Impact of pathological response on oncological outcomes in patients with upper tract urothelial cancer receiving neo-adjuvant chemotherapy.

PURPOSE: The purpose of this study is to evaluate the rates of pathological complete response (ypT0N0/X) and pathological response (ypT1N0/X or less) in patients with upper tract urothelial cancer who were treated with neo-adjuvant chemotherapy and to examine their impact on oncological outcomes. METHODS: This study is a multi-institutional retrospective analysis of patients with high-risk upper tract urothelial cancer who underwent neoadjuvant chemotherapy and radical nephroureterectomy between 2002 and 2021. Logistic regression analyses were used to investigate all clinical parameters for response after neoadjuvant chemotherapy. Cox proportional hazard models were performed to assess the effect of the response on the oncological outcomes. RESULTS: A total of 84 patients with UTUC who received neo-adjuvant chemotherapy were identified. Among them, 44 (52.4%) patients received cisplatin-based chemotherapy, and 22 (26.2%) patients had a carboplatin-based regimen. The pathological complete response rate was 11.6% (n = 10), and the pathological response rate was 42.9% (n = 36). Multifocal tumors or tumors larger than 3 cm significantly reduced the odds of pathological response. In the multivariable Cox proportional hazard model, pathological response was independently associated with better overall survival (HR 0.38, p = 0.024), cancer-specific survival (HR 0.24, p = 0.033), and recurrence-free survival (HR 0.17, p = 0.001), but it was not associated with bladder recurrence-free survival (HR 0.84, p = 0.69). CONCLUSION: Pathological response after neo-adjuvant chemotherapy and radical nephroureterectomy is strongly associated with patient survival and recurrence, and it might be a good surrogate for evaluating the efficacy of neo-adjuvant chemotherapy in the future.

An in vitro analysis of the hemostatic efficacy of fibrinogen precipitation with varied keratin fraction compositions.

In preclinical studies, human hair has demonstrated effective hemostatic properties, potentially attributed to keratin proteins facilitating rapid conversion of fibrinogen to fibrin during coagulation. However, the rational use of human hair keratin for hemostasis remains unclear, given its complex mixture of proteins with diverse molecular weights and structures, leading to variable hemostatic capacity. To optimize the rational utilization of human hair keratin for hemostasis, we investigated the effects of different keratin fractions on keratin-mediated fibrinogen precipitation using a fibrin generation assay. Our study focused on high molecular weight keratin intermediate filaments (KIFs) and lower molecular weight keratin-associated proteins (KAPs) combined in various ratios during the fibrin generation. Scanning electron microscope analysis of the precipitates revealed a filamentous pattern with a broad distribution of fiber diameters, likely due to the diversity of keratin mixtures involved. An equal proportion of KIFs and KAPs in the mixture yielded the most extensive precipitation of soluble fibrinogen in an in vitro study, potentially due to structure-induced exposure of active sites. However, all hair protein samples exhibited diverse catalytic behaviors compared to thrombin, highlighting the potential of utilizing specific hair fractions to develop hair protein-based hemostatic materials with optimized capacity.

Is Lymph Node Dissection Necessary During Radical Nephroureterectomy for Clinically Node-Negative Upper Tract Urothelial Carcinoma? A Multi-Institutional Study.

Purpose: This study aimed to compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) without clinical lymph node metastasis (cN0) undergoing lymph node dissection (LND) during radical nephroureterectomy (NU). Methods: From the updated data of the Taiwan UTUC Collaboration Group, a total of 2726 UTUC patients were identified. We only include patients with ≥ pT2 stage and enrolled 658 patients. The Kaplan-Meier estimator and Cox proportional hazards model were used to analyze overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) in LND (+) and LND (-) groups. Results: A total of 658 patients were included and 463 patients without receiving LND and 195 patients receiving LND. From both univariate and multivariate survival analysis, there are no significant difference between LND (+) and LND (-) group in survival rate. In LND (+) group, 18.5% patients have pathological LN metastasis. After analyzing pN+ subgroup, it revealed worse CSS (p = 0.010) and DFS (p < 0.001) compared with pN0 patients. Conclusions: We found no significant survival benefit related to LND in cN0 stage, ≥ pT2 stage UTUC, irrespective of the number of LNs removed, although pN+ affected cancer prognosis. However, from the result of pN (+) subgroup of LND (+) cohort analysis, it may be reasonable to not perform LND in patients with cT2N0 stage due to low positive predictive value of pN (+). In addition, performing LND may be considered for ureter cancer, which tends to cause lymphatic and hematogenous tumor spreading. Further large prospective studies are needed to validate our findings.

