Impact of modified teaching strategies used in a gross anatomy course on the academic performance of dental students during the COVID-19 pandemic.

INTRODUCTION: Modified teaching strategies (MTS), asynchronous online teaching and smaller dissection groups, were applied to a gross anatomy course for dental students in the National Taiwan University in April 2020 in response to the COVID-19 pandemic. This study aimed to investigate the effects and perceptions of MTS on dental students. MATERIALS AND METHODS: Scores for anatomy examinations for 2018-2019 (without MTS) and 2019-2020 (with MTS) cohorts were compared to explore the effect on academic performance. Moreover, questionnaire from the 2019-2020 cohort was analysed to determine dental students' perceptions about MTS. RESULTS: The lecture performance in the final examination of the second semester for the 2019-2020 cohort was significantly higher than that of the first semester (pre-COVID-19) and that for the 2018-2019 cohort. However, the laboratory performance in the midterm examination of the second semester for the 2019-2020 cohort was significantly lower than that for the 2018-2019 cohort and showed no difference in the final examination of the first semester. The questionnaires revealed that the majority of students displayed positive attitudes towards MTS and agreed with the importance of peer discussion during laboratory dissection. CONCLUSIONS: Asynchronous online learning for anatomy lecture may be beneficial for dental students; however, a smaller dissection group accompanied by reduced peer discussion may temporarily exert negative effects on their laboratory performance at the beginning of the application. Furthermore, more dental students exhibited positive perceptions towards smaller dissection groups. These findings could illuminate the learning condition of dental students in anatomy education.

Plasma riboflavin fluorescence as a diagnostic marker of mesenteric ischemia-reperfusion injury in rats.

Due to the delayed and vague symptoms, it is difficult to early diagnose mesenteric ischemia injuries in the dynamics of acute illness, leading to a 60-80 % mortality rate. Here, we found plasma fluorescence spectra can rapidly assess the severity of mesenteric ischemia injury in animal models. Ischemia-reperfusion damage of the intestine leads to multiple times increase in NADH, flavins, and porphyrin auto-fluorescence of blood. The fluorescence intensity ratio between blue-fluorophores and flavins can reflect the occurrence of shock. Using liquid chromatography and mass spectroscopy, we confirm that riboflavin is primarily responsible for the increased flavin fluorescence. Since humans absorb riboflavin from the intestine, its increase in plasma may indicate intestinal mucosa injury. Our work suggests a self-calibrated and reagent-free approach to identifying the emergence of fatal mesenteric ischemia in emergency departments or intensive care units.

Oncological outcomes of large gastrointestinal stromal tumors treated by laparoscopic resection.

BACKGROUND: The resection of large gastric gastrointestinal stromal tumors (GISTs) by laparoscopic has been controversial. Extending from our prior study, the long-term oncological outcome of laparoscopic resection of large (5-8 cm) gastric GISTs was reported. METHODS: From 2002 to 2018, a consecutive 66 patients with gastric GISTs of 5-8 cm were treated at National Taiwan University Hospital. Among them, 30 patients received open surgery, and 36 received laparoscopic surgery. The clinicopathological data, peri-operative and oncological outcomes were compared between groups. RESULTS: The clinical demographics including sex, age, BMI, tumor locations and ratio of wedge resection were similar between groups. The mean tumor size was 6.0 ± 0.83 cm versus 6.3 ± 1.07 cm (Open vs. Laparoscopic, p = 0.3). The operation time, blood loss, and post-operative complications, were also similar. The mean hospital stay was shorter in the laparoscopic group (8.8 ± 2.5 days) than in the open group (12.0 ± 8.9 days), though not significantly different. The median follow-up time was 108 ± 58 months (97 ± 50 in laparoscopic group; 122 ± 64 in open group). All except three patients remain disease-free. One in the open group and two in the laparoscopic group had recurrence of tumor, and they were stable of disease under Imatinib treatment. Eight patients died in non-GIST causes during follow-up. The 5-year recurrence-free survival were 100% for the open and 94.2% for the laparoscopic group (p = 0.2). CONCLUSION: Our data showed that laparoscopic surgery for gastric GIST between 5 and 8 cm was safe and oncologically feasible.

