2592 Background: Advanced soft tissue sarcomas (STSs) have limited treatment options and exhibit low responsiveness to immunotherapy, largely due to an immunosuppressive tumor microenvironment (TME). In situ vaccination (ISV) represents a promising strategy to convert immunologically “cold” tumors into “hot” ones. FOLactis, a food-grade probiotic Lactococcus lactis engineered to express a fusion protein of Fms-like tyrosine kinase 3 ligand (Flt3L) and OX40 ligand (OX40L), has shown antitumor immune activity in preclinical models. This study investigates the synergistic antitumor effect and safety of intratumoral FOLactis in combination with hypofractionated radiotherapy and anti-PD-1 therapy in clinical settings. Methods: In this investigator-initiated, single-arm trial, patients with advanced STS who had failed standard therapies received intratumoral injections of FOLactis combined with hypofractionated radiotherapy and PD-1 blockade. Primary endpoints included safety and efficacy, secondary endpoints encompassed abscopal responses and mechanistic exploration of treatment efficacy. Results: Between July 2022 to July 2025, 16 advanced STS patients were enrolled. The R-ISV-FOLactis regimen was well-tolerated, with grade 3 adverse events occurring in 37.5% of patients. Injected lesions showed a best objective response rate (ORR) of 56.25% and a disease control rate (DCR) of 100%. Median progression-free survival (mPFS) for all lesions was 6.3 months, while mPFS for injected lesions was not reached. Abscopal responses were observed in 56.25% of patients. Immunological analyses revealed increased frequencies of peripheral memory CD8⁺ T cells, PD-1⁺ CD8⁺ T cells, and dendritic cells (DCs), alongside decreased regulatory T cells (Tregs) and tissue-resident CD103⁺CD4⁺ T cells in responders, indicating systemic immune activation. Furthermore, reshaped TME with reduced fibroblasts and increased immune cell infiltration were associated with enhanced antitumor immunity. Moreover, significant increase of CD8⁺ T cell density in regions distal to neutrophil clusters, along with elevated 4−Cresol Sulfate levels suggesting neutrophil modulation. Conclusions: R-ISV-FOLactis exhibited a favorable safety profile and encouraging efficacy against both local and distant tumors. The treatment induced systemic immune activation and metabolic remodeling, supporting its further development as a novel ISV strategy for advanced STSs. Clinical trial information: ChiCTR2200060660.
11558 Background: As for most refractory solid tumors, especially sarcoma, immunotherapy still lacks meaningful improvement in their outcomes. The novel 'R-ISV-RO' in situ vaccine, in which we merged radiotherapy, intratumoral delivery of R837 and OX-40 ligand, together with systemic use of immune-checkpoint blockades, may be clinically beneficial. Methods: This was an exploratory, single-center, single-arm clinical trial aimed at evaluating the efficacy and safety of the 'R-ISV-RO' in situ vaccine therapy for advanced solid tumors. Thirty patients aged 18 years or older with advanced solid tumors and at least one measurable lesion were enrolled. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), time to progression (TTP), and clinical benefit rate (CBR). The safety of the treatment and the injection procedures were also evaluated. Results: The ORR and DCR for injected lesions were 44.4% and 96.3%. Sarcoma patients exhibited superior outcomes, with a 100% DCR in injected lesions. The median PFS was 15.9 months for injected lesions and median OS was 23.6 months. The abscopal effect occurred in 12 patients. 'R-ISV-RO' treatment was well tolerated, with only 6.7% of patients experiencing grade 3 or higher adverse events. Improved clinical responses were associated with enhanced CD4⁺/CD8⁺ T-cell infiltration and peripheral expansion. Metabolomics analysis revealed therapy-induced metabolic remodeling. Conclusions: In this exploratory trial, 'R-ISV-RO' with concurrent immunotherapy demonstrated promising efficacy for both primary and distant tumors, especially for sarcomas. Systemic immune response and metabolic remodeling were also observed after the therapy. Clinical trial information: ChiCTR2100053870.
