A Phase 2 Trial of Intravesical Gemcitabine and Docetaxel in the Treatment of Bacillus Calmette-Guérin‒Naïve Nonmuscle-Invasive Urothelial Carcinoma of the Bladder.

PURPOSE: Combination intravesical gemcitabine and docetaxel (GemDoce) has demonstrated efficacy as second-line therapy for patients with bacillus Calmette-Guérin (BCG)‒unresponsive nonmuscle-invasive urothelial carcinoma of the bladder (NMIBC). In the context of widespread BCG shortages, we performed a phase 2 prospective trial to assess GemDoce for BCG-naïve NMIBC. MATERIALS AND METHODS: This study is a prospective, single-arm, open-label phase 2 trial for patients with BCG-naïve high-risk NMIBC. Intravesical GemDoce was given weekly for 6 weeks as induction followed by monthly maintenance therapy for 2 years among responders. The primary end point was 3-month complete response, and key secondary end points included adverse events (AEs) and 12-month recurrence-free survival. RESULTS: Twenty-five patients were enrolled between August 2020 and August 2022 with median follow-up of 19.6 months. The pretreatment pathologic stages were high-grade (HG) T1 with carcinoma in situ (CIS; n = 7), HGT1 without CIS (n = 6), HGTa (n = 9), and CIS alone (n = 3). The 3-month complete response rate was 100% and recurrence-free survival at 12 months was 92%. Two patients with pretreatment HGT1 had HGT1 recurrences at 9 and 12 months. No patients progressed to T2 disease, underwent radical cystectomy, or had any radiographic evidence of progressive disease. Grade 1 AEs were common (23/25 patients) including hematuria, urinary frequency, urgency, and fatigue. Five patients (20%) experienced a grade 3 AE including hematuria and UTI. CONCLUSIONS: In this single-arm phase 2 trial, GemDoce was well tolerated with promising efficacy for patients with BCG-naïve high-risk NMIBC.

Intestinal dysbiosis and inflammation in children with repaired esophageal atresia.

OBJECTIVES: This study aims to compare the intestinal microbiota and intestinal inflammation of children with esophageal atresia (EA) to matched healthy controls, and to investigate the relationship between these factors and clinical outcomes. METHODS: A cross-sectional study of 35 children with EA and 35 matched healthy controls (HC) from a single tertiary pediatric hospital in Australia was conducted. Demographic and dietary data were collected using surveys. Stool samples were analyzed using 16S rRNA sequencing, and fecal calprotectin measurements were used to measure intestinal inflammation. Comparisons were made between the groups, and correlations between the microbiota and clinical factors were investigated in the EA cohort. RESULTS: Compared to HC, children with EA had similar alpha diversity, but beta diversity analysis revealed clustering of EA and HC cohorts. Children with EA had a significantly higher relative abundance of the order Lactobacillales, and a lower abundance of the genus uncultured Bacteroidales S24-7. Fecal calprotectin was significantly higher in children with EA compared to HC. In the EA cohort, children taking proton pump inhibitors (PPI's) had lower alpha diversity and higher calprotectin levels compared to those not taking PPI's. There was a negative correlation between calprotectin and length/height-for-age z scores, and children with higher calprotectin levels had a greater burden of gastrointestinal symptoms. CONCLUSIONS: Children with EA have an altered intestinal microbiota compared to HC, which is likely related to PPI use, and may be impacting on growth and quality of life. It is important to rationalize PPI use in this cohort.

Bronchial branch tracing navigation in ultrathin bronchoscopy-guided radial endobronchial ultrasound for peripheral pulmonary nodule.

