Validation of a computer-based bronchoscopy simulator developed in Taiwan.

BACKGROUND/PURPOSE: Conventional training in bronchoscopy may increase patient's discomfort and procedure-related morbidity. Computer-based bronchoscopy simulator (CBBS) permits the acquisition and evaluation of the necessary skills through a realistic bronchoscopic experience. This study was conducted to validate the use of a CBBS system developed in Taiwan as a learning and assessment tool. METHODS: Twenty novice bronchoscopists and 10 expert bronchoscopists were enrolled as subjects in this prospective study. The 20 novice bronchoscopists were randomized into two groups, which received conventional bronchoscopic training or CBBS training and then completed a satisfaction survey. Subsequently, the novices who received CBBS training underwent an observational performance trial and the results were compared with those of expert bronchoscopists. All 10 expert bronchoscopists completed a realism survey and observational trial after CBBS performance. RESULTS: The satisfaction survey showed that the CBBS training program significantly increased participants' satisfaction (p = 0.002) and interest in learning (p < 0.001). The realism survey by the 10 expert bronchoscopists indicated that CBBS provides a favorable degree of realism with regard to the mechanical and visual parameters examined. Analysis of the performance results showed that the following parameters were capable of differentiating the participants by level of expertise: total procedure time (p = 0.002), percentage of bronchial segments entered (p = 0.012), percentage of bronchial segments identified (p < 0.001), percentage of repeated bronchial segments entered (p = 0.004), percentage of pathologies identified (p < 0.001), number of times that the bronchoscope tip collided with airway walls (p = 0.013), and number of times oral instruction was needed (p = 0.01). CONCLUSION: CBBS is a valid training method that increases interest in learning and provides a favorable degree of virtual realism. It can also distinguish various levels of competence at actual bronchoscopy and may have a useful role in the bronchoscopic training curriculum.     

Spinal pseudoarthrosis: a rare complication in psoriatic arthritis.

Discovertebral erosion with pseudoarthrosis is a well-known complication in ankylosing spondylitis but it is seldom mentioned in psoriatic arthritis. We report a 53-year-old woman with an 8-year history of psoriatic arthritis who developed severe low back pain followed by sudden onset of numbness in the lower limbs, weakness and dysesthesia. Abnormal contour of L1 and L2 vertebrae and intervertebral disc space was noted during radiologic examination. Pseudoarthrosis was suspected based on extensive osseous resorption and reactive sclerosis about the discovertebral junction on magnetic resonance imaging study. She underwent emergency operation due to spinal instability with neurologic deficit. Pseudoarthrosis was confirmed intraoperatively. No evidence of infection or neoplasms was found. This case shows that pseudoarthrosis can be complicated in patients with psoriatic arthritis, and this possibility should be considered in patients with previously quiescent disease.     

Promoter hypermethylation is the predominant mechanism in hMLH1 and hMSH2 deregulation and is a poor prognostic factor in nonsmoking lung cancer.

PURPOSE AND EXPERIMENTAL DESIGN: The etiologic association and prognostic significance of mismatch repair gene/protein alterations have never been examined in nonsmoking lung cancer. Therefore, we investigated protein expression and promoter hypermethylation of hMLH1 and hMSH2 genes in the tumor specimens from 105 nonsmoking female non-small cell lung cancer (NSCLC) patients. Immunohistochemistry and restriction enzyme-based multiplex PCR were used to examine the protein expression and promoter hypermethylation, respectively. The occurrence of gene/protein alteration for each gene was compared with the patients' clinicopathologic variables as well as the overall survival and cancer-specific survival rates. RESULTS: Protein expression alteration and promoter hypermethylation were observed in 66% to 67% and 30% to 34% of tumor specimens for hMLH1 and hMSH2 genes, respectively. Loss of hMLH1 and hMSH2 protein expression was significantly associated with their promoter hypermethylation (P < 0.0001 and P = 0.049). The overall survival and cancer-specific survival rates were significantly lower in patients with promoter hypermethylation of hMSH2 gene than in those without hypermethylation (P = 0.038 and P = 0.004). The poor prognosis was still especially significant in adenocarcinoma (P = 0.035 and P = 0.061) and early-stage NSCLC patients (P = 0.067 and P = 0.041). CONCLUSION: Our data suggest that hMLH1 is the major altered mismatch repair gene involved in nonsmoking NSCLC tumorigenesis and that promoter methylation is the predominant mechanism in hMLH1 and hMSH2 deregulation. In addition, promoter methylation of the hMSH2 gene may be a potential prognostic factor in nonsmoking female lung cancer.     

