Gastric IgG4-related disease mimicking a gastrointestinal stromal tumor in a child: A case report.

BACKGROUND: Gastric IgG4-related disease (IgG4-RD) is rarely encountered in clinical practice, and especially more so among pediatric patients. To our knowledge, this is the first report of IgG4-RD presenting as a calcifying gastric mass in a child. We describe how this entity was difficult to differentiate from a gastrointestinal stromal tumor (GIST) imaging-based approaches. Therefore, this case highlights the importance of considering IgG4-RD in the differential diagnosis of gastric tumor before performing surgical resection, especially to distinguish it from malignancy to avoid unnecessary surgery. CASE SUMMARY: The patient suffered from epigastric pain for several days. Panendoscopy and computed tomography scan revealed a submucosal tumor. Differential diagnoses included GIST, leiomyoma, teratoma, and mucinous adenocarcinoma. However, laparoscopic proximal gastrectomy allowed for the definitive diagnosis of IgG4-related stomach disease. CONCLUSION: We emphasize the importance of considering IgG4-RD in the differential diagnosis of gastric submucosal tumors before performing surgical resection.

Secreted frizzled-related protein 4 induces gastric cancer progression and resistance to cisplatin and oxaliplatin via ß-catenin dysregulation.

INTRODUCTION: Gastric cancer is the 5th most common cancer and 3rd leading cause of cancer-related death worldwide. There are three main ways to treat gastric cancer: surgical resection, radiation therapy, and drug therapy. Furthermore, combinations of two to three regimens can improve survival. However, the survival outcomes of chemotherapy in advanced gastric cancer patients are still unsatisfactory. Unfortunately, no widely useful biomarkers have been verified to predict the efficacy of chemotherapy for locally advanced gastric cancer. METHODS: An MTT assay was used to determine the cell viability after cisplatin or oxaliplatin treatment. Western blotting and immunohistochemistry were utilized to examine the sFRP4 level and associated signaling pathways. Immunofluorescence staining was utilized to analyze the location of ß-catenin. Colony formation and Transwell assays were used to analyze the functions related with cisplatin, oxaliplatin and sFRP4. RESULTS: We have found that gastric cancer patients treated with combinations of 5-fluorouracil (5-FU) and cisplatin regimens have better survival rates than those treated with 5-FU-based chemotherapy alone. Secreted frizzled-related protein 4 (sFRP4) was selected as a potential target from stringent analysis and intersection of 5-FU and cisplatin resistance-related gene sets. sFRP4 was shown to be overexpressed in clinical gastric tumor tissues and positively correlated with a worse survival rate. In addition, sFRP4 and ß-catenin were upregulated in cisplatin-resistant and oxaliplatin-resistant gastric cancer cells compared to parental cells. Immunofluorescence staining and nuclear fractionation showed that ß-catenin translocated from the cytosol into the nucleus. Moreover, sFRP4 was detected in the conditioned medium of these resistant cells, which indicates that sFRP4 might have an extracellular role in chemotherapy resistance. Increased migration capacity and dysregulation of epithelial-mesenchymal transition-related markers, which might result from the dysregulation of sFRP4, were observed in cisplatin-resistant and oxaliplatin-resistant gastric cancer cells. DISCUSSION/CONCLUSION: In summary, sFRP4 might play a critical role in resistance to cisplatin and oxaliplatin, cell metastasis and poor prognosis in gastric cancer via the Wnt-ß-catenin pathway. Investigations of the molecular mechanism underlying sFRP4-modulated cancer progression and chemotherapeutic outcomes can provide additional therapeutic strategies for gastric cancer.

Influence of preoperative body mass index on prognosis for patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