BACKGROUND: Most malignant peripheral pulmonary lesions (PPLs) are situated in the peripheral region of the lung. Although the ultrathin bronchoscope (UTB) can access these areas, a robust navigation system is essential for precise localisation of these small peripheral PPLs. Since many UTB procedures rely on automated virtual bronchoscopic navigation (VBN), this study aims to determine the accuracy and diagnostic yield of the manual bronchial branch tracing (BBT) navigation in UTB-guided radial endobronchial ultrasound (rEBUS) procedures. METHODS: Single-centre retrospective study of UTB-rEBUS patients with PPLs smaller than 3 cm over a two year period. RESULTS: Our cohort consisted of 47 patients with a mean age of 61.6 (SD 9.53) years and a mean target size of 1.91 (SD 0.53) cm. Among these lesions, 46.8% were located in the 6th airway generation, and 78.7% exhibited a direct bronchus sign. Navigation success using BBT was 91.5% based on positive rEBUS identification. The index diagnostic yield was 82.9%, increasing to 91.5% at 12 months of follow-up. Malignant lesions accounted for 65.1% of cases, while 34.9% were non-malignant. The presence of a direct bronchus sign was the sole factor associated with higher navigation success and diagnostic yield. Cryobiopsy outperformed forceps biopsy in non-concentric rEBUS lesions (90.9% vs. 50.0%, p < 0.05), but not in concentric orientated lesions. One pneumothorax occurred in our cohort. CONCLUSIONS: BBT as an exclusive navigation method for small PPLs in UTB-rEBUS procedures has proved to be safe and feasible. Combination of UTB with cryobiopsy remains efficient for eccentric and adjacently oriented rEBUS lesions.

Rhythmic auditory stimulation incorporated in training improved movements in individuals with psychotic-like experiences.

Movement abnormalities, including movement slowing and irregular muscle contraction, exist in individuals with psychotic-like experiences (PLEs) and serve as vulnerable factors of developing psychotic diseases in the psychosis continuum. To date scarce studies have developed early intervention programs tackling these initial impairments, which may be caused by basal ganglia alterations, in the early stage of the psychosis course. Rhythmic auditory stimulation (RAS) is a technique of neurological music therapy and has been proved effective in inducing faster movements in patients with psychotic diseases. This pilot study examined if RAS incorporated in functional movement training reduced severity of movement slowing and irregular muscle contraction in individuals with PLEs. Seventeen individuals with PLEs were randomly allocated to receiving RAS or receiving no RAS and underwent daily 40-min movement training (picking up beans) for three weeks. This study used motion analysis to measure movement performance at pretest and posttest. Eighteen age- and gender-matched individuals without PLEs were also recruited to provide data of intact movements. Results showed that RAS may reduce severity of movement slowing and irregular muscle contraction in individuals with PLEs. This pilot study is one of the pioneering studies validating effectiveness of early intervention programs tackling movement abnormalities, which are initial impairments in the psychosis continuum, in individuals with PLEs.

Evaluating the Dietary Intake of Children With Esophageal Atresia: A Prospective, Controlled, Observational Study.

OBJECTIVES: Children with esophageal atresia (EA) often have feeding difficulties and dysphagia, which may compromise their nutritional status. This study aimed to compare dietary intake between children with EA and matched healthy controls (HC) and to investigate the relationship between dietary factors, growth, dysphagia, and feeding difficulties in the EA cohort. METHODS: This cross-sectional cohort study recruited children with EA and HC aged 2-17 years from a tertiary pediatric hospital in Australia. Growth parameters were measured. Dietary intake was assessed using the validated Australian Child and Adolescent Eating Survey. Dysphagia and feeding difficulties were assessed using objective questionnaires. RESULTS: Twenty-one children with EA were matched for age and sex with 21 HC. Compared to HC, children with EA had lower mean z scores for height-for-age, but mean weight-for-age and body mass index-for-age z scores were similar. Energy intake was similar between the groups. The diet of children with EA consisted of a higher proportion of fats and lower proportion of carbohydrates compared to matched HC. Dysphagia severity in children with EA positively correlated with proportion of energy from fats and saturated fats. CONCLUSIONS: Children with EA have similar energy intake and growth parameters to HC, but their diet consists of a higher proportion of fats and lower proportion of carbohydrates compared to HC. Targeted dietary interventions and parental education are necessary.

