Clinicopathologic and Molecular Characterization of Inflammatory Bowel Disease-Associated Neuroendocrine Carcinomas and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms.

The pathogenesis of neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) in the gastrointestinal tract remains poorly understood. This study seeks to characterize the clinicopathologic and molecular features of NEC/MiNEN in patients with inflammatory bowel disease (IBD). Eighteen surgically resected IBD-associated intestinal carcinomas with a minimum of 30% neuroendocrine component were collected from 6 academic centers and compared to a control group of 12 IBD-associated carcinomas lacking neuroendocrine differentiation. Both groups exhibited a male predominance and similar age distribution. The NEC/MiNEN group was more likely to have a higher percentage of Crohn's disease (9/18 vs. 1/12, P=0.024), occur in the rectum (9/18 vs. 3/12) and small intestine (4/18 vs. 0/12) (P<0.01), be diagnosed on resection without a preceding biopsy (6/18 vs. 0/12, P=0.057), and have unidentifiable precursor lesions (10/18 vs. 1/12, P=0.018) than the control group. Synchronous carcinoma, advanced tumor stage (pT3 and pT4), and lymph node metastasis occurred at similar rates; however, the NEC/MiNEN group had a higher incidence of angiovascular invasion (14/18 vs. 4/12, P=0.024), distant metastasis (8/18 vs. 1/12, P=0.049), mortality (8/18 vs. 2/12, P=0.058), and worse survival (Kaplan-Meier, P=0.023) than the control group. All tested cases were mismatch repair proficient. A Ki-67 proliferation index ranged from 25% to 100%. Next-generation sequencing in 11 NEC/MiNEN cases revealed low tumor mutational burdens but complex genetic abnormalities commonly involving TP53 (9/11, 82%), FBXW7 (4/11, 36%), and APC (3/11, 27%), with the other genetic alterations randomly occurring in one or two cases. The neuroendocrine component, which shared similar molecular alterations as the non-neuroendocrine component, was subcategorized into intermediate (G3a)- and high-grade (G3b); the higher-grade correlated with more genetic alterations. In conclusion, IBD-associated NEC/MiNEN shows diverse histologic features, variable precursor lesions, intricate genetic abnormalities, and aggressive biologic behavior. The classification and grading of GI-NEC/MiNEN may be refined for better clinical management.

A Rare Case of Paraganglioma Syndrome Associated With Polycythemia and Blindness.

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors. They can be diagnosed independently or as part of a syndrome, especially with germline mutations. Rarely, a somatic mutation can present as part of a syndrome associated with recurrent PPGL, congenital polycythemia, and vascular malformation. We report a case of a 44-year-old man with a history of congenital blindness, stroke in utero, cerebral ataxia, and polycythemia since age 12, treated with phlebotomies who presented with back pain and hypertension. Abdominal computer tomography with IV contrast showed a right adrenal enhancing lesion measuring 1.4 x 1.2 cm and a conglomerate of heterogeneously enhancing periaortic lesions measuring up to 5 cm in the mid-abdomen. Biochemical workup revealed plasma free normetanephrine 27.5 nmol/L (0.00-0.89) and plasma free metanephrine 0.49 nmol/L (0.00-0.49). Histopathology confirmed synchronous pheochromocytoma and paraganglioma. This case illustrates the importance of taking a detailed past medical history and the relevance of polycythemia in the paraganglioma workup.

The non-negligible non-specific adsorption of oligonucleotides in target-immobilized Mag-SELEX.

Target-immobilized magnetic beads-based Systematic Evolution of Ligands by Exponential Enrichment (target-immobilized Mag-SELEX) has emerged as a powerful tool for aptamer selection owing to its convenience, efficiency, and versatility. However, in this study we systematically investigated non-specific adsorption in target-immobilized Mag-SELEX and found that the non-specific adsorption of the oligonucleotides to target-labeled magnetic beads was comparable to that of the screening libraries, indicating a substantial portion of captured sequences likely stem from non-specific adsorption. Longer nucleic acid sequences (80 nt and above, such as polyA80 and yeast tRNA) were found to attenuate this non-specific adsorption, with more complex higher-order structures demonstrating greater efficacy, while dNTP and short sequences such as primer sequences (20 nt), polyT(59), or polyA(59), did not possess this capability. Various evidence suggested that hydrophobic interactions and other weak interactions may be the primary underlying cause of non-specific adsorption. Additionally, surface modification of magnetic beads with polar molecule polyethylene glycol (PEG) also yielded a significant reduction in non-specific adsorption. In conclusion, our research underscores the critical importance of closely monitoring non-specific adsorption in target-immobilized Mag-SELEX.

