Using cryoprobes of different sizes combined with cone-beam computed tomography-derived augmented fluoroscopy and endobronchial ultrasound to diagnose peripheral pulmonary lesions: a propensity-matched study.

BACKGROUND: Endobronchial ultrasound (EBUS) and cone-beam computed tomography-derived augmented fluoroscopy (CBCT-AF) are utilized for the diagnosis of peripheral pulmonary lesions (PPLs). Combining them with transbronchial cryobiopsy (TBC) can provide sufficient tissue for genetic analysis. However, cryoprobes of different sizes have varying degrees of flexibility, which can affect their ability to access the target bronchus and potentially impact the accuracy. The aim of this study was to compare the diagnostic efficacy of cryoprobes of varying sizes in CBCT-AF and EBUS for the diagnosis of PPLs. METHODS: Patients who underwent endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) and TBC combined with CBCT-AF for PPLs diagnosis between January 2021 and May 2022 were included. Propensity score matching and competing-risks regression were utilized for data analysis. Primary outcome was the diagnostic accuracy of TBC. RESULTS: A total of 284 patients underwent TBC, with 172 using a 1.7-mm cryoprobe (1.7 group) and 112 using a 1.1-mm cryoprobe (1.1 group). Finally, we included 99 paired patients following propensity score matching. The diagnostic accuracy of TBC was higher in the 1.1 group (80.8% vs. 69.7%, P = 0.050), with a similar rate of complications. Subgroup analysis also revealed that the 1.1 group had better accuracy when PPLs were located in the upper lobe (85.2% vs. 66.1%, P = 0.020), when PPLs were smaller than 20 mm (78.8% vs. 48.8%, P = 0.008), and when intra-procedural CBCT was needed to be used (79.5% vs. 42.3%, P = 0.001). TBC obtained larger specimens than TBB in both groups. There is still a trend of larger sample size obtained in the 1.7 group, but there is no statistically different between our two study groups (40.8 mm2 vs. 22.0 mm2, P = 0.283). CONCLUSIONS: The combination of TBC with CBCT-AF and EBUS is effective in diagnosing PPLs, and a thin cryoprobe is preferred when the PPLs located in difficult areas.

Impact of coronavirus disease 2019 (COVID-19) on antimicrobial resistance among major pathogens causing healthcare-associated infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused great impact on healthcare systems, including antibiotic usage and multi-drug resistant (MDR) bacterial infections at hospitals. We aim to investigate the trends of antimicrobial resistance among the major pathogens causing healthcare-associated infection (HAI) at intensive care units (ICU). MATERIAL AND METHODS: The demographic characteristics of hospitalization, usage of antimicrobial agents, counted by half-an-year DID (defined daily dose per 1000 patient-days), and HAI density of five major MDR bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), of ICU patients at a medical center in Taiwan during January 2017 to December 2021 were collected and analyzed. RESULTS: The total antibiotic usage, counted by DID, had a significant increasing trend, before COVID-19 occurrence in 2017-2019, but no further increase during the pandemic period in 2020-2021. However, comparing the two time periods, antibiotics consumption was significantly increased during pandemic period. There was no significant change of HAI density in MRSA, VRE, CRAB, CRKP, and CRPA, comparing the pandemic to the pre-pandemic period. Although, CRKP and CRPA infection rates were increasing during the pre-pandemic period, there was no further increase of CRKP and CRPA HAI rates during the pandemic period. CONCLUSION: During COVID-19 pandemic, there was no significant increase in HAI density of five major MDR bacteria at ICU in Taiwan, despite increased antibiotic usage. Strict infection prevention measures for COVID-19 precautions and sustained antimicrobial stewardship probably bring these effects.

Impact of Telemedicine on Blood Glucose Control and Ophthalmic Screenings for Patients with Diabetes in Remote Areas During the COVID-19 Pandemic: A Real-World Study in Northern Taiwan.