Combination of 1.1 mm flexible cryoprobe with conventional guide sheath and therapeutic bronchoscope in biopsy of apical upper lobe solitary pulmonary nodule.

BACKGROUND: Lung cancer is frequently situated peripherally in the upper lobes of the lung. Acquiring adequate tissue from this difficult-to-reach area remains a challenge. Transbronchial cryobiopsy (TBCB) has the ability to acquire larger specimens, but the rigidity of the standard 1.9 mm and 2.4 mm cryoprobes frequently poses challenges when used with a guide sheath (GS). The novel 1.1 mm cryoprobe, being both smaller and more flexible, may address this limitation. We describe the usage of this 1.1 mm flexible cryoprobe with GS in the biopsy of solitary pulmonary nodules (SPN) in the apical segment of the upper lobe in two cases. CASE REPORT: Both procedures were conducted with advanced airway under total intravenous anaesthesia. 2.6 mm GS was used in combination with a 2.2 mm rEBUS probe, using a therapeutic bronchoscope. Case 1 describes a SPN in the apical segment of the right upper lobe that was inconclusive by forceps biopsy due to GS displacement and inadequate biopsy depth. A steerable GS combined with the novel cryoprobe subsequently overcame this issue. Case 2 describes a SPN in the apical segment of the left upper lobe in which the standard cryoprobe failed to advance through the GS due to steep angulation. It also highlights with shorter activation time, the novel cryoprobe enable biopsied tissue to be retrieved through the GS while the bronchoscope-GS remains wedgend in the airway segment. There were no bleeding or pneumothorax complications in both cases, and histopathological examination confirmed adenocarcinoma of the lung. CONCLUSION: The 1.1 mm flexible cryoprobe in combination with GS and therapeutic bronchoscope offers an option to acquire adequate tissue in difficult-to-reach regions in the lung such as the apical segment of upper lobes. Further prospective series to evaluate its performance and safety in SPN biopsy is highly anticipated.

Parental Demandingness and Executive Functioning in Predicting Anxiety among Children in a Longitudinal Community Study.

Theoretical models and empirical studies of anxiety have predominately focused on the main effects of various predictors such as executive functioning deficits on anxiety. This study examined the moderating role of parental demandingness in the relationship between executive functioning deficits and anxiety in children. Ninety children (46.67% female) aged from 9 to 14 years completed several executive functioning tasks and a measure of anxiety. Parental demandingness was rated based on an observation of parent-child interactions. The children completed the anxiety measure again at one-year follow-up. The results showed that parental demandingness significantly moderated the prospective relationship between executive functioning deficits and anxiety, such that the association between executive functioning deficits and anxiety in children was weaker when parental demandingness was lower. These findings suggest that low parental demandingness may serve as a protective factor that buffers the detrimental effects of executive functioning deficits on anxiety.

Characterizing the mode of action of extracellular Connexin43 channel blocking mimetic peptides in an in vitro ischemia injury model.

BACKGROUND: Non-selective Connexin43 hemichannels contribute to secondary lesion spread. The hemichannel blocking peptidomimetic Peptide5, derived from the second extracellular loop of the human Connexin43 protein, prevents lesion spread and reduces vascular permeability in preclinical models of central nervous system injury. The molecular mode of action of Peptide5, however, was unknown and is described here. METHODS: Human cerebral microvascular endothelial cells and APRE-19 cells were used. Scrape loading was used to assess gap junction function and hypoxic, acidic ion-shifted Ringer solution induced ATP release used to assess hemichannel function. Peptide modifications, including amino acid substitutions and truncations, and competition assays were used to demonstrate Peptide5 functional specificity and site of action respectively. RESULTS: Peptide5 inhibits Connexin43 hemichannel-mediated ATP release by acting on extracellular loop two of Connexin43, adjacent to its matching sequence within the protein. Precise sequence specificity is important for hemichannel block, but less so for uncoupling of gap junction channels (seen only at high concentrations). The SRPTEKT motif is central to Peptide5 function but on its own is not sufficient to inhibit hemichannels. Both the SRPTEKT motif and Peptide5 reduce gap junction communication, but neither uncoupling below 50%. CONCLUSIONS: Reduced gap junction coupling at high peptide concentrations appears to be relatively non-specific. However, Peptide5 at low concentrations acts upon extracellular loop two of Connexin43 to block hemichannels in a precise, sequence specific manner. GENERAL SIGNIFICANCE: The concentration dependent and sequence specific action of Peptide5 supports its development for the treatment of retinal injury and chronic disease, as well as other central nervous system injury and disease conditions.