PURPOSE: The impact of body mass index (BMI) on patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) is controversial. Increasing evidence suggests an age-dependent relationship between obesity and outcomes for some solid organ tumors. Herein, we aimed to assess the prognostic value of preoperative BMI in UTUC patients treated with RNU in Taiwan. METHODS: This was a retrospective single-center study of 468 UTUC patients undergoing RNU during January 2010-December 2017, with preoperative BMI classification and subgroup analysis based on ages of < or ≥ 70 years. All UTUC patients underwent RNU and bladder cuff excision. Overall survival (OS), cancer-specific survival, and disease-free survival (DFS) were analyzed. Fisher's exact test, Mann-Whitney U test, Kaplan-Meier method, and Cox regression model were used for data analysis. RESULTS: The median follow-up duration was 36 months. Patients with higher versus lower BMI (cutoff: 25 kg/m2) showed no differences in OS; older patients had poor OS (hazard ratio [HR] 1.74; 95% confidence interval [CI] 1.24-2.40; p < 0.001). Older age was an independent predictor of poor OS in multivariate Cox regression analysis (p = 0.001). Younger patients with higher BMI (p = 0.02) had better DFS than older patients with no BMI-related survival differences. Higher BMI was an independent predictor of favorable DFS in younger patients in multivariate Cox regression analysis (HR, 0.53; 95% CI 0.28-0.99; p = 0.043). CONCLUSION: Younger UTUC patients with higher BMI were independently associated with a favorable DFS.

Self-Nanoemulsifying Drug Delivery System-Containing the Poorly Absorbed Drug - Valsartan in Post-Bariatric Surgery.

Purpose: Morbid obesity and its related metabolic syndrome are an important health issue. Recently, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) have accounted for the most popular bariatric surgeries. Valsartan (VST) is a common hypertension drug, and nano-carriers can increase its solubility and bioavailability. This study aims to explore the nano-VST formula in bariatric surgery subjects. Methods: High-fat fed animals were used as obese models. Operations were performed according to a standardized protocol. The drug was administrated by gavage, and blood samples were taken by serial tail vein sampling. Caco-2 cells were used for examining cell viability and drug uptake. A self-nano-emusifying drug delivery system (SNEDDS) formula was composed of sefsol-218, RH-40 and propylene glycol by a specified ratio, while high-performance liquid chromatography (HPLC) was used for determining drug concentrations. Results: Post-operatively, subjects that underwent RYGB lost more body weight compared to the SG group. The SNEDDS did not exhibit cytotoxicity after adequate dilution, and the cytotoxicity was not related to VST dose. A better cellular uptake of SNEDDS was observed in vitro. The SNEDDS formula achieved a diameter of 84 nm in distilled water and 140 nm in simulated gastric fluid. In obese animals, the maximum serum concentration (Cmax) of VST was increased 1.68-folds by SNEDDS. In RYGB with SUS, the Cmax was reduced to less than 50% of the obese group. SNEDDS increased the Cmax to 3.5 folds higher than SUS and resulted in 3.28-folds higher AUC0-24 in the RYGB group. Fluorescence imaging also confirmed a stronger signal of SNEDDS in the gastrointestinal mucosa. SNEDDS accumulated a higher drug concentration than suspension alone in the liver of the obese group. Conclusion: SNEDDS could reverse the VST malabsorption in RYGB. Further studies are mandatory to clarify post-SG change of drug absorption.

Comparison of stone-free rate between percutaneous nephrolithotomy and retrograde intrarenal surgery.

BACKGROUND: The management of urolithiasis in the kidney has been drastically changed in the era of endourology, mainly consisting of three surgical procedures: extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), and retrograde intrarenal surgery (RIRS). Since ESWL is usually less invasive via ambulatory clinic routes, this study aimed to examine the stone-free rate (SFR) between PCNL and RIRS. METHODS: We retrospectively reviewed patients who had renal stones and were treated with either PCNL or RIRS from June 2016 to June 2018. Staghorn stones, stones with diameters <1 cm, and stones with diameters >2 cm were excluded. Patients who underwent multiple surgeries for bilateral renal stones and those with graft kidney stones were excluded from the study. X-ray, sonography, and/or computed tomography (CT) were used to calculate the size of the stones. Follow-up was evaluated by the same image examination within three months after surgery. Stone-free was defined as no residual stone or the presence of asymptomatic calculi <4 mm. The operation time was defined as a skin-to-skin interval. RESULTS: Following exclusion criteria, there were 39 patients in each arm, with no difference in age, sex, or any other demographic data. The average stone size in the PCNL and RIRS groups was 16.3 and 14.0 mm, respectively ( p = 0.009). There was no significant difference in SFR (71.8% vs 61.5%, p = 0.337); the operation time was significant longer ( p < 0.001), and the hospital stay was significantly shorter ( p < 0.001) in the RIRS group. CONCLUSION: PCNL and RIRS are both feasible options for managing kidney stones. However, the initial stone size might affect the selection of operation. The SFR in the PCNL group was numerically but not statistically higher. The RIRS group, on the other hand, had a longer operation time but a shorter hospital stays.

