The impact of body mass index on survival endpoints among patients with metastatic urothelial carcinoma undergoing treatment with immune checkpoint inhibitors: A real-world multicenter analysis.

BACKGROUND: Studies on the correlation between high body mass index (BMI) and extended survival among patients receiving immune checkpoint inhibitors (ICIs) have been made, although findings have shown variability. Our research explored the phenomenon of the "obesity paradox" in patients with metastatic urothelial carcinoma (mUC) undergoing treatment with ICIs. MATERIALS AND METHODS: We conducted a retrospective analysis of patients diagnosed with mUC who received a minimum of one cycle of ICI treatment at two medical centers in Taiwan from September 2015 to January 2023. Features of patients' clinicopathologic factors, including age, sex, primary or metastatic location, treatment line, and BMI were examined. The primary outcome were overall survival (OS) and progression-free survival (PFS), which were assessed utilizing the Kaplan-Meier method. We employed the Cox-regression model to adjust for multiple covariates. RESULTS: A total of 215 patients were included, with 128 (59.5%) being male, and the median age was 70 years. In the obese group (BMI ≥25 kg/m2 ), patients demonstrated significantly better median OS compared to the non-obese group (BMI <25 kg/m2 ) (21.9 vs. 8.3 months; p = 0.021). However, there was no significant difference in median PFS between the high and low BMI groups (4.7 vs. 2.8 months; p = 0.16). Post-hoc subgroup revealed a survival benefit from ICI treatment in male patients within the BMI ≥25 kg/m2 group (HR 0.49, 95% CI 0.30-0.81, p = 0.005). CONCLUSION: Based on real-world data from the Asia-Pacific region, there appears to be a correlation between obesity and prolonged OS in patients receiving ICI treatment for mUC.

Real-world efficacy and safety of low-dose pembrolizumab in patients with advanced and refractory gynecologic cancers.

OBJECTIVE: The approved standard dose of pembrolizumab (200 mg administrated every 3 weeks) for cancer treatment imposes a significant financial burden on patients. However, no study has analyzed the clinical outcomes of low-dose pembrolizumab among individuals diagnosed with gynecologic cancer. The primary objective of this study was to assess the effectiveness and safety of a low-dose pembrolizumab regimen in real-world clinical practice. METHODS: We retrospectively assessed the efficacy and safety data of patients with gynecologic malignancies who received pembrolizumab between 2017 and 2022 at Kaohsiung Chang Gung Memorial Hospital. Furthermore, we conducted a comparative analysis of the objective response rate (ORR) and progression-free survival (PFS) between patients with deficient mismatch repair (dMMR) and proficient MMR (pMMR). RESULTS: A total of thirty-nine patients were included and received pembrolizumab at fixed dosages of 50 mg (5.1%), 100 mg (84.6%) and 200 mg (10.3%) per cycle. Compared to the pMMR group, the dMMR group exhibited a tendency toward improved ORR (45.5% vs. 13.0%, p = 0.074), and notably, the median duration of response remained unreached. There was no significant difference in PFS between the dMMR and pMMR groups; however, the patients with dMMR in tumor tissue had a trend of better survival (p = 0.079). Incidence of immune-related adverse events (irAEs) of any grade was observed in 13 patients (33.3%), with 3 individuals (7.7%) experiencing grade 3 or 4 events. CONCLUSION: Low-dose pembrolizumab may be a cost-effective and safe treatment option without compromising clinical outcomes in patients with refractory gynecologic cancers.

The prognostic significance of histologic variant on survival outcomes in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitor therapy.