Identification of fluency and word-finding difficulty in samples of children with diverse language backgrounds.

BACKGROUND: Stuttering and word-finding difficulty (WFD) are two types of communication difficulty that occur frequently in children who learn English as an additional language (EAL), as well as those who only speak English. The two disorders require different, specific forms of intervention. Prior research has described the symptoms of each type of difficulty. This paper describes the development of a non-word repetition test (UNWR), applicable across languages, that was validated by comparing groups of children identified by their speech and language symptoms as having either stuttering or WFD. AIMS: To evaluate whether non-word repetition scores using the UNWR test distinguished between children who stutter and those who have a WFD, irrespective of the children's first language. METHODS & PROCEDURES: UNWR was administered to ninety-six 4-5-year-old children attending UK schools (20.83% of whom had EAL). The children's speech samples in English were assessed for symptoms of stuttering and WFD. UNWR scores were calculated. OUTCOMES & RESULTS: Regression models were fitted to establish whether language group (English only/EAL) and symptoms of (1) stuttering and (2) WFD predicted UNWR scores. Stuttering symptoms predicted UNWR, whereas WFD did not. These two findings suggest that UNWR scores dissociate stuttering from WFD. There were no differences between monolingual English-speakers and children who had EAL. CONCLUSIONS & IMPLICATIONS: UNWR scores distinguish between stuttering and WFD irrespective of language(s) spoken, allowing future evaluation of a range of languages in clinics or schools.

Systemic treatment for inoperable pancreatic adenocarcinoma: review and update.

There have been many clinical trials conducted to evaluate novel systemic regimens for unresectable pancreatic cancer. However, most of the trial results were negative, and gemcitabine monotherapy has remained the standard systemic treatment for years. A number of molecular targeted agents, including those against epidermal growth factor receptor and vascular endothelial growth factor receptors, have also been tested. In recent years, there have been some breakthroughs in the deadlock: three regimens, namely gemcitabine-erlotinib, FOLFIRINOX, and gemcitabine-nab-paclitaxel, have been shown to prolong the overall survival of patients when compared with gemcitabine monotherapy. In addition, emerging data suggested that the membrane protein human equilibrative nucleotide transporter 1 is a potential biomarker with which to predict the efficacy of gemcitabine. Here we review the literature on the development of systemic agents for pancreatic cancer, discuss the current choices of treatment, and provide future directions on the development of novel agents.

Virtual reality-enhanced interventions on preoperative anxiety symptoms in adults undergoing elective surgery: A meta-analysis and meta-regression.