Clinicopathologic Features of Gastrointestinal Tract Langerhans Cell Histiocytosis.

Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin and CD1a, S100, and Langerin immunohistochemical-stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months. All pediatric patients had concurrent multisystem LCH, presented with GI symptoms, and showed nonpolypoid lesions. Seven (88%) showed multifocal GI disease, including 5 with multiple GI organ involvement. All sampled lesions from children exhibited infiltrative growth. More than half had died of the disease or manifested persistent LCH at last follow-up. Twenty-five of 39 (64%) adults had LCH involving only the GI tract (single system), with the remaining 14 (36%) exhibiting multisystem disease. Adult single-system GI LCH was typically encountered incidentally on screening/surveillance endoscopy (72%). Most exhibited isolated colorectal involvement (88%) as a solitary polyp (92%), with a well-demarcated/noninfiltrative growth pattern (70%), and excellent prognosis (100%). In comparison, adult patients with multisystem LCH more frequently presented with GI symptoms (92%, P < .001), noncolorectal GI site involvement (50%, P = .02), multifocal GI lesions (43%, P = .005), nonpolypoid lesions (71%, P < .001), infiltrative histologic growth pattern (78%, P = .04), and persistent disease (57%, P < .001). Adult patients with multisystem LCH appear to exhibit similar clinicopathologic features to those of pediatric patients. These results demonstrated that adults with single-system LCH involving the GI tract have an excellent prognosis, whereas multisystem LCH occurring at any age carries an unfavorable prognosis. High-risk features of GI LCH include pediatric age, GI symptomatology, noncolorectal GI involvement, multifocal GI disease, nonpolypoid lesions, and infiltrative growth pattern.

Clinicopathologic Characterization of Sarcina ventriculi in the Upper Gastrointestinal Tract.

The bacterium Sarcina ventriculi (SV) is rarely identified in the upper gastrointestinal (GI) tract and has been associated with diverse clinical presentations. We aimed to characterize the clinicopathologic features of SV in the GI tract. Seventeen specimens (3 gastrectomy and 14 biopsy specimens) with histologic diagnosis of SV were identified and analyzed. The patients (9 female, 8 male) had a median age of 65 (range 32-86) years. Five (30%) patients presented acutely with GI bleeding or altered mental status. Other relevant symptoms included abdominal pain (n = 6, 35%), diarrhea (n = 4, 24%), dysphagia/dyspepsia (n = 3, 18%), and nausea/vomiting (n = 3, 18%). SV organisms were mainly identified in the stomach (n = 14, 82%), rarely at the gastroesophageal junction (n = 2, 12%), esophagus (n = 2, 12%), or duodenum (n = 1, 6%). Endoscopically, retained food debris was found in 5 of 13 (38%) examined patients. Histologically, the majority of specimens (12 out of 17, 71%) showed mild alterations including reactive gastropathy, inactive gastritis, or reflux (Grade 1). The other 5 specimens (29%) demonstrated erosion, ulcer, necrosis, or perforation (Grade 2). The most commonly associated comorbidities were diabetes mellitus (n = 10, 59%), gastroparesis/outlet obstruction (n = 10, 59%), and gastroesophageal reflux disease (n = 6, 35%). Upon follow-up, 3 (18%) patients with acute phlegmonous gastritis died shortly after gastrectomy. Our case series, the largest reported so far, describes a spectrum of histologic severity associated with SV infection. Diabetes and gastroparesis/outlet obstruction manifested as retained food debris endoscopically are common findings with SV, and may provide a growth medium for this organism and provoke pathogenicity contributing to fatality in acute conditions.

Dysplasia Detected in Patients With Serrated Epithelial Change Is Frequently Associated With an Invisible or Flat Endoscopic Appearance, Nonconventional Dysplastic Features, and Advanced Neoplasia.