Associations of Chinese Herbal Medicine Use with the Risks of Acute Exacerbation and Mortality in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Retrospective Cohort Study.

Objectives: This study aimed to assess the correlation of exacerbation and the mortality rate in patients with chronic obstructive pulmonary disease (COPD) between biomedical treatments with or without Chinese herbal medicine (CHM) as an adjunct. Design: A total of 81,261 COPD patients were identified from the National Health Insurance Research Database in Taiwan between 2001 and 2012. After screening and matching, 3176 COPD patients were included in the study. Statistical analyses were performed to assess the differences in the baseline characteristics. The authors used the Cox proportional hazard regression analysis to calculate the risks of mortality and hospitalization due to acute exacerbation of COPD within 1 year between a CHM user cohort and non-CHM user cohort. The cumulative incidence of mortality in COPD patients with or without CHM treatment was calculated by the Kaplan-Meier method. Results: COPD patients in the CHM user cohort demonstrated a significantly lower risk of mortality (p < 0.001) and acute exacerbation (p < 0.05), compared with the non-CHM user cohort. In addition, the CHM users exhibited a reduced cumulative incidence of mortality compared with the non-CHM user cohort (p < 0.001). Xiao Qing Long Tang and Fritillariae thunbergii were the most common Chinese herbal formula and single Chinese herb prescribed for COPD patients. Conclusion: Combining CHM with biomedical treatment might reduce the risk of acute exacerbation and incidence of mortality in patients with COPD.

Prognostic factors of functional outcome in post-acute stroke in the rehabilitation unit.

BACKGROUND/PURPOSE: This retrospective study aimed to determine which factors, such as cognition, motor recovery, swallowing function, and bladder and bowel functions, significantly predicted independence in the activities of daily living (ADL) at hospital discharge in a domestic population of patients experiencing post-acute stroke who received in-hospital rehabilitation. METHODS: We reviewed medical records that were retrieved from the Integrated Medical Database, National Taiwan University Hospital (NTUH-iMD) of 3000 patients who suffered from stroke and were admitted to NTUH from 2014 to 2017. The main outcome measure was independence in the basic ADL (modified Barthel index [mBI]) at discharge. Regression analyses were used to identify prognostic factors for the basic ADL (mBI). RESULTS: The total mBI improved from 40.7 ± 33.0 to 63.1 ± 34.1 in eligible 2538 patients during their hospital stay. The baseline daily activity function (R2 change = 0.042) was the most important prognostic factor associated with independence at discharge, followed by dependence in sitting up (R2 change = 0.014), impaired sitting balance (R2 change = 0.010), the Brunnstrom stage of hemiplegic lower limb (R2 change = 0.006), and the presence of bladder incontinence (R2 change = 0.006) assessed by physician upon rehabilitation admission (R2 = 0.53, p < 0.05). Dependency in sitting up, impaired sitting balance, and the presence of urinary incontinence were negative prognostic factors of ADL independence at discharge (p < 0.05). By contrast, the Brunnstrom stage of hemiplegic lower limb and baseline mBI scores at rehabilitation admission were positive prognostic factors of ADL independence at discharge (p < 0.05). CONCLUSION: Baseline ADL function was the most important prognostic factor of functional independence in post-acute stroke. Moreover, the activity limitation of dependency on sitting up and motor function impairment of hemiplegic lower limb prognosticated functional independence.