Laparoscopic versus open distal gastrectomy for elderly patients with advanced gastric cancer: a retrospective comparative study.

BACKGROUND: Laparoscopic radical distal gastrectomy (LDG) has been more frequently performed for locally advanced distal gastric cancer (AGC) than open distal gastrectomy (ODG). However, the benefits of LDG for elderly AGC patients (AGC-lap) remain unclear. METHODS: Patients aged ≥ 70 years who underwent D2 distal gastrectomy from July 2014 to July 2021 were enrolled consecutively. Perioperative parameters, pathological features, and oncological outcomes of AGC-lap patients (n = 39) were compared with those of elderly AGC patients receiving ODG (AGC-open; n = 37) and elderly early gastric cancer patients receiving LDG (EGC-lap; n = 41) respectively. RESULTS: The median age of all AGC patients was 77 years, and 28% of them had an Eastern Cooperative Oncology Group score ≥ 2. Most of the perioperative and pathological features (including the number of lymph nodes harvested) were similar between the AGC-lap and AGC-open groups. AGC-lap patients had longer median operative times (215 min versus 192 min) but significantly less surgical complications (10.3% versus 37.8%) and shorter median hospital stays (11 days versus 13 days) than did AGC-open patients (all p < 0.05). The 3-year recurrence-free and overall survival was 66.2% and 88.8% in the AGC-lap group and 51% and 66.3% in the AGC-open group (both p = 0.1). The perioperative features, including operative time, number of lymph nodes harvested, hospital stay, and complication rates, were similar between the AGC- and EGC-lap groups. CONCLUSIONS: LDG was safely and effectively performed in elderly AGC patients, resulting in faster recovery and a lower complication rate than ODG, without compromising oncological outcomes.

Coronavirus Disease Pandemic Effect on Medical-Seeking Behaviors Even in One Resource-Competent Community: A Case Controlled Study.

(1) Background: The coronavirus disease 2019 (COVID-19) pandemic had overwhelming impacts on medical services. During its initial surge, Taiwan was unique in maintaining its medical services without imposing travel restrictions, which provided an ideal environment in which to test if the fear of becoming infected with COVID-19 interfered with health-seeking behavior (HSB). We tested this hypothesis among adults with acute complicated appendicitis (ACA). (2) Methods: Adults with acute appendicitis were enrolled between 1 January and 30 June 2020 (COVID-19 period). The first two quarters of the preceding 3 years were defined as a historical control group. Outcome measures included the rate of ACA and the number of hospital stays. (3) Results: The COVID-19 era included 145 patients with acute appendicitis. Compared to the historical control (320 patients), the COVID-19 era was significantly associated with a higher length of symptom duration until presentation to the emergency room within >48 h (17.2% vs. 9.1%, p = 0.011), a higher incidence of ACA (29.7% vs. 19.4%, p = 0.014), and a longer length of hospital stays (5.0 days vs. 4.0 days, p = 0.043). The adjusted models showed that the COVID-19 period had a significant relationship with a higher rate of ACA (odds ratio (OR) = 1.87; 95% confidence interval (CI): 1.23-2.52; p = 0.008) and longer length of hospital stays (OR= 2.10; 95% CI: 0.92 to 3.31; p < 0.001). (4) Conclusions: The fear of COVID-19 may prohibit patients from seeking medical help, worsening their clinical outcomes. The surgical community should take action to provide scientific information to relive mental stress.

The management of postoperative upper alimentary tract fistulas: A single-center experience of endoscopic tissue glue repair and recommendations of a systematic review.