The significance of serrated epithelial change (SEC), defined as endoscopically invisible hyperplastic polyp (HP)-like mucosal change identified in patients with inflammatory bowel disease (IBD), remains unclear. Although some studies reported an increased risk of synchronous and/or metachronous colorectal neoplasia in patients with SEC, including advanced neoplasia (high-grade dysplasia or colorectal cancer), the development of SEC is not significantly associated with increased colonic inflammation. This contrasts with the reported positive correlation between increased colonic inflammation and the risk of colorectal neoplasia in ulcerative colitis, arguing against the notion that SEC may represent a form of dysplasia. As such, this study aimed to characterize the features of synchronous and metachronous dysplasia detected in patients with SEC to identify factors contributing to the increased risk of colorectal neoplasia, including advanced neoplasia, observed in a subset of these patients. Clinicopathologic features of 46 IBD patients with SEC (n=109) and synchronous and/or metachronous dysplasia (n=153) were analyzed. All dysplastic lesions were subtyped as either conventional or nonconventional dysplasia. As controls, 45 IBD patients with endoscopically visible or polypoid HP (n=75) and synchronous and/or metachronous dysplasia (n=87) were analyzed. The SEC group included 28 (61%) men and 18 (39%) women with a mean age of 58 years and a long history of IBD (mean duration: 23 years). The majority of patients (n=34; 74%) had ulcerative colitis, and 12 (26%) had Crohn's disease. Thirty-nine (85%) patients had a history of pancolitis, and 2 (4%) had concomitant primary sclerosing cholangitis. Twenty-seven (59%) patients had multifocal SEC. SEC was predominantly found in the left colon (n=52; 48%) and rectum (n=34; 31%). Dysplasia in the SEC group was often endoscopically invisible or flat (n=42; 27%) and demonstrated nonconventional dysplastic features (n=49; 32%). Six nonconventional subtypes were identified in the SEC group, including 17 (11%) dysplasia with increased Paneth cell differentiation, 12 (8%) hypermucinous dysplasia, 8 (5%) crypt cell dysplasia, 7 (5%) goblet cell deficient dysplasia, 3 (2%) sessile serrated lesion-like dysplasia, and 2 (1%) traditional serrated adenoma-like dysplasia. Advanced neoplasia was detected in 11 (24%) patients. The SEC group was more likely to have nonconventional dysplasia (32%, P<0.001), invisible/flat dysplasia (27%, P<0.001), and advanced neoplasia (24%, P<0.001) than the control group (7%, 2%, and 0%, respectively). High-risk nonconventional subtypes (ie, hypermucinous, crypt cell, and goblet cell deficient dysplasias) accounted for 18% of all dysplastic lesions in the SEC group, which were not seen in the control group (P<0.001). The SEC group (n=35; 76%) also had a higher rate of concordance between the location of SEC and the area of synchronous/metachronous dysplasia than the control group (n=22; 49%) (P=0.007). In conclusion, dysplasia detected in patients with SEC is often endoscopically invisible/flat (27%), nonconventional (32%, including the high-risk subtypes), and found in the same colonic segment as SEC (76%), which may in part explain why some patients with SEC are associated with an increased risk of colorectal neoplasia, including advanced neoplasia. The finding of SEC may warrant a careful follow-up colonoscopy with increased random biopsy sampling, especially in the segment of colon with SEC.

High risk features in colorectal adenomatous polyps: A multi-institutional study.

High risk features in colorectal adenomatous polyps include size >1 cm and advanced histology: high-grade dysplasia and villous architecture. We investigated whether the diagnostic rates of advanced histology in colorectal adenomatous polyps were similar among institutions across the United States, and if not, could differences be explained by patient age, polyp size, and/or CRC rate. Nine academic institutions contributed data from three pathologists who had signed out at least 100 colorectal adenomatous polyps each from 2018 to 2019 taken from patients undergoing screening colonoscopy. For each case, we recorded patient age and sex, polyp size and location, concurrent CRC, and presence or absence of HGD and villous features. A total of 2700 polyps from 1886 patients (mean age: 61 years) were collected. One hundred twenty-four (5 %) of the 2700 polyps had advanced histology, including 35 (1 %) with HGD and 101 (4 %) with villous features. The diagnostic rate of advanced histology varied by institution from 1.7 % to 9.3 % (median: 4.3 %, standard deviation [SD]: 2.5 %). The rate of HGD ranged from 0 % to 3.3 % (median: 1 %, SD: 1.2 %), while the rate of villous architecture varied from 1 % to 8 % (median: 3.7 %, SD: 2.5 %). In a multivariate analysis, the factor most strongly associated with advanced histology was polyp size >1 cm with an odds ratio (OR) of 31.82 (95 % confidence interval [CI]: 20.52-50.25, p < 0.05). Inter-institutional differences in the rate of polyps >1 cm likely explain some of the diagnostic variance, but pathologic subjectivity may be another contributing factor.

GlmS plays a key role in the virulence factor expression and biofilm formation ability of Staphylococcus aureus promoted by advanced glycation end products.