PI3K inhibitors in trastuzumab-resistant HER2-positive breast cancer cells with PI3K pathway alterations

The activation of the PI3K signaling pathway resulting from genetic alterations induces carcinogenesis and resistance to anticancer therapies. Breast cancer is a major malignancy that is associated with dysregulation of the PI3K signaling pathway. PIK3CA mutations and PTEN loss occur in every subtype of breast cancer. PI3K inhibitors are being evaluated in breast cancer after the success of an alpha isoform-specific PI3K inhibitor in estrogen receptor (ER)-positive/HER2-negative metastatic breast cancer. Some preclinical data indicate the potential for PI3K/mTOR targeting in combination with trastuzumab for HER2-positive breast cancer with or without expression of the estrogen receptor. However, the role of this therapy in HER2-positive breast cancer with PIK3CA mutations and/or PTEN loss remains unclear. We examined three HER2-positive, ER-negative breast cancer cell lines to determine the efficacy of a novel alpha isoform-specific PI3K inhibitor in combination with trastuzumab. The results indicated that this combination was effective in PIK3CA-mutant or PTEN-deficient breast cancer cells by inducing apoptosis and inhibiting the expression of downstream proteins. PTEN loss by siRNA modulation in parental HER2-positive cancer cells with PI3K signaling pathway alterations could not confer resistance to alpelisib or GDC-0077 plus trastuzumab. We selected the CK-MB-1 cell line without alterations in the PI3K pathway to demonstrate that PI3K inhibitors plus trastuzumab represented a biomarker-specific treatment. In vivo effects of alpelisib plus trastuzumab were tested and confirmed in a mouse model, showing the combination strategy offered the best opportunity to achieve tumor volume reduction. With known safety profiles, this cytotoxic chemotherapy-free regimen warrants further attention as a biomarker-driven strategy for treating HER2-positive breast cancer.     

Cardiovascular Medication Use and Risk of Acute Exacerbation in Patients With Asthma-COPD Overlap (CVACO Study)

PurposeCurrent clinical guidelines are unclear regarding the association of cardiovascular medication with the risk of acute exacerbation (AE) in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO).MethodsWe conducted a retrospective cohort study by interrogating the claims database of Taipei Veterans General Hospital. Patients with coexistent fixed airflow limitation and asthma were enrolled as an ACO cohort between 2009 and 2017. Exposure to cardiovascular medications, including angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), non-selective beta-blockers, cardioselective beta-blockers, dihydropyridine (DHP) calcium channel blockers (CCBs), and non-DHP CCBs, in 3-month period each served as time-dependent covariates. Patients receiving a cardiovascular medication ≥ 28 cumulative daily doses were defined as respective cardiovascular medication users. Patients were followed up until December 31, 2018. The primary endpoint was severe AE, defined as hospitalization or emergency department visit for either asthma, COPD, or respiratory failure. The secondary outcome was moderate AE.ResultsThe final study cohort consisted of 582 ACO subjects, with a mean follow-up period of 2.98 years. After adjustment, ARB (hazard ratio [HR], 0.64, 95% confidence interval [CI], 0.44–0.93, P = 0.019), cardioselective beta-blocker (HR, 0.29, 95% CI, 0.11–0.72, P = 0.008) and DHP CCB (HR, 0.66, 95% CI, 0.45–0.97, P = 0.035) therapies were associated with lower risks of severe AE. ARB (HR, 0.42, 95% CI, 0.30–0.62, P < 0.001) and DHP CCB (HR, 0.55, 95% CI, 0.38–0.80, P = 0.002) therapies were associated with lower risks of moderate AE. Cardioselective beta-blockers, ARBs, and DHP CCBs were associated with lower risks of severe AE in frequent exacerbators. ACEI, non-selective beta-blocker, or non-DHP CCB use did not change the risk of severe AE.ConclusionsARB, cardioselective beta-blocker, and DHP CCB therapies may lower the risk of AE in patients with ACO.     

Neonatal clavicular fracture: clinical analysis of incidence, predisposing factors, diagnosis, and outcome

The objective of this study is to identify maternal, perinatal, and fetal risk factors for clavicular fracture in a single institution. We performed a prospective study of all deliveries during a 14-month period to identify confirmed cases of neonatal clavicular fracture. The control group consisted of the deliveries immediately preceding and following the index cases. Fifty-three cases of clavicular fracture were identified among the 4789 deliveries from October 1995 through November 1996 for an incidence of 1.11%. Three neonates in the clavicular fracture group were delivered through cesarean section. Neonates with fracture were significantly heavier at birth than those without (3564 vs. 3283 g, p <0.001), and had a lower mean head-to-abdominal circumference ratio (0.93 vs. 1.08, p <0.001), history of giving birth to a macrosomia (21 vs. 4%, p <0.05). The anterior shoulder was the predominant site of fracture (30/53). Fracture was detected mostly during the first 3 days of neonatal life (46/53). The outcome was benign, with complete recovery in all cases and no associated neurological sequelae. Neonatal clavicular fracture tended to be associated with neonatal somatometric characteristics and difficult deliveries. Considering the benign nature of this birth trauma, more invasive intrapartum management to lower its incidence is not advised.     

