Ultrasensitive Upconversion Nanoparticle Immunoassay for Human Serum Cardiac Troponin I Detection Achieved with Resonant Waveguide Grating.

Selective detection of biomarkers at low concentrations in blood is crucial for the clinical diagnosis of many diseases but remains challenging. In this work, we aimed to develop an ultrasensitive immunoassay that can detect biomarkers in serum with an attomolar limit of detection (LOD). We proposed a sandwich-type heterogeneous immunosensor in a 3 × 3 well array format by integrating a resonant waveguide grating (RWG) substrate with upconversion nanoparticles (UCNPs). UCNPs were used to label a target biomarker captured by capture antibody molecules immobilized on the surface of the RWG substrate, and the RWG substrate was used to enhance the upconversion luminescence (UCL) of UCNPs through excitation resonance. The LOD of the immunosensor was greatly reduced due to the increased UCL of UCNPs and the reduction of nonspecific adsorption of detection antibody-conjugated UCNPs on the RWG substrate surface by coating the RWG substrate surface with a carboxymethyl dextran layer. The immunosensor exhibited an extremely low LOD [0.24 fg/mL (9.1 aM)] and wide detection range (1 fg/mL to 100 pg/mL) in the detection of cardiac troponin I (cTnI). The cTnI concentrations in human serum samples collected at different times during cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) chemotherapy in a breast cancer patient were measured by an immunosensor, and the results showed that the CEF chemotherapy did cause cardiotoxicity in the patient. Having a higher number of wells in such an array-based biosensor, the sensor can be developed as a high-throughput diagnostic tool for clinically important biomarkers.

Comparative effectiveness and safety of inhaled corticosteroid plus long-acting ß2-agonist fixed-dose combinations vs. long-acting muscarinic antagonist in bronchiectasis.

BACKGROUND: This study aimed to evaluate the effectiveness and safety of fixed-dose combination (FDC) inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) in bronchiectasis. RESEARCH DESIGN AND METHODS: A retrospective cohort study analyzed electronic medical records of bronchiectasis patients initiating ICS/LABA FDC or LAMA between 2007 and 2021. All bronchiectasis diagnoses were made by radiologists using high-resolution computed tomography. RESULTS: Of the 1,736 patients, 1,281 took ICS/LABA FDC and 455 LAMA. Among the 694 propensity score matched patients, ICS/LABA FDC had comparable outcomes to LAMA, with HRs of 1.22 (95% CI 0.81-1.83) for hospitalized respiratory infection, 1.06 (95% CI 0.84-1.33) for acute exacerbation, and 1.06 (95% CI 0.66-1.02) for all-cause hospitalization. Beclomethasone/formoterol (BEC/FOR) or budesonide/formoterol (BUD/FOR) led to a lower risk of acute exacerbation compared to fluticasone/salmeterol (FLU/SAL) (BEC/FOR HR 0.59, 95% CI 0.43-0.81; BUD/FOR HR 0.68, 95% CI 0.50-0.93). BEC/FOR resulted in lower risks of hospitalized respiratory infection (HR 0.48, 95% 0.26-0.86) and all-cause hospitalization (HR 0.55, 95% 0.37-0.80) compared to FLU/SAL. CONCLUSION: Our findings provide important evidence on the effectiveness and safety of ICS/LABA FDC compared with LAMA for bronchiectasis. BEC/FOR and BUD/FOR were associated with better outcomes than FLU/SAL.

The impacts of water storage infrastructure on real property values and crop production.

Water storage infrastructure is an indispensable part of many water supply systems, and its importance is experiencing a resurgence due to the increasing water irregularity induced by climate change and ever-growing water demand. Leveraging the commission of Hushan Reservoir in Taiwan as a quasi-experiment, this study provides some of the first causal evidence of the economic benefits of a reservoir from housing market and crop production for guiding sustainable water management. Using the administrative property transaction data and a spatial difference-in-differences framework, we find that the commission of Hushan Reservoir increases the values of residential property and farmlands by 4.1 and 8.9 %, respectively. We also find that enhanced irrigation water availability increases rice yield by over 4 % but has no impact on planted areas. Despite expectations of reduced groundwater use, our results show no evidence of a rebound in groundwater levels in the four years following the commission of the reservoir.