Staphylococcus aureus (S. aureus) is well known for its biofilm formation ability and is responsible for serious, chronic refractory infections worldwide. We previously demonstrated that advanced glycation end products (AGEs), a hallmark of chronic hyperglycaemia in diabetic tissues, enhanced biofilm formation by promoting eDNA release via sigB upregulation in S. aureus, contributing to the high morbidity and mortality of patients presenting a diabetic foot ulcer infection. However, the exact regulatory network has not been completely described. Here, we used pull-down assay and LC-MS/MS to identify the GlmS as a candidate regulator of sigB in S. aureus stimulated by AGEs. Dual-luciferase assays and electrophoretic mobility shift assays (EMSAs) revealed that GlmS directly upregulated the transcriptional activity of sigB. We constructed NCTC 8325 ∆glmS for further validation. qRT-PCR analysis revealed that AGEs promoted both glmS and sigB expression in the NCTC 8325 strain but had no effect on NCTC 8325 ∆glmS. NCTC 8325 ∆glmS showed a significant attenuation in biofilm formation and virulence factor expression, accompanied by a decrease in sigB expression, even under AGE stimulation. All of the changes, including pigment deficiency, decreased haemolysis ability, downregulation of hla and hld expression, and less and sparser biofilms, indicated that sigB and biofilm formation ability no longer responded to AGEs in NCTC 8325 ∆glmS. Our data extend the understanding of GlmS in the global regulatory network of S. aureus and demonstrate a new mechanism by which AGEs can upregulate GlmS, which directly regulates sigB and plays a significant role in mediating biofilm formation and virulence factor expression.

Discharge within 24 h, transvaginal natural orifice transluminal endoscopic surgery- more suitable for ambulatory surgery in gynecology procedures: a retrospective study.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is an achievement in the field of minimally invasive surgery. However, the vantage point of vaginal natural orifice transluminal endoscopic surgery (vNOTES) in gynecologicalprocedures remains unclear. The main purpose of this study was to compare vNOTES with laparo-endoscopic single-site surgery, and to determine which procedure is more suitable for ambulatory surgery in gynecologic procedures. METHODS: This retrospective observational study was conducted at the Department of Gynecology, Chengdu Women's and Children's Central Hospital. The 207 enrolled patients had accepted vNOTES and laparo-endoscopic single-site surgery in gynecology procedures from February 2021 to March 2022. Surgically relevant information regarding patients who underwent ambulatory surgery was collected, and 64 females underwent vNOTES. RESULTS: Multiple outcomes were analyzed in 207 patients. The Wilcoxon Rank-Sum test showed that there were statistically significant differences between the vNOTES and laparo-endoscopic single-site surgery groups in terms of postoperative pain score (0 vs. 1 scores, p = 0.026), duration of anesthesia (90 vs. 101 min, p = 0.025), surgery time (65 vs. 80 min, p = 0.015), estimated blood loss (20 vs. 40 mL, p < 0.001), and intestinal exhaustion time (12.20 vs. 17.14 h, p < 0.001). Treatment with vNOTES resulted in convenience, both with respect to time savings and hemorrhage volume in surgery and with respect to the quality of the prognosis. CONCLUSION: These comprehensive data reveal the capacity of vNOTES to increase surgical efficiency. vNOTES in gynecological procedures may demonstrate sufficient feasibility and provide a new medical strategy compared with laparo-endoscopic single-site surgery for ambulatory surgery in gynecological procedures.

Stressful Life Events, Sleep Quality and Non-Suicidal Self-Injury in Chinese Adolescents: The Moderating Effect of Sensation Seeking.

Despite the growing evidence that stressful life events are associated with adolescent non-suicidal self-injury (NSSI), few studies have investigated the mediating and moderating mechanisms underlying this link. The current study examined whether sleep quality mediated the link between stressful life events and NSSI and whether this mediating process was moderated by adolescent sensation seeking. The participants were 1006 Chinese adolescents (48.21% boys; mean age = 13.16 years, SD = 0.67). They completed the Life Events Checklist, Pittsburgh Sleep Quality Index, UPPS-P Impulsive Behavior Scale, and NSSI Questionnaire. The PROCESS macro for SPSS was used to examine the hypothesized moderated mediation model. The results showed that sleep quality significantly mediated the positive association between stressful life events and adolescent NSSI. Moreover, this mediating pathway was moderated by sensation seeking. Specifically, the risk impact of stressful life events on NSSI through sleep quality was significant only among adolescents with high-level sensation seeking but not among those with low-level sensation seeking. These findings provide intervention insights to reduce the risk of adolescent NSSI.

Nonconventional Dysplasia is Frequently Associated With Goblet Cell Deficient and Serrated Variants of Colonic Adenocarcinoma in Inflammatory Bowel Disease.

