Upper Gastrointestinal Involvement in Crohn's Disease as an Independent Predictor of New-Onset Strictures: Insights from an Extensive Retrospective Cohort Analysis.

BACKGROUND/AIMS: Crohn's Disease (CD) can affect the entire gastrointestinal tract, including the upper sections (UGI), which is often overlooked, especially in Asian populations. There's a notable gap in research regarding the impact of UGI involvement on the intricate landscape of ensuing complications. This study aims to address this gap. METHODS: Conducting a retrospective study at Chang Gung Memorial Hospital from January 2001 to September 2023, we compared CD patients with UGI (Montreal L4) involvement against non-L4 counterparts, focusing on baseline characteristics, post-diagnosis complications, and overall outcomes. Routine UGI endoscopy was performed around the time of diagnosis in all patients followed in our inflammatory bowel disease (IBD) center, and all CD patients with adequate follow-up were included in this study. RESULTS: The study included 212 CD patients, 111 in the L4 group and 101 in the non-L4 group, with an average follow-up of 40.8 ± 15.1 months. At baseline, individuals in the L4 category demonstrated elevated smoking rates, increased Crohn's Disease Activity Index scores, a higher prevalence of strictures, and a more prevalent usage of biologics and proton pump inhibitors. Moreover, this group was characterized by reduced albumin levels. Upon concluding the follow-up, those with L4 involvement continued to show escalated CDAI scores and hospitalization frequencies, alongside heightened C-reactive protein levels and diminished albumin concentrations. Additionally, the occurrence of UGI involvement, stricturing disease at the time of diagnosis, and a younger age at the onset of CD were pinpointed as independent predictors for the development of new-onset strictures. CONCLUSIONS: CD patients with UGI involvement exhibit elevated disease activity and serve as independent predictors for the development of intestinal strictures. Thorough UGI evaluations at the time of diagnosis, coupled with assertive treatment strategies, are essential for managing these patients effectively.

Impact of completely histological remission on reducing flare-ups in moderate-to-severe, biologics-experienced ulcerative colitis patients with endoscopic remission.

BACKGROUND/PURPOSE: Endoscopic remission is presently recognized as the standard therapeutic target in the treatment of ulcerative colitis (UC). However, achieving histological remission is increasingly viewed as a pivotal objective. This study investigates the effects of attaining completely histological remission on the clinical outcomes for UC patients with a high disease burden who have already reached endoscopic remission. This is the inaugural study to concentrate on this specific patient demographic. METHODS: This retrospective cohort study enrolled moderate-to-severe, biologics-experienced UC patients with completely endoscopic remission (Mayo endoscopic subscore of 0) between June 2017 and October 2023 at Chang Gung Memorial Hospital, Linkou. Patients were classified into histological remission (HR) and non-histological remission (non-HR) groups based on the Nancy index (NI). HR was defined as an NI score of 0, with all other patients categorized as non-HR. The definition of flare-ups was based on both clinical and endoscopic evidence. Comparative analyses focused on baseline characteristics and clinical outcomes at follow-up. RESULTS: A total of 42 patients (HR group: 23, non-HR group: 19) were included. The average follow-up duration was 17.6 months. Baseline characteristics were comparable between the groups. At the end of follow-up, the HR group showed a significantly lower rate of acute flare-ups (26.1% vs. 68.4%, P = 0.006). Although not statistically significant, the HR group also experienced fewer emergency department visits and hospital admissions. CONCLUSIONS: For moderate-to-severe, biologics-experienced UC patients in endoscopic remission, achieving completely histological remission is associated with a substantial reduction in flare-ups, suggesting its potential as a valuable therapeutic target.

Comparative Efficacy of Fecal Microbiota Transplantation in Treating Refractory or Recurrent Clostridioides difficile Infection among Patients with and without Inflammatory Bowel Disease: A Retrospective Cohort Study.