BACKGROUND/PURPOSE: The appropriate management of postoperative upper alimentary tract fistula (UATF) remains uncertain. The efficacy of esophagogastroduodenoscopy (EGD) tissue glue repair in the treatment of patients with postoperative UATF was explored. We also conducted a systematic review of the literature regarding the inpatient management of UATF. METHODS: Totally 24 patients received EGD tissue glue repair for postoperative UATF at our institute from April 2014 to April 2020. Independent characteristics of size of fistula, location of the UATF, complications, and recurrences were analyzed. PubMed and Cochrane Library databases were reviewed. A pooled analysis was performed, and subgroup analysis was conducted separately for different anatomic locations and techniques. RESULTS: With a mean follow-up of 40 months, the fistula failed to close with EGD tissue glue repair in 2 of 24 patients (8.3%). Eight patients required repeated EGD tissue glue repair, which was more frequent in oral or thoracic UATF (p = 0.053), but all achieved a successful seal in the EGD tissue after glue repair alone (n = 22). The fistula size was correlated with the demand for repeated EGD tissue glue repair (p = 0.017). Besides, a total of 30 studies regarding 2356 cases of postoperative UATF between 2010 and 2021 were retrieved and analyzed. Several non-operative methods were generally accepted as the initial approach, with a non-inferior success rate compared to operative techniques. CONCLUSION: The results suggest that no single approach toward UATF is superior in terms of success rate and healing time. The potential advantages of EGD tissue glue repair after drainage were more suitable for patients with postoperative UATF and multiple comorbidities.

Relationship Between Symptom Distress and Fatigue Characteristics in Patients with Gastric Cancer During 1 Month after Gastrectomy.

This study's purpose was to describe changes in symptom distress and fatigue characteristics identifying which symptoms significantly impacted fatigue characteristics of patients with Gastric Cancer (GC) within 1 month after gastrectomy. A prospective longitudinal study was conducted. Patients with GC who were scheduled for gastrectomy were recruited from surgical outpatient clinics and surgery wards in northern Taiwan. Data were collected using a set of questionnaires before (T0) and 7 (T1) and 28 days (T2) after gastrectomy. Over all, 86 patients experienced mild levels of fatigue and symptom distress. The changes in worst fatigue and fatigue interference were greatest at T1. Anxiety had a significant negative effect on both worst fatigue and fatigue interference. Dry mouth, pain, and body image had significant deleterious effects on worst fatigue. The co-occurring symptoms affecting fatigue for patients with GC in the acute phase after gastrectomy should be actively assessed to ensure optimal fatigue management.

Adjuvant tegafur-uracil (UFT) or S-1 monotherapy for advanced gastric cancer: a single center experience.

BACKGROUND: Adjuvant tegafur-gimeracil-oteracil (S-1) is commonly used for gastric cancer in Asia, and tegafur-uracil (UFT) is another oral fluoropyrimidine when S-1 is unavailable. The real-world data of adjuvant UFT has less been investigated. METHODS: Patients with pathological stage II-IIIB (except T1) gastric cancer receiving adjuvant UFT or S-1 monotherapy after D2 gastrectomy were included. Usage of UFT or S-1 was based on reimbursement policy of the Taiwanese healthcare system. The characteristics, chemotherapy completion rates, and 5-year recurrence-free survival (RFS) and overall survival (OS), were compared between these two groups. RESULTS: From 2005 to 2016, 86 eligible patients were included. Most tumor characteristics were similar between the UFT group (n = 37; age 59.1 ± 13.9 years) and S-1 group (n = 49; age 56.3 ± 10.7 years), except there were significantly more Borrmann type III/IV (86.5% versus 67.3%; p = 0.047) and T4 (56.8% versus 10.2%; p < 0.001) lesions in the UFT group than in the S-1 group. The chemotherapy complete rates were similar in the two groups. The 5-year RFS was 56.1% in the UFT group and 59.6% in the S-1 group (p = 0.71), and the 5-year OS was 78.3% in the UFT group and 73.1% in the S-1 group (p = 0.48). The hazard ratio of adjuvant chemotherapy (S-1 versus UFT) on RFS was 1.25 (95% confidence interval = 0.53-2.94) when Borrmann type and T and N stages were adjusted. CONCLUSIONS: This small cohort study showed adjuvant UFT, and S-1 monotherapy had a comparable long-term outcome for pathological stage II-IIIB gastric cancer following D2 gastrectomy.

Parenteral glutamine supplementation improves serum albumin values in surgical cancer patients.