Various subtypes of nonconventional dysplasia have been recently described in inflammatory bowel disease (IBD). We hypothesized that goblet cell deficient dysplasia and serrated dysplasia may be the primary precursor lesions for goblet cell deficient (GCDAC) and serrated (SAC) variants of colonic adenocarcinoma, respectively. Clinicopathologic features of 23 GCDAC and 10 SAC colectomy cases were analyzed. All dysplastic lesions found adjacent to the colorectal cancers (n = 22 for GCDACs and n = 10 for SACs) were subtyped as conventional, nonconventional, or mixed-type dysplasia. As controls, 12 IBD colectomy cases with well to moderately differentiated adenocarcinoma that lacked any mucinous, signet ring cell, low-grade tubuloglandular, or serrated features while retaining goblet cells throughout the tumor (at least 50% of the tumor) were evaluated. The cohort consisted of 19 (58%) men and 14 (42%) women, with a mean age of 53 years and a long history of IBD (mean duration: 18 y). Twenty-seven (82%) patients had ulcerative colitis. GCDACs (57%) were more often flat or invisible than SACs (10%) and controls (25%; P = 0.023). The GCDAC and SAC groups were more likely to show lymphovascular invasion (GCDAC group: 52%, SAC group: 50%, control group: 0%, P = 0.001) and lymph node metastasis (GCDAC group: 39%, SAC group: 50%, control group: 0%, P = 0.009) than the control group. Notably, GCDACs and SACs were more frequently associated with nonconventional dysplasia than controls (GCDAC group: 77%, SAC group: 40%, control group: 0%, P < 0.001). Goblet cell deficient dysplasia (73%) was the most prevalent dysplastic subtype associated with GCDACs ( P = 0.049), whereas dysplasias featuring a serrated component (60%) were most often associated with SACs ( P = 0.001). The GCDAC group (75%) had a higher rate of macroscopically flat or invisible synchronous dysplasia compared with the SAC (20%) and control (33%) groups ( P = 0.045). Synchronous dysplasia demonstrated nonconventional dysplastic features more frequently in the GCDAC (69%) and SAC (40%) groups compared with the control group (0%; P = 0.016). In conclusion, goblet cell deficient dysplasia and dysplasias featuring a serrated component could potentially serve as high-risk markers for GCDACs and SACs, respectively.

Prognostic implications of tumor histology and microenvironment in surgically resected intrahepatic cholangiocarcinoma: a single institutional experience.

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignant neoplasm. Certain histologic features and the tumor microenvironment may impact disease progression. We aim to characterize the clinicopathologic features of ICC to identify prognostic factors. A total of 50 surgically resected ICC (partial or transplant) cases were analyzed. The cohort included 26 men and 24 women with a median age of 62 years. Eighteen (36%) cases were multifocal ICC with a mean largest tumor size of 6.5 cm. Neoadjuvant and adjuvant chemotherapy was done in eight (16%) and 33 (66%) patients, respectively. Histologically, 42 (84%) were small duct type, seven (14%) large duct type, and one mixed (2%). Thirty (60%) cases showed lymphovascular invasion (LVI) and 11 (22%) with perineural invasion (PNI). Twenty-eight (56%) cases demonstrated dense intratumoral hyaline fibrosis and 18 (36%) with tumor necrosis, each ≥ 10% tumor volume. On follow-up, 35 (70%) patients died of disease after a median disease-specific survival (DSS) of 21 months. Univariate analysis revealed that hyaline fibrosis and adjuvant chemotherapy were associated with better DSS, while tumor size, multifocality, necrosis, and peritumoral neutrophil to lymphocyte ratio were associated with worse DSS. In contrast, age, sex, small vs. large duct types, LVI, and individual inflammatory cell counts were not significant prognostic factors. In summary, ICC is a heterogeneous malignancy with variable clinical courses associated with tumor burden, histology, and microenvironment. Targeting specific components within the tumor microenvironments may be a promising approach for treatment in the future.

Intestinal "Piggybacking Lipoma", A Unique Lipoma Composed of Lipoma and Overlying Epithelial Lesions: A Case-control Study and Review of Literature.