Risk factors for hemorrhagic complications following robotic-assisted partial nephrectomy.

BACKGROUND: The aim of this study was to analyze the risk factors for hemorrhagic complications in patients who underwent robotic-assisted partial nephrectomy. METHODS: We retrospectively reviewed the records of 260 patients who underwent robotic-assisted partial nephrectomy. Hemorrhagic complications were defined as bleeding, hematoma, or arteriovenous fistula requiring hemostatic medication, blood transfusion, or therapeutic intervention. Hemorrhagic complications were graded according to the modified Clavien classification system, and the hemorrhagic complication group comprised only those complications with Clavien grade II or higher. Thereafter, we investigated the presence of any relevant association between perioperative factors and hemorrhagic complications. RESULTS: Of 260 patients included in the study, 32 (12.3%) had hemorrhagic complications. The postoperative hemoglobin level was significantly lower in the hemorrhagic complication group than in the group without complications. The hemorrhagic complication group had significantly more essential blood loss and a significantly longer length of hospital stay. In the univariate analysis, type 2 diabetes mellitus, Radius-scores tumor size as maximal diameter exophytic/endophytic properties of the tumor nearness of the deepest portion of the tumor to the collecting system or renal sinus anterior (a)/posterior (p) descriptor location relative to the polar line., sum of the renal size plus renal sinus involvement in the PADUA score is a simple anatomical system that can be used to predict the risk of surgical and medical perioperative complications in patients undergoing open NSS, prolonged console time (>180 minutes), prolonged warm ischemic time (>25 minutes), and method of pedicle control were statistically significant risk factors. In the multivariate logistic regression analysis, warm ischemic time >25 minutes was the only significant risk factor for hemorrhagic complications (odds ratio, 3.51; 95% confidence interval, 1.28-9.59; p = 0.01). CONCLUSION: Patients who undergo robotic-assisted partial nephrectomy with a warm ischemic time >25 minutes are significantly more likely to have hemorrhagic complications and should hence receive careful perioperative follow-up.

Exciplex-Forming Cohost Systems with 2,3-Dicyanopyrazinophenanthrene-based Acceptors to Achieve Efficient Near Infrared OLEDs.

Two new 2,3-dicyanopyrazinophenanthrene-based acceptors (A) p-QCN and m-QCN were synthesized to blend with a donor (D) CPTBF for the exciplex formation. The energy levels of p-QCN and m-QCN are modulated by the peripheral substituents 4- and 3-benzonitrile, respectively. Exciplex-forming blends were identified by the observation of the red-shifted emissions from various D : A blends with higher ratios of donor for suppressing the aggregation of acceptor. The two-component relaxation processes observed by time-resolved photoluminescence support the thermally activated delayed fluorescence (TADF) character of the exciplex-forming blends. The device employing CPTBF : p-QCN and (2 : 1) and CPTBF : m-QCN (2 : 1) blend as the emitting layer (EML) gave EQEmax of 1.76 % and 5.12 %, and electroluminescence (EL) λmax of 629 nm and 618 nm, respectively. The device efficiency can be further improved to 4.32 % and 5.57 % with CPTBF : p-QCN and (4 : 1) and CPTBF : m-QCN (4 : 1) as the EML, which is consistent with their improved photoluminescence quantum yields (PLQYs). A new fluorescent emitter BPBBT with photoluminescence (PL) λmax of 726 nm and a high PLQY of 67 % was synthesized and utilized as the dopant of CPTBF : m-QCN (4 : 1) cohost system. The device employing CPTBF : m-QCN (4 : 1): 5 wt.% BPBBT as the EML gave an EQEmax of 5.02 % and EL λmax centered at 735 nm, however, the weak residual exciplex emission remains. By reducing the donor ratio, the exciplex emission can be completely transferred to BPBBT and the corresponding device with CPTBF : m-QCN (2 : 1): 5 wt.% BPBBT as the EML can achieve EL λmax of 743 nm and EQEmax of 4.79 %. This work manifests the high efficiency near infrared (NIR) OLED can be realized by triplet excitons harvesting of exciplex-forming cohost system, followed by the effective energy transfer to an NIR fluorescent dopant.

