BMC Gastroenterology

The methylation SEPT9 (mSEPT9) appeared to be effective for hepatocellular carcinoma (HCC) detection. However, its performance in high-risk population has not been validated. We designed a pilot study and aimed to investigate the performance of mSEPT9, AFP, PIVKA-II and their combination in hepatic cirrhosis (HC) population. A training cohort was established including 103 HCC and 114 HC patients. 10 ml blood was collected from each patient with K2EDTA tubes, and 3–4 ml plasma was extracted for subsequent tests. The performance of mSEPT9, AFP, PIVKA-II and their combination was optimized by the training cohort. Test performance was prospectively validated with a validation cohort, including 51 HCC and 121 HC patients. At the optimal thresholds in the training cohort, the sensitivity, specificity and area under curve (AUC) was 72.82%, 89.47%, 0.84, and 48.57%, 89.92%, 0.79, and 63.64%, 95.95%, 0.79 for mSEPT9, AFP and PIVKA-II, respectively. The combined test significantly increased the sensitivity to 84.47% (P < 0.05) at the specificity of 86.84% with an AUC of 0.91. Stage-dependent performance was observed with all single markers and their combination in plasma marker levels, positive detection rate (PDR) and AUC. Moderate correlation was found between mSEPT9 and AFP plasma levels (r = 0.527, P < 0.0001). Good complementarity was found between any two of the three markers, providing optimal sensitivity in HCC detection when used in combination. Subsequent validation achieved a sensitivity, specificity and AUC of 65.31%, 92.86%, 0.80, and 44.24%, 89.26%, 0.75, and 62.22%, 95.27%, 0.78 for mSEPT9, AFP and PIVKA-II, respectively. The combined test yielded a significantly increased sensitivity of 84.00% (P < 0.05) at 85.57% specificity, with an AUC at 0.89. The performance was optimal by the combination of mSEPT9, AFP, PIVKA-II compared with any single marker, and the combination may be effective for HCC opportunistic screening in HC population.

Colonoscopy is the primary method to detect mucosal abnormalities in the colon, rectum, and terminal ileum. Inadequate bowel preparation is a common problem and can impede successful visualization during colonoscopy. Although studies identified hospitalization as a predictor of inadequate bowel preparation, acuity of care vary greatly within this patient population. The current study aims to examine the effect of patient characteristics and care level predictors on inadequate bowel preparation quality within the inpatient setting. This retrospective study was conducted in a single urban level 1 trauma medical center and included adult patients undergoing diagnostic colonoscopy while admitted in the hospital from January 1, 2015 to June 30, 2020. We examined the level of inpatient care between the General Medical Floor (GMF), Intensive Care Units (ICU) and Telemetry Unit (TU) and assessed this association with bowel preparation quality, adjusting for known and unknown predictors. Of 538 patients undergoing colonoscopy, 47.4% were admitted into TU, 43.7% into GMF and 8.9% into ICU. For the entire sample, 72.7% of patients achieved good or excellent preparation and quality of bowel preparation differed by care level (P = 0.01). Patients from the critical care units were less likely to achieve adequate bowel preparation when compared to GMF (Odds Ratio [OR] 0.36; 95% Confidence Interval [CI] 0.17,0.77), after adjusting for patient characteristics, medications, physical status, and preparation regimen. No significant difference in Bowel Preparation Quality (BPQ) was identified between patients from GMF and TU (OR 0.96; 95%CI 0.61, 1.52). Furthermore, adequate BPQ was associated with withdrawal time and cecal intubation, but not higher adenoma detection rates. Results suggest the ICU setting is an independent predictor for inadequate bowel preparation and patients with prior opioid and laxative use may be more likely to have inadequate bowel preparation in the hospital. Future interventions should prioritize preprocedural clinician meetings for critical care unit patients, including a more detailed readiness assessment and thorough medication history.