BACKGROUND: While the treatment guidelines have been established for pure urothelial carcinoma (pUC), patients with variant type urothelial carcinoma (vUC) face limited effective treatment options. The effectiveness of immune checkpoint inhibitors (ICI) in patients with vUC remains uncertain and necessitates additional research. METHOD: We conducted a retrospective, multicenter study to explore the effectiveness of ICI in patients with pUC or vUC in Taiwan. We evaluated the overall response rate (ORR) through univariate logistic regression analysis and examined the overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis. Additionally, we employed univariate and multivariate Cox proportional hazards models to analyze the data. RESULT: A total of 142 patients (116 pUC, 26 vUC) were included in our final analysis. The ORR was marginally higher in patients with pUC compared to those with vUC (34.5% vs. 23.1%, p = 0.26). Among all patients, 12.9% with pUC achieved a complete response (CR) after ICI treatment, while no vUC cases achieved CR (p = 0.05). There were no significant differences in PFS (median 3.6 months vs. 4.1 months, p = 0.34) or OS (median 16.3 months vs. 11.0 months, p = 0.24) when comparing patients with pUC or vUC. In the subgroup analysis, patients with pUC who underwent first-line ICI treatment exhibited significantly improved OS compared to those with vUC (24.6 months vs. 9.1 months, p = 0.004). CONCLUSION: The use of ICI as monotherapy is a feasible and effective treatment approach for patients with metastatic vUC.

Inhibiting WEE1 Augments the Antitumor Efficacy of Cisplatin in Urothelial Carcinoma by Enhancing the DNA Damage Process.

Urothelial carcinoma (UC) is characterized by a high incidence of TP53 mutation, and overcoming resistance to cisplatin-based chemotherapy in UC is a major concern. Wee1 is a G2/M phase regulator that controls the DNA damage response to chemotherapy in TP53-mutant cancers. The combination of Wee1 blockade with cisplatin has shown synergistic efficacy in several types of cancers, but little is known regarding UC. The antitumor efficacy of the Wee1 inhibitor (AZD-1775) alone or in combination with cisplatin was evaluated in UC cell lines and a xenograft mouse model. AZD-1775 enhanced the anticancer activity of cisplatin by increasing cellular apoptosis. AZD-1775 inhibited the G2/M checkpoint, improving the sensitivity of mutant TP53 UC cells to cisplatin by enhancing the DNA damage process. We confirmed that AZD-1775 combined with cisplatin reduced tumor volume and proliferation activity and increased the markers of cell apoptosis and DNA damage in the mouse xenograft model. In summary, the Wee1 inhibitor AZD-1775 combined with cisplatin elicited a promising anticancer efficacy in UC, and constitutes an innovative and promising therapeutic strategy.

In silico repurposing of midostaurin as a therapeutic candidate for head and neck cancer via targeting SPARC/MMP9/CD44 Cancer-Associated Fibroblasts (CAFs) oncogenic signature.

Head and neck squamous carcinoma (HNSCC) affects more than half a million individuals and ranks the ninth leading cause of death globally each year. Many patients develop treatment resistance leading to poor clinical outcomes. The poor treatment responses are in part due to the heterogeneity of HNSCC tumor and tumor microenvironment (TME). The interaction of tumor cells with their TME has been studied vigorously in recent years because of their pivotal roles in tumorigenesis and determining the treatment response. Cancer-associated fibroblasts (CAFs) are one of the most abundant tumor-infiltrating cells, which have been shown to associate with the aggressive behavior of HNSCC. Hence, targeting and disrupting the tumor-CAFs interactions represents a rational therapeutic approach. To develop targeted therapeutic drugs against CAFs, the identification of CAF-associated gene signature is essential. Here, we analyzed multiple sequencing databases including microarrays and single-cell RNA-sequencing databases and identified SPARC/MMP9/CD44 as HNSCC targetable gene signatures encompassing cancer-associated fibroblasts (CAFs). We found SPARC/MMP9CD44 signature was highly expressed in HNSC tissues compared to adjacent normal tissues. Increased SPARC/MMP9/CD44 signature levels strongly correlated with tumor-infiltrating CAFs, suggesting the functional importance of this signature for HNSCC-CAFs interaction and progression. Subsequently, we utilized a genomics approach and identified midostaurin as the top-ranking drug candidate for targeting SPARC/MMP9/CD44 signature. For validation, we performed molecular docking of midostaurin in complex with SPARC/MMP9/CD44 and demonstrated midostaurin's high binding affinities compared to their respective standard inhibitors. In summary, our study provided a rapid genomics approach for identifying targetable gene signature and drug candidate for HNSCC.

First-line Immune Checkpoint Inhibitor Versus Immune Checkpoint Inhibitor With Chemotherapy for Cisplatin-ineligible Metastatic Urothelial Carcinoma: Evidence From a Real-world, Multicenter Analysis.