Clostridioides difficile infection (CDI) worsens inflammatory bowel disease (IBD) prognosis. While fecal microbiota transplantation (FMT) is effective for refractory or recurrent CDI (rrCDI), comparative success rates between IBD and non-IBD patients are scarce. This study addresses this gap. A retrospective cohort study was conducted at Chang Gung Memorial Hospital from April 2019 to October 2023. Patients receiving FMT for rrCDI were categorized into IBD and non-IBD groups. Baseline characteristics and outcomes were compared at one month and one year, with successful FMT defined as the resolution of diarrhea without CDI recurrence. The study included 88 patients: 30 with IBD and 58 without IBD. The IBD group was younger, with fewer comorbidities. Success rates at one month were similar between groups (IBD: 80.0% vs. non-IBD: 78.9%, p = 0.908), as were negative toxin tests (IBD: 83.3% vs. non-IBD: 63.8%, p = 0.174). One-year success rates (IBD: 70.0% vs. non-IBD: 67.6%, p = 0.857) and eradication rates (IBD: 94.4% vs. non-IBD: 73.9%, p = 0.112) were also similar. Poor bowel preparation predicted FMT failure at one month (OR = 0.23, p = 0.019). No safety issues were reported. FMT is a safe, effective treatment for rrCDI, demonstrating similar success rates in patients with and without IBD.

Human papillomavirus prevalence, genotype distribution, and prognostic factors of vaginal cancer.

We aimed to investigate human papillomavirus (HPV) prevalence and genotype distribution and prognostic factors in vaginal cancer (VC). VC patients who received treatment between 1989 and 2020 were retrospectively reviewed. L1 general polymerase chain reaction (PCR) followed by HPV Blot (King Car, I-Lan, Taiwan) and E6 type-specific-PCR were performed for genotyping firstly. P16 and p53 immunohistochemistry staining was performed. Univariate and multivariate analyses identified predictors of clinical outcomes.79 VC patients were eligible for analysis. 73 patients (92.4%) were squamous cell carcinoma (SCC) and 6 (7.6%) as non-SCC. The median follow-up time was 134.3 months (range 0.9-273.4). Among nine initially HPV-negative cases, seven were identified as being positive through HPV16/18/45/52/58 whole-genome amplification followed by Sanger sequencing (WGASS). HPV DNA sequences were detected in 98.6% of SCC and 83.3% of non-SCC, respectively, with HPV16 (49.4%), HPV52 (15.2%) and HPV58 (8.9%) being predominant. Patients with paraaortic lymph node (LN) metastasis had a 5-year cancer-specific survival (CSS) rate of 0%. Multivariate analysis revealed that only p16 and stage were significantly correlated with prognosis. Variables with strong correlations (p16- and HPV-positivity, LN metastasis and stage), were included in models 2-5 alternatively. Stage III/IV (hazard ratio [HR] = 3.64-4.56) and LN metastasis (HR = 2.81-3.44) were significant negative predictors of CSS, whereas p16-positivity (HR = 0.29-0.32) and HPV-positivity (HR = 0.14) were related to better prognosis. In conclusion, 97.5% of VCs were HPV-positive with WGASS. Stage III/IV and LN metastasis were significant negative predictors, whereas p16- and HPV-positivity were significantly associated with better prognosis.

Enhanced versus standard hydration in acute ischemic stroke: REVIVE-A randomized clinical trial.