INTRODUCTION: Patients with gastric adenocarcinoma (GA) often develop malnutrition, which deteriorates after cancer surgery and negatively affects surgical outcomes. Despite being an abundant and versatile amino acid involved in the immune system and metabolic functions, glutamine levels are significantly depleted among patients who are critically ill or hypercatabolic. Therefore, this study aimed to investigate whether parenteral glutamine supplementation may improve nutritional status and surgical outcomes. METHODS: This retrospective, single-center cohort study included patients with GA who underwent gastrectomy between January 2007 and June 2019. Patients were classified into either the non-glutamine or glutamine group. Propensity score matching was used to minimize the bias in patient demographics. Furthermore, the average parenteral glutamine dose from the day of surgery to postoperative day four was calculated in g/kg/day. Surgical outcomes (length of hospitalization, major complication, and mortality) and changes in lymphocyte count and serum albumin levels 7 days post-surgery were assessed in both matched groups using adjusted models. RESULTS: A total of 1950 patients were reviewed, among whom 522 (26.8%) received parenteral glutamine supplementation (glutamine dose ranging from 0.05 to 0.49 g/kg/day). Among the included patients, 57.2% were males, and the median age was 64.9 years. After matching, there were 478 cases in each group. No differences in surgical outcomes and changes in lymphocyte count were observed between both matched groups. The glutamine group exhibited a smaller decrease in serum albumin levels compared to the non-glutamine group (-0.6 vs. -1.1 g/dL; P < 0.001). The adjusted matched model showed that glutamine dose contributed significantly toward increasing serum albumin levels (coefficient = 0.08 per 0.1 g/day/kg increment in glutamine; 95% confidence interval: 0.04 to 0.10; P < 0.001). CONCLUSIONS: Perioperative parenteral glutamine supplementation had a positive dose-dependent impact on the recovery of serum albumin levels among patients with GA undergoing gastrectomy, implying that glutamine supplementation improved postoperative nutritional suppression and ameliorated stress-associated inflammation. Although glutamine supplementation was not associated with surgical outcomes, further studies should be conducted to evaluate the clinical significance of serum albumin restoration.

Loss of SFRP1 expression is a key progression event in gastrointestinal stromal tumor pathogenesis.

The mechanism of high-grade transformation in gastrointestinal stromal tumors (GISTs) remains to be clarified. We aim to discover the key progression events by studying biphasic GISTs. The study group included 101 GISTs. Nineteen of these had been screened from 263 GISTs to represent the early stage of GIST high-grade transformation, characterized by juxtaposed low-grade and high-grade regions in the same tumor (so-called biphasic GISTs). Mutational analyses, fluorescence in situ hybridization (FISH), NanoString analyses, telomere analysis, and gene expression profiling were carried out, followed by in silico analyses, cell line study, and immunohistochemical validation. Using gene expression analysis, downregulation of SFRP1 was revealed to be the main event in GIST high-grade transformation (p = 0.013), accompanied by upregulation of EZH2. In silico analyses revealed that downregulation of SFRP1 was a common feature in GIST progression across several different series. Immunohistochemically, the expression of SFRP1 was validated to be significantly lower in high-grade GISTs (WHO risk group 3a or higher) than in low-grade GISTs (p < 0.001), and attenuation/loss of SFRP1 was associated with GIST tumor progression (p < 0.001). By NanoString and FISH analyses, chromosomal 9/9p loss was the only recurrent large-scale chromosome aberration in biphasic GISTs, with a correlation with SFRP1 downregulation. Subclones containing chromosome 9/9p loss could be appreciated in the low-grade parts of biphasic GISTs. TP53 mutation, RB1 loss, KIT/PDGFRA mutation, and alternative lengthening of telomeres did not play a significant role in GIST high-grade transformation. In conclusion, high-grade transformation of GISTs features SFRP1 downregulation and chromosome 9/9p loss.

Endoscopic submucosal dissection comparing with surgical resection in patients with early gastric cancer - A single center experience in Taiwan.