Immune checkpoint inhibitors (ICIs) are widely used for first-line cisplatin-ineligible patients with metastatic urothelial carcinoma (mUC). However, whether to use ICIs as monotherapy or in combination with chemotherapy is still uncertain. We retrospectively analyzed cisplatin-ineligible patients with mUC who underwent first-line ICI monotherapy or ICI plus chemotherapy at 2 medical centers in Taiwan from 2016 to 2021. We calculated the objective response rate, progression-free survival, and overall survival (OS) using the Kaplan-Meier method and Cox regression model for multivariable analysis. In total, 130 patients were enrolled and categorized into 2 groups: an ICI monotherapy group [immunotherapy (IO), n=101] and an ICI plus noncisplatin chemotherapy group [immunotherapy and chemotherapy (IC), n=29]. The median OS of patients in the IO and IC groups was 19.5 and 9.7 months ( P =0.33). Among patients with high programmed cell death ligand-1-expressing tumors, the median OS was significantly prolonged in the IO group compared with the IC group (not reached vs. 6.3 mo, P =0.02). First-line ICI monotherapy demonstrated robust antitumor activity in cisplatin-ineligible patients with mUC. Combining noncisplatin chemotherapy with ICI did not improve clinical outcomes.

Detection of Amyloid-ß(1-42) Aggregation With a Nanostructured Electrochemical Sandwich Immunoassay Biosensor.

Amyloid-ß(1-42) [Aß(1-42)] oligomer accumulations are associated with physiologic alterations in the brains of individuals with Alzheimer's disease. In this study, we demonstrate that a nanostructured gold electrode with deposited gold nanoparticles, induced via electrochemical impedance spectroscopy (EIS), may be used as an Aß(1-42) conformation biosensor for the detection of Alzheimer's disease. Monoclonal antibodies (12F4) were immobilized on self-assembled monolayers of the electrochemical sandwich immunoassay biosensor to capture Aß(1-42) monomers and oligomers. Western blot and fluorescence microscopy analyses were performed to confirm the presence of Aß(1-42) monomers and oligomers. EIS analysis with an equivalent circuit model was used to determine the concentrations of different Aß(1-42) conformations in this study. We identified conformations of Aß(1-42) monomers and Aß(1-42) oligomers using probe antibodies (12F4) by employing EIS. R Aß ( 1 - 42 ) indicates the sum resistance of impedance measured during Aß(1-42) immobilization. Δ R 12 F 4 refers to the concentration of probe antibody (12F4) binding with Aß(1-42). The concentration of Aß(1-42) oligomer was defined as the percentage of Aß(1-42) aggregation R 12 F 4 / R Aß ( 1 - 42 ) . The experimental results show that the biosensor has high selectivity to differentiate Aß(1-40) and Aß(1-42) monomers and Aß(1-42) oligomers and that it can detect Aß(1-42) oligomer accurately. The linear detection range for Aß(1-42) oligomers was between 10 pg/ml and 100 ng/ml. The limit of detection was estimated to be 113 fg/ml.

Antifungal Sesquiterpenoids from Michelia formosana Leaf Essential Oil against Wood-Rotting Fungi.

Michelia formosana (Kanehira) Masamune is a broad-leaved species widespread in East Asia; the wood extract and its constituents possess antifungal activity against wood-decay fungi. Antifungal activities of leaf essential oil and its constituents from M. formosana were investigated in the present study. Bioassay-guided isolation was applied to isolate the phytochemicals from leaf essential oil. 1D and 2D NMR, FTIR, and MS spectroscopic analyses were applied to elucidate the chemical structures of isolated compounds. Leaf essential oil displayed antifungal activity against wood decay fungi and was further separated into 11 fractions by column chromatography. Four sesquiterpenoids were isolated and identified from the active fractions of leaf essential oil through bioassay-guided isolation. Among these sesquiterpenoids, guaiol, bulnesol, and ß-elemol have higher antifungal activity against brown-rot fungus Laetiporus sulphureus and white-rot fungus Lenzites betulina. Leaf essential oil and active compounds showed better antifungal activity against L. sulphureus than against L. betulina. The molecular structure of active sesquiterpenoids all contain the hydroxyisopropyl group. Antifungal sesquiterpenoids from M. formosana leaf essential oil show potential as natural fungicides for decay control of lignocellulosic materials.