BACKGROUND/AIM: Lipomas are rare but the most common benign mesenchymal lesions of the gastrointestinal (GI) tract, composed of mature adipose cells. The "piggybacking lipoma" is formed by lipomas with overlying polypoid epithelial lesions, such as sessile serrated lesion, tubular adenoma, or hyperplastic polyp, and the literature on these lesions is limited. In this study, we systematically investigated the clinical, endoscopic, and pathologic characteristics of these unique lipomas. PATIENTS AND METHODS: This is a single-institution retrospective study of gastrointestinal tract lipomas diagnosed from 2016-2021. Those with concurrent polypoid epithelial or mesenchymal lesions during the same endoscopic episode were included and reviewed in this study, and the lipomas were classified as "piggybacking lipoma" or "non-piggybacking lipoma" depending on whether the concurrent lesion was overlying the lipoma or was at a different location in the intestine. Demographic, clinical, and endoscopic data were obtained from electronic medical records. RESULTS: A total of 100 lipomas with concurrent epithelial or mesenchymal lesions were included in this study. Among them, 21 cases were classified as "piggybacking lipoma" and 79 were classified as "non-piggybacking lipoma". Patients with piggybacking lipomas showed a female predilection, and were more likely to be symptomatic and less likely to exhibit classic endoscopic features of lipoma. Histologically, the piggybacking polyps showed overlying sessile serrated lesions (SSL) (76.2%) and tubular adenoma (TA) (19%), whereas the non-piggybacking group had differing characteristic lesions with TA (57.5%) and SSL (6.0%). CONCLUSION: Piggybacking lipomas are rare lipomas with overlying polypoid epithelial lesions, most commonly SSL. They present different clinical, endoscopic, and pathologic features compared to non-piggybacking lipomas.

Transvaginal natural orifice transluminal endoscopic surgery for myomectomy: A more suitable surgical approach for enhanced recovery after surgery.

OBJECTIVE: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is widely recognized for its potential benefits, including reducing post-surgical pain and leaving no discernible scarring. However, the anatomical specificity of the vNOTES approach may elevate the risk of nearby organ damage, such as the rectum and bladder. Thus, this study aims to demonstrate the safety and relative merits of vNOTES over transumbilical laparoendoscopic single-site surgery (LESS). METHODS: The Longitudinal Vaginal Natural Orifice Transluminal Endoscopic Surgery Study (LovNOTESS), which was conducted in Chengdu, China. A total of 110 patients who underwent myomectomy in vNOTES or LESS from January 2021 to December 2022. This study prospectively collected and compared perioperative and follow-up data of the two groups. RESULTS: In the vNOTES group, patients had shorter postoperative anal exhaust time, lower pain medications use rate, shorter hospital stay but higher intraoperative conversion rate, and higher postoperative fever rate. vNOTES decreased the anal exhaust time by approximately 8.7 h (95 %CI: -16.182, -1.262, p = 0.007). Moreover, vNOTES reduces pain medication use risk by 73.1 % (OR: 0.269, 95 %CI: 0.172, 0.318, p = 0.016). CONCLUSION: Relative to LESS, vNOTES can make patients mitigate postoperative discomfort, accelerate the recovery of gastrointestinal function, curtail hospitalization duration, and enable a more rapid return to daily activities in myomectomy. However, vNOTES has a higher risk of surgical conversion and adjacent organ injury. Therefore, larger scale prospective studies are needed to prove its security and promote the widespread application of vNOTES in myomectomy.

Transvaginal natural orifice endoscopic surgery for tubal ectopic pregnancy: A more suitable surgical approach for enhanced recovery after surgery.

Objective: We aimed to determine the safety of Vaginal natural orifice transluminal endoscopic surgery (vNOTES) in terms of the Enhanced Recovery after Surgery (ERAS) concept for tubal pregnancy surgery and provide a detailed process of vNOTES for tubal pregnancy surgery, including experience and key points for surgeons performing this procedure. Methods: The Longitudinal Vaginal Natural Orifice Transluminal Endoscopic Surgery Study (LovNOTESS), which was conducted in Chengdu, China. A total of 219 patients who underwent tubal ectopic pregnancy surgery between September 2021 and March 2022. The patients underwent salpingectomy or salpingostomy using transumbilical laparoendoscopic single-site surgery (LESS) or vNOTES, according to their preferences. This study prospectively collected perioperative and one-year follow-up data on tubal pregnancy outcomes after vNOTES and compared them with those after LESS. Results: The vNOTES group showed a shorter surgical duration, hospitalization duration, and postoperative exhaust time and a lower analgesic medication usage rate, but it showed a higher surgical conversion rate. The vNOTES approach reduced the postoperative exhaust time by approximately 9 h (95% confidence interval [CI]: -11.93, -5.57 h, p < .001) and the risk of postoperative analgesic drug use by 77% (odds ratio, 0.23; 95% CI: 0.10, 0.61, p = .023). Conclusion: vNOTES can shorten the exhaust time and duration of hospitalization, reduce postoperative pain, and avoid surface surgical scars in tubal pregnancy surgeries, consistent with the ERAS concept. However, more comprehensive preoperative evaluation of patients who choose vNOTES is required to reduce the occurrence of intraoperative conversion.Trial registration: ChiCTR2100053483.