BACKGROUND/PURPOSE: The choice of endoscopic submucosal dissection (ESD) as first line treatment for selected early gastric cancer (EGC) patients was proved as effective as surgical treatment in studies over many countries. Yet there is no such cohort comparison in Taiwan. This study is aimed to describe our experience in ESD treated EGC and to compare the outcomes with those underwent surgical treatment. METHODS: This was a retrospective cohort study reviewing the patients with EGC underwent ESD and surgical treatments in a single tertiary referral center in Taiwan. The primary endpoint was disease specific survival. Recurrence free survival and length of hospital stay were also compared. RESULTS: The disease specific survival between indicated ESD and surgery showed no significant difference (cumulative survival 100% vs. 97.03%, p = 0.39), so as the recurrence free survival (cumulative survival 92.31% vs. 94.06%, p = 0.60). In subgroup analyses of ESD treated patients, a non-significant recurrence rate difference between indicated and non-indicated ESD was found (cumulative recurrence 7.69% vs. 20%, p = 0.39) and a higher recurrence rate in patients with non-R0 resection compared with R0 resection (cumulative recurrence 0% vs. 40%, p < 0.01). However, the shorter duration of hospital stay in ESD group was noted in comparison to surgery (mean 5.67 days vs. 15.75 days, p < 0.01). The ESD patients have minor complications including bleeding, perforation and fever than surgery. CONCLUSION: ESD is a reasonable first line treatment in selected early gastric cancer in additional to surgery. Pre-treatment evaluation and post-ESD review of curability is crucial to further surveillance program or definite therapy including surgery.

Laparoscopic distal gastrectomy for clinical stage I gastric adenocarcinoma: Techniques evolution and oncological outcomes of the first 100 cases.

BACKGROUND/PURPOSE: While gaining more acceptance, the use of laparoscopic distal gastrectomy (LDG) to treat gastric cancer were still limited in Taiwan. This study reviewed our experience about the technique evolution and outcome of using LDG for the patients with clinical stage (c-stage) I gastric cancers. METHODS: A retrospective review of the patients undergoing LDG for c-stage I gastric cancers at a medical center of Taiwan was performed. The demographics, peri-operative parameters, reconstruction methods, morbidities, pathologic and oncological outcomes were analyzed. RESULTS: A total of 100 patients with c-stage I gastric cancers between October 2005 and September 2016 were enrolled. Laparoscopy-assisted distal gastrectomy (LADG) was performed in the initial 69 cases. Total laparoscopic distal gastrectomy (TLDG) was done in the following 31 cases. There was no conversion of procedures, nor surgical mortality. The surgical morbidity rate was 13%, including 3 major complications. The ratio of using Billroth I reconstruction (83.9% versus 43.5%, p < 0.01) and the mean number of harvested lymph nodes (38.6 ± 14.8 versus 31.2 ± 15.2, p = 0.02) were both higher in the TLDG group than in the LADG group. The pathologic examination confirmed 78 patients were stage I, while 22 were stage II disease. Seven of the 24 patients with lymph node metastasis received adjuvant chemotherapy. Two patients had recurrence of diseases. The 3-year recurrence-free and overall survival were 93.3% and 95.8% separately. CONCLUSION: These results suggested that laparoscopic gastrectomy could be performed safely and feasibly for patients with early gastric cancers. LADG is recommended for the establishment of the demanding technique.

Three Nurse-administered Protocols Reduce Nutritional Decline and Frailty in Older Gastrointestinal Surgery Patients: A Cluster Randomized Trial.