An Electromechanical Model for Clamped-Edge Bimorph Disk Type Piezoelectric Transformer Utilizing Kirchhoff Thin Plate Theory.

In this paper, an analytical solution for a clamped-edge bimorph disk-type piezoelectric transformer with Kirchhoff thin plate theory is proposed. The electromechanical equations for transient motions are first derived, and coupled expressions for mechanical response and voltage output are obtained. For the case of excitation around the first resonant frequency, the resulting equations are further simplified. There are analytical solutions for a mechanical response, voltage, current, and power outputs. According to the analytical model, the output voltage is affected by the inner radius of the input and output electrodes, the radius of the piezoelectric transformer (PT), and the thickness ratio between the lead zirconate titanate (PZT) layer and the substrate. When the inner radius of the input electrode approaches zero (electrode becomes circular shape), it achieves maximum output voltage at the first resonance frequency excitation. On the contrary, when the inner radius of the output electrode approaches zero, the output voltage reaches its minimum value. Voltage ratios remain constant as the disk radius changes, and the first resonance frequency is inversely proportional to the square of the disk radius. The voltage ratio is fixed even with the miniaturization of the PT.

Saliva-based COVID-19 detection: A rapid antigen test of SARS-CoV-2 nucleocapsid protein using an electrical-double-layer gated field-effect transistor-based biosensing system.

Facing the unstopped surges of COVID-19, an insufficient capacity of diagnostic testing jeopardizes the control of disease spread. Due to a centralized setting and a long turnaround, real-time reverse transcription polymerase chain reaction (real-time RT-PCR), the gold standard of viral detection, has fallen short in timely reflecting the epidemic status quo during an urgent outbreak. As such, a rapid screening tool is necessitated to help contain the spread of COVID-19 amid the countries where the vaccine implementations have not been widely deployed. In this work, we propose a saliva-based COVID-19 antigen test using the electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET). The detection of SARS-CoV-2 nucleocapsid (N) protein is validated with limits of detection (LoDs) of 0.34 ng/mL (7.44 pM) and 0.14 ng/mL (2.96 pM) in 1× PBS and artificial saliva, respectively. The specificity is inspected with types of antigens, exhibiting low cross-reactivity among MERS-CoV, Influenza A virus, and Influenza B virus. This portable system is embedded with Bluetooth communication and user-friendly interfaces that are fully compatible with digital health, feasibly leading to an on-site turnaround, an effective management, and a proactive response taken by medical providers and frontline health workers.

Peptide-based electrochemical sensor with nanogold enhancement for detecting rheumatoid arthritis.

Rheumatoid arthritis (RA), an autoimmune and chronic inflammatory disorder, is an incurable disease. We developed a peptide-based electrochemical sensor using electrochemical impedance spectroscopy that can be used to detect autoantibodies for RA diagnostics. We first validated that the developed peptide showed high sensitivity and could compliment the current gold standard method of an anti-cyclic citrullinated peptide antibody (anti-CCP) ELISA. The developed peptide can be modified on the nanogold surface of the working electrode of sensing chips through the method of a self-assembling monolayer. The sensing process was first optimized using a positive control cohort and a healthy control cohort. Subsequently, 10 clinically confirmed samples from RA patients and five healthy control samples were used to find the threshold value of the impedance between RA and healthy subjects. Furthermore, 10 clinically confirmed samples but with low values of anti-CCP autoantibodies were used to evaluate the sensitivity of the present method compared to the conventional method. The proposed method showed better sensitivity than the current conventional anti-CCP ELISA method.

Development and Validation of a Novel Serum Prognostic Marker for Patients with Metastatic Colorectal Cancer on Regorafenib Treatment.