Artificial Neural Network-Based Activities Classification, Gait Phase Estimation, and Prediction.

Gait patterns are critical to health monitoring, gait impairment assessment, and wearable device control. Unrhythmic gait pattern detection under community-based conditions is a new frontier in this area. The present paper describes a high-accuracy gait phase estimation and prediction algorithm built on a two-stage artificial neural network. This work targets to develop an algorithm that can estimate and predict the gait cycle in real time using a portable controller with only two IMU sensors (one on each thigh) in the community setting. Our algorithm can detect the gait phase in unrhythmic conditions during walking, stair ascending, and stair descending, and classify these activities with standing. Moreover, our algorithm is able to predict both future intra- and inter-stride gait phases, offering a potential means to improve wearable device controller performance. The proposed data-driven algorithm is based on a dataset consisting of 5 able-bodied subjects and validated on 3 different able-bodied subjects. Under unrhythmic activity situations, validation shows that the algorithm can accurately identify multiple activities with 99.55% accuracy, and estimate ([Formula: see text]: 6.3%) and predict 200-ms-ahead ([Formula: see text]: 8.6%) the gait phase percentage in real time, which are on average 57.7 and 54.0% smaller than the error from the event-based method in the same conditions. This study showcases a solution to estimate and predict gait status for multiple unrhythmic activities, which may be deployed to controllers for wearable robots or health monitoring devices.

Is Robotic Superior to Laparoscopic Approach for Radical Nephroureterectomy with Bladder Cuff Excision in Treating Upper Urinary Tract Urothelial Carcinoma?

Background: Laparoscopic nephroureterectomy (LNU) has become popular in treating upper urinary tract urothelial carcinoma (UTUC) and an emerging trend was observed in robotic approaches. Therefore, we compared robot-assisted radical nephroureterectomy (RANU) and LNU for the treatment of UTUC. Materials and Methods: This observational and retrospective case-series study included UTUC patients who underwent LNU or RANU. A pure laparoscopic approach was adopted in the LNU treatment group, and bladder cuff excision (BCE) was performed mostly with the open approach. Either the da Vinci Si or Xi surgical system was used for RANU. Extravesical BCE was performed, and bladder defects were closed intracorporeally. Perioperative and oncologic outcomes were compared between the LNU and RANU groups. Results: A total of 231 patients who underwent RANU (n = 87) or LNU (n = 144) were included. No significant differences were noted between the groups in terms of demographics, tumor characteristics, operative time, catheter time, or complications. Compared with LNU, RANU had a lower intraoperative blood loss (30 vs. 150 mL, p < 0.001) and shorter postoperative hospital stay (8 vs. 9 days, p = 0.009). The 5-year overall survival, cancer-specific survival, and bladder recurrence-free survival were comparable between the groups. Conclusion: Compared with LNU, RANU had similar perioperative and oncologic outcomes but was superior in terms of intraoperative blood loss and postoperative length of hospital stay. However, considering the potential biases owing to the heterogeneity of our cases, the interpretation of the results must be very cautious.

Combining prostate health index and multiparametric magnetic resonance imaging may better predict extraprostatic extension after radical prostatectomy.

BACKGROUND: In patients undergoing radical prostatectomy (RP) for prostate cancer (PCa), preoperative prediction of extraprostatic extension (EPE) can facilitate patient selection for nerve-sparing procedures. Since both multiparametric magnetic resonance imaging (mpMRI) and prostate health index (PHI) have shown promise for the diagnosis and prognostication of PCa, we investigated whether a combination of mpMRI and PHI evaluations can improve the prediction of EPE after RP. METHODS: Patients diagnosed with PCa and treated with RP were prospectively enrolled between February 2017 and July 2019. Preoperative blood samples were analyzed for PHI (defined as [p2PSA/fPSA] × âˆštPSA), and mpMRI examinations were performed and interpreted by a single experienced uroradiologist retrospectively. The area under the receiver operating characteristic curve (ROC) was used to determine the performance of mpMRI, PHI, and their combination in predicting EPE after RP. RESULTS: A total of 163 patients were included for analysis. The pathological T stage was T3a or more in 59.5%. Overall staging accuracy of mpMRI for EPE was 72.4% (sensitivity and specificity: 73.2% and 71.2%, respectively). The area under the ROC of the combination of mpMRI and PHI in predicting EPE (0.785) was higher than those of mpMRI alone (0.717; p = 0.0007) and PHI alone (0.722; p = 0.0236). mpMRI showed false-negative non-EPE results in 26 patients (16%), and a PHI threshold of >40 could avoid undiagnosed EPE before RP in 21 of these 26 patients. CONCLUSION: The combination of PHI and mpMRI may better predict the EPE preoperatively, facilitating preoperative counseling and tailoring the need for nerve-sparing RP.