OBJECTIVE: To evaluate the effects of the modified Hospital Elder Life Program (mHELP) comprising 3 nurse-administered protocols in older patients undergoing gastrointestinal (GI) surgery. DESIGN: Cluster randomized trial. SETTING: Two 36-bed GI wards at a university-affiliated medical center in Taiwan. PARTICIPANTS: Older patients (≥65 years, N = 377) were recruited if they were scheduled for elective GI surgery with an expected length of hospital stay >6 days. After transferring to the GI ward after surgery, participants were randomly assigned to the mHELP or control group (1:1) by room rather than individually because most patient units are double- or triple-occupancy rooms. INTERVENTION: The mHELP protocols (early mobilization, oral and nutritional assistance, and orienting communication) were administered daily with usual care by a trained nurse until hospital discharge. The control group received usual care only. MEASURES: Outcomes were in-hospital nutritional decline, measured by body weight and Mini-Nutritional Assessment (MNA) scores, and Fried's frailty phenotype. Return of GI motility was examined as a potential mechanism contributing to observed outcomes. RESULTS: Participants (mean age = 74.5 years; 56.8% male) primarily underwent colorectal (56.5%), gastric (21.2%), and pancreatobiliary (13.8%) surgery. Participants who received the mHELP [for a median of 7 days (interquartile range = 6-10 days)] had significantly lower in-hospital weight loss and decline in MNA scores (weight -2.1 vs -4.0 lb, P = .002; score -3.2 vs -4.0, P = .03) than the control group. The mHELP group also had significantly lower rates of incident frailty during hospitalization (12.0% vs 21.7%, P = .022), and persistent frailty (50.0% vs 92.9%, P = .03). Participants in the mHELP group had trends toward an accelerated return of GI motility. CONCLUSION AND IMPLICATIONS: The mHELP effectively reduced nutritional decline, prevented new frailty, and promoted recovery of frailty present before admission. These nurse-administered protocols might be useful in other settings, including conditions managed at home or in nursing facilities.

The O-glycosylating enzyme GALNT2 suppresses the malignancy of gastric adenocarcinoma by reducing EGFR activities.

Aberrant glycosylation affects the malignant progression of cancers. Here, we report that N-acetyl-galactosaminyltransferase 2 (GALNT2), an enzyme that initiates the mucin type-O glycosylation, suppresses malignant phenotypes in gastric adenocarcinoma (GCA) cells by modifying epidermal growth factor receptor (EGFR) activity. GALNT2 was knocked down using siRNA in AGS and MKN28 cells. The expression of phosphorylated EGFR (pEGFR), phosphorylated Akt (pAkt) and Tn antigen were detected by western blotting. Proliferation, migration and invasion of cells with/without GLANT2-knockdown were assessed. Expression of pEGFR in the resected gastric cancer tissue was analyzed by Immunohistochemical staining, and was correlated with clinicopathological factors. The results showed that GALNT2 knockdown enhanced phosphorylation of EGFR and decreased expression of the Tn antigen on EGFR. Inhibiting EGFR activity with Gefitinib decreased the migration/invasion abilities and reversed the increase pAkt caused by GALNT2 knockdown in GCA cells. The addition of MK2206 (Akt inhibitor) mitigated the migration and invasion abilities of the GALNT2-knockdown cells. Patients with increased expressions of pEGFR in their cancer tissues were associated more metastasis, advanced stage and recurrence after surgical resection. Our results indicate that GALNT2 suppresses the malignant potential of GCA cells through the EGFR-Akt signaling pathway. The significance of O-glycosylation in receptor tyrosine kinases activities and GCA progression deserve further studies.

Exosomal TGF-ß1 is correlated with lymphatic metastasis of gastric cancers.

Exosomes are nano-vesicles transporting bioactive material between cells. This study explored the prognostic association of exosomal TGF-ß1 with lymph node (LN) metastasis of gastric cancer (GC). TGF-ß1 expressions in the exosomes isolated from the gastroepiploic veins of 61 GC patients analyzed by ELISA. The regulatory T (Treg) cells in celiac LNs of gastric cancer analyzed by immunohistochemistry. Exosomal TGF-ß1 expression and the ratio of Treg cells in draining LNs were both significantly associated with pathological stages and LN metastasis of gastric cancer. Besides, the exosomal TGF-ß1 expression and Treg proportion in LN were also significantly correlated in gastric cancer patients. Recombinant TGF-ß1 and exosomes isolated from GC patients were used to induce FOXP3+ Treg cells from naïve T cells in vitro. Compared to the control, recombinant TGF-ß1 induced more CD25 (41%), FOXP3 (19%) and CTLA-4 (47%), while reduced CD45RA expression by 38% in primary naïve T cell cultures (p<0.01). Exosomes treatment induced more CD25 and 45% higher CTLA-4 expression, and increased 29% higher of CD45RA-negative cells than recombinant TGF-ß1 did (p<0.01). Adding TGF-ß1 neutralizing antibody partially abrogated the effects of exosomes on Treg induction. Our study showed exosomal TGF-ß1 related to lymph node metastasis and the ratio of Treg cells in lymph nodes of gastric cancers. Exosomes from gastric cancer patients could induce Treg cells formation through the effect of TGF-ß1.

