with negative group (19.5 days). Moreover, CS/O-HTCC prevented the lung infections by Escherichia coli or Streptococcus pneumoniae (less bacterial residual) and reduced lung damages. CONCLUSIONS: CS/O-HTCC can induce trained immunity through enhancing the metabolism of macrophages and enhance the non-specific protection against pathogens through intranasal immunization.

A description of the THRIVE ("The study of host-bacterial relationships in different vaginal environments") bacterial vaginosis observational study.

Bacterial vaginosis contributes to poor reproductive health and is characterized by a displacement of Lactobacillus in the vaginal microbiome. However, treatment for bacterial vaginosis is limited to antibiotics and half of women treated experience recurrence within a year. OBJECTIVES: THRIVE is a prospective study in XXXXX, which is designed to capture daily variation of the microbiome and host mucosal immunity during treatment. The objective of this study is to identify host and bacterial factors that associate with vaginal microbiome stability to better inform therapeutic interventions. METHODS: Women treated for bacterial vaginosis, and controls, are followed for 6 months collecting daily vaginal swabs and monthly questionnaires. Comprehensive mucosal sampling, including swabs, cytobrushes, biopsies, and blood are collected at baseline, months 1 and 6 post-enrollment. RESULTS: We performed analysis on the first 52 participants, (19 BV+, 33 BV-). Molecular profiling by 16s RNA sequencing showed 20 women with non-Lactobacillus dominant microbiomes and 32 with Lactobacillus-dominant microbiomes, with increased microbial diversity in non-Lactobacillus dominant microbiomes (P = 3.1E-05). A pilot analysis in 2 participants demonstrates that multi-omics profiling of self-collected daily swabs provides high-quality data identifying 73 bacterial species, 1773 mucosal proteins and 117 metabolites. Initial flow cytometry analysis showed increased CD4+ T cells and neutrophil activation (CD11b+CD62Lneg/dim) in the positive participant at baseline, while after treatment these shifted and resembled the control participant. CONCLUSION: This study provides a framework to comprehensively investigate the kinetics of vaginal mucosal microbiome alterations, providing further insight into host and molecular features predicting bacterial vaginosis recurrence. RéSUMé: La vaginose bactérienne contribue à une mauvaise santé reproductive et se caractérise par un remplacement des lactobacilles dans le microbiome vaginal. Cependant, le traitement de la vaginose bactérienne se limite aux antibiotiques et la moitié des femmes traitées connaissent une récidive dans l'année qui suit. OBJECTIFS: THRIVE est une étude prospective menée à XXXXX et conçue pour mesurer les variations quotidiennes du microbiome et de l'immunité muqueuse de l'hôte pendant le traitement. L'objectif de cette étude est de déterminer les facteurs hôtes et bactériens qui sont associés à la stabilité du microbiome vaginal afin de mieux orienter les interventions thérapeutiques. MéTHODES: Les femmes traitées pour une vaginose bactérienne, ainsi que les témoins, sont suivies pendant 6 mois au moyen de prélèvements vaginaux quotidiens et de questionnaires mensuels. Une analyse détaillée des muqueuses a été effectuée au recrutement puis à 1 et 6 mois après le recrutement par divers prélèvements, à savoir par écouvillon, cytobrosse, biopsie et prise de sang. RéSULTATS: Nous avons effectué une analyse auprès des 52 premières participantes (19 VB+, 33 VB-). Le profilage moléculaire par séquençage de l'ARN 16S a montré que 20 femmes avaient un microbiome à dominance non-lactobacille et 32 avaient un microbiome à dominance lactobacille, la diversité microbienne étant accrue dans les microbiomes à dominance non-lactobacille (P = 3,1E-05). Une analyse pilote sur 2 participantes démontre que le profilage multiomique d'écouvillonnages quotidiens autoadministrés fournit des données de haute qualité permettant d'identifier 73 espèces bactériennes, 1773 protéines des muqueuses et 117 métabolites. L'analyse initiale par cytométrie en flux a montré une élévation des cellules T CD4+ et une activation des neutrophiles (CD11b+CD62Lnég/faible) chez la patiente positive au recrutement, alors qu'après le traitement, ces cellules ont changé pour finalement ressembler à celles de la participante témoin. CONCLUSION: Cette étude donne un cadre pour étudier de manière exhaustive la cinétique des altérations du microbiome de la muqueuse vaginale, ce qui permet de mieux comprendre les caractéristiques de l'hôte et les caractéristiques moléculaires prédisant la récidive de la vaginose bactérienne.