Introduction: The purpose of this study was to assess the impact of telemedicine on ophthalmic screening and blood glucose control for patients with diabetes in remote areas of Northern Taiwan during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Telemedicine was implemented in Shiding and Wanli Districts using a 5G platform from April 2021 to December 2022. Patients with poorly controlled diabetes received real-time consultations from endocrinologists at Far Eastern Memorial Hospital, 50 km away, for medication adjustment, diet control, and lifestyle recommendations. The study also provided cloud-upload blood glucose meters for self-monitoring and regular medical advice from hospital nurses. Ophthalmic screenings included fundus imaging, external eye image, and intraocular pressure measurement, with instant communication and diagnosis by ophthalmologists through telemedicine. A satisfaction questionnaire survey was conducted. Results: The study enrolled 196 patients with diabetes. Blood glucose and glycosylated hemoglobin levels were significantly reduced after applying telemedicine (p = 0.01 and p = 0.005, respectively). Ophthalmic screenings led to hospital referrals for 16.0% with abnormal fundus images, 15.6% with severe cataract or anterior segment disorders, and 27.9% with ocular hypertension or glaucoma. Fundus screening rates remained high at 86.3% and 80.4% in 2022, mainly using telemedicine, comparable with the traditional screening rate in the past 5 years. The overall satisfaction rate was 98.5%. Conclusions: Telemedicine showed effectiveness and high satisfaction in managing diabetes and conducting ophthalmic screenings in remote areas during the COVID-19 pandemic. It facilitated early diagnosis and treatment of ocular conditions while maintaining good blood glucose control and fundus screening rates.

Using the deformity index of vital structures to predict outcome of patients with large vestibular schwannomas after Gamma Knife radiosurgery.

PURPOSE: Microsurgery is the mainstay of treatment for large vestibular schwannomas (VS), but the benefits of radiosurgery remain incompletely defined. Here, we aim to use automated volumetric analysis software to quantify the degree of brain stem deformity to predict long-term outcomes of patients with large VS following GKRS. METHODS: Between 2003 and 2020, 39 patients with large VS (volume > 8 cc) undergoing GKRS with a margin dose of 10-12 Gy were analyzed. The reconstruction 3D MRI was used to evaluate the extent of deformity for predicting the long-term outcome of patients. RESULTS: Their mean tumor volume was 13.7 ± 6.3 cc, and their mean follow-up after GKRS was 86.7 ± 65.3 months. Favorable clinical outcome was observed in 26 (66.7%) patients, while 13 (33.3%) patients had treatment failure. Patients with small tumor volumes, low vital structure deformity indice [(TV/(BSV + CerV) and (TV + EV)/(BSV + CerV)], and long distance of tumor to the central line were more likely to have favorable clinical outcome after GKRS. Significant prognostic value was with tumor shrinkage ratio (< 50%) were CV, CV/TV, TV/CerV, (TV + EV)/(BSV + CerV), and the distance of tumor to the central line. In cox regression, favorable clinical outcome was correlated with the Charlson comorbidity index and cochlear dosage (both p < 0.05). In multivariant analysis, tumor regression was highly correlated with the CV/TV ratio (p < 0.001). CONCLUSIONS: The brainstem deformity ratio is likely a useful index to assess the clinical and tumor regression outcomes. Clinical outcomes are multifactorial and the tumor regression was highly correlated with the ratio of cystic components.

MOAP-1-mediated dissociation of p62/SQSTM1 bodies releases Keap1 and suppresses Nrf2 signaling.

Nrf2 signaling is vital for protecting cells against oxidative stress. However, its hyperactivation is frequently found in liver cancer through excessive build-up of p62/SQSTM1 bodies that sequester Keap1, an adaptor of the E3-ubiquitin ligase complex for Nrf2. Here, we report that the Bax-binding protein MOAP-1 regulates p62-Keap1-Nrf2 signaling through disruption of p62 bodies. Upon induction of cellular stresses that stimulate formation of p62 bodies, MOAP-1 is recruited to p62 bodies and reduces their levels independent of the autophagy pathway. MOAP-1 interacts with the PB1-ZZ domains of p62 and interferes with its self-oligomerization and liquid-liquid phase separation, thereby disassembling the p62 bodies. Loss of MOAP-1 can lead to marked upregulation of p62 bodies, enhanced sequestration of Keap1 by p62 and hyperactivation of Nrf2 antioxidant target genes. MOAP-1-deficient mice exhibit an elevated tumor burden with excessive levels of p62 bodies and Nrf2 signaling in a diethylnitrosamine (DEN)-induced hepatocarcinogenesis model. Together, our data define MOAP-1 as a negative regulator of Nrf2 signaling via dissociation of p62 bodies.