Focusing of surface plasmon polaritons propagating at the SiO2/Ag interface with 2-level and 4-level Fresnel phase zone pad structures.

We propose and demonstrate dielectric Fresnel phase zone pad (FPZP) structures for focusing surface plasmon polaritons (SPPs) propagating at the SiO2/Ag interfaces. We exploited up-conversion fluorescence microscopy to characterize the SPP focusing. We first report on the SPP focusing with 2-level FPZP structures that introduced a π-phase shift in the SPP wavefront between adjacent zones. We optimized the SPP focusing by fine-tuning the longitudinal width of the FPZP structure. This led to the enhancement of the peak intensity of the SPP focal spot and the reduction of the focal spot size in both the longitudinal and transverse directions. Such focusing was also demonstrated with different focal lengths. To further improve the SPP focusing, we developed a 4-level FPZP structure, which introduced a π/2-phase shift in the SPP wavefront between adjacent zones. With the optimized 4-level FPZP structure, the SPP focal spot peak intensity is further improved, and the spot size is reduced. To assist the design of the FPZP structures, we carried out theoretical analysis and numerical calculations to determine the SPP wavelengths at various oxide/Ag interfaces. We also carried out finite difference time domain (FDTD) calculations to simulate the SPP focusing with the FPZP structures. The results of the FDTD simulation agree with the experimental results qualitatively.

Comparative cardiovascular safety of LABA/LAMA FDC versus LABA/ICS FDC in patients with chronic obstructive pulmonary disease: a population-based cohort study with a target trial emulation framework.

BACKGROUND: Use of combinations of long-acting ß2 agonists/long-acting muscarinic antagonists (LABA/LAMA) in patients with chronic obstructive pulmonary disease (COPD) is increasing. Nevertheless, existing evidence on cardiovascular risk associated with LABA/LAMA versus another dual combination, LABA/inhaled corticosteroids (ICS), was limited and discrepant. AIM: The present cohort study aimed to examine comparative cardiovascular safety of LABA/LAMA and LABA/ICS with a target trial emulation framework, focusing on dual fixed-dose combination (FDC) therapies. METHODS: We identified patients with COPD who initiated LABA/LAMA FDC or LABA/ICS FDC from a nationwide Taiwanese database during 2017-2020. The outcome of interest was a hospitalized composite cardiovascular events of acute myocardial infarction, unstable angina, heart failure, cardiac dysrhythmia, and ischemic stroke. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for composite and individual cardiovascular events after matching up to five LABA/LAMA FDC initiators to one LABA/ICS FDC initiator using propensity scores (PS). RESULTS: Among 75,926 PS-matched patients, use of LABA/LAMA FDC did not show a higher cardiovascular risk compared to use of LABA/ICS FDC, with a HR of 0.89 (95% CI, 0.78-1.01) for the composite events, 0.80 (95% CI, 0.61-1.05) for acute myocardial infarction, 1.48 (95% CI, 0.68-3.25) for unstable angina, 1.00 (95% CI, 0.80-1.24) for congestive heart failure, 0.62 (95% CI, 0.37-1.05) for cardiac dysrhythmia, and 0.82 (95% CI, 0.66-1.02) for ischemic stroke. The results did not vary substantially in several pre-specified sensitivity and subgroup analyses. CONCLUSION: Our findings provide important reassurance about comparative cardiovascular safety of LABA/LAMA FDC treatment among patients with COPD.

Arthroscopic cartilage regeneration facilitating procedure can modify the clinical course of knee osteoarthritis.