RATIONALE:Thyroid storm (TS), also known as thyroid crisis, is a life-threatening condition that involves multiple organ dysfunction and high mortality due to uncontrolled hyperthyroidism. TS in children is extremely rare, early diagnosis and treatment can significantly improve the prognosis of the children.PATIENT CONCERNS:Three female children who diagnosed as "thyroid storm" were admitted to Pediatric Intensive Care Unit (PICU). One of them had a family history of hyperthyroidism and others had infection factors induced TS. They presented with characteristic manifestations of TS and were evaluated with Burch-Wartofsky Point Scale (BWPS) hyperthyroidism score.DIAGNOSES:Three cases showed that free triiodothyronine 3 (FT3) and free triiodothyronine 4 (FT4) were increased and Thyroid-Stimulating-Hormone was significantly decreased, which were characteristic in hyperthyroidism. They presented with characteristic manifestations of TS and were evaluated with BWPS hyperthyroidism score.INTERVENTIONS:All the cases were given antithyroid drugs (ATDs) for treatment. In addition, 1 of them underwent therapeutic plasma exchange (TPE) after transferring to PICU.OUTCOMES:One of the cases was declared dead and others were survived.LESSONS:TS should be identified timely and treated early. Further studies are needed to determine the diagnostic criteria and scoring system for TS in pediatric.
Immune monotherapy does not appear to work in patients with pancreatic cancer so far. We are conducting a clinical trial that combines programmed cell death protein-1 (PD-1) inhibitor with chemotherapy and concurrent radiotherapy as induction therapy for patients with locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC). Here, we report a case with a pathologic complete response (pCR) and no postoperative complications after the induction therapy. The patient received four cycles of induction therapy and achieved a partial response (PR) with a significant decline of tumor marker carbohydrate antigen 19-9 (CA19-9). Also, peripheral blood samples were collected during the treatment to investigate serial circulating tumor DNA (ctDNA) dynamic changes in predicting the tumor response and outcomes in patients. Our result suggested that PD-1 blockade plus chemotherapy and concurrent radiotherapy is a promising mode as induction therapy for patients with potentially resectable pancreatic cancer. In this case, serial ctDNA alterations accurately provide a comprehensive outlook of the tumor status and monitor the response to the therapy, as validated by standard imaging.
Background Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with a low resection rate. Chemotherapy and radiotherapy (RT) are the main treatment approaches for patients with advanced pancreatic cancer, and neoadjuvant chemoradiotherapy is considered a promising strategy to increase the resection rate. Recently, immune checkpoint inhibitor (ICI) therapy has shown remarkable efficacy in several cancers. Therefore, the combination of ICI, chemotherapy, and concurrent radiotherapy is promising for patients with potentially resectable pancreatic cancer, mainly referring to locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC), to increase the chances of conversion to surgical resectability and prolong survival. This study aims to introduce the design of a clinical trial. Methods This is an open-label, single-arm, and single-center phase II trial. Patients with pathologically and radiographically confirmed LAPC or BRPC without prior anti-cancer treatment or severe morbidities will be enrolled. All patients will receive induction therapy and will be further evaluated by the Multiple Disciplinary Team (MDT) for the possibility of surgery. The induction therapy consists of up to four cycles of gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 via intravenous (IV) infusion on days 1 and 8, along with tislelizumab (a PD-1 monoclonal antibody) 200 mg administered through IV infusion on day 1 every 3 weeks, concurrently with stereotactic body radiation therapy (SBRT) during the third cycle of treatment. After surgery, patients without progression will receive another two to four cycles of adjuvant therapy with gemcitabine, nab-paclitaxel, and tislelizumab. The primary objectives are objective response rate (ORR) and the R0 resection rate. The secondary objectives are median overall survival (mOS), median progression free survival (mPFS), disease control rate (DCR), pathological grade of tumor tissue after therapy, and adverse reactions. Besides, we expect to explore the value of circulating tumor DNA (ctDNA) in predicting tumor response to induction therapy and survival outcome of patients. Discussion This is a protocol for a clinical trial that attempts to evaluate the safety and efficacy of the combination of anti-PD-1 antibody plus chemotherapy and radiotherapy as the induction therapy for LAPC and BRPC. The results of this phase II study will provide evidence for the clinical practice of this modality. Clinical Trial Registration http://www.chictr.org.cn/edit.aspx?pid=53720&htm=4 , identifier ChiCTR2000032955.