BACKGROUND: Virtual reality exposure and distraction are recent novel technologies for reducing preoperative anxiety symptoms. However, the effectiveness of virtual reality-enhanced interventions in adults is still controversial and has yet to be evaluated in a systematic review. OBJECTIVES: The study aimed to (1) evaluate the effectiveness of virtual reality-enhanced interventions on preoperative anxiety symptoms in adults compared to comparators; and (2) identify the factors affecting the effectiveness of interventions. DESIGN: Systematic review, meta-analysis, and meta-regression analysis of randomised controlled trials. METHODS: We conducted a three-step systematic search from inception until May 1, 2024, using (1) eleven databases, (2) two clinical registries, and (3) citation and grey literature searches in either English or Chinese. The package meta of R software version 4.3.1 was used to perform the meta-analysis, subgroup analysis, and meta-regression analyses. We adopted the restricted maximum likelihood estimator for random-effects meta-analysis and univariate random-effects meta-regression analyses. The Cochrane risk-of-bias tool version 2 and the Grading of Recommendations, Assessment, Development, and Evaluation criteria were used to examine quality assessment and the certainty of evidence. RESULTS: We selected 26 randomised controlled trials with 2357 participants from 12 different countries. Random-effects meta-analyses showed that virtual reality-enhanced interventions had a statistically significant reduction in preoperative anxiety symptoms (t = -5.58, p < 0.001) with a moderate to large effect size (Hedges' g = -0.76, 95 % confidence interval: -1.03 to -0.48) compared to usual care. Statistically significant subgroup differences were found for the nature of the intervention, geographical region, country, and type of surgery. The improvement in preoperative anxiety symptom outcomes was greater when the virtual reality-enhanced interventions were chosen by patients (g = -2.55, 95 % CI: -3.08 to -2.02) when compared to virtual reality exposure interventions with educational content (g = -0.72, 95%CI: -1.07 to -0.38) or virtual reality distraction interventions (g = -0.64, 95 % CI: -1.04 to -0.23). Trials conducted in Asia had a greater effect on preoperative anxiety symptom outcomes (g = -0.98, 95 % CI: -1.33 to -0. 62) in comparison with those conducted in non-Asia (g = -0.23, 95 % CI: -0.54 to 0.07). The random-effects meta-regression identified sample size (ß = -0.008, p = 0.031) as a statistically significant covariate of preoperative anxiety symptoms. The overall certainty of the evidence was very low. CONCLUSIONS: Virtual reality-enhanced interventions can be considered supplementary interventions for adults undergoing elective surgery. Future trials on a large scale with follow-up assessments are needed. REGISTRATION: PROSPERO registration ID: CRD42024486343.

Modified two-scope technique for transbronchial lung cryobiopsy of peripheral pulmonary lesions.

Bleeding mitigation is an important part of any transbronchial lung cryobiopsy (TBLC) procedure, either for interstitial lung disease (ILD) or peripheral pulmonary lesions (PPL). The two-scope technique has been previously described for ILD and PPL-TBLC, but it has its own limitations and technical and logistical complexities. In this case series, we describe a modified two-scope technique that enhances the conventional two-scope technique by maintaining a small equipment footprint and longer bronchoscopic vision without the need for intra-procedure switching of bronchoscopes. Three cases of PPLs were navigated by standard radial endobronchial ultrasound and biopsied with the 1.1 mm flexible ultrathin cryoprobe. All cases achieved a conclusive diagnosis with adequate specimens for immunohistochemical staining and molecular analysis; only Grade 1 bleeding reported in two cases. The challenges and limitations of this modified two-scope technique were also explored in this series.

Design of Multi-Functional Bio-Safe Dental Resin Composites with Mineralization and Anti-Biofilm Properties.

This study aims to develop multi-functional bio-safe dental resin composites with capabilities for mineralization, high in vitro biocompatibility, and anti-biofilm properties. To address this issue, experimental resin composites consisting of UDMA/TEGDMA-based dental resins and low quantities (1.9, 3.8, and 7.7 vol%) of 45S5 bioactive glass (BAG) particles were developed. To evaluate cellular responses of resin composites, MC3T3-E1 cells were (1) exposed to the original composites extracts, (2) cultured directly on the freshly cured resin composites, or (3) cultured on preconditioned composites that have been soaked in deionized water (DI water), a cell culture medium (MEM), or a simple HEPES-containing artificial remineralization promotion (SHARP) solution for 14 days. Cell adhesion, cell viability, and cell differentiation were, respectively, assessed. In addition, the anti-biofilm properties of BAG-loaded resin composites regarding bacterial viability, biofilm thickness, and biofilm morphology, were assessed for the first time. In vitro biological results demonstrated that cell metabolic activity and ALP expression were significantly diminished when subjected to composite extracts or direct contact with the resin composites containing BAG fillers. However, after the preconditioning treatments in MEM and SHARP solutions, the biomimetic calcium phosphate minerals on 7.7 vol% BAG-loaded composites revealed unimpaired or even better cellular processes, including cell adhesion, cell proliferation, and early cell differentiation. Furthermore, resin composites with 1.9, 3.8, and 7.7 vol% BAG could not only reduce cell viability in S. mutans biofilm on the composite surface but also reduce the biofilm thickness and bacterial aggregations. This phenomenon was more evident in BAG7.7 due to the high ionic osmotic pressure and alkaline microenvironment caused by BAG dissolution. This study concludes that multi-functional bio-safe resin composites with mineralization and anti-biofilm properties can be achieved by adding low quantities of BAG into the resin system, which offers promising abilities to mineralize as well as prevent caries without sacrificing biological activity.