Plate osteosynthesis of single metacarpal fracture: WALANT technique is a cost-effective approach to reduce postoperative pain and discomfort in contrast to general anesthesia and wrist block.

BACKGROUND: The WALANT (wide-awake local anesthesia with no tourniquet) technique was based on local infiltration of lidocaine and epinephrine. This technique has rapidly gained popularity in recent years and can perform most hand operations. This study aimed to investigate the time spent on anesthesia and operation and perform an economic analysis among general anesthesia, wrist block with a tourniquet, and the WALANT technique for the internal fixation of metacarpal fractures. METHODS: We retrospectively reviewed all the single metacarpal fractures managed with the same procedure, open reduction, and internal fixation with the plate between January 2015 and December 2019. They were divided into three groups according to the method of anesthesia: (1) general anesthesia (GA group), (2) wrist block with a tourniquet (WB group), and (3) WALANT technique (WALANT group). We collected and analyzed patient demographic data, perioperative or postoperative complications, number of hospital days, and postoperative functional recovery assessment. RESULTS: A total of 63 patients met the inclusion criteria, including 24 in the GA group, 28 in the wrist block group using a tourniquet, and 11 in the WALANT group. There were no complications during the operation and follow-up in each group. The GA group had an average of 32.8 min of anesthesia time, significantly longer than the other two groups. However, there is no significant difference regarding surgical time among the presenting three groups. The discomfort of vomiting and nausea after surgery occurred in 20 patients in the GA group (38.1%). Nevertheless, there was no postoperative vomiting and nausea present in both the WB and WALANT groups. Most patients achieved full recovery of pre-injury interphalangeal and metacarpophalangeal motion at the final assessment of functional recovery. CONCLUSIONS: The patients undergoing metacarpal fixation surgery under WALANT or WB had significantly less anesthesia time and postoperative vomiting and nausea. Moreover, there was no difference in surgical time and intraoperative complications. The time-related reduction improved the utilization of the operation room for additional cases. The reduction of the preoperative examination, anesthesia fee, postoperative recovery room observation, and hospitalization can effectively reduce medical costs. Furthermore, the WALANT group is more acceptable because of no tourniquet, which commonly causes discomfort.

Non-Muscular Invasive Bladder Cancer: Re-envisioning Therapeutic Journey from Traditional to Regenerative Interventions.

Non-muscular invasive bladder cancer (NMIBC) is one of the most common cancer and major cause of economical and health burden in developed countries. Progression of NMIBC has been characterized as low-grade (Ta) and high grade (carcinoma in situ and T1). The current surgical intervention for NMIBC includes transurethral resection of bladder tumor; however, its recurrence still remains a challenge. The BCG-based immunotherapy is much effective against low-grade NMIBC. BCG increases the influx of T cells at bladder cancer site and inhibits proliferation of bladder cancer cells. The chemotherapy is another traditional approach to address NMIBC by supplementing BCG. Notwithstanding, these current therapeutic measures possess limited efficacy in controlling NMIBC, and do not provide comprehensive long-term relief. Hence, biomaterials and scaffolds seem an effective medium to deliver therapeutic agents for restructuring bladder post-treatment. The regenerative therapies such as stem cells and PRP have also been explored for possible solution to NMIBC. Based on above-mentioned approaches, we have comprehensively analyzed therapeutic journey from traditional to regenerative interventions for the treatment of NMIBC.

Large inguinal synovial sarcoma mimics a vascular lesion: A case report and literature review.