Background: Ankylosing spondylitis is a complex and progressive autoimmune inflammatory disease with a worldwide prevalence ranging up to 0.9%. Several systematic reviews and meta-analyses of traditional Chinese medicine alternative therapies, such as acupuncture or moxibustion, have demonstrated the effectiveness of moxibustion and acupuncture in the treatment of ankylosing spondylitis. However, there is no relevant literature to comprehensively evaluate the evidence. The purpose of this overview is to synthesize and evaluate the reliability of evidence generated in the systematic review (SR) and meta-analysis of moxibustion and acupuncture as a primary or complementary therapy for patients with ankylosing spondylitis. Methods: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database were searched for systematic reviews and meta-analysis that review the efficacy of acupuncture or moxibustion as the primary treatment for patients with Ankylosing Spondylitis. The literature published before August 2020 will be selected. Additionally, the relevant SRs and meta-analyses that unpublished or ongoing will be searched in PROSPERO and INPLASY. The methodological guidelines for overviews will be used to review and extract data by 2 reviewers, and their will do it independently. Methodology quality will be analyzed by the assessment of multiple systematic reviews-2and the risk of bias by POBIS. For the included studies, we will adopt the following results as primary evaluation indicators: effective rate, visual analogue scale and bath AS disease activity index. Reviewers will assess the certainty of evidence by Grading of Recommendations Assessment, Development and Evaluation. Results: The results will be published in a peer-reviewed journal. Conclusion: This overview will provide comprehensive evidence of moxibustion and acupuncture for patients with Ankylosing Spondylitis.
Background: Pancreatic trauma surgery is a complicated surgical procedure for severe pancreatic injuries, accompanied by a high incidence of complications and mortality. This study was designed to explore the long-term prognosis of pancreatic surgery because of abdominal trauma. Patients and Methods: The clinical data of 103 patients who were admitted to Jinling Hospital between August 2012 and August 2019 who had pancreatic trauma surgery were analyzed retrospectively. Results: All admissions involved pancreatic trauma surgery performed at an outside hospital network, which later transferred patients to our institution because of post-operative later-stage complications. Eight patients received American Association for the Surgery of Trauma (AAST) grade 1 or 2 pancreatic injuries and 95 received AAST grade 3, 4, or 5 pancreatic injuries. The primary surgical management of pancreatic injuries included drainage of the pancreatic injury (n = 28), repair of the pancreas (n = 35), partial pancreatectomy (n = 15), pancreaticojejunostomy (n = 6), and pancreaticoduodenectomy (n = 19). The most common mechanism of trauma was motor vehicle collision (n = 72), crush injury (n = 26), and stab wound (n = 5). Of 103 patients suffered varying degrees of gastrointestinal fistulae and intra-abdominal infections, there were 66 cases of pancreatic fistulae (64.1%), 49 cases of enteric fistulae (47.6%), 26 cases of colonic fistulae (25.2%), 14 cases of gastric or gastrointestinal anastomotic fistulae (13.6%), and 13 cases of biliary fistulae (12.6%). Ninety-five patients survived and eight patients died after therapy; the mean length of intensive care unit stay was 33 days. The number of patients who underwent emergency pancreaticoduodenectomy (EPD), the incidence of blood transfusion, the number of fistulae per patient, and the duration of mechanical ventilation and bacteremia in the mortality group were substantially higher than in the survival group (p < 0.05 each). The patients who underwent EPD had more grade 5 pancreatic injuries, more blood transfusions, higher peak total bilirubin, greater numbers of fistulae and open abdomen, and longer duration of mechanical ventilation and mortality than other patients (p < 0.05 each). Conclusions: The grade of pancreatic injury was associated with mortality and post-operative complications. The post-operative mortality and occurrence of complications of EPD because of abdominal trauma were significant; use of damage control surgery could potentially reduce the morbidity and mortality related to this procedure.