Topical Application of Dexamethasone-Loaded Core-Multishell Nanocarriers Against Oral Mucosal Inflammation.

Topical treatment of oral inflammatory diseases is challenging due to the intrinsic physicochemical barriers of the mucosa and the continuous flow of saliva, which dilute drugs and limit their bioavailability. Nanocarrier technology can be an innovative approach to circumvent these problems and thus improve the efficacy of topical drug delivery to the mucosa. Core-multishell (CMS) nanocarriers are putative delivery systems with high biocompatibility and the ability to adhere to and penetrate the oral mucosa. Ester-based CMS nanocarriers release the anti-inflammatory compound dexamethasone (Dx) more efficiently than a conventional cream. Mussel-inspired functionalization of a CMS nanocarrier with catechol further improves the adhesion of the nanocarrier and may enhance the efficacy of the loaded drugs. In the present study, the properties of the ester-based CMS 10-E-15-350 nanocarrier (CMS-NC) are further evaluated in comparison to the catechol-functionalized variant (CMS-C0.08). While the mucoadhesion of CMS-NC is inhibited by saliva, CMS-C0.08 exhibits better mucoadhesion in the presence of saliva. Due to the improved adhesion properties, CMS-C0.08 loaded with dexamethasone (Dx-CMS-C0.08) shows a better anti-inflammatory effect than Dx-CMS-NC when applied dynamically. These results highlight the superiority of CMS-C0.08 over CMS-NC as an innovative drug delivery system (DDS) for the treatment of oral mucosal diseases.

Primary Melanoma of the Urinary Bladder: Clinical, Histopathologic, and Comprehensive Molecular Analysis of a Rare Tumor.

Primary melanoma of the urinary bladder is extremely rare and generally has a poor prognosis. The histopathological diagnosis can be challenging as tumors can be unpigmented and of varying morphology. Here we report a rare example of primary urinary bladder melanoma with clinical, imaging, gross anatomical, histopathologic, immunohistochemical, and molecular findings to illustrate the utility of an integrated approach in establishing the diagnosis and guide therapy. A comprehensive, integrated approach, including molecular studies, may be helpful in further establishing an accurate diagnosis and informing therapies of this rare but poorly behaved entity.

Cronkhite-Canada syndrome tends to be accompanied by colorectal cancer: Report of seven cases.

Cronkhite-Canada syndrome (CCS) can be difficult to diagnose. To diagnose CCS, it is important to perform endoscopic examination for patients with chronic diarrhea, check for the presence or absence of polyposis, and evaluate inflammation in the mucosa between the polyps. This study reported seven cases of CCS. The age of the patients, which included four men and three women, ranged 48-72 years, and all patients were Asian. The most common symptom among these patients was chronic diarrhea. Three of the patients had rectal cancer. In two patients, the lesions were detected at an early stage and resected via endoscopic treatment. CCS is associated with a high risk of malignant gastrointestinal lesions, especially rectal cancers, and periodic surveillance endoscopy and careful observation are required.

Oral Mucosal Lesions in Patients Attending Dermatology Outpatient Department of a Tertiary Care Center in Kathmandu: A Descriptive Cross-sectional Study.

INTRODUCTION: Oral mucosal lesions though mostly benign, may impair the quality of life of patients. Some may even progress to malignancies. Many physicians, including dermatologists, tend to skip oral examinations, missing many important diagnoses. Understanding the frequency and types of oral mucosal lesions in dermatological settings can help in early diagnosis, referral and adequate treatment. This study was done to determine demographic characteristics and clinical presentations of patients with oral mucosal lesions presenting to the out-patient department (OPD) of dermatology in Nepal Armed Police Force (APF) Hospital, Kathmandu. METHODS: This cross-sectional descriptive study was conducted after obtaining the ethical approval from the Institutional Review Committee of Nepal APF Hospital. Retrospective data of 264 patients presenting with oral mucosal lesions to the dermatology OPD were collected from 1st January 2021 to 31st December 2023 by using a pre-formed proforma. Data was entered in SPSS software and descriptive statistics were computed. RESULTS: Out of 13,832 cases, oral mucosal lesion was seen in 264 (1.90%) cases among which 153 (57.96%) cases were males with male female ratio of 1.37:1. Most common age group affected was 31-45 years 96 (36.36%). Buccal mucosa 86 (32.57%) was the commonest site involved followed by tongue 73 (27.65%). Aphthous ulcer 82 (31.06%) was the commonest lesion found followed by oral candidiasis 25 (9.46%) and oral lichen planus 24 (9.09%). CONCLUSIONS: Aphthous ulcer was the commonest oral mucosal lesion seen in patients visiting dermatology outpatient department of Nepal APF Hospital, with buccal mucosa being the commonest site affected.