Cone-beam computed tomography image-guided percutaneous microwave ablation for lung nodules in a hybrid operating room: an initial experience.

OBJECTIVES: The experience of thermal ablation of lung lesions is limited, especially performing the procedure under localisation by cone-beam CT in the hybrid operation room (HOR). Here, we present the experience of microwave ablation (MWA) of lung nodules in the HOR. METHODS: We reviewed patients who underwent image-guide percutaneous MWA for lung nodules in the HOR under general anaesthesia between July 2020 and July 2022. The workflow in the HOR including the pre-procedure preparation, anaesthesia consideration, operation methods, and postoperative care was clearly described. RESULTS: Forty lesions in 33 patients who underwent MWA under general anaesthesia (GA) in the HOR were analysed. Twenty-seven patients had a single pulmonary nodule, and the remaining six patients had multiple nodules. The median procedure time was 41.0 min, and the median ablation time per lesion was 6.75 min. The median global operation room time was 115.0 min. The median total dose area product was 14881 µGym2. The median ablation volume was 111.6 cm3. All patients were discharged from the hospital with a median postoperative stay of 1 day. Four patients had pneumothorax, two patients had pleural effusion during the first month of outpatient follow-up, and one patient reported intercostal neuralgia during the 3-month follow-up. CONCLUSIONS: Thermal ablation of pulmonary nodules under GA in the HOR can be performed safely and efficiently if we follow the workflow provided. The procedure provides an alternative to managing pulmonary nodules in patients. CLINICAL RELEVANCE STATEMENT: Thermal ablation of pulmonary nodules under GA in the HOR can be performed safely and efficiently if the provided workflow is followed. KEY POINTS: • We tested the feasibility of microwave ablation of lung lesions performed in a hybrid operating room. • To this end, we provide a description of microwave ablation of the lung under cone-beam CT localisation. • We describe a workflow by which ablation of the pulmonary nodule can be performed safely under general anaesthesia.

Lung adenocarcinoma with neuroendocrine differentiation: Molecular markers testing and treatment outcomes.

BACKGROUND: Among the histologic types of lung cancer, adenocarcinoma is the most common. Moreover, lung adenocarcinoma with neuroendocrine differentiation (LANED) is a rare histologic character. So far, the clinical significance remains unclear. MATERIAL AND METHODS: We searched for the patients diagnosed with LANED from the electronic pathology database between January 2000 and June 2020 in a tertiary hospital. The tumor specimens were reviewed by a pathologist to confirm the diagnosis. EGFR mutation, ALK translocation, as well as programmed death ligand 1 (PD-L1) and rearranged during transfection (RET) expression were tested in the specimens of LANED. The clinical data were also collected and analyzed. RESULTS: A total of 10 patients diagnosed with LANED were included. Most were male (80%) and ever smokers (70%). The median age was 71.5 years old. At diagnosis, most had tumors harboring no EGFR mutation (70%), negative ALK translocation (88.9%), and without PD-L1 expression (90%). All specimens tested by immunohistochemical staining for RET expression (n = 9) showed positive results. Among the 10 patients, five underwent operation (stage I, n = 4; stage II, n = 1). The patient with stage II disease had recurrence 11 months later. For patients with advanced stages (stage III, n = 1; stage IV, n = 4), the treatment modalities varied and the overall survival ranged from 11.0 to 46.7 months. CONCLUSION: LANED might be associated with a high proportion of RET expression, whereas EGFR mutation, ALK alteration, and PD-L1 expression were uncommon. Further large-scale prospective studies on molecular testing profile and clinical significance of LANED are warranted.

SARS-CoV-2 infection among healthcare workers whom already received booster vaccination during epidemic outbreak of omicron variant in Taiwan.