(1) Background: To investigate the prognostic value of cancer-inflammation prognostic index (CIPI) in patients with metastatic colorectal cancer (mCRC) on regorafenib treatment; (2) Methods: Patients with mCRC who were given regorafenib as later-line treatment at Kaohsiung and Linkou Chang-Gung Memorial Hospital between November 2014 and January 2021 were consecutively enrolled. All relevant clinicopathologic, laboratory data and survival status were recorded. Independent prognostic factors were determined by the multivariate Cox regression method; (3) Results: In total, 106 patients in the training cohort and 250 in the validation cohort were enrolled. The median OS for patients with CIPI ≥ 300 and < 300 in the training cohort was 3.8 and 9.0 months, respectively (hazard ratio (HR) 2.78, 95% confidence interval (CI) 1.82-4.23; p < 0.0001). Time to regorafenib, liver metastasis and CIPI were independent factors by multivariate Cox regression analyses. A new scoring model demonstrated a good discriminatory ability to risk stratification of a patient's survival; (4) Conclusions: We identified CIPI as a novel serum marker highly associated with overall survival in patients with mCRC receiving regorafenib treatment. Further confirmatory studies are warranted.

Machine-Based Hand Massage Ameliorates Preoperative Anxiety in Patients Awaiting Ambulatory Surgery.

BACKGROUND: Hand massage therapies have been used to relieve anxiety and pain in various clinical situations. The effects of machine-based hand massage on preoperative anxiety in ambulatory surgery settings have not been evaluated. PURPOSE: This prospective study was designed to investigate the effect of machine-based hand massage on preoperative anxiety and vital signs in ambulatory surgery patients. METHODS: One hundred ninety-nine patients aged 18 years and older who were scheduled to receive ambulatory surgery were recruited from the Taipei Municipal Wanfang Hospital in Taipei City, Taiwan. The patients were assigned randomly to the experimental group (n = 101), which received presurgical machine-based hand massage therapy, and the control group (n = 98), which received no intervention. The patients in both groups completed the Spielberger State-Trait Anxiety Inventory short form at preintervention (baseline) and postintervention. RESULTS: Within-group comparisons of Spielberger State-Trait Anxiety Inventory short form scores showed significant decreases between preintervention and postintervention scores in the experimental group (44.3 ± 11.2 to 37.9 ± 8.7) and no significant change in the control group. Within-group comparisons of vital signs revealed a significant increase in mean respiration rate between baseline and postintervention in both groups (both ps < .05). Blood pressure was found to have decreased significantly only in the control group at postintervention (p < .05). No significant preintervention to postintervention change in pulse was observed in either group. CONCLUSIONS: The findings of this study indicate that machine-based hand massage reduces anxiety significantly in patients awaiting ambulatory surgery while not significantly affecting their vital signs.

Safety and Efficacy of Immune Checkpoint Inhibitors for Patients With Metastatic Urothelial Carcinoma and End-Stage Renal Disease: Experiences From Real-World Practice.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are used widely for treating metastatic urothelial carcinoma (mUC). In practical settings, evidence is lacking on the efficacy of ICIs in some difficult-to-treat patients, such as those with end-stage renal disease (ESRD). Herein, we evaluate the safety and efficacy of ICIs for patients with mUC and ESRD. METHODS: For this retrospective study, patients with mUC who were given ICIs at Kaohsiung Chang Gang Memorial Hospital and Linkou Chang Gung Memorial Hospital between April 2016 and November 2019 were consecutively enrolled. All clinicopathologic data, treatment responses, and adverse events were recorded. The immune-related adverse events (AEs), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between ESRD and non-ESRD groups. RESULTS: In total, 129 patients with mUC were enrolled, with 11 patients categorized as the ESRD group. Among these patients with ESRD receiving ICIs, 7 of 11 (63.6%) had high-grade (grade ≥3) AEs, chiefly hematologic toxicity. Some rarely encountered AEs were noted, including toxic epidermal necrolysis, tuberculosis reactivation, ascites, and cytokine release syndrome. Patients in the ESRD group had numerically higher ORR (54.5% vs. 28.8%, p = 0.09), PFS (7.1 vs. 3.5 months, p = 0.42), and OS (not reached vs. 15.4 months) than the non-ESRD group. A multivariate Cox regression model demonstrated that leukocytosis (hazard ratio [HR]: 2.63; 95% confidence interval [CI]: 1.23-5.63; p = 0.01) and neutrophil-to-lymphocyte ratio (HR 2.91; 95% CI: 1.30-6.53; p = 0.01) were independent prognostic factors. CONCLUSION: Administration of ICIs in patients with mUC and ESRD demonstrated a modest antitumor activity, and should be used with caution for increasing risk of hematologic toxicity.