RATIONALE: Early neurological deterioration (END) within 72 h of stroke onset is associated with poor prognosis. Optimizing hydration might reduce the risk of END. AIMS: This study aimed to determine in acute ischemic stroke patients if enhanced hydration versus standard hydration reduced the incidence of major (primary) and minor (secondary) END, as well as whether it increased the incidence of early neurological improvement (secondary), at 72 h after admission. SAMPLE SIZE ESTIMATE: A total of 244 participants per arm. METHODS AND DESIGN: A prospective, double-blinded, multicenter, parallel-group, randomized controlled trial conducted at four hospitals from April 2014 to July 2020, with data analyzed in August 2020. The sample size estimated was 488 participants (244 per arm). Ischemic stroke patients with measurable neurological deficits of onset within 12 h of emergency department presentation and blood urea nitrogen/creatinine (BUN/Cr) ratio ⩾ 15 at point of admission were enrolled and randomized to 0.9% sodium chloride infusions of varying rates-enhanced hydration (20 mL/kg body weight, one-third given via bolus and remainder over 8 h) versus standard hydration (60 mL/h for 8 h), followed by maintenance infusion of 40-80 mL/h for the subsequent 64 h. The primary outcome measure was the incidence of major END at 72 h after admission, defined as an increase in National Institutes of Health Stroke Scale of ⩾ 4 points from baseline. RESULTS: Overall, 487 participants were randomized (median age 67 years; 287 females). At 72 h, 7 (2.9%) in the enhanced hydration arm and 5 (2.0%) in the standard hydration developed major END (p = 0.54). The incidence of minor END and early neurological improvement did not differ between treatment arms. CONCLUSION AND RELEVANCE: Enhanced hydration did not reduce END or improve short-term outcomes in acute ischemic stroke. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02099383, https://clinicaltrials.gov/study/NCT02099383).

Adequate antiviral treatment lowers overall complications of cytomegalovirus colitis among inpatients with inflammatory bowel diseases.

BACKGROUND: Cytomegalovirus (CMV) colitis significantly complicates the course of inflammatory bowel disease (IBD), frequently leading to severe flare-ups and poor outcomes. The role of antiviral therapy in hospitalized IBD patients with CMV colitis is currently under debate. This retrospective analysis seeks to clarify the influence of antiviral treatment on these patients. METHODS: We retrospectively reviewed IBD patients diagnosed with CMV colitis via immunohistochemistry staining from colonic biopsies at a major tertiary center from January 2000 to May 2021. The study focused on patient demographics, clinical features, risk factors, prognostic indicators, and antiviral treatment outcomes. RESULTS: Among 118 inpatients, 42 had CMV colitis. Risk factors included hypoalbuminemia and antibiotic use. IBD patients with CMV colitis receiving < 14 days of antiviral therapy had higher complication (72% vs. 43%, p = 0.028) and surgery rates (56% vs. 26%, p = 0.017) compared to those without CMV. Adequate antiviral therapy (≥ 14 days) significantly reduced complications in the CMV group (29% vs. 72%, p = 0.006), especially in Crohn's disease (20% vs. 100%, p = 0.015). Independent predictors of IBD-related complications were CMV colitis (Odds Ratio [OR] 3.532, 90% Confidence Interval [CI] 1.012-12.331, p = 0.048), biological treatment failure (OR 4.953, 95% CI 1.91-12.842, p = 0.001), and adequate antiviral therapy (OR 0.108, 95% CI 0.023-0.512, p = 0.005). CONCLUSION: CMV colitis and a history of biological treatment failure increase complication risks in IBD patients. Adequate antiviral therapy significantly mitigates these risks, highlighting its importance in managing IBD patients with CMV colitis.

Comparison of outcomes of laparotomic and minimally invasive radical hysterectomy in women with early-stage cervical cancer.