BACKGROUND: The effectiveness of arthroscopic treatment for knee osteoarthritis (OA) has been controversial. This study compares the clinical outcomes of the arthroscopic cartilage regeneration facilitating procedure (ACRFP) and conservative treatment. METHODS: During the year of 2016, 524 patients (882 knees) who were older than 40 years of age and diagnosed with different stages of knee OA were scheduled for ACRFP under the protocol of knee health promotion option (KHPO) for knee OA. Of those, 259 patients (413 knees) eventually received ACRFP (the ACRFP group), and 265 patients (469 knees) didn't receive ACRFP but received conservative treatment (the non-ACRFP group). A telephone questionnaire was used to evaluate the subjective satisfaction and the incidence of receiving arthroplasty for these patients. RESULTS: After the mean follow-up period of 61.6 months (SD 4.5), there were 220 patients (374 knees, 90.6%) in the ACRFP group and 246 patients (431 knees, 90.0%) in the non-ACRFP group completed the outcome study. The satisfactory rate was statistically higher for the ACRFP group (90.64%) than for the non-ACRFP group (70.3%) and the difference in subjective satisfaction was more obvious in patients with more advanced knee OA. As for the incidence of patients having subsequently received arthroplasty, it was higher (13.46%) in the non-ACRFP group than in the ACRFP group (4.28%). CONCLUSION: Compared with conservative treatment, ACRFP could satisfy more patients with knee OA and modify their natural course by decreasing the incidence of subsequent arthroplasty.

Effectiveness and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation and advanced kidney disease.

BACKGROUND: The effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and advanced kidney disease (AKD) has not been fully established. OBJECTIVES: To determine the effectiveness and safety related to pooled or specific DOACs to that with warfarin in patients with AF and AKD. METHODS: Patients with AF and AKD (estimated glomerular filtration rate < 30 mL/min) who received DOAC or warfarin from July 2011 to December 2020 were retrospectively identified in a medical center in Taiwan. Primary outcomes were hospitalized for stroke/systemic embolism and major bleeding. Secondary outcomes included any ischemia and any bleeding. RESULTS: A total of 1,011 patients were recruited, of whom 809 (80.0%) were in the DOACs group (15.3% dabigatran, 25.4% rivaroxaban, 25.2% apixaban, and 14.1% edoxaban), and 202 (20.0%) in the warfarin group. DOACs had considerably lower risks of stroke/systemic embolism (adjusted hazard ratio [aHR] 0.29; 95% CI, 0.09-0.97) and any ischemia (aHR, 0.42; 95% CI, 0.22-0.79), but had comparable risks of major bleeding (aHR, 0.99; 95% CI, 0.34-2.92) and any bleeding (aHR, 0.74; 95% CI, 0.50-1.09) than warfarin. Apixaban was linked to considerably lower risks of any ischemia (aHR, 0.13; 95% CI, 0.04-0.48) and any bleeding (aHR, 0.53; 95% CI, 0.28-0.99) than warfarin. CONCLUSION: Among patients with AF and AKD, DOACs were linked to a lower risk of ischemic events, and apixaban was linked to a lower risk of any ischemia and any bleeding than warfarin.

Factors Impacting Advance Decision Making and Health Care Agent Appointment among Taiwanese Urban Residents after the Passage of Patient Right to Autonomy Act.

In recent years, advance care planning (ACP) promotion in Taiwan has expanded beyond clinical practice to the broader population. This study aims to investigate people's attitudes toward ACP and to identify factors influencing their signing of advance directives (ADs) and appointment of health care agents (HCAs). METHODS: We identified 2337 ACP participants from consultation records between 2019 and 2020. The relationships among the participants' characteristics, AD completion, and HCA appointment were investigated. RESULTS: Of 2337 cases, 94.1% completed ADs and 87.8% were appointed HCAs. Welfare entitlement (OR = 0.47, p < 0.001), the place ACP progressed (OR = 0.08, p < 0.001), the participation of second-degree relatives (OR = 2.50, p < 0.001), and the intention of not being a family burden (OR = 1.65, p = 0.010) were significantly correlated with AD completion. The probability of appointing HCAs was higher in participants with family caregiving experience (OR = 1.42, p < 0.05), who were single (OR = 1.49, p < 0.05), and who expected a good death with dignity (OR = 1.65, p < 0.01). CONCLUSIONS: Our research shows that adopting ACP discussion in Taiwan is feasible, which encourages ACP conversation and facilitates AD completion. IMPLICATIONS: Male and younger adults may need extra encouragement to discuss ACP matters with their families. LIMITATIONS: due to sampling restrictions, our data were chosen from an urban district to ensure the integrity of the results. Furthermore, interview data could be collected in future research to supplement the quantitative results.