Effect of infiltrating nasal packing with local anesthetics in postoperative pain and anxiety following sinonasal surgeries: a systemic review and meta-analysis / Efeito do tamponamento nasal infiltrado com anestésicos locais na dor e ansiedade pós-operatórias após cirurgias nasosinusais: revisão sistêmica e metanálise

Abstract Introduction: Packing of the nasal cavity has traditionally been used for postoperative bleeding control and decreasing synechia formation in patients undergoing nasal surgeries. Although absorbable nasal packing has been gaining popularity in the recent years, nonabsorbable nasal packing is still often used in nasal surgeries in various parts of the world. It is known to be associated with pain and discomfort especially upon and during removal, and previous reviews have only evaluated the effects of local anesthetic infiltration of nasal packing in septal surgeries. Objective: To evaluate the effect of infiltrating nasal packing with local anesthetics in postoperative pain and anxiety following sinonasal surgeries Materials and methods: We searched the PubMed and Embase databases from their earliest record to April 27, 2019, randomized controlled trials and prospective controlled trials for review, and included only randomized controlled trials for data analysis. We included studies using topical anesthetics-infiltrated nasal packing following sinonasal surgeries and evaluated the effectiveness compared to placebo packing in pain reduction during postoperative follow up, as well as the effectiveness in anxiety reduction. Results: Among 15 studies included for review, 9 studies involving 765 participants contributed to the meta-analysis. In terms of pain reduction, our analysis showed significant standard mean differences regarding effectiveness at postoperative 1, 12, 24 h interval for all surgical groups combined, in the sinus surgery group, as well as during nasal packing removal. There was no consistent evidence to support the effectiveness in anxiety reduction. Conclusions: Our study supports anesthetics infiltration of nasal packing as an effective method in managing pain in patients with nasal packing after sinonasal surgeries. However, the level of evidence is low. More high-quality randomized controlled trials are needed to establish its effectiveness in reducing anxiety. We believe this review is of great clinical significance due to the vast patient population undergoing sinonasal surgeries. Postoperative local hemorrhage remains the greatest concern for ear nose and throat surgeons due to the rich vasculature of the nose and sinuses. Sinonasal packing provides structural support and serves as an important measure for hemostasis and synechia formation. Although absorbable packing has been gaining popularity in the recent years, nonabsorable packing materials are still used in many countries due to lower cost. Infiltration of nasal packing with local anesthetic provides a solution to the discomfort, nasal pressure and nasal pain experienced commonly by the patients as evidenced by our analysis.

Resumo Introdução: O tamponamento da cavidade nasal tem sido usado tradicionalmente para controle do sangramento pós-operatório e diminuição da formação de sinéquia em pacientes submetidos a cirurgias nasais. Embora o tamponamento nasal absorvível tenha ganhado popularidade nos últimos anos, o tampão nasal não absorvível ainda é frequentemente usado em várias partes do mundo. Sabe-se que o tamponamento está associado a dor e desconforto, especialmente na sua remoção, e revisões anteriores avaliaram apenas os efeitos do tampão com anestésico local em cirurgias do septo nasal. Objetivo: Avaliar o efeito do tamponamento nasal infiltrado com anestésicos locais na dor e ansiedade pós-operatórias após cirurgias nasosinusais. Material e métodos: Para a revisão, pesquisamos nos bancos de dados PubMed e Embase desde o registro mais antigo até 27 de abril de 2019, incluímos ensaios clínicos controlados e randomizados, a ensaios clínicos prospectivos controlados e apenas ensaios clínicos controlados e randomizados para análise de dados. Incluímos estudos que usaram tamponamento nasal infiltrado com anestésicos tópicos após cirurgias nasosinusais e avaliamos a eficácia em comparação com o tamponamento com placebo na redução da dor durante o acompanhamento pós-operatório, bem como os efeitos na redução da ansiedade. Resultados: Entre os 15 estudos incluídos, 9, que envolveram 765 participantes, contribuíram para a metanálise. Em termos de redução da dor, nossa análise mostrou diferenças médias padrão significantes em relação à eficácia no pós-operatório nos intervalos de 1, 12, 24 horas para todos os grupos cirúrgicos combinados, no grupo da cirurgia sinusal e durante a remoção do tamponamento nasal. Não houve evidências consistentes para apoiar a eficácia na redução da ansiedade. Conclusões: Nosso estudo apoia o uso de tamponamentos nasais infiltrados com anestésicos locais como um método eficaz no tratamento da dor em pacientes após cirurgias nasosinusais. No entanto, o nível de evidência é baixo. São necessários mais ensaios clínicos randomizados de alta qualidade para estabelecer sua eficácia na redução da ansiedade. Acreditamos que esta revisão seja de grande significado clínico devido à vasta população submetida a cirurgias nasosinusais. A hemorragia local pós-operatória continua a ser a maior preocupação para os cirurgiões otorrinolaringológicos devido à rica vasculatura do nariz e seios nasais. O tamponamento nasosinusal fornece suporte estrutural e serve como uma medida importante para a hemostasia e formação de sinéquias. Embora o tamponamento absorvível tenha ganhado popularidade nos últimos anos, os materiais de tamponamento não absorvíveis ainda são usados em muitos países devido ao menor custo. A infiltração do tamponamento nasal com anestésicos locais fornece uma solução para desconforto, pressão e dor nasal comumente referida pelos pacientes, como evidenciado por nossa análise.