OBJECTIVE: This study compared the outcomes of laparotomic radical hysterectomy (LRH) and minimally invasive radical hysterectomy (MISRH) in patients with early-stage cervical cancer. METHODS: The clinical data of patients with early-stage cervical cancer who underwent LRH or MISRH (laparoscopic/robotic) at Chang Gung Memorial Hospital, Linkou Branch, from 2002 to 2017 were retrospectively reviewed. The surgical safety (operation time, blood loss, blood transfusion rate, length of postoperative stay, and perioperative complications), overall survival (OS), disease-free survival (DFS), and recurrence pattern were analyzed. Propensity score matching (PSM) at a 3:1 ratio was performed to balance prognostic variables. RESULTS: Of the 760 patients (entire cohort), 614 underwent LRH and 146 underwent MISRH. After PSM, 394 and 140 patients were included in the LRH and MISRH groups, respectively. The 5-year OS rate was significantly lower in the MISRH group than in the LRH group (85.6% vs. 93.2%, p=0.043), and the 5-year DFS rate (p=0.21) did not differ significantly. After PSM, the 5-year OS rates did not differ significantly between the MISRH and LRH groups (87.1% vs. 92.1%, p=0.393). The MISRH group had a significantly shorter operation time (p<0.001), lower intraoperative blood loss (p<0.001), lower blood transfusion rate (p<0.001), and shorter postoperative stay (p<0.001) but a significantly higher rate of intraoperative bladder injury (p<0.001) than the LRH group. CONCLUSION: After PSM, MISRH is associated with nonsignificantly lower OS but a significantly higher risk of intraoperative urological complications than LRH.

Comparative Analysis of Cytomegalovirus Gastrointestinal Disease in Immunocompetent and Immunocompromised Patients.

BACKGROUND: Cytomegalovirus (CMV) gastrointestinal (GI) diseases impact both immunocompromised and immunocompetent individuals, yet comprehensive studies highlighting the differences between these groups are lacking. METHODS: In this retrospective study (January 2000 to July 2022) of 401 patients with confirmed CMV GI diseases, we categorized them based on immunological status and compared manifestations, treatments, outcomes, and prognostic factors. RESULTS: The immunocompromised patients (n = 193) showed older age, severe illnesses, and higher comorbidity rates. GI bleeding, the predominant manifestation, occurred more in the immunocompetent group (92.6% vs. 63.6%, p = 0.009). Despite longer antiviral therapy, the immunocompromised patients had higher in-hospital (32.2% vs. 18.9%, p = 0.034) and overall mortality rates (91.1% vs. 43.4%, p < 0.001). The independent factors influencing in-hospital mortality in the immunocompromised patients included GI bleeding (OR 5.782, 95% CI 1.257-26.599, p = 0.024) and antiviral therapy ≥ 14 days (OR 0.232, 95% CI 0.059-0.911, p = 0.036). In the immunocompetent patients, age (OR 1.08, 95% CI 1.006-1.159, p = 0.032), GI bleeding (OR 10.036, 95% CI 1.183-85.133, p = 0.035), and time to diagnosis (OR 1.029, 95% CI 1.004-1.055, p = 0.021) were significant prognostic factors, with the age and diagnosis time cut-offs for survival being 70 years and 31.5 days, respectively. CONCLUSIONS: GI bleeding is the most common manifestation and prognostic factor in both groups. Early diagnosis and effective antiviral therapy can significantly reduce in-hospital mortality.

Cytomegalovirus Diseases of the Gastrointestinal Tract in Immunocompetent Patients: A Narrative Review.

Cytomegalovirus (CMV) is a potential pathogen that causes gastrointestinal (GI) tract diseases regardless of host immunity. In contrast to immunocompromised individuals, immunocompetent patients lack a comprehensive overview of the gastrointestinal manifestations. This study aims to provide a comprehensive summary of the current evidence regarding presentations, diagnostics, management, risk assessment, and outcomes in immunocompetent patients with CMV GI disease. A thorough literature search of English publications up to April 2022 was conducted across electronic databases to identify relevant articles, with eligible case series selected for detailed analysis. The majority of immunocompetent patients affected by CMV GI disease are typically elderly, critically ill, or burdened with comorbidities that compromise immunity. Clinical presentations range from subtle symptoms to severe surgical conditions, including instances of mortality. Specific clinical presentations, blood test results, or endoscopic features are lacking, necessitating reliance on histopathological tests such as immunohistochemistry staining for diagnosis. While antiviral therapy may offer benefits in improving outcomes, careful individual assessment is warranted due to diverse comorbidities and potential side effects. Mortality rates vary considerably based on underlying medical conditions and therapeutic approaches. It is imperative for clinicians to maintain vigilance for CMV GI disease among high-risk groups, despite their baseline immunocompetence, in order to enhance clinical outcomes.