Mutation-Driven S100A8 Overexpression Confers Aberrant Phenotypes in Type 1 CALR-Mutated MPN.

Numerous pathogenic CALR exon 9 mutations have been identified in myeloproliferative neoplasms (MPN), with type 1 (52bp deletion; CALRDEL) and type 2 (5bp insertion; CALRINS) being the most prevalent. Despite the universal pathobiology of MPN driven by various CALR mutants, it is unclear why different CALR mutations result in diverse clinical phenotypes. Through RNA sequencing followed by validation at the protein and mRNA levels, we found that S100A8 was specifically enriched in CALRDEL but not in CALRINS MPN-model cells. The expression of S100a8 could be regulated by STAT3 based on luciferase reporter assay complemented with inhibitor treatment. Pyrosequencing demonstrated relative hypomethylation in two CpG sites within the potential pSTAT3-targeting S100a8 promoter region in CALRDEL cells as compared to CALRINS cells, suggesting that distinct epigenetic alteration could factor into the divergent S100A8 levels in these cells. The functional analysis confirmed that S100A8 non-redundantly contributed to accelerated cellular proliferation and reduced apoptosis in CALRDEL cells. Clinical validation showed significantly enhanced S100A8 expression in CALRDEL-mutated MPN patients compared to CALRINS-mutated cases, and thrombocytosis was less prominent in those with S100A8 upregulation. This study provides indispensable insights into how different CALR mutations discrepantly drive the expression of specific genes that contributes to unique phenotypes in MPN.

Hypoglycemia risk with inappropriate dosing of glucose-lowering drugs in patients with chronic kidney disease: a retrospective cohort study.

The incidence rates and consequences of inappropriate dosing of glucose-lowering drugs remain limited in patients with chronic kidney disease (CKD). A retrospective cohort study was conducted to estimate the frequency of inappropriate dosing of glucose-lowering drugs and to evaluate the subsequent risk of hypoglycemia in outpatients with an estimated glomerular filtration rate (eGFR) of < 50 mL/min/1.73 m2. Outpatient visits were divided according to whether the prescription of glucose-lowering drugs included dose adjustment according to eGFR or not. A total of 89,628 outpatient visits were included, 29.3% of which received inappropriate dosing. The incidence rates of the composite of all hypoglycemia were 76.71 and 48.51 events per 10,000 person-months in the inappropriate dosing group and in appropriate dosing group, respectively. After multivariate adjustment, inappropriate dosing was found to lead to an increased risk of composite of all hypoglycemia (hazard ratio 1.52, 95% confidence interval 1.34, 1.73). In the subgroup analysis, there were no significant changes in the risk of hypoglycemia regardless of renal function (eGFR < 30 vs. 30-50 mL/min/1.73 m2). In conclusion, inappropriate dosing of glucose-lowering drugs in patients with CKD is common and associated with a higher risk of hypoglycemia.

Evaluation of the timing of using direct oral anticoagulants after ischemic stroke for patients with atrial fibrillation.