BACKGROUND:Ganglion cysts (GCs) are tumor-like lesions that often occur in the soft tissues, which are mostly caused by the degeneration of mucin produced by the joint capsule and tendon sheath on the carpal dorsal joints of extremities. GCs may appear asymptomatic as benign tumors, but some patients also seek treatment because of the pain caused by these fluid-filled cysts. As a kind of complementary and alternative therapy, there have been some studies published in China which have proved that the fire needle has a better therapeutic effect on ganglion cyst. The purpose of this systematic review is to evaluate the efficacy of fire needle in the treatment of GCs. METHODS:PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure, Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database were searched by 2 reviewers from the inception until August 2020. The original study that randomised control trials of fire needle for GCs will be selected and is not limited by country or language. In addition, researches in progress, the reference lists and the citation lists of identified publications will be retrieved similarly. Study selection, data extraction, and assessment of the quality will be performed independently by 2 reviewers who have been trained prior to data extraction. A meta-analysis will be conduct if the quantity and quality of the original studies included are satisfactory; otherwise, a descriptive analysis will be conducted. Review Manager V5.4: (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) software will be using for data synthesis and assessment the risk of bias according by Cochrane Handbook. RESULT:This study will provide a comprehensive review of current evidence for the treatment of fire needle on GCs. CONCLUSION:The conclusion of this study will provide a judging basis that whether the treatment of GCs with fire needle is effective. INPLASY REGISTRATION NUMBER:INPLASY202080032.
Background Accurately evaluate the stages of liver fibrosis are critical for the management of patients with autoimmune hepatitis (AIH). We evaluated the accuracy of red cell distribution width (RDW) to platelet (PLT) ratio (RPR) in predicting liver fibrosis in AIH patients.Methods One hundred and nineteen AIH patients with liver biopsy was retrospectively enrolled. Scheuer scoring system was used to stage liver fibrosis. Receiver operating characteristic curve (AUROC) was performed to evaluate the diagnostic accuracy of RPR.Results The median RPR values were 0.10, 0.10 and 0.14 for AIH patients with S2-S4, S3-S4 and S4, which were significantly higher than patients with S0-S1 (0.07, P<0.001), S0-S2 (0.08, P=0.025) and S0-S3 (0.09, P=0.014), respectively. The RPR levels were positively associated with the fibrosis stages (r=0.412, P<0.001), whereas there were no associations between liver fibrosis stages and aspartate transaminase to platelet ratio index (APRI) and fibrosis-4 score (FIB-4). The AUROCs of RPR were 0.780 (95%CI 0.696 to 0.865), 0.639 (95%CI 0.530 to 0.748) and 0.724 (95%CI 0.570 to 0.878) in diagnosing significant fibrosis (S2-S4), advanced fibrosis (S3-S4) and cirrhosis (S4) for AIH patients, respectively. The AUROCs of RPR were significantly higher than those of APRI and FIB-4 in staging liver fibrosis for AIH patients.Conclusion RPR is a simple predictor of liver fibrosis and is superior to APRI and FIB-4 in identifying liver fibrosis in AIH patients.
Background: Facial spasm causes a lot of troubles to patients daily life and seriously affects their mental and physical health. Relevant studies have shown that fire needle therapy has certain benefits for facial spasm, is an integral part of acupuncture therapy. However, there is no unanimous conclusion. The main purpose of our study is to measure whether fire needle therapy is effective for facial spasm. Methods: The following electronic databases will be searched for the collection of fire-needle related randomized controlled trials (RCTS) for facial spasm, including 4 English databases (Web of Science, the Cochrane Library, EMBASE, Pubmed) and 3 Chinese databases (Chinese National Knowledge Infrastructure [CNKI], Wanfang data, Chinese VIP Information). The cure rate and total effective rate are the main outcomes, while the intensity, frequency, recurrence rate and adverse events are the secondary outcomes. We will use Endnote software X9 for study selection, Review Manager software 5.4 and STATA 13.0 software for analysis and synthesis. Results: We will evaluate the efficacy of fire needles in the treatment of facial spasm in combination with current studies. Conclusion: The conclusion of this study will provide evidence for the efficacy of fire needle in the treatment of facial spasm.