Periplakin (PPL) is a rod-shaped cytolinker protein thought to connect cellular adhesion junctional complexes to cytoskeletal filaments. PPL serves as a structural component of the cornified envelope in the skin and interacts with various types of proteins in cultured cells; its level decreases dramatically during tumorigenic progression in human epithelial tissues. Despite these intriguing observations, the physiological roles of PPL, especially in non-cutaneous tissues, are still largely unknown. Because we observed a marked fluctuation of PPL expression in mouse liver in association with the bile acid receptor farnesoid X receptor (FXR) and cholestasis, we sought to characterize the role of PPL in the liver and determine its contributions to the etiology and pathogenesis of cholestasis. Time- and context-dependent expression of PPL in various mouse models of hepatic and renal disorders were examined by immunohistochemistry, western blotting, and quantitative real-time polymerase chain reactions. The hepatic expression of PPL was significantly decreased in Fxr −/− mice. In contrast, the expression was dramatically increased during cholestasis, with massive PPL accumulation observed at the boundaries of hepatocytes in wild-type mice. Interestingly, the hepatic accumulation of PPL resulting from cholestasis was reversible. In addition, similar accumulation of PPL at cellular boundaries was found in epithelial cells around renal tubules upon ureteral obstruction. PPL may be involved in the temporal accommodation to fluid stasis in different tissues. Further examination of the roles for PPL may lead to the discovery of a novel mechanism for cellular protection by cytolinkers that is applicable to many tissues and in many contexts.

Terminal ileal (TI) ulcers are occasionally detected in asymptomatic individuals and mostly resolve without any treatment. In patients with ulcerative colitis (UC), TI ulcers are infrequently observed without evidence of backwash ileitis. However, the clinical significance and natural course of the lesions are unclear. The aim of our study was to evaluate the frequency and clinical implications of TI ulcers in patients with UC. We retrospectively reviewed 397 patients with UC via successful TI intubation during colonoscopy. We compared the clinical characteristics of patients manifesting TI ulcers with those who did not. The natural course of TI lesions was also investigated during the follow-up periods. Forty-one patients (10.3%) showed TI ulcers without evidence of inflammation in the right colon. The patients with and without TI ulcers were not different in terms of baseline characteristics, disease activity and extent at the time of the UC diagnosis, proximal extension, Mayo endoscopic score at the last endoscopic examination, medication history, UC-related hospitalization, and relapse during follow-up periods. Of the 30 patients who underwent follow-up colonoscopy in patients with TI ulcers, 23 (76.7%) showed resolution of TI ulcer. In addition, patients with remaining TI ulcers did not differ in disease activity and biopsy results compared with those with resolving TI ulcers. Discrete TI ulcers are more common in patients with UC, compared with the healthy cohort. No significant clinical impact on disease extension and severity is found.

The need for pain management is increasing in pediatrics, but the side effects of overuse or abuse of analgesics can be harmful to children’s health and even life-threatening in severe cases. Patients who underwent resection of Meckel’s diverticulum at the Children’s Hospital of Chongqing Medical University from July 1, 2019, to July 1, 2022, were included in this study. Opioids were administered through patient-controlled analgesia (PCA). Based on the preoperative choices made by the legal guardians, patients were stratified into two groups: PCA Group (PCAG) and Non-PCA Group (NPCAG). Data pertaining to the clinical characteristics and prognoses of these patients were subsequently collected and analyzed to assess the impact of opioid administration. In the study, a total of 126 patients were enrolled, with 72 allocated to the Patient-Controlled Analgesia Group (PCAG) and 54 to the Non-Patient-Controlled Analgesia Group (NPCAG). When compared to the NPCAG, the PCAG exhibited a longer duration of postoperative fasting (median 72 vs. 62 h, p = 0.044) and increased utilization of laxatives (12[16.7%] vs. 2[3.7%], p = 0.022). However, the PCAG also experienced higher incidences of intestinal stasis and abnormal intestinal dilation (13[18.1%] vs. 3[5.6%], p = 0.037). No statistically significant differences were observed in pain assessments at the conclusion of the surgical procedure (0 vs. 1[1.9%], p = 0.429) or within the first 24 h postoperatively (16[22.2%] vs. 18[33.3%], p = 0.164). Additionally, NPCAG patients did not necessitate increased administration of rescue analgesics (2[2.8%] vs. 4[7.4%], p = 0.432). The administration of opioids did not demonstrably ameliorate postoperative pain but was associated with a heightened incidence of postoperative gastrointestinal tract dysfunction. The retrospective nature of the current research should be considered and should be clarified further.

