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.

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.

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.

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.

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.

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.

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.

Neoadjuvant enoblituzumab in localized prostate cancer: a single-arm, phase 2 trial.

B7 homolog 3 (B7-H3; CD276), a tumor-associated antigen and possible immune checkpoint, is highly expressed in prostate cancer (PCa) and is associated with early recurrence and metastasis. Enoblituzumab is a humanized, Fc-engineered, B7-H3-targeting antibody that mediates antibody-dependent cellular cytotoxicity. In this phase 2, biomarker-rich neoadjuvant trial, 32 biological males with operable intermediate to high-risk localized PCa were enrolled to evaluate the safety, anti-tumor activity and immunogenicity of enoblituzumab when given before prostatectomy. The coprimary outcomes were safety and undetectable prostate-specific antigen (PSA) level (PSA0) 1 year postprostatectomy, and the aim was to obtain an estimate of PSA0 with reasonable precision. The primary safety endpoint was met with no notable unexpected surgical or medical complications, or surgical delay. Overall, 12% of patients experienced grade 3 adverse events and no grade 4 events occurred. The coprimary endpoint of the PSA0 rate 1 year postprostatectomy was 66% (95% confidence interval 47-81%). The use of B7-H3-targeted immunotherapy in PCa is feasible and generally safe and preliminary data suggest potential clinical activity. The present study validates B7-H3 as a rational target for therapy development in PCa with larger studies planned. The ClinicalTrials.gov identifier is NCT02923180.

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.

Point-of-care ultrasound in pre-bronchoscopy assessment of acute dyspnea: A case of concurrent massive pulmonary embolism and deep vein thrombosis.

Point-of-care ultrasound (POCUS) leads to efficient real-time diagnosis in a wide range of medical specialties. We describe the use of cardiac, lung and lower limb POCUS to rapidly diagnose massive pulmonary embolism and deep vein thrombosis in a 64-year-old patient presenting with acute dyspnea prior to elective bronchoscopy. Left femoral vein thrombus and features of increased right heart pressure on POCUS led to the decision to administer fibrinolytic therapy, with subsequent CT pulmonary angiogram confirming bilateral PE. The use of POCUS allowed for rapid imaging and interpretation leading to a rapid diagnosis of PE, thus fast-tracking lifesaving anticoagulation, especially in an outpatient setting.

Synthesis and Biological Evaluation of Termini-Modified and Cyclic Variants of the Connexin43 Inhibitor Peptide5.

Peptide5 is a 12-amino acid mimetic peptide that corresponds to a region of the extracellular loop 2 (EL2) of connexin43. Peptide5 regulates both cellular communication with the cytoplasm (hemichannels) and cell-to-cell communication (gap junctions), and both processes are implicated in neurological pathologies. To address the poor in vivo stability of native peptide5 and to improve its activity, twenty-five novel peptide5 mimetics were designed and synthesized. All the analogues underwent biological evaluation as a hemichannel blocker and as a gap junction disruptor, and several were assessed for stability in human serum. From this study, it was established that several acylations on the N-terminus were tolerated in the hemichannel assay. However, the replacement of the L-Lys with an N-methylated L-Lys to give H-VDCFLSRPTE-N-MeKT-OH showed good hemichannel and gap junction activity and was more stable in human serum. The cyclic peptide variants generally were not tolerated in either the hemichannel and gap junction assay although several possessed outstanding stability in human serum.

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.

Investigation of mechanical performances and polymerization shrinkage of dual-cured resin composites as core build-up material.

This study systematically compared the mechanical performances and polymerization shrinkage of two novel dual-cured resin composites (DCRC) with one conventional packable light-cured resin composite (LCRC) for their application as core build-up material by micro-hardness test, flexural strength test, push-out test, and digital image correlation analysis. The LCRC had a significantly higher micro-hardness (p<0.05) whereas the bond strength demonstrated no difference. The mean values of three materials ranged from 35.16 and 64.82 for the Vickers hardness and from 4.66 MPa to 11.53 MPa for the bond strength. The flexure strength of the three materials was not statistically different from each other. LCRC demonstrated 1.88% of volumetric shrinkage while the two DCRC showed 5.06% and 4.91%, respectively. In general, the DCRC demonstrated a comparable flexural strength and bond strength as the LCRC, however, the significant polymerization shrinkage of DCRC should be emphasized.

Images of the month: Pulmonary cement embolism.

Percutaneous vertebroplasty (PV) involves injection of polymethylmethacrylate bone cement into vertebral body for relief of pain and strengthening of bone in symptomatic vertebral compression fractures.Passage of bone cement into vertebral venous plexus and then into the lungs is a rare and serious complication of PV. The reported incidence up to 26%.We present an incidental finding of pulmonary cement embolism (PCE) after PV. A 68-year-old woman with history of PV 3 years previously for T11 osteoporotic fracture presented to us with cough for 3 weeks following choking on a fish bone.Chest X-ray showed left lower zone consolidation and a high-density opacity in a tubular branching pattern, corresponding to pulmonary arterial distribution. Contrasted computed tomography of the thorax showed segmental pulmonary cement embolism of both lungs and left lower lobe consolidation.She underwent bronchoscopy with findings of a purulent secretion from the left lower lobe. Her symptoms resolved after 2 weeks of antibiotics. She was managed conservatively for the PCE as she remained asymptomatic.This case highlights the need for a standard post-PV chest X-ray, as patients with cement embolisms can be completely asymptomatic. Measures to minimise the risk of pulmonary cement embolisms during PV need to be taken.