Background and objective: Patients with atrial fibrillation (AF) are prescribed oral anticoagulants for stroke prevention; however, no evidence indicates that the use of direct oral anticoagulants (DOACs) in the first few days after ischemic stroke (IS) would result in favorable outcomes. This study evaluated the association between the timing of using DOACs after IS and their effectiveness and safety to determine the optimal timing. Methods: In this retrospective cohort study, we reviewed the electronic medical records of Taipei Veterans General Hospital. The 1-year outcomes of patients after DOAC initiation were evaluated. Different initiation time windows were compared (initiation time ≤3 days and >3 days in primary analysis). The primary composite outcome was stroke, transient ischemic attack, systemic embolism, or death due to IS. The primary safety outcome was major bleeding or clinically relevant nonmajor bleeding. The secondary composite outcome was all-cause mortality, thromboembolic event, or acute myocardial infarction/hemorrhagic events. Results: This study included 570 patients. The median initiation time of DOACs after IS in the patients with AF was 14 days. Compared the patients in whom DOACs were initiated after >3 days with those DOACs were initiated after ≤3 days, the adjusted hazard ratios (aHRs) of the primary composite outcome was 0.73 (95% confidence interval [CI]: 0.23-1.79), the aHR of primary safety outcome was 0.87 (95% CI: 0.34-1.90), and the aHR of secondary composite outcome was 0.65 (95% CI: 0.32-1.19). All the results were not statistically significant. In secondary analysis, we tested multiple time points of initiating DOACs. Compared with DOAC initiation after >14 days, the primary composite outcomes in the patients in whom DOACs were initiated ≤3, 4-7, and 8-14 days after IS were the same as the findings of the main analysis. After separating patients into different stroke severity groups, the results were similar to those in the main analysis. Conclusion: No significant association was observed between the timing of using DOACs and ischemic or hemorrhagic outcomes. The findings did not differ among different time points. Although we do not recommend avoiding the initiation of DOACs in the first few days after IS, we should consider that the early initiation of DOACs (≤3 days) would be appropriate only for patients who tend to experience thromboembolic events and have a low risk of bleeding. The optimal timing of initiation still must be confirmed by randomized controlled trials.

HCH6-1, an antagonist of formyl peptide receptor-1, exerts anti-neuroinflammatory and neuroprotective effects in cellular and animal models of Parkinson's disease.

Microglial activation-induced neuroinflammation contributes to onset and progression of sporadic and hereditary Parkinson's disease (PD). Activated microglia secrete pro-inflammatory and neurotoxic IL-1ß, IL-6 and TNF-α, which subsequently promote neurodegeneration. Formyl peptide receptor-1 (FPR1) of CNS microglia functions as pattern recognition receptor and is activated by N-formylated peptides, leading to microglial activation, induction of inflammatory responses and resulting neurotoxicity. In this study, it was hypothesized that FPR1 activation of microglia causes loss of dopaminergic neurons by activating inflammasome and upregulating IL-1ß, IL-6 or TNF-α and that FPR1 antagonist HCH6-1 exerts neuroprotective effect on dopaminergic neurons. FPR1 agonist fMLF induced activation of microglia cells by causing activation of NLRP3 inflammasome and upregulation and secretion of IL-1ß, IL-6 or TNF-α. Conditioned medium (CM) of fMLF-treated microglia cells, which contains neurotoxic IL-1ß, IL-6 and TNF-α, caused apoptotic death of differentiated SH-SY5Y dopaminergic neurons by inducing mitochondrial oxidative stress and activating pro-apoptotic signaling. FPR1 antagonist HCH6-1 prevented fMLF-induced activation of inflammasome and upregulation of pro-inflammatory cytokines in microglia cells. HCH6-1 co-treatment reversed CM of fMLF-treated microglia-induced apoptotic death of dopaminergic neurons. FPR1 antagonist HCH6-1 inhibited rotenone-induced upregulation of microglial marker Iba-1 protein level, cell death of dopaminergic neurons and motor impairment in zebrafish. HCH6-1 ameliorated rotenone-induced microglial activation, upregulation of FPR1 mRNA, activation of NLRP3 inflammasome, cell death of SN dopaminergic neurons and PD motor deficit in mice. Our results suggest that FPR1 antagonist HCH6-1 possesses anti-neuroinflammatory and neuroprotective effects on dopaminergic neurons by inhibiting microglial activation and upregulation of inflammasome activity and pro-inflammatory cytokines.

Potential short-term outcome advantage of low vs. high ligation of inferior mesenteric artery for sigmoid and rectal cancer: propensity score matching analysis.