BACKGROUND/PURPOSE: Healthcare workers (HCWs) are at risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to occupational exposure. We aim to investigate the prevalence and risk factors of SARS-CoV-2 infection among HCWs during epidemic outbreak of omicron variant in Taiwan. METHODS: Sequential reserved serum samples collected from our previous study during December 2021 and July 2022 were tested for antibodies against SARS-CoV-2 nucleocapsid protein (NP). Diagnosis of SARS-CoV-2 infection was defined as positive either of anti-SARS-CoV-2 nucleoprotein, rapid antigen test or polymerase chain reaction. Retrospective chart review and a questionnaire were used to access the symptoms and risk factors for SARS-CoV-2 infection. RESULTS: Totally 300 participants (69.3% female) with a median age of 37.9 years were enrolled. A significant increase incidence of SARS-CoV-2 infection was found before and during community outbreak (11.91 versus 230.93 per 100,000 person-days, P < 0.001), which was a trend paralleling that observed in the general population. For 61 SARS-CoV-2 infected participants, nine (14.8%) were asymptomatic. Multivariate analysis revealed recent contact with a SARS-CoV-2 infected household (odds ratio [OR], 7.01; 95% confidence interval [95% CI], 3.70-13.30; P < 0.001) and co-existed underlying autoimmune diseases (OR, 4.46; 95% CI, 1.28-15.51; P = 0.019) were significant risk factors associated with acquisition of SARS-CoV-2 infection among HCWs. CONCLUSION: Community factors, such as closely contact with SARS-CoV-2 infected individuals and underlying immune suppression status, were significant factors for acquisition of SARS-CoV-2 infection among HCWs. We suggest the application of appropriate infection control measures for HCWs should be maintained to reduce risk of SARS-CoV-2 infection.

Characteristics of primary signet ring cell carcinoma of colon and rectum: a case control study.

BACKGROUND: Primary signet ring cell carcinoma of the colon and rectum (PSRCCR) is rare, usually diagnosed at advanced stage with poor outcomes. We aimed to find possible diagnostic clues in order to help diagnosis. METHODS: A retrospective study of PSRCCR patients from 1993 to 2018 was reviewed at a single tertiary center. Colorectal adenocarcinoma patients as control group with 1:4 ratio was also enrolled. RESULTS: 18 patients with PSRCCR were identified. The prevalence rate was 0.16% (18 of 11,515). The mean age was 50.2 years-old in PSRCCR group and 63 years-old in non-SRCC colorectal cancer patients (p < 0.001). Diagnosis tool depends on colonoscopy were much less in PSRCCR group than control group (44.4% vs 93%, p < 0.001). SRCC patients had higher level of CEA (68.3 vs 17.7 ng/mL, p = 0.004) and lower level of Albumin (3.4 vs 4.3 g/dL, p < 0.001). The majority of PSRCCR tumor configuration was ulcerative and infiltrative. More PSRCCR pathology presented as high-grade carcinoma (66.7 vs 1.4%, p < 0.001) and lymphovascular invasion (77.8 vs 44.4%, p = 0.011) than control group. More PSRCCR patients were diagnosed at advanced stage (88.8 vs 40.3%, p = 0.001). Higher mortality was also noticed in PSRCCR group than control group (72.2 vs 20.8%, p < 0.001). CONCLUSION: For young patients with long segment colonic stenosis and ulcerative/ infiltrative mucosa but endoscopic biopsy failed to identify malignant cells, earlier operation or non-colon site biopsy is suggested for diagnosing the PSRCCR.

Forecasting of Typhoon-Induced Wind-Wave by Using Convolutional Deep Learning on Fused Data of Remote Sensing and Ground Measurements.