Clinical factor-based risk stratification for precision therapy in locally advanced squamous cell carcinoma of the uterine cervix.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard of care for locally advanced cervical cancer. In this study, we analyzed the pretreatment clinical and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) characteristics of patients with locally advanced cervical squamous cell carcinoma (SCC) to develop a scoring prototype for risk stratification. METHODS: Two cohorts were constructed in this study. Cohort 1 comprised patients with cervical SCC with 2009 FIGO stage III-IVA or stage I-II with positive pelvic or para-aortic lymph node (PALN) on PET/CT from AGOG09-001 trial. Cohort 2 comprised patients with similar characteristics who had received adequate therapy in our hospital between 2016 and 2021. Pretreatment patient characteristics and PET/CT parameters including maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of primary tumor and nodal SUVmax were assessed for cancer-specific survival (CSS) using multivariate Cox regression. RESULTS: Analysis of combined data from cohorts 1 (n = 55) and 2 (n = 128) indicated age ≥ 66 years, primary tumor MTV ≥87 mL, and positive PALN on PET/CT to be independently significant adverse predictors for CSS (p < 0.001, p = 0.014, and p = 0.026, respectively) with a median follow-up duration of 51 months. Assigning a score of 1 to each adverse predictor, patients with cumulative risk scores of 0, 1, 2, and 3 were discovered to have a 5-year CSS of 86.9%, 71.0%, 32.2%, and 0%, respectively (p < 0.001). CONCLUSION: Age, primary tumor MTV, and positive PALN on PET/CT may serve as independent predictors of poor survival in patients with locally advanced cervical SCC. Our findings indicate that patients without any adverse factors can receive standard CCRT, whereas those with at least one adverse factor can consider novel combination therapies or clinical trials.

Correction: Intracellular regulation of zinc by metal-organic framework-mediated genome editing for prostate cancer therapy.

Correction for 'Intracellular regulation of zinc by metal-organic framework-mediated genome editing for prostate cancer therapy' by Yanan Xue et al., Biomater. Sci., 2023, https://doi.org/10.1039/d3bm00002h.

Comparison of active versus passive robotic-endoscope-holder-assisted unisurgeon uniportal thoracoscopic surgery in terms of surgical efficacy and patient safety.

Background: Few studies have compared robotic-arm-assisted unisurgeon uniportal surgeries with conventional human-assisted uniportal video-assisted thoracoscopic surgeries (VATSs) in terms of surgical efficacy and patient safety. In the present study, we compared the aforementioned surgeries. Methods: We explored two robotic endoscope holders-a passive robotic platform (ENDOFIXexo, EA group) and a pedal-controlled active robotic platform (MTG-100, MA group)-for unisurgeon uniportal surgeries and compared the surgical outcomes with those of human-assisted uniportal surgeries (HA group) in 228 patients with a lung lesion (size, <5 cm). The primary parameters for this comparison were surgical efficacy, patient safety, and short-term patient outcomes. Results: No significant differences were observed among the EA, MA, and HA groups. The success rate of robotic-arm-assisted unisurgeon uniportal wedge resection was 100%, regardless of the group. No major differences were noted in preparation time between the EA and MA groups. Segmentectomy was more favorable in the EA group than in the MA group. The rates of surgical conversion were 5% and 60% in the EA and MA groups, respectively. The EA and MA groups did not differ considerably from the HA group in terms of postoperative complications. Conclusions: Unisurgeon uniportal wedge resection may be effectively performed using a robotic endoscope holder, without the need for any human assistants with an expert hand. However, the rate of surgical conversion increases with the complexity of uniportal anatomic resections. The passive platform appears to be more suitable for unisurgeon uniportal surgery than the active pedal-controlled platform given the equipment in contemporary operating rooms.