BACKGROUND: Whether to ligate the inferior mesenteric artery at its root during anterior resection for sigmoid colon or rectal cancer is still under debate. This study compared the surgical outcomes, postoperative recovery, and anastomotic leakage between high and low ligation of the inferior mesenteric artery through a subgroup analysis. METHODS: This was a retrospective analysis of prospectively collected data. All patients who underwent colorectal resection for rectosigmoid cancer between December 2016 and December 2019 were enrolled. According to the surgical ligation level of the inferior mesenteric artery, the patients were categorized into either the high or low ligation group. The investigated population was matched using the propensity score method. RESULTS: Overall, 894 patients with sigmoid or rectal cancer underwent elective anterior resection with high (577 patients) or low (317 patients) ligation of the inferior mesenteric artery. After the propensity score matching, 245 patients in each group were compared. High ligation of the inferior mesenteric artery was associated with higher incidence of anastomotic leakage (14.9% vs. 5.6%, P = 0.041) for mid- to low-rectum tumors and a higher incidence of complications (8.6% vs. 3.3%, P = 0.013) of grades 1-2 according to the Clavien-Dindo classification system. CONCLUSION: Compared with high ligation, low ligation of the inferior mesenteric artery resulted in lower likelihood of morbidity and mortality in rectal and sigmoid cancers. Moreover, low ligation was less likely to result in anastomosis leakage in mid- to low-rectal cancers.

Changes of ECG parameters after BNT162b2 vaccine in the senior high school students.

The purpose of this study is to determine the ECG parameter change and the efficacy of ECG screening for cardiac adverse effect after the second dose of BNT162b2 vaccine in young population. In December 2021, in cooperation with the school vaccination system of Taipei City government, we performed a ECG screening study during the second dose of BNT162b2 vaccines. Serial comparisons of ECGs and questionnaire survey were performed before and after vaccine in four male-predominant senior high schools. Among 7934 eligible students, 4928 (62.1%) were included in the study. The male/female ratio was 4576/352. In total, 763 students (17.1%) had at least one cardiac symptom after the second vaccine dose, mostly chest pain and palpitations. The depolarization and repolarization parameters (QRS duration and QT interval) decreased significantly after the vaccine with increasing heart rate. Abnormal ECGs were obtained in 51 (1.0%) of the students, of which 1 was diagnosed with mild myocarditis and another 4 were judged to have significant arrhythmia. None of the patients needed to be admitted to hospital and all of these symptoms improved spontaneously. Using these five students as a positive outcome, the sensitivity and specificity of this screening method were 100% and 99.1%, respectively.  Conclusion: Cardiac symptoms are common after the second dose of BNT162b2 vaccine, but the incidences of significant arrhythmias and myocarditis are only 0.1%. The serial ECG screening method has high sensitivity and specificity for significant cardiac adverse effect but cost effect needs further discussed. What is Known: • The incidence of cardiac adverse effects was reported to be as high as 1.5 per 10 000 persons after the second dose BNT162b2 COVID-19 vaccine in the young male population based on the reporting system. What is New: • Through this mass ECG screening study after the second dose of BNT162b2 vaccine we found: (1) The depolarization and repolarization parameters (QRS duration and QT interval) decreased significantly after the vaccine with increasing heart rate; (2) the incidence of post-vaccine myocarditis and significant arrhythmia are 0.02% and 0.08%; (3) The serial ECG screening method has high sensitivity and specificity for significant cardiac adverse effect.

Graphene woven fabric-polydimethylsiloxane piezoresistive films for smart multi-stimuli responses.