Endonasal Thermal Imaging Before and After Nasal Airway Surgery.

OBJECTIVE: Nasal airway surgery is often applied when treatment fails to relieve nasal obstruction. However, surgery that improves airflow does not always alleviate the symptoms of nasal obstruction. The perception of nasal breathing is likely more related to changes in mucosal temperature than the mechanical sensation of flow or pressure. This study aims to measure intranasal mucosal temperature pre-and post-surgery using endonasal thermal imaging, exploring its correlation with subjective nasal breathing and objective airflow measurements. METHODS: A prospective study of adult patients with nasal obstruction managed with nasal airway surgery was performed. Intranasal mucosal temperatures were determined using the thermal endonasal image of the nasal passage produced by the infrared radiometric thermal camera (FILR VS290). A comparison was made between the mean values of mid-expiration (ExT) and mid-inspiration (InT) temperature data (internal nasal valve, nasal cavity, inferior turbinate, and overall airway [mean value]) and visual analog scale (VAS), Nasal Obstruction Symptom Evaluation (NOSE) scale and nasal airway resistance (NAR) before and after surgery. RESULTS: Seven patients (35.14 ± 16.45 years, 57.14% female) were included. All NOSE, VAS, and NAR improved after surgery (59.29 ± 10.89 vs 17.14 ± 14.64; P < .001, 64.50 ± 26.79 vs 18.57 ± 19.99; P < .001, 0.82 ± 0.48 vs 0.34 ± 0.11 Pa/cm3/s; P = .002, respectively). ExT, InT, and the difference between ExT and InT of three areas and overall airway were similar between pre-and post-surgery. No statistically significant correlations were found between intranasal mucosal temperature, VAS, NOSE, and NAR at pre-and post-surgery except for the difference between ExT and InT of overall airway and NOSE pre-operative (Pearson r = 0.57; 95% CI 0.06-1.09; P = .03). CONCLUSION: Endonasal thermal imaging can assess the intranasal mucosal temperature of a patient. However, more precise imaging of the nasal passages and data acquisition are required to establish mucosal temperature as an objective measure of nasal obstruction before and after nasal airway surgery in a clinical setting.

A Dual-Adjuvanted Parenteral-Intranasal Subunit Nanovaccine generates Robust Systemic and Mucosal Immunity Against SARS-CoV-2 in Mice.

Existing parenteral SARS-CoV-2 vaccines produce only limited mucosal responses, essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters can overcome the shortcomings of parenteral vaccines and enhance pre-existing systemic immunity. Here, a new protein subunit nanovaccine is developed by utilizing dual-adjuvanted (RIG-I: PUUC RNA and TLR-9: CpG DNA) polysaccharide-amino acid-lipid nanoparticles (PAL-NPs) along with SARS-CoV-2 S1 trimer protein, that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal-systemic SARS-CoV-2 immunity. Mice receiving IM-Prime PUUC+CpG PAL subunit nanovaccine, followed by an IN-Boost, developed high levels of IgA, IgG, and cellular immunity in the lungs and showed robust systemic humoral immunity. Interestingly, as a purely intranasal subunit vaccine (IN-Prime/IN-Boost), PUUC+CpG PAL-NPs induced stronger lung-specific T cell immunity than IM-Prime/IN-Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS-CoV-2 vaccination may also be feasible. The data suggest that PUUC+CpG PAL subunit nanovaccine is a promising candidate for generating SARS-CoV-2 specific mucosal immunity.

PRP improves the outcomes of autologous skin graft transplantation on the esophagus by promoting angiogenesis and inhibiting fibrosis and inflammation.