Effect of infiltrating nasal packing with local anesthetics in postoperative pain and anxiety following sinonasal surgeries: a systemic review and meta-analysis.

INTRODUCTION: Packing of the nasal cavity has traditionally been used for postoperative bleeding control and decreasing synechia formation in patients undergoing nasal surgeries. Although absorbable nasal packing has been gaining popularity in the recent years, nonabsorbable nasal packing is still often used in nasal surgeries in various parts of the world. It is known to be associated with pain and discomfort especially upon and during removal, and previous reviews have only evaluated the effects of local anesthetic infiltration of nasal packing in septal surgeries. OBJECTIVE: To evaluate the effect of infiltrating nasal packing with local anesthetics in postoperative pain and anxiety following sinonasal surgeries MATERIALS AND METHODS: We searched the PubMed and Embase databases from their earliest record to April 27, 2019, randomized controlled trials and prospective controlled trials for review, and included only randomized controlled trials for data analysis. We included studies using topical anesthetics-infiltrated nasal packing following sinonasal surgeries and evaluated the effectiveness compared to placebo packing in pain reduction during postoperative follow up, as well as the effectiveness in anxiety reduction. RESULTS: Among 15 studies included for review, 9 studies involving 765 participants contributed to the meta-analysis. In terms of pain reduction, our analysis showed significant standard mean differences regarding effectiveness at postoperative 1, 12, 24 h interval for all surgical groups combined, in the sinus surgery group, as well as during nasal packing removal. There was no consistent evidence to support the effectiveness in anxiety reduction. CONCLUSIONS: Our study supports anesthetics infiltration of nasal packing as an effective method in managing pain in patients with nasal packing after sinonasal surgeries. However, the level of evidence is low. More high-quality randomized controlled trials are needed to establish its effectiveness in reducing anxiety. We believe this review is of great clinical significance due to the vast patient population undergoing sinonasal surgeries. Postoperative local hemorrhage remains the greatest concern for ear nose and throat surgeons due to the rich vasculature of the nose and sinuses. Sinonasal packing provides structural support and serves as an important measure for hemostasis and synechia formation. Although absorbable packing has been gaining popularity in the recent years, nonabsorable packing materials are still used in many countries due to lower cost. Infiltration of nasal packing with local anesthetic provides a solution to the discomfort, nasal pressure and nasal pain experienced commonly by the patients as evidenced by our analysis.

A Piezoelectric Wave-Energy Converter Equipped with a Geared-Linkage-Based Frequency Up-Conversion Mechanism.