Pressure sores are sometimes refractory to treatment, often due to malnutrition. Small intestinal bacterial overgrowth (SIBO) obstructs absorption in the digestive tract and causes malnutrition. However, little is known about the association between pressure sore wound healing and SIBO. Here, we report a case of a patient with a refractory sacral pressure sore and SIBO. A 66-year-old woman who was spinal cord injured 14 years before visiting our hospital presented with the chief complaint of a sacral pressure sore, 10.0 × 6.5 cm in size, which was refractory to treatment. Physical examination showed abdominal distension and emaciation, with a body mass index of 15. Further examination revealed elevated serum alkaline phosphatase (1260 U/L), bilateral tibial fracture, multiple rib fracture, and osteoporosis. We diagnosed the patient with osteomalacia with vitamin D deficiency. Despite oral supplementation, serum levels of calcium, phosphorous, and vitamin D remained low. Also, despite concentrative wound therapy for the sacral pressure sore by plastic surgeons, no wound healing was achieved. Due to a suspicion of disturbances in nutrient absorption, we performed bacterial examination of collected gastric and duodenal fluid, which showed high numbers of bacteria in gastric content (104 E. coli, 105 Streptococcus species, and 105 Neisseria species) and duodenal content (106 E. coli, 104 Candida glabrata). Therefore, we diagnosed the patient with SIBO and started selective decontamination of the digestive tract using polymyxin B sulfate and amphotericin B. After starting treatment for SIBO, the sacral pressure sore began to heal and was nearly healed after 285 days. The patient’s serum levels of calcium, phosphorous, vitamin D, and other fat-soluble vitamins also gradually increased after starting treatment for SIBO. We report a case of a patient with a refractory sacral pressure sore that healed after starting treatment for SIBO. We conclude that SIBO may be an overlooked cause of malnutrition and poor wound healing in patients with chronic pressure sores.

Exocrine pancreatic insufficiency (EPI) stems from a deficiency of functional pancreatic enzymes with consequent maldigestion and malnutrition. EPI shares clinical symptoms and manifestations with other disorders and is a considerable burden to individuals affected. In this narrative review, we analyzed the literature to identify relevant publications on living with EPI with the scope of individuating evidence gaps, including those related to symptoms, health-related quality of life (HRQoL), emotional functioning, disease burden, presence of comorbidities, and the use of pancreatic enzyme replacement therapy (PERT). Abdominal pain emerged as one of the most prominent symptoms. HRQoL was affected in EPI, but no articles examined emotional functioning. Comorbidities reported involved other pancreatic disorders, diabetes, gastrointestinal disorders, sarcopenia and osteopenia, cardiovascular disorders, bacterial overgrowth, and nutritional deficiencies. PERT was found to be effective in improving EPI symptoms and was well tolerated by most individuals. Our review revealed a dearth of literature evidence on patients’ experience with EPI, such as emotional functioning and disease burden. We also revealed that studies on long-term effects of PERT are missing, as are studies that would help advance the understanding of the disease and its progression, risk/mitigating factors, and comorbidities. Future studies should address these identified gaps.