Background: Pregnancy-related low back pain (PLPB) and pelvic pain (PP) are common in pregnancy. In spite of its high prevalence rate, treatment of the disorder is a challenging topic. Women commonly utilize complementary exercise therapies such as yoga, motor control exercises, breathing exercises, core stability exercise, pelvic stability exercise, and so on to manage their symptoms. However, it is currently unknown whether exercise produces more beneficial effects than other treatment in patients with PLPB and PP. The aim of this study is to explore the therapeutic effect of exercise for pregnancy-related low back pain and PP. Methods: This review will only include randomized controlled trials. Published articles from July 1999 to July 2019 will be identified using electronic searches. Search strategy will be performed in 3 English databases, 1 Chinese database, and the World Health Organization International Clinical Trials Registry Platform. Two reviewers will screen, select studies, extract data, and assess quality independently. The methodological quality including the risk of bias of the included studies will be evaluated using a modified assessment form, which is based on Cochrane assessment tool and Physiotherapy Evidence Database scale. Review Manager Software (Revman5.3) will be used for heterogeneity assessment, generating funnel-plots, data synthesis, subgroup analysis, and sensitivity analysis. We will use GRADE system to evaluate the quality of our evidence. Results: We will provide some more practical and targeted results investigating the effect of exercise therapy (ET) for PLPB and PP in the current meta-analysis. Meanwhile, we will ascertain study progress of ET for PLPB and PP and find out defects or inadequacies of previous studies, so that future researchers could get beneficial guidance for more rigorous study. Conclusion: The stronger evidence about PLPB and PPs rehabilitative effect and safety will be provided for clinicians and policymakers. Systematic review registration: PROSPERO CRD 42017075099.
The management of enterocutaneous fistulas (ECF) can be challenging because of massive fluid loss, which can lead to electrolyte imbalance, severe dehydration, malnutrition and sepsis. Nutritional support plays a key role in the management and successful closure of ECF. The principle of nutritional support for patients with ECF should be giving enteral nutrition (EN) priority, supplemented by parenteral nutrition if necessary. Although total parenteral nutrition (TPN) may be indicated, use of enteral feeding should be advocated as early as possible if patients are tolerant to it, which can protect gut mucosal barrier and prevent bacterial translocation. A variety of methods of enteral nutrition have been developed such as fistuloclysis and relay perfusion. ECF can also be occluded by special devices and then EN can be implemented, including fibrin glue application, Over-The-Scope Clip placement and three-dimensional (3D)-printed patient-personalized fistula stent implantation. However, those above should not be conducted in acute fistulas, because tissues are edematous and perforation could easily occur.
Lung cancer is a malignancy with high morbidity and mortality worldwide. More evidences indicated that gut microbiome plays an important role in the carcinogenesis and progression of cancers by metabolism, inflammation and immune response. However, the study about the characterizations of gut microbiome in lung cancer is limited. In this study, the fecal samples were collected from 16 healthy individuals and 30 lung cancer patients who were divided into 3 groups based on different tumor biomarkers (cytokeratin 19 fragment, neuron specific enolase and carcinoembryonic antigen, respectively) and were analyzed using 16S rRNA gene amplicon sequencing. Each lung cancer group has characterized gut microbial community and presents an elimination, low-density, and loss of bacterial diversity microbial ecosystem compared to that of the healthy control. The microbiome structures in family and genera levels are more complex and significantly varied from each group presenting more different and special pathogen microbiome such as Enterobacteriaceae, Streptococcus, Prevotella, etc and fewer probiotic genera including Blautia, Coprococcus, Bifidobacterium and Lachnospiraceae. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and COG annotation demonstrated decreased abundance of some dominant metabolism-related pathways in the lung cancer. This study explores for the first time the features of gut microbiome in lung cancer patients and may provide new insight into the pathogenesis of lung cancer system, with the implication that gut microbiota may serve as a microbial marker and contribute to the derived metabolites, development and differentiation in lung cancer system.