Exploring the optimal freeze time and passes of the ultrathin cryoprobe in transbronchial cryobiopsy of peripheral pulmonary lesions.

In PPL-TBLC, quality of tissue matters more than quantity for accurate diagnosis. Comparable diagnostic yield with 1.1-mm cryoprobe can potentially be achieved in 6 s of freezing and three or more passes. https://bit.ly/49cbmbW.

Feasibility of Cryobiopsy Specimen Retrieval Through Standard Guide Sheath for Peripheral Pulmonary Lesions Without Bronchoscope Removal.

BACKGROUND: Transbronchial cryobiopsy is a promising technique for biopsy of peripheral pulmonary lesions (PPL). However, cryobiopsy specimen retrieval can pose problems due to the risk of bleeding during the blind period when the bronchoscope and cryoprobe are removed en bloc. Artificial airways and prophylactic balloon placement are risk-reducing measures, but the latter is challenging in upper lobe PPL. Specimen retrieval through standard guide sheath (GS) system without the need for bronchoscope removal may now be feasible with the ultrathin cryoprobe. METHODS: Retrospective review of radial endobronchial ultrasound (rEBUS)-guided transbronchial cryobiopsy for PPL cases in which cryobiopsy specimen was retrieved through the GS over a 6-month period. RESULTS: Twenty patients were included with an overall median age of 66.50 (IQR: 53.0 to 76.7). The median procedural time was 30 (IQR: 25.0 to 33.7) minutes. Median target size was 3.20 (IQR: 2.17 to 4.84) cm with 85% of lesions demonstrated "within" rEBUS orientation. Overall technical feasibility was 85% with median cryoactivation of 4.0 (IQR: 3.0 to 4.0) seconds. No specimen was retrieved in 3 patients. The diagnostic yield for forceps and cryobiopsy was 70% and 60%, respectively, and the combined diagnostic yield was 85% (P<0.01 vs. forceps biopsy). Median aggregate size for forceps and cryobiopsy was 8.0 (IQR: 5.3 to 10.0) and 4.5 (IQR: 2.3 to 7.0) mm respectively (P<0.01). No pneumothorax was reported and mild self-limiting bleeding was encountered in 30% of cases. CONCLUSION: Retrieval of cryoprobe through standard GS appears to be a safe and feasible method that can simplify the transbronchial cryobiopsy procedure and complement forceps biopsy in specific cases.

An explorative analysis on the optimal cryo-passes and freezing time of the ultrathin cryoprobe in endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy.