Hepatitis C virus (HCV) infection is associated with high percentage of chronicity which implies the ability of the virus to evade or modulate host cell immune system. Modulation of chemokines, such as RANTES may be part of the virus induced pathogenicity. We examined the effect of core and structural proteins of HCV on RANTES expression in two liver derived cell lines, HepG2 and Chang Liver (CHL). HepG2 and Chang Liver (CHL) cell lines were established and selected for constitutive expression of HCV core and structural genes. Flow cytometry and quantitative RT-PCR analysis were performed to examine the effect of HCV core protein on RANTES expression. Luciferase analysis after RANTES-Luc-promoter transfection of established cell lines was assayed by luminometer measurements (RLU) of RANTES promoter activity. IRF-1 and IRF-7 expression was then examined by immunoblotting analysis. Results of flow cytometry and RT-PCR analysis indicated that RANTES is differentially regulated by HCV core protein in the two cell lines examined as its expression was inhibited in HepG2 cells, by a reduction of RANTES promoter activity. Conversely, RANTES protein and mRNA were induced by the core protein in CHL cells, through the induction of the promoter. Since HCV genome modulates IRF-1 and IRF-7 in replicon system and IRF-1, IRF-3 and IRF-7 have been reported to regulate RANTES promoter in various cell systems, analysis of the mechanism underlying RANTES modulation by the core protein revealed that IRF-1 expression was induced in HepG2 cells by the core protein, whereas in CHL cells it was expressed at a very low level that was not influenced by transfection with the core protein construct. This suggested that IRF-1 level may mediate the expression of RANTES in cell lines of liver origin. The effect of the core protein on RANTES promoter was countered by co-transfection with NF90, a double-stranded-RNA binding protein that activates some interferon response genes and acts as a component of cell defense against viral infection. HCV core protein have opposite effects on the expression of RANTES in different cell types in vitro, possibly reflecting a similar scenario in different microenvironments in vivo.

Enterocutaneous fistula after removal of the jejunostomy tube leads to multiple problems, such as cosmetic problems, decreased quality of life, electrolyte imbalances, infectious complications, and increased medical costs. However, the risk factors for refractory enterocutaneous fistula (REF) after button jejunostomy removal remain unclear. Therefore, in this study, we assessed the risk factors for REF after button jejunostomy removal in patients with oesophageal cancer and reported the surgical outcomes of the novel extraperitoneal approach (EPA) for REF closure. This retrospective cohort study included 47 patients who underwent button jejunostomy removal after oesophagectomy for oesophageal cancer. We assessed the risk factors for REF in these patients and reported the surgical outcomes of the novel EPA for REF closure at the International University of Health and Welfare Hospital between March 2013 and October 2021. The primary endpoint was defined as the occurrence of REF after removal of the button jejunostomy, which was assessed using a maintained database. The risk factors and outcomes of the EPA for REF closure were retrospectively analysed. REFs occurred in 15 (31.9%) patients. In the univariate analysis, REF was significantly more common in patients with albumin level < 4.0 g/dL (p = 0.026), duration > 12 months for button jejunostomy removal (p = 0.003), and with a fistula < 15.0 mm (p = 0.002). The multivariate analysis revealed that a duration > 12 months for button jejunostomy removal (odds ratio [OR]: 7.15; 95% confidence interval [CI]: 1.38–36.8; p = 0.019) and fistula < 15.0 mm (OR: 8.08; 95% CI: 1.50–43.6; p = 0.002) were independent risk factors for REF. EPA for REF closure was performed in 15 patients. The technical success rate of EPA was 88.2%. Of the 15 EPA procedures, fistula closure was achieved in 12 (80.0%). The complications of EPA (11.7%) were major leakages (n = 3) and for two of them, EPA procedure was re-performed, and closure of the fistula was finally achieved. This study suggested that duration > 12 months for button jejunostomy removal and fistula < 15.0 mm are the independent risk factors for REF after button jejunostomy removal. EPA for REF closure is a novel, simple, and useful surgical option for patients with REF after oesophagectomy.