Taiwan is an island, and its economic activities are primarily dependent on maritime transport and international trade. However, Taiwan is also located in the region of typhoon development in the Northwestern Pacific Basin. Thus, it frequently receives strong winds and large waves brought by typhoons, which pose a considerable threat to port operations. To determine the real-time status of winds and waves brought by typhoons near the coasts of major ports in Taiwan, this study developed models for predicting the wind speed and wave height near the coasts of ports during typhoon periods. The forecasting horizons range from 1 to 6 h. In this study, the gated recurrent unit (GRU) neural networks and convolutional neural networks (CNNs) were combined and adopted to formulate the typhoon-induced wind and wave height prediction models. This work designed two wind speed prediction models (WIND-1 and WIND-2) and four wave height prediction models (WAVE-1 to WAVE-4), which are based on the WIND-1 and WIND-2 model outcomes. The Longdong and Liuqiu Buoys were the experiment locations. The observatory data from the ground stations and buoys, as well as radar reflectivity images, were adopted. The results indicated that, first, WIND-2 has a superior wind speed prediction performance to WIND-1, where WIND-2 can be used to identify the temporal and spatial changes in wind speeds using ground station data and reflectivity images. Second, WAVE-4 has the optimal wave height prediction performance, followed by WAVE-3, WAVE-2, and WAVE-1. The results of WAVE-4 revealed using the designed models with in-situ and reflectivity data directly yielded optimal predictions of the wind-based wave heights. Overall, the results indicated that the presented combination models were able to extract the spatial image features using multiple convolutional and pooling layers and provide useful information from time-series data using the GRU memory cell units. Overall, the presented models could exhibit promising results.

Investigating the role of super-enhancer RNAs underlying embryonic stem cell differentiation.

BACKGROUND: Super-enhancer RNAs (seRNAs) are a kind of noncoding RNA transcribed from super-enhancer regions. The regulation mechanism and functional role of seRNAs are still unclear. Although super-enhancers play a critical role in the core transcriptional regulatory circuity of embryonic stem cell (ESC) differentiation, whether seRNAs have similar properties should be further investigated. RESULTS: We analyzed cap analysis gene expression sequencing (CAGE-seq) datasets collected during the differentiation of embryonic stem cells (ESCs) to cardiomyocytes to identify the seRNAs. A non-negative matrix factorization algorithm was applied to decompose the seRNA profiles and reveal two hidden stages during the ESC differentiation. We further identified 95 and 78 seRNAs associated with early- and late-stage ESC differentiation, respectively. We found that the binding sites of master regulators of ESC differentiation, including NANOG, FOXA2, and MYC, were significantly observed in the loci of the stage-specific seRNAs. Based on the investigation of genes coexpressed with seRNA, these stage-specific seRNAs might be involved in cardiac-related functions such as myofibril assembly and heart development and act in trans to regulate the co-expressed genes. CONCLUSIONS: In this study, we used a computational approach to demonstrate the possible role of seRNAs during ESC differentiation.

Laminar shear stress promotes mitochondrial homeostasis in endothelial cells.

Vascular endothelial cells (ECs) are constantly subjected to flow-induced shear stress that is crucial for endothelial functions. Laminar shear stress (LSS) exerts atheroprotection to ECs. Mitochondrial homeostasis is essential for cellular survival. However, the effects of LSS on mitochondrial homeostasis in ECs remain unclear. Mitochondrial homeostasis in ECs exposed to LSS was examined. Cultured human umbilical vein ECs were subjected to LSS (12 dynes/cm2 ) generated by a parallel-plate flow chamber system. ECs subjected to LSS demonstrated an increment of mitochondria in tubular form coupled with the increase of fusion proteins (Mfn2, OPA1) and the decrease of fission protein (Fis1). An increase of both long- and short- OPA1 along with a higher protease YME1L level were observed. LSS triggered a rapid phosphorylation on S637 but a decrease on S616 of fission-controlled protein Drp1. Consistently, Drp1 translocation to mitochondria was decreased in sheared ECs, suggesting that LSS promotes mitochondrial fusion. Enhanced mitochondrial biogenesis in sheared ECs was shown by the increase of mitochondrial mass and its regulatory proeins (PGC1α, TFAM, Nrf1). LSS enhances the expression of mitochondrial antioxidant enzymes and improves mitochondrial functions indicated by the increase of mitochondrial membrane potential (ΔΨm) and ATP generation. TNFα treatment decreased mitochondrial tubular network and its functions in ECs. LSS mitigated TNFα-induced mitochondrial impairments in ECs. Our results clearly indicate that LSS promotes mitochondrial homeostasis and attenuates inflammation-induced mitochondrial impairments in ECs. Our results provide novel insights into the manner of mitochondrial dynamics and functions modulated by LSS that contribute to endothelial integrity.

Mechanochemical Reactivity of a 1,2,4-Triazoline-3,5-dione-Anthracene Diels-Alder Adduct.