Intracellular regulation of zinc by metal-organic framework-mediated genome editing for prostate cancer therapy.

Normal prostate tissues generally exhibit a higher level of zinc to maintain their special "citrate-producing" metabolism, while its level dramatically decreases during prostate tumorigenesis. Despite the significant antitumor effects, the intracellular accumulation of zinc in prostate cancer cells also promotes the expression of ZNT1, which in turn results in the efflux of zinc and attenuated cytotoxicity against cancer cells. To solve the dilemma, we developed a 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid (DUPA)-decorated zeolitic imidazolate framework-8 (ZIF8), which is able to load plasmid DNA encoding the Cas9 editor and single-guide RNA to form Cas9@ZIF8-DUPA nanocomplexes. The intracellular delivery of Cas9@ZIF8-DUPA simultaneously increases the level of zinc and inhibits the ZNT-1 function by disrupting the SLC30A1 gene to prevent the efflux of zinc in prostate cancer cells. Due to the high affinity between DUPA and the prostate-specific membrane antigen, Cas9@ZIF8-DUPA nanocomplexes exhibit excellent prostate tumor-targeting ability. The internalization and degradation of Cas9@ZIF8-DUPA not only release free zinc and Cas9 editors, but also reduce zinc efflux through Cas9-mediated genome editing that disables the function of ZNT1. As a result, Cas9@ZIF8-DUPA nanocomplexes exhibit significant antitumor activity and extended survival in the mouse model bearing prostate tumors. The current platform offers an alternative therapeutic strategy and holds tremendous translational potential as an anticancer nanomedicine for prostate cancer treatment.

Clinical outcomes in women with endometrial polyps underwent conservative management.

OBJECTIVE: To evaluate the regression rate of endometrial polyps (EPs) in a cohort of asymmetric women after conservative follow-up. MATERIALS AND METHODS: In this retrospective cohort study, a total of 1006 women with asymptomatic EPs were treated with expectant management or hormonal drugs between June 1999 and May 2018. Four hundred forty-eight women (44.5%) were administered with hormonal medications and 558 women were managed expectantly (55.5%). Office hysteroscopy was performed to confirm the diagnosis and regression of EPs. Hormonal administration included oral contraceptives, progestin and cyclic estrogen/progestin regimen according to physicians' preferences. Clinical characteristics, including the patient's age, body mass index, parity, and type of conservative management were collected. RESULTS: The mean observation time was 14.1 ± 18.5 months (range, 1-162 months). The overall regression rate of EPs in this cohort was 33.5%, 24.6% occurred after medication and 8.9% after expectant management. Patient age (<50 years) (p < 0.001), follow-up period (p = 0.005) and hormonal drugs used (p < 0.001) were significantly associated with EP regression. Twenty-four (7.1%) of the 337 EP regression patients later developed recurrent disease. Follow-up period (p < 0.001) and hormonal drugs used (p = 0.032) were closely related to polyp recurrence after initial regression. Nevertheless, multivariate logistic regression analysis revealed that hormonal drugs used was significantly associated with the regression (p < 0.001) and recurrence (p = 0.016) of EPs. CONCLUSION: Women aged 50 or less are more suitable for conservative treatment for EPs. Hormonal drugs used could increase the incidence of EP regression.

Birth outcomes following pelvic ring injury: A retrospective study.