Modeling and Stiffness-based Continuous Torque Control of Lightweight Quasi-Direct-Drive Knee Exoskeletons for Versatile Walking Assistance.

State-of-the-art exoskeletons are typically limited by low control bandwidth and small range stiffness of actuators which are based on high gear ratios and elastic components (e.g., series elastic actuators). Furthermore, most exoskeletons are based on discrete gait phase detection and/or discrete stiffness control resulting in discontinuous torque profiles. To fill these two gaps, we developed a portable lightweight knee exoskeleton using quasi-direct drive (QDD) actuation that provides 14 Nm torque (36.8% biological joint moment for overground walking). This paper presents 1) stiffness modeling of torque-controlled QDD exoskeletons and 2) stiffness-based continuous torque controller that estimates knee joint moment in real-time. Experimental tests found the exoskeleton had high bandwidth of stiffness control (16 Hz under 100 Nm/rad) and high torque tracking accuracy with 0.34 Nm Root Mean Square (RMS) error (6.22%) across 0-350 Nm/rad large range stiffness. The continuous controller was able to estimate knee moments accurately and smoothly for three walking speeds and their transitions. Experimental results with 8 able-bodied subjects demonstrated that our exoskeleton was able to reduce the muscle activities of all 8 measured knee and ankle muscles by 8.60%-15.22% relative to unpowered condition, and two knee flexors and one ankle plantar flexor by 1.92%-10.24% relative to baseline (no exoskeleton) condition.

Quality of life and symptom distress after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/ HIPEC) for peritoneal surface malignancy can effectively control the disease, however it is also associated with adverse effects which may affect quality of life (QoL). AIM: To investigate early perioperative QoL after CRS/HIPEC, which has not been discussed in Taiwan. METHODS: This single institution, observational cohort study enrolled patients who received CRS/HIPEC. We assessed QoL using the Taiwanese version of the MD Anderson Symptom Inventory (MDASI-T) and European Organization Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Participants completed the questionnaires before CRS/HIPEC (S1), at the first outpatient follow-up (S2), and 3 mo after CRS/HIPEC (S3). RESULTS: Fifty-eight patients were analyzed. There was no significant perioperative difference in global health status. Significant changes in physical and role functioning scores decreased at S2, and fatigue and pain scores increased at S2 but returned to baseline at S3. Multiple regression analysis showed that age and performance status were significantly correlated with QoL. In the MDASI-T questionnaire, distress/feeling upset and lack of appetite had the highest scores at S1, compared to fatigue and distress/feeling upset at S2, and fatigue and lack of appetite at S3. The leading interference items were working at S1 and S2 and activity at S3. MDASI-T scores were significantly negatively correlated with the EORTC QLQ-C30 results. CONCLUSION: QoL and symptom severity improved or returned to baseline in most categories within 3 mo after CRS/HIPEC. Our findings can help with preoperative consultation and perioperative care.

Bio-inspired design of a self-aligning, lightweight, and highly-compliant cable-driven knee exoskeleton.

Powered knee exoskeletons have shown potential for mobility restoration and power augmentation. However, the benefits of exoskeletons are partially offset by some design challenges that still limit their positive effects on people. Among them, joint misalignment is a critical aspect mostly because the human knee joint movement is not a fixed-axis rotation. In addition, remarkable mass and stiffness are also limitations. Aiming to minimize joint misalignment, this paper proposes a bio-inspired knee exoskeleton with a joint design that mimics the human knee joint. Moreover, to accomplish a lightweight and high compliance design, a high stiffness cable-tension amplification mechanism is leveraged. Simulation results indicate our design can reduce 49.3 and 71.9% maximum total misalignment for walking and deep squatting activities, respectively. Experiments indicate that the exoskeleton has high compliance (0.4 and 0.1 Nm backdrive torque under unpowered and zero-torque modes, respectively), high control bandwidth (44 Hz), and high control accuracy (1.1 Nm root mean square tracking error, corresponding to 7.3% of the peak torque). This work demonstrates performance improvement compared with state-of-the-art exoskeletons.