In this paper, a piezoelectric wave-energy converter (PWEC), consisting of a buoy, a frequency up-conversion mechanism, and a piezoelectric power-generator component, is developed. The frequency up-conversion mechanism consists of a gear train and geared-linkage mechanism, which converted lower frequencies of wave motion into higher frequencies of mechanical motion. The slider had a six-period displacement compared to the wave motion and was used to excite the piezoelectric power-generation component. Therefore, the operating frequency of the piezoelectric power-generation component was six times the frequency of the wave motion. The developed, flexible piezoelectric composite films of the generator component were used to generate electrical voltage. The piezoelectric film was composed of a copper/nickel foil as the substrate, lead-zirconium-titanium (PZT) material as the piezoelectric layer, and silver material as an upper-electrode layer. The sol-gel process was used to fabricate the PZT layer. The developed PWEC was tested in the wave flume at the Tainan Hydraulics Laboratory, Taiwan (THL). The maximum height and the minimum period were set to 100 mm and 1 s, respectively. The maximum voltage of the measured value was 2.8 V. The root-mean-square (RMS) voltage was 824 mV, which was measured through connection to an external 495 kΩ resistive load. The average electric power was 1.37 µW.

Comparative Study of the Safety and Efficacy of First-Line Cisplatin and Carboplatin Chemotherapy in Elderly Patients with Metastatic Urothelial Carcinoma.

OBJECTIVES: Platinum-based chemotherapy is the standard treatment for metastatic urothelial carcinoma (mUC). However, considering elderly patients often experience comorbidities and frailty, the utility of cisplatin-based chemotherapy for elderly patients is still debatable. We conducted this study to compare the safety and efficacy of carboplatin and cisplatin in elderly patients with mUC. METHODS: This retrospective study enrolled elderly patients with mUC (defined as aged ≥70 years) who underwent first-line platinum-based chemotherapy between September 2001 and October 2018. The primary endpoints were chemotherapy-related adverse events (AEs), including treatment-related hospitalization or death. The secondary outcomes were overall survival (OS) and progression-free survival calculated by Kaplan-Meier analysis. RESULTS: In total, 108 elderly patients with mUC were enrolled and allocated into the cisplatin or carboplatin group. Patients treated with carboplatin-based chemotherapy had a significantly higher incidence of all grade ≥3 AEs (78.8 vs. 50.0%, p = 0.008) than those on cisplatin. AE-related hospitalization (47.5 vs. 19.1%, p = 0.002) and treatment-related death (17.5 vs. 4.4%, p = 0.02) were significantly increased in the carboplatin group. In the univariate analysis, the median OS in the cisplatin group was significantly increased compared with the carboplatin group (13.6 vs. 7.2 months, p = 0.045). The Cox multivariate regression model indicated that leukocytosis (HR 3.17, 95% CI 1.84-5.46, p < 0.001) and anemia (HR 2.02, 95% CI 1.11-3.65, p = 0.02) were independent prognostic factors. CONCLUSION: Elderly patients with mUC treated with cisplatin-based chemotherapy had better survival and safety profiles than those treated with carboplatin. Age itself was not a crucial factor in determining cisplatin eligibility.

Presence of Chronic Obstructive Pulmonary Disease (COPD) Impair Survival in Lung Cancer Patients Receiving Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI): A Nationwide, Population-Based Cohort Study.

The emergence of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) caused a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). Although several clinicopathologic factors to predict the response to and survival on EGFR-TKI were recognized, its efficacy has not been confirmed for patients with underlying pulmonary disease, such as chronic obstructive pulmonary disease (COPD). We conducted the study to evaluate the impact of COPD on survival for NSCLC patients that underwent EGFR-TKI treatment. The nationwide study obtained clinicopathologic data from the National Health Insurance Research Database in Taiwan between 1995 and 2013. Patients receiving EGRR-TKI were divided into COPD and non-COPD groups, and adjusted for age, sex, comorbidities, premium level and cancer treatments. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier analysis. In total, 21,026 NSCLC patients were enrolled, of which 47.6% had COPD. After propensity score (PS) matching, all covariates were adjusted and balanced except for age (p < 0.001). In the survival analysis, the median OS (2.04 vs. 2.28 years, p < 0.001) and PFS (0.62 vs. 0.69 years, p < 0.001) of lung cancer with COPD were significantly worse than those without COPD. Lung cancer patients on EGFR-TKI treatment had a worse survival outcome if patients had pre-existing COPD.