Force-responsive molecules that produce fluorescent moieties under stress provide a means for stress-sensing and material damage assessment. In this work, we report a mechanophore based on Diels-Alder adduct TAD-An of 4,4'-(4,4'-diphenylmethylene)-bis-(1,2,4-triazoline-3,5-dione) and initiator-substituted anthracene that can undergo retro-Diels-Alder (rDA) reaction by pulsed ultrasonication and compressive activation in bulk materials. The influence of having C-N versus C-C bonds at the sites of bond scission is elucidated by comparing the relative mechanical strength of TAD-An to another Diels-Alder adduct MAL-An obtained from maleimide and anthracene. The susceptibility to undergo rDa reaction correlates well with bond energy, such that C-N bond containing TAD-An degrades faster C-C bond containing MAL-An because C-N bond is weaker than C-C bond. Specifically, the results from polymer degradation kinetics under pulsed ultrasonication shows that polymer containing TAD-An has a rate constant of 1.59×10-5  min-1 , while MAL-An (C-C bond) has a rate constant of 1.40×10-5  min-1 . Incorporation of TAD-An in a crosslinked polymer network demonstrates the feasibility to utilize TAD-An as an alternative force-responsive probe to visualize mechanical damage where fluorescence can be "turned-on" due to force-accelerated retro-Diels-Alder reaction.

Nontraumatic intraoperative pulmonary nodule localization with laser guide stamping in a hybrid operating room.

Lung nodule localization using conventional image-guided video-assisted thoracoscopic surgery involves lung puncture, which increases the risk of needle-related complications. We aimed to evaluate the feasibility and safety of a single-stage non-invasive laser-guided stamping localization technique followed by resection under general anesthesia in a hybrid operating room. We retrospectively reviewed consecutive patients who underwent thoracoscopic surgery for small pulmonary nodules using laser-guided dye-stamping localization methods in a hybrid operating room between June 2023 and October 2023. During the study period, 18 patients with 20 lesions underwent single-stage intraoperative image-guided stamping video-assisted thoracoscopic surgery in the hybrid operating room. The median size of the nodules was 7.4 mm (interquartile range [IQR] 5.7-9.8 mm), and median distance from the pleural surface was 9.8 mm (IQR 7.7-14.6 mm). The median localization time was 26 min (IQR 23-34 min), whereas median operation time was 69 min (IQR 62-87 min). The total median operating room time was 146 min (IQR 136-157 min). Twelve patients underwent less than two cone-beam computed tomography scans, while 6 underwent more than two scans. The total median dose area product, including cone-beam computed tomography scans, was 5731.4 uGym2. No localization-related complications were observed, and the postoperative length of stay was 1 day (IQR 1-2 days). The single-stage image-guided pleural stamping technique for localizing small pulmonary nodules in a hybrid operating room is feasible and safe. Future research with larger cohorts is required to further explore the benefits of this workflow.

Augmented fluoroscopy-guided dye localization for small pulmonary nodules in hybrid operating room: intrathoracic stamping versus transbronchial marking.

PURPOSE: We developed a novel augmented fluoroscopy-guided intrathoracic stamping technique for localizing small pulmonary nodules in the hybrid operating room. We conducted an observational study to investigate the feasibility of this technique and retrospectively compared two augmented fluoroscopy-guided approaches: intrathoracic and transbronchial. METHODS: From August 2020 to March 2023, consecutive patients underwent single-stage augmented fluoroscopy-guided localization under general anaesthesia. This included intrathoracic stamping and bronchoscopic lung marking, followed by thoracoscopic resection in a hybrid operating room. Comparative analyses were performed between the two groups. RESULTS: The data of 50 patients in the intrathoracic stamping and 67 patients in the bronchoscopic lung marking groups were analysed. No significant difference was noted in demographic data between the groups, except a larger lesion depth in the bronchoscopic lung marking group (14.7 ± 11.7 vs 11.0 ± 5.8 mm, p = 0.029). Dye localization was successfully performed in 49 intrathoracic stamping group patients (98.0%) and 67 bronchoscopic lung marking group patients (100%). No major procedure-related complications occurred in either group; however, the time flow (total anaesthesia time/global operating room time) was longer, and the radiation exposure (fluoroscopy duration/total dose area product) was larger in the bronchoscopic lung marking group. CONCLUSIONS: Augmented fluoroscopic stamping localization under intubated general anaesthesia is feasible and safe, providing an alternative with less global operating room time and lower radiation exposure for image-guided thoracoscopic surgery in the hybrid operating room.