Protein-bound polysaccharide K prolonged overall survival in gastric cancer patients from a non-Japanese Asian country who received gastrectomy and adjuvant chemotherapy.

Adding protein-bound polysaccharide K (PSK) to adjuvant chemotherapy with mitomycin and fluorouracil after gastrectomy for gastric cancer was demonstrated to improve survival in a previous study in Japan. However, the efficacy of PSK outside Japan and in combination with other adjuvant chemotherapeutic agents remains unclear. The aims of this study were to evaluate the efficacy of PSK. We conducted a population-based historical cohort study using the National Health Insurance Research Database of Taiwan. We performed sensitivity analysis with propensity score matching to control for possible confounders. Patients who used PSK (PSK group) were matched at a 1:4 ratio to those who had never used PSK (control group) after adjusting for covariates including sex, age, urbanization, income and comorbidities. The primary outcome was overall survival. Multivariate hazard ratios from competing risk analysis were calculated by adjusting for demographic data and all confounding factors. From 1999 to 2008, we identified 10,617 patients with gastric cancer received gastrectomy and adjuvant chemotherapy. 1295 patients used PSK (PSK group) and 5180 patients never used PSK (control group) were analyzed after propensity score matching. The median overall survival was 6.49 years (95% confidence interval [CI] 5.22-7.63) in the PSK group and 3.59 years (95% CI 3.38-3.80) in the control group. After adjusting for age, sex, urbanization, income, and comorbidities, adding PSK to adjuvant chemotherapy was the most significant prognostic factor for improved survival (hazard ratio 0.76, P < .0001). Adjuvant chemotherapy combined with PSK significantly prolonged overall survival in gastric cancer patients after gastrectomy.

High-Throughput Sequencing of Complementarity Determining Region 3 in the Heavy Chain of B-Cell Receptor in Renal Transplant Recipients: A Preliminary Report.

BACKGROUND: Graft failure resulting from rejection or any other adverse event usually originates from an aberrant and/or exaggerated immune response and is often catastrophic in renal transplantation. So, it is essential to monitor patients' immune status for detecting a rejection/graft failure early on. METHODS: We monitored the sequence change of complementary determining region 3 (CDR3) in B-cell receptor (BCR) immunoglobulin heavy-chain (IGH) immune repertoire (iR) in 14 renal transplant patients using next-generation sequencing (NGS), correlating its diversity to various clinical events occurring after transplantation. BCR-IGH-CDR3 in peripheral blood mononuclear cells was sequenced along the post-transplantation course by NGS using the iRweb server. RESULTS: Datasets covering VDJ regions of BCR-IGH-CDR3 indicated clonal diversity (D50) variations along the post-transplant course. Furthermore, principal component analysis showed the clustering of these sequence variations. A total of 544 shared sequences were identified before transplantation. D50 remained low in three patients receiving rituximab. Among them, one's D50 resumed after 3 m, indicating graft tolerance. The D50 rapidly increased after grafting and decreased thereafter in four patients without rejection, decreased in two patients with T-cell-mediated rejection (TCMR) and exhibited a sharp down-sliding after 3 m in two patients receiving donations after cardiac death (DCD). In another two patients with TCMR, D50 was low just before individual episodes, but either became persistently low or returned to a plateau, depending on the failure or success of the immunosuppressive treatments. Shared CDR3 clonal expansions correlated to D50 changes. Agglomerative hierarchical clustering showed a commonly shared CDR3 sequence and at least two different clusters in five patients. CONCLUSIONS: Clonal diversity in BCR-IGH-CDR3 varied depending on clinical courses of 14 renal transplant patients, including B-cell suppression therapy, TCMR, DCD, and graft tolerance. Adverse events on renal graft failure might lead to different clustering of BCR iR. However, these preliminary data need further verification in further studies for the possible applications of iR changes as genetic expression biomarkers or laboratory parameters to detect renal graft failure/rejection earlier.

Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells.