One-year efficacy of tenofovir alafenamide in patients with chronic hepatitis B: An observational study

Non-inferior antiviral efficacy and better renal safety have been reported in chronic hepatitis B patients with tenofovir alafenamide (TAF) treatment. The experience in real-world clinical practice is limited.We aimed to explore the efficacy after 1-year TAF treatment.A total of 148 patients (42 HBeAg-positive and 106 HBeAg-negative) with TAF treatment ≥1 year were included. Virological suppression (<20 IU/mL or undetectable), HBsAg level, alanine aminotransferase (ALT) normalization (≤36 U/L), and estimated glomerular filtration rate (eGFR) were analyzed at 1 year. Multivariate logistic regression analysis was performed to determine the associated factors for virological suppression and ALT normalization.Virological suppression was achieved in 83% and the 1-year median decline of hepatitis B virus DNA was 5.18 log IU/mL. ALT normalization occurred in 75.7%. HBsAg level decreased at a median of 0.27 log IU/mL with significant difference from baseline (P < .001). Baseline ALT (odds ratio [OR] 1.005, 95% confidence interval [CI] 1.000–1.010, P = .036) and hepatitis B virus DNA (OR 0.222, 95% CI 0.079–0.621, P = .004) were significant factors for 1-year virological suppression. Age (OR 1.064, 95% CI 1.003–1.130, P = .041) was associated with ALT normalization. Significant changes were observed in creatinine (mean increase 0.03 mg/dL, P = .011) and eGFR (mean decrease 2.6 mL/min/1.73 m², P = .004) after 1-year TAF treatment.One-year TAF treatment came to good virological response, modest ALT normalization rate and significant HBsAg decline. The observation of significant changes in eGFR warranted further studies.     

Characteristics and immune checkpoint inhibitor effects on non-smoking non-small cell lung cancer with KRAS mutation: A single center cohort (STROBE-compliant)

Kirsten rat sarcoma (KRAS) mutation (KRASm) is associated with poor prognosis in non-small cell lung cancer (NSCLC) patients. We have aimed to survey NSCLC patients harboring KRASm in Taiwan, where never-smoking lung adenocarcinoma predominates, and analyze the immune checkpoint inhibitor effect on NSCLC harboring KRASm.NSCLC patients with KRASm were enrolled and tested on programmed death-ligand 1 (PD-L1) expression using available tissue. We analyzed their clinical features, PD-L1 status, responses to ICIs, and overall survival (OS).We studied 93 patients with a median age 66.0 years, 23.7% of whom were women, and 22.6% were never-smokers. The results showed that G12C (36.6%) was the most common KRASm. In 47 patients with available tissue for PD-L1 testing, PD-L1 expression was positive in 66.0% of patients, while PD-L1 ≥50% was higher in ever-smokers (P = .038). Among 23 patients receiving ICI treatment, those with PD-L1 ≥50% experience a 45.5% response rate to ICI. There were benefits from ICI treatment on OS compared with no ICI treatment (median OS 35.6 vs 9.8 months, P = .002) for all of our patients, and for patients with PD-L1 ≥50% (median OS not-reached vs 8.4 months, P = .008). There were no differences in survival across different KRAS subtypes (P = .666).Never-smokers composed more than one-fifth of KRASm in NSCLC in Taiwan. A high PD-L1 expression was related to smoking history and responded well to ICI. ICI treatment improved the OS in NSCLC patients with KRASm, particularly those with PD-L1 ≥50%.     

Correction: Discovery of 8-prenylnaringenin from hop (Humulus lupulus L.) as a potent monoacylglycerol lipase inhibitor for treatments of neuroinflammation and Alzheimer’s disease

Correction for ‘Discovery of 8-prenylnaringenin from hop (Humulus lupulus L.) as a potent monoacylglycerol lipase inhibitor for treatments of neuroinflammation and Alzheimer’s disease’ by Min-Che Tung et al., RSC Adv., 2021, 11, 31062–31072, https://doi.org/10.1039/D1RA05311F.

The authors regret that the name of one of the authors (Hsing-Mien Hsu) was shown incorrectly in the original article. The corrected author list is as shown above.The authors also regret an incorrect version of Fig. 7 was included in the original article. The correct version of Fig. 7 is presented below.Open in a separate windowFig. 7The dose-dependent inhibitions of the identified inhibitors against hMAGL.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.