Spray nozzle for topical anaesthesia during flexible bronchoscopy: a randomised controlled trial.

Background: The effectiveness of using a spray nozzle to deliver lidocaine for superior topical airway anaesthesia during non-sedation flexible bronchoscopy (FB) remains a topic of uncertainty when compared with conventional methods. Methods: Patients referred for FB were randomly assigned to receive topical lidocaine anaesthesia via the bronchoscope's working channel (classical spray (CS) group) or through a washing pipe equipped with a spray nozzle (SN group). The primary outcome was cough rate, defined as the total number of coughs per minute. Secondary outcomes included subjective perceptions of both the patient and operator regarding the FB process. These perceptions were rated on a visual analogue scale, with numerical ratings ranging from 0 to 10. Results: Our study enrolled a total of 126 (61 CS group; 65 SN group) patients. The SN group exhibited a significantly lower median cough rate compared with the CS group (4.5 versus 7.1 counts·min-1; p=0.021). Patients in the SN group also reported less oropharyngeal discomfort (4.5±2.7 versus 5.6±2.9; p=0.039), better tolerance of the procedure (6.8±2.2 versus 5.7±2.7; p=0.011) and a greater willingness to undergo a repeat FB procedure (7.2±2.7 versus 5.8±3.4; p=0.015) compared with those in the CS group. From the operator's perspective, patient discomfort (2.7±1.7 versus 3.4±2.3; p=0.040) and cough scores (2.3±1.5 versus 3.2±2.4; p=0.013) were lower in the SN group compared with the CS group, with less disruption due to coughing observed among those in the SN group (1.6±1.4 versus 2.3±2.3; p=0.029). Conclusions: This study illustrates that employing a spray nozzle for the delivery of lidocaine provides superior topical airway anaesthesia during non-sedation FB compared with the traditional method.

Oral fecal transplantation enriches Lachnospiraceae and butyrate to mitigate acute liver injury.

While fecal microbiota transplantation (FMT) shows promise in treating human diseases, oral capsule FMT is more accepted and accessible to patients. However, microbe selection in the upper gastrointestinal tract (UGIT) through oral administration remains unclear. Here, we demonstrate that short-term oral fecal gavage (OFG) alleviates acetaminophen-induced acute liver injury (AILI) in mice, regardless of the divergent effects of commensal gut microbes. Pasteurized fecal gavage yields similar therapeutic effects. OFG enriches gut Lachnospiraceae and butyrate compared to donor feces. Butyrate mitigates AILI-induced ferroptosis via AMPK-ULK1-p62 signaling to simultaneously induce mitophagy and Nrf2 antioxidant responses. Combined N-acetylcysteine and butyrate administration significantly improves AILI mouse survival rates. These observations indicate the significance of the UGIT in modulating the implanted fecal microbes through oral administration and its potential biological and clinical impacts. Our findings also highlight a possible strategy for applying microbial metabolites to treat acute liver injury.

p62/SQSTM1 in liver diseases: the usual suspect with multifarious identities.

p62/Sequestosome-1 (SQSTM1) is a selective autophagy receptor that recruits and delivers intracellular substrates for bulk clearance through the autophagy lysosomal pathway. Interestingly, p62 also serves as a signaling scaffold to participate in the regulation of multiple physiological processes, including oxidative stress response, metabolism, inflammation, and programmed cell death. Perturbation of p62 activity has been frequently found to be associated with the pathogenesis of many liver diseases. p62 has been identified as a critical component of protein aggregates in the forms of Mallory-Denk bodies (MDBs) or intracellular hyaline bodies (IHBs), which are known to be frequently detected in biopsy samples from alcoholic steatohepatitis (ASH), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC) patients. Importantly, abundance of these p62 inclusion bodies is increasingly recognized as a biomarker for NASH and HCC. Although the level of p62 bodies seems to predict the progression and prognosis of these liver diseases, understanding of the underlying mechanisms by which p62 regulates and contributes to the development and progression of these diseases remains incomplete. In this review, we will focus on the function and regulation of p62, and its pathophysiological roles in the liver, by critically reviewing the findings from preclinical models that recapitulate the pathogenesis and manifestation of these liver diseases in humans. In addition, we will also explore the suitability of p62 as a predictive biomarker and a potential therapeutic target for the treatment of liver diseases, including NASH and HCC, as well as recent development of small-molecule compounds for targeting the p62 signaling axis.