The outstanding properties of graphene, including its electromechanical property, could be engineered for wearable electronic sensor platforms. The tubular graphene weaved into a mesh or graphene woven fabrics (GWF) has been reported as one of the most sensitive materials for deformation detection, as well as a promising temperature sensor. Herein, we present the performance of our developed flexible, stretchable, and multiple sensitive sensors fabricated from GWF embedded in polydimethylsiloxane (PDMS) film substrate. The GWF/PDMS sensor shows a pressure sensitivity of 0.0142 kPa-1 in a wide linearity range of 0-20 kPa, an outstanding Gauge factor (GF) of 582 at a strain of 6.2 %, and a very high positive sensitivity of 0.0238 °C-1 in the temperature range of 25-80 °C. A practical application as a high sensitivity air pressure sensor able to measure low pressures (in the range of Pa to kPa) was also demonstrated. This sensor platform having desirable performance characteristics is an excellent candidate for wearable devices in the healthcare sector.

A hyaluronic acid granular hydrogel nerve guidance conduit promotes regeneration and functional recovery of injured sciatic nerves in rats.

A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro, suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration. However, in vivo experiments have not been conducted. In this study, we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap. The Basso, Beattie, and Bresnahan locomotor rating scale, sciatic nerve compound muscle action potential recording, Fluoro-Gold retrograde tracing, growth related protein 43/S100 immunofluorescence staining, transmission electron microscopy, gastrocnemius muscle dry/wet weight ratio, and Masson's trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath, and recovery of the electrophysiological function and motor function as autologous nerve transplantation. The conduit results were superior to those of a bulk hydrogel or silicone tube transplant. These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve. The nerve conduits have the potential as a material for repairing peripheral nerve defects.

Letrozole as premedication of high intensity focused ultrasound treatment of uterine fibroids: A retrospective observation study.

Background: No reports on Letrozole as a pretreatment before ablation of uterine fibroid with high intensity focused ultrasound (HIFU), so a retrospective observation study was performed to evaluate the response of different pre-HIFU medication. Methods: We collected patients with single uterine fibroid receiving HIFU ablation from January 2018 to April 2021. All enrolled patients were classified into three group: group A (no pre-HIFU medication use), group B (Pre-HIFU letrozole use), group C (pre-HIFU gonadotrophin releasing hormone analog, GnRHa). Further associated clinical data and treatment response after HIFU treatment were reviewed and evaluated. Results: A total of 39 patients including 21, 7, and 11 in group A, B, and C were collected respectively. After pre-HIFU medication, no difference of fibroid volume was found (A: 251.4, B: 360.6, C: 409.4 cm3, p = 0.250), and GnRHa group had significantly larger volume reduction than Letrozole users (38.6% vs. 16.4%, p = 0.007). The incidence of hypoestrogenic symptoms was higher in GnRHa group than in letrozole users (27.3% vs. 0, p = 0.170). GnRHa group had more sonication time (p = 0.001), treatment duration (p = 0.002), and ablated energy (p = 0.001) than group A and B. The treatment efficiency was higher in letrozole group than that in other 2 groups (4.52 vs. 2.39 vs. 2.34 cm3/min, p = 0.050). For patients with fibroid over 10 cm in diameter, letrozole group had even better energy efficiency (p = 0.067), treatment speed (p = 0.007), treatment efficiency (p = 0.001), NPV per energy (p = 0.005), and NPV per sonication (p = 0.004) than other 2 groups. Conclusion: Letrozole as a pretreatment medication before HIFU treatment might increase the energy efficiency and treatment efficiency of its ablation of uterine leiomyoma, especially for fibroid over 10 cm. Future study of larger patient number is needed to confirm our results.

Arthroscopic cartilage regeneration facilitating procedure: A decompressing arthroplasty for knee osteoarthritis.