INTRODUCTION: Synovial sarcoma (SS) is one of soft tissue sarcomas (STS), characterized by t(X;18)(p11;q11) chromosomal translocation. Clinical diagnosis of SS in groin is difficult owing to rarity and various manifestations. We reported a rare and interesting case of inguinal biphasic SS with initial impression of a vascular lesion. PRESENTATION OF CASE: We reported a 72-year-old man who presented with a right inguinal progressively enlarged mass for 5 years. The mass became ulcerative with active bleeding after blunt trauma. Computed tomography (CT) showed a large heterogeneous tumor with focal vivid enhanced area, and an inguinal vascular lesion was impressed. Angiography revealed faint tumor stain without contrast extravasation or aneurysm lesion. Surgical resection of the tumor was performed. Final pathology and fluorescence in situ examination (FISH) demonstrated biphasic SS with SS18 gene rearrangement. No evidence of recurrence after one-year follow-up. DISCUSSION: SS constitutes 5%-10% of STS. The most primary sites are extremities (68.7%) and trunk (15.7%). Treatment options for SS include surgery, chemotherapy, radiotherapy, targeted therapy, and novel therapies. In our case, the initial impressions of large inguinal tumor were hematoma or pseudoaneurysm. Preoperative angiography assisted in differentiating the lesion, evaluating tumor vessels, and preventing bleeding by embolization. Our patient recovered satisfactorily after surgical excision without major complications. CONCLUSION: Primary inguinal SS is an extremely rare tumor which can present as a vascular lesion. Diagnosis is confirmed by pathology and FISH exam. Further studies are required to determine the manifestation and management of SS.

The effectiveness of cardiac rehabilitation in non-ischemic dilated cardiomyopathy patients: A pilot study.

BACKGROUND/PURPOSE: We aimed to investigate the efficacy of cardiac rehabilitation (CR) through parameters of cardiopulmonary exercise testing (CPET) and echocardiography in non-ischemic dilated cardiomyopathy (DCM) patients. METHODS: We retrospectively identified non-ischemic DCM patients through medical records (between October 2011 and October 2018) in rehabilitation outpatient-clinics. Patients were divided into rehabilitation and control groups. Patients in the rehabilitation group eligible for inclusion had CR for 3-6 months. Control group patients were without rehabilitation. We recorded CPET and echocardiography parameters at the baseline and follow-up time-points. For safety evaluation, we investigated all adverse effects during training sessions. We utilized Mann-Whitney U test for between- and Wilcoxon signed-rank test for within-group comparisons. RESULTS: Twenty-five patients (14 in rehabilitation and 11 in control group) were included. In the rehabilitation group, significantly increased peak V˙O2/kg, peak V˙O2%, peak workload and peak O2 pulse were observed after completing CR, and echocardiographic parameters including left ventricular ejection fraction and end-systolic volume. Rehabilitation group patients demonstrated better improvement (change from the baseline) in peak V˙O2/kg, peak V˙O2% and peak workload vs. control. No adverse effects during rehabilitation trainings were observed. CONCLUSION: For non-ischemic DCM, rehabilitation led to superior cardiopulmonary outcomes vs. no rehabilitation, without adverse effects.

Adjuvant therapy with traditional Chinese medicine in a heart failure patient complicated by hospital-acquired pneumonia: A case report.

OBJECTIVE: We report a case of congestive heart failure complicated by hospital-acquired pneumonia that was successfully treated with traditional Chinese medicine (TCM) and antibiotics. CLINICAL FEATURES AND OUTCOME: A 33-year-old man with a history of heart failure developed pneumonia during hospitalization. After the standard antibiotic therapy for 3 days, he continued to experience persistent fever and progressive cough with purulent sputum. Broad spectrum antibiotics did not relieve the fever or the purulent sputum; therefore, the patient requested TCM for integrated therapy, and was subsequently treated with a regiment of "clearing heat and damp excreting" decoction according to TCM theory. After three days of TCM combination therapy, the pneumonia patches significantly improved on chest X-ray. His sputum was obviously decreased in amount and the fever was complete remission in the 5th day of TCM adjuvant therapy. CONCLUSION: Integrated therapy with a "clearing heat and damp excreting" decoction may have improved hospital-acquired pneumonia in a patient comorbid with congestive heart failure. The anti-pyretic, anti-inflammatory, antitussive and diuretic effects of TCM may be responsible for the observed improvement. Further experimental studies are warranted to confirm the efficacy and mechanism of TCM action in the treatment of pneumonia.