Cone-Beam Computed-Tomography-Derived Augmented Fluoroscopy-Guided Biopsy for Peripheral Pulmonary Nodules in a Hybrid Operating Room: A Case Series.

Lung cancer is the most lethal cancer type in Taiwan and worldwide. Early detection and treatment advancements have improved survival. However, small peripheral pulmonary nodules (PPN) biopsy is often challenging, relying solely on bronchoscopy with radial endobronchial ultrasound (EBUS). Augmented fluoroscopy overlays the intra-procedural cone-beam computed tomography (CBCT) images with fluoroscopy enabling real-time three-dimensional localization during bronchoscopic transbronchial biopsy. The hybrid operating room (HOR), equipped with various types of C-arm CBCT, is a perfect suite for PPN diagnosis and other interventional pulmonology. This study shares the single institute experience of EBUS transbronchial biopsy of PPN with the aid of augmented fluoroscopic bronchoscopy (AFB) and CBCT in an HOR. We retrospectively enrolled patients who underwent robotic CBCT, augmented fluoroscopy-guided, radial endobronchial ultrasound-confirmed transbronchial biopsy and cryobiopsy in a hybrid operating room. Patient demographic characteristics, computed tomography images, rapid on-site evaluation cytology, and final pathology reports were collected. Forty-one patients underwent transbronchial biopsy and 6 received additional percutaneous transthoracic core-needle biopsy during the same procedure. The overall diagnostic yield was 88%. The complications included three patients with pneumothorax after receiving subsequent CT-guided percutaneous transthoracic needle biopsy, and two patients with hemothorax who underwent transbronchial cryobiopsy. Overall, the bronchoscopic biopsy of PPN using AFB and CBCT as precise guidance in the hybrid operating room is feasible and can be performed safely with a high diagnostic yield.

Microbiological and clinical characteristics of vancomycin-resistant Enterococcus faecium bacteraemia in Taiwan: implication of sequence type for prognosis.

OBJECTIVES: Vancomycin-resistant enterococci (VRE), particularly vancomycin-resistant Enterococcus faecium (VREfm), have emerged among the leading pathogens causing hospital-acquired infections worldwide. We aimed to examine whether there were newly introduced clones contributing to this increase and to assess the risk factors for mortality in patients with VREfm bacteraemia. METHODS: Between 2003 and 2010, all medical records of adult patients diagnosed with VREfm bacteraemia at a university hospital in Taiwan were reviewed. Antibiotic susceptibility, genotyping and multilocus sequence typing of the VREfm isolates were performed. RESULTS: During the study period, the prevalence of non-duplicated blood VRE isolates increased significantly from 3.9% in 2003 to 18.9% in 2010 (P < 0.0001). One-hundred-and-forty-nine patients with VREfm bacteraemia were noted and 102 isolates of VREfm were available for microbiological characterization. All isolates were susceptible to daptomycin and linezolid. Sequence type (ST) 18 and ST414 were the two predominant emerging STs from 2009 to 2010, accounting for 29.7% and 25.0% of all isolates, respectively. Patients who received immunosuppressives, had a high Charlson comorbidity index or experienced septic shock had a significantly higher 14 day mortality rate. Patients who had bacteraemia caused by ST414 isolates and received appropriate antibiotics had a lower 14 day mortality rate. CONCLUSIONS: The prevalence of the VRE that caused bacteraemia increased from 2003 to 2010. This increase might be attributed to the clonal spread of VREfm belonging to ST18 and ST414. The all-cause 14 day mortality rate was lower in patients with bacteraemia due to VREfm isolates that belonged to ST414.