Objective To evaluate the prognostic value of pathological characteristics of microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC).Methods 289 consecutive HCC patients who underwent curative hepatectomy at Nanjing Drum Tower Hospital from January 2007 to December 2015 were retrospectively studied.These patients were divided into three groups:the no-MVI group (n =176),the low-MVI group (the number of invaded microvessels ≤ 5 and the distance of invasion ≤ 1 cm,n =53) and the high-MVI group (the number of invaded microvessels > 5 or the distance of invasion > 1 cm,n =60).The clinical and pathological data and the survival outcomes of these HCC patients were analyzed.We further compared the prognosis among the three groups.Results Kaplan-Meier survival indicated that the number of invaded microvessels > 5 and the distance of invasion > 1 cm were associated with cumulative and recurrence-free survival rates of HCC patients.The cumulative and recurrence-free survival rates of the high-MVI group were significantly poorer than those of the low-MVI and the no-MVI groups.Multivariate analysis showed ICG-R15 (HR =1.049,95% CI:1.002 ~ 1.097),tumor size (HR =1.138,95% CI:1.043 ~ 1.241),and high-MVI (HR =3.245,95% CI:1.946 ~ 5.413) were independent risk factors for cumulative survival.Tumor size (HR =1.117,95% CI:1.050 ~ 1.188),and high-MVI (HR =2.222,95% CI:1.540 ~ 3.205) were independent risk factors for recurrence-free survival.The prognosis of the no-MVI and low-MVI groups were significantly better than the high-MVI group (P < 0.05).The recurrence rates of the low-MVI and no-MVI groups (49.4% and 67.9%) were significantly lower than the high-MVI group (80.0%,P < 0.05).Conclusions The risk classification of MVI based on histopathological features was valuable in predicting prognosis of HCC patients.We could use the risk classification of MVI to establish a follow-up and individualized treatment plan for HCC patients.
Objective To study the clinical, endoscopic and pathological features of gastrointestinal and mesenteric reactive nodular fibrous pseudotumor (RNFPT). Methods A retrospective analysis was conducted on data of 24 RNFPT patients in Nanjing Drum Tower Hospital admitted from October 2008 to June 2016. The clinical, endoscopic, pathological and immunohistochemical characteristics were analyzed. Results Among the 24 patients, 16 complained about discomfort in the upper abdomen and 10 had a history of surgery or trauma. Twenty-one had isolated masses and 3 had multiple masses, with diameter of 0. 5-4. 0 cm. Endoscopically, the tumors were mainly hard submucosal masses with broad base, and smooth surface with no mucosal bridge. Seventeen patients underwent endoscopic ultrasonography, which showed low echoes in lesions and nonuniform echoes partly. Among them, 13 lesions derived from muscularis, 4 others from submucosa. Microscopically, the tumors had clear boundary with no envelope, and most areas showed disorderly arranged spindle cells and extensively collagenous degenerated mesenchyma. The spindle cells had shuttle fibroblast-like morphology and elongated nucleus with no visible necrosis or mitosis. Inflammatory cells scattered between the tumor cells, and lymphoid follicles and calcium deposition could be seen in local areas. Immunohistochemically, SMA was focally positive in 7 cases and only 4 cases expressed CD117 scattered. Desmin, Dog-1, CD34, ALK-1 and S-100 were all negative, and Ki-67 proliferation index was lower than 1%. Conclusion RNFPT has diverse clinical manifestations, with a good prognosis and unlikely recurrences, and should be distinguished from spindle cell tumors.