Effect of a Modified Hospital Elder Life Program on Delirium and Length of Hospital Stay in Patients Undergoing Abdominal Surgery: A Cluster Randomized Clinical Trial.

IMPORTANCE: Older patients undergoing abdominal surgery commonly experience preventable delirium, which extends their hospital length of stay (LOS). OBJECTIVE: To examine whether a modified Hospital Elder Life Program (mHELP) reduces incident delirium and LOS in older patients undergoing abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized clinical trial of 577 eligible patients enrolled 377 older patients (≥65 years of age) undergoing gastrectomy, pancreaticoduodenectomy, and colectomy at a 2000-bed urban medical center in Taipei, Taiwan, from August 1, 2009, through October 31, 2012. Consecutive older patients scheduled for elective abdominal surgery with expected LOS longer than 6 days were enrolled, with a recruitment rate of 65.3%. Participants were cluster randomized by room to receive the mHELP or usual care. INTERVENTIONS: The intervention (implemented by an mHELP nurse) consisted of 3 protocols administered daily: orienting communication, oral and nutritional assistance, and early mobilization. Intervention group participants received all 3 mHELP protocols postoperatively, in addition to usual care, as soon as they arrived in the inpatient ward and until hospital discharge. Adherence to protocols was tracked daily. MAIN OUTCOMES AND MEASURES: Presence of delirium was assessed daily by 2 trained nurses who were masked to intervention status by using the Confusion Assessment Method. Data on LOS were abstracted from the medical record. RESULTS: Of 577 eligible patients, 377 (65.3%) were enrolled and randomly assigned to the mHELP (n = 197; mean [SD] age, 74.3 [5.8] years; 111 [56.4%] male) or control (n = 180; mean [SD] age, 74.8 [6.0] years; 103 [57.2%] male) group. Postoperative delirium occurred in 13 of 196 (6.6%) mHELP participants vs 27 of 179 (15.1%) control individuals, representing a relative risk of 0.44 in the mHELP group (95% CI, 0.23-0.83; P = .008). Intervention group participants received the mHELP for a median of 7 days (interquartile range, 6-10 days) and had a shorter median LOS (12.0 days) than control participants (14.0 days) (P = .04). CONCLUSIONS AND RELEVANCE: For older patients undergoing abdominal surgery who received the mHELP, the odds of delirium were reduced by 56% and LOS was reduced by 2 days. Our findings support using the mHELP to advance postoperative care for older patients undergoing major abdominal surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01045330.

Distinct Clinicopathological Features and Prognosis of Helicobacter pylori Negative Gastric Cancer.

BACKGROUND: Whether the characteristics and prognosis of gastric cancer (GC) are different in patients with and without Helicobacter pylori (HP) remains controversial. The definitions of HP status in patients with atrophic gastritis but negative tests for HP are heterogeneous. We aimed to assess the impact of HP on the prognosis of GC using different definitions. METHODS: From 1998 Nov to 2011 Jul, five hundred and sixty-seven consecutive patients with GC were included. HP status was determined by serology and histology. Patients with any positive test were defined as HP infection. Patients without HP infection whose serum pepsinogen (PG) I <70 ng/dl and PG I/II ratio < 3.0 were defined as atrophic gastritis and they were categorized into model 1: HP positive; model 2: HP negative; and model 3: exclusion of these patients. RESULTS: We found four characteristics of HP negative GC in comparison to HP positive GC: (1) higher proportion of the proximal tumor location (24.0%, P = 0.004), (2) more diffuse histologic type (56.1%, p = 0.008), (3) younger disease onset (58.02 years, p = 0.008) and (4) more stage IV disease (40.6%, p = 0.03). Patients with negative HP had worse overall survival (24.0% vs. 35.8%, p = 0.035). In Cox regression models, the negative HP status is an independent poor prognostic factor (HR: 1.34, CI:1.04-1.71, p = 0.019) in model 1, especially in stage I, II and III patients (HR: 1.62; CI:1.05-2.51,p = 0.026). CONCLUSION: We found the distinct characteristics of HP negative GC. The prognosis of HP negative GC was poor.

microRNA-183 Mediates Protective Postconditioning of the Liver by Repressing Apaf-1.