Can performance status mediate the relationship between therapy-related symptoms and health-related quality of life in children with cancer? A mediation model.

PURPOSE: Understanding the interplay among health-related quality of life (HRQoL), therapy-related symptoms, and performance status can offer insights into potential strategies to enhance HRQoL for pediatric cancer patients. This study aimed to examine the mediating effect of performance status on the relationship between symptom burden and HRQoL in children and adolescents with cancer. METHOD: A cross-sectional study was conducted. Participants were recruited from two tertiary hospitals located in Guangzhou, China. HRQoL, therapy-related symptoms, and performance status were assessed using the DISAKIDS Chronic Generic Measure (DCGM-37), Therapy-Related Symptom Checklist for Children (TRSC-C), and Lansky Play Performance Scale (LPPS), respectively. RESULTS: A total of 287 children with cancer (aged 11.08 ± 2.34 years) were included. The DCGM-37 scores were 59.70 ± 9.64. Emotion (56.45 ± 14.56) and physical limitations (58.59 ± 15.38) were the most affected domains. The number of symptoms experienced was 12.49 ± 5.95. The DCGM-37 demonstrated strong negative correlations with the TRSC-C (r = -0.60, P < 0.001) and number of symptoms (r = -0.62, P < 0.001), but mild-to-moderate negative correlations (r -0.16∼ -0.42, P < 0.05) with individual symptoms. The TRSC-C demonstrated an indirect effect on the DCGM-37 via the LPPS (Bootstrap-corrected standardized ß = -0.05, 95 % CI -0.10∼ -0.01; SE = 0.02). Additional analysis showed that tripping/falling (OR = 4.02, 95 % CI 2.02-7.98; P < 0.001) and sore mouth (OR = 2.38, 95 % CI 1.56-3.64; P < 0.001) were associated factors for presenting poor performance status in children undergoing acute chemotherapy. CONCLUSIONS: The accumulated symptom burden, rather than individual symptoms, weighs heavily on the HRQoL. Performance status partially mediated the relationship between symptom burdens and HRQoL among these patients.

Assessing limb apraxia after ischemic stroke: validation of the Chinese version of the diagnostic instrument for limb apraxia-short version (DILA-S) classic subtests.

OBJECTIVE: This study aimed to translate and validate the Chinese version of the Diagnostic Instrument for Limb Apraxia-Short Version (DILA-S) classic subtests in Chinese patients after ischemic stroke. METHODS: The DILA-S was translated and adapted for use in Mandarin-speaking Chinese patients. Internal consistency, test-retest reliability, dimensionality, convergent validity, divergent validity, and concurrent validity were tested. RESULTS: A total of 112 ischemic stroke patients were included. The internal consistency (Cronbach's alpha 0.85 ~ 0.92) and test-retest reliability (ICC 0.88 ~ 0.93) were found satisfactory. Exploratory factor analysis obtained two factors for the imitation subtests and the execution scale of the pantomime of tool use. Convergent validity was supported by strong correlations (ρ > 0.7) between the scores of the DILA-S subtests and the LOTCA motor praxis subscale. Divergent validity was acceptable for weak to moderate correlations (ρ ranged from -0.25~ -0.41) between the scores of the DILA-S subtests and the NIHSS. Concurrent validity was supported by strong correlations (ρ > 0.7) between the scores of the DILA-S subtests and the MoCA, as well as strong correlations (ρ > 0.6 < 0.7) between the scores of the DILA-S subtests and the BI. CONCLUSION: The Chinese version of the DILA-S classic subtests demonstrated satisfactory psychometric properties for assessing limb apraxia in Chinese patients after ischemic stroke.

Improving oral hygiene for better cognitive health: Interrelationships of oral hygiene habits, oral health status, and cognitive function in older adults.