Effects of transabdominal preperitoneal and totally extraperitoneal inguinal hernia repair: an update systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Compared with open herniorrhaphy, laparoscopic herniorrhaphy can yield more favorable clinical outcomes. However, previous studies failed to give definite answer for comparison between laparoscopic inguinal hernia repair approaches. This study aimed to systematically determine the differences in recurrence rate, duration of return to work, pain, surgery duration, and duration of hospital stay between transabdominal preperitoneal (TAPP) and totally extraperitoneal (TEP) approach for inguinal hernia. METHODS: PubMed, Embase, and Cochrane Library (including the Cochrane Central Register of Controlled Trials) abstracts up to September 2017 were searched for randomized controlled trials (RCTs) comparing TAPP or TEP hernia repairing. The hernia recurrence rate, time to return to work, analgesic consumption, surgery duration, hospital stay, and the pain score were recorded with subgroup analysis of the hernia type. RESULTS: Sixteen RCTs that randomized 1519 patients with hernia into TEP and TAPP repair groups were analyzed in this study. The results revealed that TEP repair resulted in shorter hospital stay of primary cases (MD - 0.87, 95% CI - 1.67 to - 0.07) but was associated with a longer operative duration in recurrent hernia group (MD 3.35, 95% CI 0.16 - 6.54). CONCLUSIONS: TEP and TAPP have their own advantages. TEP repair reduces short-term postoperative pain more effectively than TAPP repair and results in shorter hospital stay of primary cases. In contrast, TAPP repair is correlated with shorter surgery duration. These findings show that shared decision-making regarding both approaches of laparoscopic hernia repair may be needed.

Revealing the influence of Cyano in Anchoring Groups of Organic Dyes on Adsorption Stability and Photovoltaic Properties for Dye-Sensitized Solar Cells.

Determining an ideal adsorption configuration for a dye on the semiconductor surface is an important task in improving the overall efficiency of dye-sensitized solar cells. Here, we present a detailed investigation of different adsorption configurations of designed model dyes on TiO2 anatase (101) surface using first principles methods. Particularly, we aimed to investigate the influence of cyano group in the anchoring part of dye on its adsorption stability and the overall photovoltaic properties such as open circuit voltage, electron injection ability to the surface. Our results indicate that the inclusion of cyano group increases the stability of adsorption only when it adsorbs via CN with the surface and it decreases the photovoltaic properties when it does not involve in binding. In addition, we also considered full dyes based on the results of model dyes and investigated the different strength of acceptor abilities on stability and electron injection ability. Among the various adsorption configurations considered here, the bidentate bridging mode (A3) is more appropriate one which has higher electron injection ability, larger VOC value and more importantly it has higher dye loading on the surface.

First principles study of organic sensitizers for dye sensitized solar cells: effects of anchoring groups on optoelectronic properties and dye aggregation.

We have designed a new set of D-π-A type organic dye sensitizers with different acceptor and anchoring groups, and systematically investigated their optoelectronic properties for efficient dye sensitized solar cell applications. Particularly, we have focused on the effects of anchoring groups on the dye aggregation phenomenon. TDDFT results indicate that the dyes with CSSH anchoring groups exhibit improved optoelectronic properties compared to other dyes. Further, molecular dynamics simulations have been performed to describe the formation of dye aggregation due to intermolecular hydrogen bonding. The observed results indicate that dyes with CSSH anchoring groups are less prone to aggregate because of their very weak intermolecular interactions.

Effect of Focused Ion Beam Imaging on the Crystallinity of InAs.