Objective To investigate the predictive value of non-thyroidal illness syndrome (NTIS) before definitive operation on postoperative surgical site infection (SSI) in patients with enterocutaneous fistula (ECF). Methods The retrospective case-control study was conducted. The clinical data of 264 ECF patients (181 with euthyroidism and 83 with NTIS) who underwent definitive operation in the Nanjing General Hospital of Nanjing Military Command between April 2014 and November 2016 were collected. After definitive operation, 86 with SSI and 178 without SSI were respectively allocated into the SSI group and non-SSI group. Observation indicators: (1) risk factor analysis of postoperative SSI; (2) effect of preoperative NTIS on postoperative SSI; (3) predictive power of serum free triiodothyronine 3 (FT3) level on postoperative SSI. Measurement data with normal distribution were represented as ±s and was analyzed using the t test. Count data were described as absolute number or percentage, and were analyzed using the chi-square test. The comparison of ordinal data was done by the nonparamentric test. The multivariate analysis was done using the logistic regression model. The receiver operating characteristic (ROC) curve was drawn, and area under the curve (AUC) was calculated for analyzing predictive power of serum FT3 level on postoperative SSI. Results (1) Risk factor analysis of postoperative SSI: cases with volume of preoperative intestinal fluid loss through fistula stoma 500 mL/24 hours, preoperative hemoglobin (Hb) level, cases with surgical site located in stomach and duodenum, small intestine, ileocolon and colorectum, cases with open surgery and laparoscopic surgery were respectively 65, 15, 6, (119±36)g/L, 5, 50, 31, 36, 58, 28 in the SSI group and 135, 27, 16, (125±39)g/L, 11, 91, 53, 71, 127, 51 in the non-SSI group, with no statistically significant difference between groups (χ2=0.471, t=1.202, χ2=0.332, 0.422, P>0.05). Cases with preoperative single and multiple fistula stoma, serum albumin (Alb) level, cases with preoperative NTIS, volume of intraoperative blood loss 3 months, incidence of postoperative SSI, postoperative superficial and deep incision infection rates and organ/space infection rate were respectively 31.3%(26/83), 72.3%(60/83), 43.4%(36/83), 9.6%(8/83), 21.7%(18/83), 7.2%(6/83) in patients with NTIS and 19.3%(35/181), 57.5%(104/181), 27.6%(50/181), 11.6%(21/181), 3.9%(7/181), 8.8%(16/181) in patients with euthyroidism, with statistically significant differences in incidence of multiple intestinal fistula, proportion of cases with preoperative enteral nutrition time > 3 months, incidence of postoperative SSI, superficial and deep incision infection rates (χ2=4.603, 5.319, 6.426, 4.256, 4.377, P 0.05). (3) Predictive power of serum FT3 level on postoperative SSI: the ROC curve showed that optimal cut-off point of serum FT3 predicting postoperative SSI was 3.5 pmol/L, AUC, sensibility and specificity were respectively 0.75, 72.6% and 68.7%. Conclusion The presence of NTIS is associated with occurrence of postoperative SSI in patients with ECF before definitive operation, and optimal cut-off point of serum FT3 predicting postoperative SSI is 3.5 pmol/L. Key words: Enterocutaneous fistula; Non-thyroidal illness syndrome; Surgical site infection; Definitive surgery; Low triiodothyronine syndrome
Purpose. Translocation of bacteria across the intestinal barrier is important in the pathogenesis of systemic sepsis. In inflammatory conditions, commensal bacteria exploit transcytotic pathways to cross the intestinal epithelium in a TLR4-dependent manner. The aim of this study was to test the hypothesis that Lactobacillus plantarum ameliorates tumour necrosis factor-induced bacterial translocation by regulation of Toll-like receptor-4 expression.Methodology. L. plantarum strains were investigated to determine their capacity to inhibit the initial adhesion of Escherichia coli B5 to Caco-2 cells. The inhibitory effects of L. plantarum on TNF-α-induced E. coli B5 translocation across Caco-2 cells were studied. Barrier function and integrity were simultaneously assessed by transepithelial electrical resistance, HRP permeability, LDH release and distribution of tight junctional proteins. Expression of TLR4 was assessed by RT-PCR.Results/Key findings. Pretreatment of monolayers with L. plantarum L2 led to a significant decrease in E. coli B5 adhesion and cell internalization (P<0.01). Exposure to TNF-α for six hours caused a significant increase in E. coli B5 translocation across Caco-2 cells, which was uncoupled from increases in paracellular permeability and disruption of tight junction proteins. Manipulations that induced bacterial translocation were associated with a marked increase in TLR4 mRNA expression and IL-8 secretion. L. plantarum L2 significantly abrogated TNF-α-induced bacterial translocation of E. coli B5, and also downregulated expression of TLR4 and IL-8 in intestinal epithelial cells.Conclusion. Live L. plantarum L2 can inhibit TNF-α-induced transcellular bacterial translocation via regulation of TLR4 expression.