The effectiveness of arthroscopic treatment for knee osteoarthritis (OA) has always been a subject of debate. This study presents an innovative concept for the arthroscopic management of knee OA and investigates its clinical outcomes. An arthroscopic cartilage regeneration facilitating procedure (ACRFP) was performed on 693 knees of 411 patients with knee OA, with a mean age of 60 years (34-90 years), to eliminate the medial abrasion phenomenon (MAP) and decompress the patellofemoral joints. The Knee Society Score (KSS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) were used to determine the subjective outcome. Roentgenographic changes in all cases and magnetic resonance imaging (MRI) variations in 20 randomly selected cases were evaluated for objective outcomes. We evaluated 634 knees in 369 patients (93.7%) with more than 3 years of follow-up (mean, 40 months; SD, 9) and found that the overall subjective satisfaction rate was 91.1%. Scores for KSS and all KOOS subscales improved statistically. Reversal of cartilage degeneration was observed in 80.1% of the entire series (radiographic outcome study) and 72.2% of the 18 randomly selected cases (1-year MRI outcome study). We found significant association between gender and OA severity, with regards to the subjective outcomes. Age, body mass index, pre-operative hyaluronic acid injection, OA severity, and type and severity of the medial plica were found to be important predictors of radiographic outcomes. An analysis of failed cases reaffirmed the need for early ACRFP and skilled post-operative care. ACRFP is an effective treatment for knee OA. It can benefit most patients and modify their degeneration processes if performed in time. However, further investigations are needed to confirm our concept of treatment.

Drug-related problem characterization and the solved status associated factor analysis in a pharmacist-managed anticoagulation clinic.

Drug-related problems (DRPs) in a pharmacist-managed anticoagulation clinic (AC) have not been extensively studied. We aimed to characterize the DRPs in a pharmacist-managed AC, identify the factors associated with the solved status of DRPs, and analyze the secondary outcomes, including the safety and efficacy of AC service. The patients receiving services at a pharmacist-managed AC in a medical center for the first time from March 2019 to August 2020 were reviewed retrospectively. The DRPs were retrieved from a self-developed Intelligent AC Service System and classified according to the Pharmaceutical Care Network Europe Foundation v9.0 classification system. Logistic regression models were performed to identify the potential factors associated with the solved status of DRPs. A total of 78 direct oral anticoagulant (DOAC) and 34 warfarin users were included. The major types of DRPs identified at the initial service were adverse drug events (ADEs) (68.4%) and untreated symptoms or indications (14.8%) in the DOAC group, and ADEs (51.6%) and suboptimal effect of drug treatment (38.7%) in the warfarin group. The rates of totally solved DRPs were 56.8% and 51.6% in the DOAC and warfarin groups, respectively. According to the multivariable analysis, receiving AC services 3 times or more in 180 days (OR 3.11, 95% CI 1.30-7.44) was associated with the totally solved status of DRPs in the DOAC group, but no relevant factor was identified in the warfarin group. The secondary outcomes showed that DOAC users demonstrated fewer thromboembolism events, major bleeding, and bleeding-related hospitalizations after AC services, whereas the warfarin users increased percentage time in therapeutic range (TTR% 55.0% vs. 74.6%, P = 0.006) after AC services. These findings may be utilized to develop DOAC and warfarin AC services.

The Genomic Landscape in Philadelphia-Negative Myeloproliferative Neoplasm Patients with Second Cancers.

Patients with myeloproliferative neoplasms (MPNs) are characterized by systemic inflammation. With the indolent nature of the diseases, second cancers (SCs) have emerged as a challenging issue in afflicted patients. Epidemiological studies have confirmed the excessive risk of SCs in MPNs, but little is known about their molecular basis. To explore further, we used whole exome sequencing to explore the genetic changes in the granulocytes of 26 paired MPN patients with or without SC. We noticed that MPN−SC patients harbor genomic variants of distinct genes, among which a unique pattern of co-occurrence or mutual exclusiveness could be identified. We also found that mutated genes in MPN−SC samples were enriched in immune-related pathways and inflammatory networks, an observation further supported by their increased plasma levels of TGF-ß and IL-23. Noteworthily, variants of KRT6A, a gene capable of mediating tumor-associate macrophage activity, were more commonly detected in MPN−SC patients. Analysis through OncodriveCLUST disclosed that KRT6A replaces JAK2V617F as the more prominent disease driver in MPN−SC, whereas a major mutation in this gene (KRT6A c.745T>C) in our patients is linked to human carcinoma and predicted to be pathogenic in COSMIC database. Overall, we demonstrate that inflammation could be indispensable in MPN−SC pathogenesis.