We investigated the effect of focused ion beam (FIB) imaging on the crystallinity of InAs using Raman scattering. A spatial correlation model was used to fit the broad band induced by FIB imaging. The fitting gives a correlation length of ~42 Å for the noisiest image condition (with an ion fluence of 7.4×1010 cm-2), implying severe damage in the surface layer of InAs. However, further increasing the fluence by several orders of magnitude only decreases the correlation length from 42 to 35 Å. We attribute the severe damage to the high beam current density and the low scanning speed of the FIB imaging process. These process conditions, along with low InAs thermal conductivity, also leads to a high local temperature in the exposed region that largely annihilated the defects and resulted in the nearly fluence-independent behavior.

A highly selective turn-on fluorescent probe for hypochlorous acid based on hypochlorous acid-induced oxidative intramolecular cyclization of boron dipyrromethene-hydrazone.

A BODIPY-based fluorescent probe, HBP, was developed for the detection of hypochlorous acid based on the specific hypochlorous acid-promoted oxidative intramolecular cyclization of heterocyclic hydrazone in response to the amount of HOCl. The reaction is accompanied by a 41-fold increase in the fluorescent quantum yield (from 0.004 to 0.164). The fluorescence intensity of the reaction between HOCl and HBP is linear in the HOCl concentration range of 1-8 µM with a detection limit of 2.4 nM (S/N=3). Confocal fluorescence microscopy imaging using RAW264.7 cells showed that the new probe HBP could be used as an effective fluorescent probe for detecting HOCl in living cells.

Controlling available active sites of Pt-loaded TiO2 nanotube-imprinted Ti plates for efficient dye-sensitized solar cells.

The counter electrode (CE) of dye-sensitized solar cells (DSSCs) plays an important role for transferring electrons and catalyzing the I-/I3- reduction. Active surface area of the substrate determines the reduction sites of the deposited catalyst as well as the catalytic ability of the CE. An effective method for enhancing and controlling the active surface area of metal plates is provided in this study. The Ti plates are imprinted by TiO2 nanotubes (TNT) via the technique of anodization along with the ultrasonic vibration process. The available active area of imprinted Ti plates is controlled by varying the anodization voltage to produce TNT imprints with different diameters and depths. A solar-to-electricity conversion efficiency (η) of 9.35% was obtained for the DSSC with a TNT-imprinted Ti plate as the CE substrate, while the cell with an imprint-free Ti plate shows an η of 7.81%. The enhanced η is due to the improved electrocatalytic ability of the CE by using the TNT-imprinted Ti plate as the substrate with higher active surface area.

Clusterin silencing in human lung adenocarcinoma cells induces a mesenchymal-to-epithelial transition through modulating the ERK/Slug pathway.

The ubiquitously expressed glycoprotein Clusterin (CLU) is implicated in diverse cellular processes, yet its genuine molecular function remains undefined. CLU expression has been associated with various human malignancies, yet the mechanisms by which CLU promotes cancer progression and metastasis are not elucidated. In this study, using human lung adenocarcinoma cell lines as a model, we explored the involvement of CLU in modulating invasiveness of cancer cells. We discovered that CLU levels positively correlated with the degree of invasiveness in human lung adenocarcinoma cell lines. The observation that CLU-rich cells displayed a spindle-shape morphology while those with low CLU levels were cuboidal in shape prompted us to investigate if CLU modulates epithelial-to-mesenchymal transitions (EMT). CLU silencing by siRNA in a highly invasive, CLU-rich lung adenocarcinoma cell line induced a mesenchymal-to-epithelial transition (MET) evidenced by the spindle-to-cuboidal morphological change, increased E-cadherin expression, and decreased fibronectin expression. Compared with the vector-transfected cells, CLU-knocked-down (CLUi) cells showed reduced migration and invasion in vitro, as well as decreased metastatic potential in experimental metastasis. Re-expression of CLU in CLUi cells reversed the MET and restored the mesenchymal and invasive phenotypes. We found that Slug, a zinc-finger-containing transcriptional repressor of E-cadherin, was downregulated in CLUi cells. We also discovered that levels of activated ERK correlated with those of CLU and Slug. Taken together, our data suggest that CLU may regulate EMT and aggressive behaviour of human lung adenocarcinoma cells through modulating ERK signalling and Slug expression.