AIMS: Ischemic postconditioning (iPoC) is known to mitigate ischemia-reperfusion (IR) injury of the liver, the mechanisms of which remain to be elucidated. This study explored the role of microRNA-183 (miR-183) in the protective mechanism of iPoC. RESULTS: Microarray analysis showed miR-183 was robustly expressed in rats' livers with iPoC. miR-183 repressed the mRNA expression of Apaf-1, which is an apoptosis promoting factor. Using an oxygen-glucose deprivation (OGD) injury model in Clone 9 cells, hypoxic postconditioning (HPoC) and an miR-183 mimetic significantly decreased cell death after OGD, but miR-183 inhibitors eliminated the protection of HPoC. The increased expression of Apaf-1 and the downstream activation of capsase-3/9 after OGD were mitigated by HPoC or the addition of miR-183 mimetics, whereas miR-183 inhibitor diminished the effect of HPoC on Apaf-1-caspase signaling. In the in vivo experiment, iPoC and agomiR-183 decreased the expression of serum ALT after liver IR in the mice, but antagomiR-183 mitigated the effect of iPoC. The results of hematoxylin and eosin and TUNEL staining were compatible with the biochemical assay. Moreover, iPoC and agomiR-183 decreased the expression of Apaf-1 and 4-HNE after IR injury in mouse livers, whereas the antagomiR-mediated prevention of miR-183 expression led to increased protein expression of Apaf-1 and 4-HNE in the postischemic livers. INNOVATION: Our experiment showed the first time that miR-183 was induced in protective postconditioning and reduced reperfusion injury of the livers via the targeting of apoptotic signaling. CONCLUSION: miR-183 mediated the tolerance induced by iPoC in livers via Apaf-1 repressing. Antioxid. Redox Signal. 26, 583-597.

Activation of focal adhesion kinase through an interaction with ß4 integrin contributes to tumorigenicity of colon cancer.

High expression of either ß4 integrin or focal adhesion kinase (FAK) has been reported in human colon cancer. However, it remains unclear how ß4 integrin together with FAK contributes to the tumorigenicity of colon cancer. Here, we demonstrate that the co-overexpression of ß4 integrin and FAK positively correlates with advanced stages of human colon cancer. Activated ß4 integrin interacts with FAK and subsequently induces FAK phosphorylation at Tyr397. Furthermore, ablation of the ß4 integrin/FAK complex and/or FAK activation impair colon cancer cell proliferation, anchorage-independent growth, and tumorigenicity. Our data indicate that the ß4 integrin/FAK complex and subsequent FAK activation are essential regulators during the tumorigenicity of colon cancer, and we suggest an alternative strategy for colon cancer therapy.

Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation.

Glycosylation affects malignancy in cancer. Here, we report that N- acetylgalactosaminyltransferase 2 (GALNT2), an enzyme that mediates the initial step of mucin type-O glycosylation, suppresses malignant phenotypes in gastric adenocarcinoma (GCA) by modifying MET (Hepatocyte growth factor receptor) activity. GALNT2 mRNA and protein were downregulated in GCAs, and this reduction was associated with more advanced disease stage and shorter recurrence-free survival. Suppressing GALNT2 expression in GCA cells increased cell growth, migration, and invasion in vitro, and tumor metastasis in vivo. GALNT2 knockdown enhanced phosphorylation of MET and decreased expression of the Tn antigen on MET. Inhibiting MET activity with PHA665752 decreased the malignant phenotypes caused by GALNT2 knockdown in GCA cells. Our results indicate that GALNT2 suppresses the malignant potential of GCA cells and provide novel insights into the significance of O-glycosylation in MET activity and GCA progression.