BACKGROUND: Gastric injury is the most common digestive system disease worldwide and involves inflammation, which can lead to gastric ulcer or gastric cancer (GC). Matrix metallopeptidase-9 [MMP-9 (gelatinase-B)] plays an important role in inflammation and GC progression. Quercetin and quercetin-rich diets represent potential food supplements and a source of medications for treating gastric injury given their anti-inflammatory activities. However, the effects and mechanisms of action of quercetin on human chronic gastritis and whether quercetin can relieve symptoms remain unclear. AIM: To assess whether tumor necrosis factor-α (TNF-α)-induced MMP-9 expression mediates the anti-inflammatory effects of quercetin in normal human gastric mucosal epithelial cells. METHODS: The normal human gastric mucosa epithelial cell line GES-1 was used to establish a normal human gastric epithelial cell model of TNF-α-induced MMP-9 protein overexpression to evaluate the anti-inflammatory effects of quercetin. The cell counting Kit-8 assay was used to evaluate the effects of varying quercetin doses on cell viability in the normal GES-1 cell line. Cell migration was measured using Transwell assay. The expression of proto-oncogene tyrosine-protein kinase Src (c-Src), phospho (p)-c-Src, extracellular-signal-regulated kinase 2 (ERK2), p-ERK1/2, c-Fos, p-c-Fos, nuclear factor kappa B (NF-κB/p65), and p-p65 and the effects of their inhibitors were examined using Western blot analysis and measurement of luciferase activity. p65 expression was detected by immunofluorescence. MMP-9 mRNA and protein levels were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and gelatin zymography, respectively. RESULTS: qRT-PCR and gelatin zymography showed that TNF-α induced MMP-9 mRNA and protein expression in a dose- and time-dependent manner. These effects were reduced by the pretreatment of GES-1 cells with quercetin or a TNF-α antagonist (TNFR inhibitor) in a dose- and time-dependent manner. Quercetin and TNF-α antagonists decreased the TNF-α-induced phosphorylation of c-Src, ERK1/2, c-Fos, and p65 in a dose- and time-dependent manner. Quercetin, TNF-α antagonist, PP1, U0126, and tanshinone IIA (TSIIA) reduced TNF-α-induced c-Fos phosphorylation and AP-1-Luciferase (Luc) activity in a dose- and time-dependent manner. Pretreatment with quercetin, TNF-α antagonist, PP1, U0126, or Bay 11-7082 reduced TNF-α-induced p65 phosphorylation and translocation and p65-Luc activity in a dose- and time-dependent manner. TNF-α significantly increased GES-1 cell migration, and these results were reduced by pretreatment with quercetin or a TNF-α antagonist. CONCLUSION: Quercetin significantly downregulates TNF-α-induced MMP-9 expression in GES-1 cells via the TNFR-c-Src-ERK1/2 and c-Fos or NF-κB pathways.

Interpretation According to Clone-Specific PD-L1 Cutoffs Reveals Better Concordance in Muscle-Invasive Urothelial Carcinoma.

Because immune checkpoint inhibitors have been approved for treating advanced urothelial carcinoma (UC), programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays have been widely used as companion or complementary diagnostic tests for predicting treatment outcomes. Because different clones, scoring algorithms, and cutoffs have been used for interpretation, this study investigated the variation, correlation, and concordance of four validated PD-L1 clones (SP142, SP263, 22C3, and 28-8) and proposed a practical solution for the harmonization of PD-L1 IHC. A tissue microarray, including 46 muscle-invasive UCs, was constructed for PD-L1 testing with the four clones. Tumor cell (TC) and immune cell (IC) expression was analyzed. SP142 had significantly low TC expression, whereas SP263, 22C3, and 28-8 exhibited a moderate correlation (rho ≥ 0.6), with almost perfect concordance (intraclass correlation coefficient > 0.8) in TC expression. Fair to moderate correlation and concordance were observed in IC expression in most pairwise comparisons of clones. Substantial concordance (kappa > 0.6) was noted when high PD-L1 expression was defined by applying clone-specific cutoffs to each clone. Our findings imply that a universal cutoff value is not feasible for UC; we propose that PD-L1 IHC assays for UC should be interpreted according to a clone-specific scoring algorithm and cutoff value.

Adding Value of MRI over CT in Predicting Peritoneal Cancer Index and Completeness of Cytoreduction.