OBJECTIVE: To report obstetric outcomes in pregnant women with previous pelvic ring injury (PRI) and investigate the correlation between residual pelvic deformity and the mode of delivery. DESIGN: Retrospective cohort study. SETTING: Single medical centre in Taiwan. POPULATION: Forty-one women with PRI histories from 2000 to 2021 who subsequently underwent pregnancy and delivery. METHODS: All patients had complete PRI treatment and radiological follow up for at least 1 year. The demographic data, radiological outcomes after PRI and obstetric outcomes were collected to investigate the potential factors of delivery modes using non-parametric approaches and logistic regression. Caesarean section (CS) rates among different subgroups were reported. MAIN OUTCOME MEASURES: Comparisons of demographic data and radiological outcomes (Matta/Tornetta criteria and Lefaivre criteria) after PRI among patients who had subsequent pregnancy and underwent vaginal deliveries (VD) or CS. RESULTS: There were 14 VD and 27 CS in 41 patients. Nine patients underwent CS because of their PRI history, 12 patients underwent CS for other obstetric indications and 20 underwent trial of labour. Based on the logistic regression model, retained trans-iliosacral implants did not significantly increase the risk of CS (odds ratio [OR] 1.20; 95% CI 0.17-8.38). Higher pelvic asymmetry value by Lefaivre criteria was a potential risk factor for CS after previous PRI (OR 1.52; 95% CI 1.043-2.213). CONCLUSIONS: VD is possible after PRI. Retained trans-iliosacral implants do not affect the delivery outcome. Residual pelvic asymmetry after PRI by Lefaivre criteria is a potential risk factor for CS.

Membrane-camouflaged supramolecular nanoparticles for co-delivery of chemotherapeutic and molecular-targeted drugs with siRNA against patient-derived pancreatic carcinoma.

Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine (GEM) with the molecular-targeted drug erlotinib (Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuli-responsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA (siRNA) for synergistic pancreatic cancer treatment. This "all-in-one" delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor (PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.

Exosomes and their roles in the chemoresistance of pancreatic cancer.

Pancreatic cancer (PC) remains one of the most lethal human malignancies worldwide. Due to the insidious onset and the rapid progression, most patients with PC are diagnosed at an advanced stage rendering them inoperable. Despite the development of multiple promising chemotherapeutic agents as recommended first-line treatment for PC, the therapeutic efficacy is largely limited by unwanted drug resistance. Recent studies have identified exosomes as essential mediators of intercellular communications during the occurrence of drug resistance. Understanding the underlying molecular mechanisms and complex signaling pathways of exosome-mediated drug resistance will contribute to the improvement of the design of new oncologic therapy regimens. This review focuses on the intrinsic connections between the chemoresistance of PC cells and exosomes in the tumor microenvironment (TME).

Cytomegalovirus Diseases of the Gastrointestinal Tract.

Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract can be fatal. However, very few studies have provided comprehensive analyses and specified the differences in symptoms observed in different parts of the GI tract. This study aimed to comprehensively analyze clinical manifestations and management of GI CMV disease. This retrospective cohort study enrolled the patients who had CMV diseases of the GI tract proved by CMV immunohistochemistry stain from the pathology database in a 4000-bed tertiary medical center between January 2000 and May 2021. The patient characteristics, clinical manifestations, endoscopic features, treatments, outcomes, and prognostic factors were analyzed. A total of 356 patients were enrolled, including 46 infected in the esophagus, 76 in the stomach, 30 in the small intestine, and 204 in the colon. In total, 49.4% patients were immunocompromised. The overall in-hospital mortality rate was 20.8%: CMV enteritis had the highest rate (23.3%). Sixty percent of patients received antiviral treatment and 16% were administered both intravenous and oral anti-viral drugs (Combo therapy, minimal and mean treatment duration were 14 and 39.9 ± 25 days). Prognostic factors of in-hospital mortality included age, immune status, albumin level, platelet count, GI bleeding, time-to-diagnosis, and Combo therapy. In the survival analysis, immunocompetent patients receiving Combo therapy had the best survival curve, and immunocompromised patients receiving non-Combo therapy had the worst survival curve. Combo therapy ≥14 days resulted in a better outcome for both immunocompromised and immunocompetent patients. In conclusion, CMV GI diseases affect both immunocompromised and immunocompetent hosts, and a complete treatment course should be considered for patients with poor prognostic factors.

Hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer.

BACKGROUND: To investigate outcomes and morbidity of patients undergoing secondary cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent ovarian cancer. MATERIALS AND METHODS: Between April 2014 and January 2019, a total of 51 recurrent ovarian cancer patients receiving secondary CRS and HIPEC were retrospectively reviewed. RESULTS: Among the 51 patients, median peritoneal cancer index score was 13 (range 3-34), and completeness of cytoreduction (CC) score of 0/1 was achieved in 41 patients (78.8%). Regimen of HIPEC included cisplatin and paclitaxel in 39 (75%) cases. The median follow-up duration of survivors was 20.2 months. Sixteen (30.8%) patients remained free of recurrence after HIPEC. The median progression-free survival (PFS) and overall survival (OS) were 11.8 months and 34.5 months respectively. Multivariate analysis showed previous chemotherapy <2 lines (HR 0.24, 0.11-0.52; p = 0.001), chemotherapy-free interval ≥6 months (HR 0.19, 0.09-0.37; p < 0.001) and CA125 < 35 U/mL before HIPEC (HR 0.133, 0.021-0.0832; p = 0.031) were good prognostic factors for PFS. CC0/1 was not significant in multivariate analysis. The most common grade 3/4 toxicity was anemia (17.3%), pleural effusion (11.5%) and renal insufficiency (5.7%). Patients with age ≥50, peritoneal carcinomatosis index (PCI) ≥ 11, operation time ≥10 h and diaphragm surgery had significantly higher incidence of pleural effusion. CONCLUSIONS: The current study showed adding HIPEC to secondary CRS might prolong PFS especially in patients with previous chemotherapy <2 lines, chemotherapy-free interval ≥6 months and CA125 < 35 U/mL before HIPEC.

Clostridium innocuum infection in hospitalised patients with inflammatory bowel disease.

BACKGROUND: Clostridium innocuum (CI) infection can lead to creeping fat in Crohn's disease and is associated with intestinal strictures. At present, no clinical study ever has evaluated the role of CI infection in inflammatory bowel disease (IBD). MATERIALS AND METHODS: In this retrospective cohort study, we enrolled hospitalized IBD patients with culture results for both CI and Clostridioides difficile (CD) in a medical center between October 2019 and April 2021. They were divided into the CI (CI+/CD-), control (CI-/CD-), coinfection (CI+/CD+), and CD (CI-/CD+) groups. We analyzed the risk factors, clinical presentations, and outcomes by comparing the CI and control groups. RESULTS: We enrolled a total of 90 patients, including 22, 39, 13, and 16 patients in the CI, control, coinfection, and CD groups. The incidence rates of CI (CI+) and CD (CD+) were 39% (35/90) and 32% (29/90), respectively. We analyzed the differences between CI and control groups. We identified the use of steroid (77.3% vs. 46.2%, P = 0.018) and 5-aminosalicylic acid (90.9% vs. 64.1%, P = 0.022) as risk factors of CI infection. Clinical analysis showed that more patients in CI group presented with bloody stool (77.3% vs. 51.3%, P = 0.046). Although CI group had significantly lower overall occurrence of intraabdominal abscess (0% vs. 17.9%, P = 0.042), it showed a lower clinical remission rate (50% vs. 87.5%, P = 0.044) and higher Mayo score at the end of follow-up (10 points vs. 3 points, P = 0.008) in ulcerative colitis. CONCLUSIONS: CI infection may lead to a poorer clinical remission in ulcerative colitis. We should take it into consideration in IBD patents with active inflamamtion or refractory diarrhea with or without CD infection. Precise identification of CI is imperative to guide approproate antimicrobial therapy because of its intrinsic vancomycin resistance nature.