OBJECTIVES: To explore the interrelationships between oral hygiene habits, oral health status and cognitive function in older adults. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: A total of 371 participants (age 76.79 [7.99] years) were enrolled from June 2020 to November 2021 in an aged care facility. METHODS: Cognitive function was screened using the mini-mental state examination (MMSE) with adjusted cut-off points for age and education. Periodontal status (Biofilm-Gingival Interface index based on periodontal probing depth and bleeding on probing), dental status (plaque, calculus, and caries), and tooth loss were assessed through full-mouth examination. Oral hygiene habits were based on self- or informant-reporting. RESULTS: Poor periodontal status was an associated factor for MCI (OR = 2.89, 95% CI = 1.20-6.95), while multiple tooth loss (OR = 4.90, 95% CI = 1.06 ~ 22.59), brushing teeth less than once a day (OR = 2.88, 95% CI = 1.12 ~ 7.45) and delayed dental visits (OR = 2.45, 95% CI = 1.05 ~ 5.68) were associated factors for cognitive impairment. An indirect effect of brushing teeth ≥2 daily on MMSE score through periodontal status was observed only in older adults without cognitive impairment (Bootstrap-corrected B = 0.17, 95%CI = 0.03 ~ 0.36, SE = 0.08, ß = 0.08). CONCLUSIONS AND IMPLICATIONS: Adequate toothbrushing might prevent cognitive decline indirectly by improving periodontal health only in older adults without cognitive impairment. Multiple tooth loss, infrequent toothbrushing, and delayed dental visits were associated factors for cognitive impairment. Nursing professionals and health care policymakers should advocate for the improvement of basic oral hygiene in older adults, and provide regular professional oral hygiene care for older adults with cognitive impairment. PATIENT OR PUBLIC CONTRIBUTION: The information on oral health habits of this study was based on an interview with the participants or their caregivers during the study period.

Histology Shift in Esophageal Cancer Between Biopsies and Resections After Neoadjuvant Therapy: A Pilot Study.

Preoperative neoadjuvant therapy followed by resection is the mainstay treatment for locally advanced esophageal adenocarcinoma. We recently observed the histology shift from predominant esophageal adenocarcinoma in the biopsy to neuroendocrine neoplasm with or without adenocarcinoma in the post-treatment resection. The underlying mechanism of this finding is uncertain, and there is limited information in the literature. A total of 11 patients were identified: 10 patients received presurgical chemoradiation and 1 with chemotherapy. All biopsies were diagnosed with adenocarcinoma. When neuroendocrine immunomarkers were retrospectively performed on 5 biopsies, 2 showed focal positivity, although the classic neuroendocrine morphology was not readily appreciated. All resections contained neuroendocrine neoplasm, including 8 of well-differentiated type and 3 of neuroendocrine carcinomas. Two post-treatment esophagectomies consisted of neuroendocrine neoplasm only without residual adenocarcinoma. Upon follow-up, 8 patients died of the disease (median survival = 26 months), and 3 patients were alive after a median follow-up of 14 months. The overall median survival time was better than the reported esophageal neuroendocrine carcinoma (15 months). The 5-year observed survival rate was 11.3%, which was lower than the Surveillance, Epidemiology, and End Results 5-year survival rate of adenocarcinoma (21.8%). We reported a small series of esophageal adenocarcinoma that showed histology shift between biopsy and esophagectomy after neoadjuvant therapy. Our limited data suggest that prognosis of this group is different than the conventional adenocarcinoma. Awareness of this morphological change reminds pathologists to examine the biopsy specimens thoroughly, because recognition of neuroendocrine neoplasm, especially high-grade neuroendocrine component, might potentially affect pre- and post-surgical regimens.

An efficient extraction method for short single-stranded DNA from agarose gels in aptamer screening.

With the rapid advancements in aptamer screening, the efficient extraction of short single-stranded DNA (ssDNA) from agarose gel has become a new requirement. However, the currently available products are primarily designed for double-stranded DNA (dsDNA) and exhibit limited efficacy when applied to the extraction of short ssDNA. In this study, we successfully developed a novel method based on amino-modified silica-coated magnetic particles (ASMPs) for the extraction of short ssDNA from agarose gel. The gel slices containing short ssDNA were subjected to centrifugation in a spin column/centrifugation tube assembly with silica wool, followed by the adsorption using ASMPs. Subsequently, reagents containing phosphate groups were employed to desorb ssDNA from the surface of ASMPs. Through optimization of each step, we realized remarkable efficiency in the extraction of short ssDNA. To assess the efficacy of our method, we utilized it in aptamer screening. The results demonstrated that our method outperformed three commercially available DNA gel extraction products (Q-kit, S-kit, and V-kit). The relative recovery rates of all methods were as follows: M-dNTP (100.00 %) > M-BB (63.38 %) > Q-kit (46.64 %) > S-kit (15.98 %) > V-kit (0.38 %). The results strongly suggest that the developed method holds promise for short ssDNA extraction from agarose gel.