Background and Objectives: Autologous skin graft (ASG) transplantation is a challenging approach but a promising option for patients to prevent postoperative esophageal stricture. Nonetheless, the current strategies require improvement. We aimed to investigate the effectiveness of the injection of platelet-rich plasma (PRP) before skin graft transplantation for extensive esophageal defects after endoscopic resection. Methods: Standardized complete circular endoscopic resection (5 cm in length) was performed in 27 pigs allocated into 3 groups. The artificial ulcers were treated with a fully covered esophageal stent (control group), ASG (ASG group), and submucosal injection of PRP with ASG (PRP-ASG group). Macroscopic evaluation and histological analysis of the remolded esophagus were performed 7, 14, and 28 days after surgery. Results: The macroscopic evaluation indicated that submucosal injection of PRP before transplantation effectively promoted the survival rate of skin grafts and decreased the rate of mucosal contraction compared with those treated with ASG or stent alone. Histological analysis of submucosal tissue showed that this modified strategy significantly promoted wound healing of reconstructed tissues by enhancing angiogenesis, facilitating collagen deposition, and decreasing inflammation and fibrogenesis. Conclusions: These findings suggested that PRP might be used as a biological supplement to increase the esophageal skin graft survival rate and improve submucosal tissue remolding in a clinically relevant porcine model. With extremely low mucosal contraction, this novel combination strategy showed the potential to effectively prevent stenosis in extensive esophageal ulcers.

Fc-empowered exosomes with superior epithelial layer transmission and lung distribution ability for pulmonary vaccination.

Mucosal vaccines offer potential benefits over parenteral vaccines for they can trigger both systemic immune protection and immune responses at the predominant sites of pathogen infection. However, the defense function of mucosal barrier remains a challenge for vaccines to overcome. Here, we show that surface modification of exosomes with the fragment crystallizable (Fc) part from IgG can deliver the receptor-binding domain (RBD) of SARS-CoV-2 to cross mucosal epithelial layer and permeate into peripheral lung through neonatal Fc receptor (FcRn) mediated transcytosis. The exosomes F-L-R-Exo are generated by genetically engineered dendritic cells, in which a fusion protein Fc-Lamp2b-RBD is expressed and anchored on the membrane. After intratracheally administration, F-L-R-Exo is able to induce a high level of RBD-specific IgG and IgA antibodies in the animals' lungs. Furthermore, potent Th1 immune-biased T cell responses were also observed in both systemic and mucosal immune responses. F-L-R-Exo can protect the mice from SARS-CoV-2 pseudovirus infection after a challenge. These findings hold great promise for the development of a novel respiratory mucosal vaccine approach.

Usefulness of unwinding the colonoscope shaft loop via the universal cord for colorectal endoscopic resections.

The colonoscope shaft loop can be unwound by establishing a loop in the universal cord of the colonoscope to maintain the same endoscopic view during colorectal endoscopic resections.

Battle of the Gases: How Air and Nitrous Oxide Affect Endotracheal Tube Cuff Pressure During General Anesthesia.

Background Endotracheal tube (ETT) cuff pressure changes during general anesthesia. Endotracheal cuff pressure ideally should be maintained between 20 and 30 cm of H2O. Cuff pressure of less than 25 cm of H2O increases the chances of aspiration while pressure of more than 40 cm of H2O causes tracheal mucosa damage. The study aimed to monitor and compare variations of endotracheal cuff pressure during general anesthesia with oxygen-air or oxygen-nitrous oxide. Methods This prospective, randomized, double-blinded, observational study was conducted on 40 patients. After approval from the institutional ethics subcommittee, 40 patients of either gender, aged 18-60 years, belonging to ASA grades I and II, who were undergoing elective surgery under general anesthesia, were enrolled in this study. The patients were randomly divided into two groups, with 20 in each group. In Group A, oxygen-air and Group N, oxygen-nitrous oxide was used as a gaseous mixture in general anesthesia with ETT. The ETT cuff pressure was recorded with the help of a cuff manometer at intervals of five, 10, 20, 30, 40, 50, 60, 70, 80, and 90 minutes after intubation. If pressure was more than 40 cm of H2O, it was reduced to 25-30 cm of H2O. Data were collected and analyzed using methods described in Primer of Biostatistics by Stanton A. Glantz. Quantitative data were analyzed using the Student's t-test. Qualitative data were analyzed using the chi-square test. Results An increase in cuff pressure was noted more in Group N as compared to Group A. The pressure in the endotracheal cuff started to gradually increase after 30-40 minutes in Group N after intubation, while in Group A, there was no significant increase. The average number of times the cuff deflated was 0.2 ± 0.41 in Group A and 1.55 ± 0.51 in Group N, which was highly significant. Conclusion Changes in endotracheal cuff pressure were observed when using different gas mixtures for inflation. Specifically, cuff pressure increased with oxygen and nitrous oxide compared to oxygen with air. This suggests that anesthetic gas composition can impact cuff pressure, potentially affecting tracheal mucosal perfusion and patient safety. Therefore, regular monitoring and adjustment of cuff pressure is crucial, especially when using nitrous oxide, to prevent complications and ensure optimal patient care.