BACKGROUND: This study aimed to investigate the adding value of MRI over CT for preoperative cytoreductive surgery with hyperthermic intraperitoneal chemotherapies (CRS/HIPEC). METHODS: Imaging and intraoperative peritoneal cancer index (PCI) were calculated in 62 patients with peritoneal metastasis. Predictive models for the completeness of cytoreductive score using PCI data were established using decision tree algorithms. RESULTS: In gastric cancer patients, a large discrepancy and poor agreement was appreciated between CT and surgical PCI, and a nonsignificant difference was noted between MRI and surgical PCI. In colon cancer patients, a better agreement and higher correlation with a smaller error was observed in PCI score using MRI than in that using CT. However, the addition of MRI to CT was limited for appendiceal and ovarian cancer patients. For predicting incomplete cytoreduction, CT models yielded inadequate accuracy while MRI models were more accurate with fair discrimination ability. CONCLUSIONS: CT was suitable for estimating PCI and surgery outcome in appendiceal and ovarian cancer patients, while further MRI in addition to CT was recommended for colon and gastric cancer patients. However, for classifying patients with peritoneal carcinomatosis into complete and incomplete cytoreduction, MRI was more effective than CT.

The acceptance and impact of Google Classroom integrating into a clinical pathology course for nursing students: A technology acceptance model approach.

BACKGROUND: Google Classroom (GC) is a free web-based instructional platform rarely used for nursing student education. The acceptance, intention to use, and learning outcomes of GC remain unclear in Taiwan. We sought to identify the technology acceptance level and factors affection the intention to use GC. We also explored how integrating GC into traditional teaching affects learning satisfaction and academic achievement among nursing students in Taiwan. METHODS: In this randomized controlled study, based on a technology acceptance framework, 74 nursing students were randomly assigned in clusters to experimental (n = 39) and control (n = 35) groups during the spring semester of 2018. In Weeks 3-18, each member of the experimental group received one hour of traditional and GC teaching per week. The control group received two hours of traditional teaching per week. Both groups were asked to complete questionnaires to evaluate learning satisfaction and academic achievement during weeks 10 (mid-semester) and 18 (end-of-semester). The experimental group additionally completed technology acceptance questionnaires in both situations. FINDINGS: In the experimental group, the overall end-of-semester technology acceptance score was high (141.8 out of 155); their perceived ease of use, intention to use, and technology acceptance scores increased significantly compared to mid-semester (p<0.05). At the end-of-semester, perceived playfulness and perceived usefulness explained 63.5% of the variance in intention to use. Regardless of whether the assessment was administered mid-semester or at the end-of-semester, the experimental group had higher learning satisfaction and academic achievement scores than the control group. However, the degree of progress on learning satisfaction and academic achievement demonstrated no significant between-group differences. CONCLUSIONS: The experimental group demonstrated high acceptance of GC. Playfulness and usefulness positively influenced nursing students' intention to use GC. Blended learning-in combination with GC and traditional methods-resulted in similar learning satisfaction and academic achievement when compared to traditional learning. More research is needed to explore the effectiveness of blended learning through the GC platform with different courses and ethnic groups.

The Prostate Health Index aids multi-parametric MRI in diagnosing significant prostate cancer.

To evaluate the performance of the Prostate Health Index (PHI) in magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion prostate biopsy for the detection of clinically significant prostate cancer (csPCa). We prospectively enrolled 164 patients with at least one Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) ≥ 3 lesions who underwent MRI-TRUS fusion prostate biopsy. Of the PSA-derived biomarkers, the PHI had the best performance in predicting csPCa (AUC 0.792, CI 0.707-0.877) in patients with PI-RADS 4/5 lesions. Furthermore, the predictive power of PHI was even higher in the patients with PI-RADS 3 lesions (AUC 0.884, CI 0.792-0.976). To minimize missing csPCa, we used a PHI cutoff of 27 and 7.4% of patients with PI-RADS 4/5 lesions could have avoided a biopsy. At this level, 2.0% of cases with csPCa would have been missed, with sensitivity and NPV rates of 98.0% and 87.5%, respectively. However, the subgroup of PI-RADS 3 was too small to define the optimal PHI cutoff. PHI was the best PSA-derived biomarker to predict csPCa in MRI-TRUS fusion prostate biopsies in men with PI-RADS ≥ 3 lesions, especially for the patients with PI-RADS 3 lesions who gained the most value.