Background: Non-thyroidal illness syndrome (NTIS) is common in critically ill patients and associated with adverse outcomes. Many enterocutaneous fistula (ECF) patients still suffer NTIS prior to definitive surgery. This study was designed to explore the association between preoperative NTIS and postoperative outcomes in ECF patients. Methods: A total of 264 ECF patients who underwent definitive surgery from April 2014 to November 2016 were studied. Thyroid hormones were tested for each patient before surgery, and the patients were divided into two groups (NTIS group and euthyroid group) according to the presence of NTIS. Demographics, surgery-related data, and complications during the first 30 days after surgery were recorded and analyzed. Results: Among ECF patients accepted for definitive surgery, the prevalence of NTIS was 31.4% (83/264). The most common presentation of NTIS was a single low free triiodothyronine (FT3) 28.0% (74/264), followed by low FT3 combined with low thyrotropin (TSH) 1.9% (5/264), and low free thyroxine (FT4) combined with low TSH 1.5% (4/264). Compared to the euthyroid group, more patients with NTIS had multiple ECF, received more than three months of enteral nutrition pre-operatively, and developed surgical site infections (SSI). FT3 levels correlated with risk of SSI. Receiver operating characteristic curve (ROC) analysis revealed the diagnostic effectiveness of FT3, suggesting that the optimal cut-off value was 3.5 pmol/L. Area under the curve, sensitivity and specificity were 0.75, 72.6% and 68.7%, respectively. Conclusions: ECF patients with NTIS before definitive surgery appear to have a greater risk for poor outcomes. The benefit of thyroid hormone replacement therapy or delaying definitive surgery deserves further study.
Purpose: To investigate the efficacy of histogram analysis of the entire tumor volume in apparent diffusion coefficient (ADC) maps for differentiating between histological grades in gastric cancer.Materials and Methods: Seventy-eight patients with gastric cancer were enrolled in a retrospective 3.0T magnetic resonance imaging (MRI) study. ADC maps were obtained at two different b values (0 and 1000 sec/mm(2)) for each patient. Tumors were delineated on each slice of the ADC maps, and a histogram for the entire tumor volume was subsequently generated. A series of histogram parameters (eg, skew and kurtosis) were calculated and correlated with the histological grade of the surgical specimen. The diagnostic performance of each parameter for distinguishing poorly from moderately well-differentiated gastric cancers was assessed by using the area under the receiver operating characteristic curve (AUC).Results: There were significant differences in the 5th, 10th, 25th, and 50th percentiles, skew, and kurtosis between poorly and well-differentiated gastric cancers (P < 0.05). There were correlations between the degrees of differentiation and histogram parameters, including the 10th percentile, skew, kurtosis, and max frequency; the correlation coefficients were 0.273, -0.361, -0.339, and -0.370, respectively. Among all the histogram parameters, the max frequency had the largest AUC value, which was 0.675.Conclusion: Histogram analysis of the ADC maps on the basis of the entire tumor volume can be useful in differentiating between histological grades for gastric cancer.