EBUS-guided transbronchial mediastinal cryobiopsy (TBMC) has emerged as a promising biopsy tool for diagnosing hilar and mediastinal pathologies. However, several fundamental technical aspects of TBMC remain unexplored. This study aims to determine the optimal number of cryo-passes and freezing time of the ultrathin cryoprobe in EBUS-TBMC concerning specimen size and procedural diagnostic yield. We conducted a retrospective chart review of patients with mediastinal and hilar lesions who underwent EBUS-TBMC between January 2021 and April 2023 across three hospitals in Malaysia. A total of 129 EBUS-TBMC procedures were successfully completed, achieving an overall diagnostic yield of 88.4%. Conclusive TBMC procedures were associated with larger specimen sizes (7.0 vs. 5.0 mm, p < 0.01). Specimen size demonstrated a positive correlation with diagnostic yield (p < 0.01), plateauing at specimen size of 4.1-6.0 mm. A significant positive correlation was also observed between the number of cryo-passes and both specimen size (p < 0.01) and diagnostic yield (p < 0.05). Diagnostic yield plateaued after 2-3 cryo-passes. In contrast, longer freezing times trended towards smaller specimens and lower diagnostic yield, though not reaching statistical significance. The highest diagnostic yield was recorded at the 3.1-4.0 s freezing time. The safety profile of TBMC remains favourable, with one case (0.8%) of pneumothorax and nine cases (7%) of self-limiting bleeding. In our cohort, TBMC performance with 2-3 cryo-passes and a 3.1-4.0 s freezing time to achieve a total aggregate specimen size of 4.1-6.0 mm appeared optimal. Further prospective studies are needed to validate these findings.

Performance of radial endobronchial ultrasound for peripheral pulmonary lesions without automation technology in tuberculous endemic region: real-world experience in a single institution over 6 years.

Background: Peripheral pulmonary lesions (PPLs) in tuberculous endemic regions present a unique diagnostic challenge, as tuberculous PPL can mimic malignancy and potentially delay diagnosis for both conditions without a confirmatory investigation. While bronchoscopic biopsy using radial endobronchial ultrasound (rEBUS) guidance is becoming more common among pulmonologists, it is often performed with additional automation technology such as virtual bronchoscopic and electromagnetic navigation. This study aimed to evaluate the performance of rEBUS without such automation technology over a 6-year period in our institution. Methods: Retrospective chart review of all adult patients undergoing rEBUS-guided transbronchial biopsy for PPL in our institution over 6 years duration (October 2016 to December 2022). Results: A total of 551 PPLs were included with median target lesion size of 2.70 (interquartile range, 2.10-3.70) cm. In total, 84.2% of lesion demonstrated direct bronchus sign with 46.3% demonstrating concentric rEBUS orientation. The overall diagnostic yield was 78.8% [95% confidence interval (CI): 75.1-82.1%], with 1.1% rate of pneumothorax. Among the conclusive cases, 62.7% were malignant while 37.3% were tuberculous. Bronchus sign [adjusted odds ratio (adj. OR): 2.268] and concentric rEBUS orientation (adj. OR: 3.426) are independent predictors for conclusive procedure. The sensitivity of rEBUS for malignant and tuberculous disease was 85.27% (95% CI: 80.89-88.97%) and 71.77% (95% CI: 62.99-79.49%) respectively. A significant improving trend of diagnostic yield over time with reduction of median PPL size was observed with introduction of cryobiopsy and thin bronchoscopy into rEBUS service. Conclusions: rEBUS without automation technology remains relevant and useful in this era. rEBUS provides a rapid and safe diagnosis of PPL which may translate into better patient care.

Peripheral transbronchial needle aspiration-guided pinpoint cryobiopsy of lung nodule without bronchus sign: A case report.

Peripheral transbronchial needle aspiration (pTBNA) allows the access of pulmonary nodules without bronchus sign but is limited to cytological examination. A 39-year-old man with left parotid carcinoma presented with an incidental lung nodule. Target localisation was performed with manual airway mapping, virtual bronchoscopic navigation, and pTBNA. Direct target validation using radial endobronchial ultrasound (rEBUS) was performed through the puncture defect. Targeted pinpoint biopsy with a 1.1 mm cryoprobe through the pTBNA puncture defect confirmed metastatic adenoid cystic carcinoma. Guided pTBNA with rEBUS validation followed by cryobiopsy of lung nodules without bronchus sign is potentially feasible for histological and molecular analyses.