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Abstract Background Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. Methods A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. Discussion Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. Ethics and dissemination Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. Trial registration Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

In this article, the solution to the inverse and forward kinematics of a novel three-legged, serial-parallel, compliant robot are presented. The design of the robot aims to combine properties from serial and parallel architectures, thereby targeting an agile, yet precisely controllable robot that possibly allows both for dynamic locomotion and accurate manipulation tasks. The robot embodies the series connection of two parallel architectures, a planar and a spherical mechanism, realized in a highly dense mechanical assembly, allowing for lightweight, functionally redundant and compliant 4-DOF legs. A hybrid compliance behaviour is achieved, serving as a threshold between a stiff and compliant systemic state of the robot. Based on the mechanism design, the study involves the derivation of an alternative, yet complete solution for the inverse and forward kinematics of the spherical parallel manipulator (SPM). The approach utilizes spherical trigonometry and spatial vector geometry and yields a unique solution, while being both easy to implement and numerically efficient, thereby being applicable to real time implementations. Conceptually, a reduction of the mechanism assembly and working modes was directly integrated into the solution terms, drastically simplifying the expressions as they only represents the mechanically meaningful configuration relevant for actual physical systems. In addition to the active joint coordinates, the solution yields a unique set of all passively driven joints. The derived robot kinematics are furthermore verified through a 3D simulation model, showing the robot performing several motions. Thereby, the simulations portray the characteristics of the motor units by means of their corresponding phase profiles, revealing a balanced utilisation.

Abstract Background Bronchoscopy is commonly utilized for non-surgical sampling of indeterminant pulmonary lesions, but nondiagnostic procedures are common. Accurate assessment of the risk of malignancy is essential for decision making in these patients, yet we lack tools that perform well across this heterogeneous group of patients. We sought to evaluate the accuracy of three previously validated risk models and physician-assessed risk (PAR) in patients with a newly identified lung lesion undergoing bronchoscopy for suspected lung cancer where the result is nondiagnostic. Methods We performed an analysis of prospective data collected for the Percepta Bronchial Genomic Classifier Multicenter Registry. PAR and three previously validated risk models (Mayo Clinic, Veteran’s Affairs, and Brock) were used to determine the probability of lung cancer (low, intermediate, or high) in 375 patients with pulmonary lesions who underwent bronchoscopy for possible lung cancer with nondiagnostic pathology. Results were compared to the actual adjudicated prevalence of malignancy in each pre-test risk group, determined with a minimum of 12 months follow up after bronchoscopy. Results PAR and the risk models performed poorly overall in the assessment of risk in this patient population. PAR most closely matched the observed prevalence of malignancy in patients at 12 months after bronchoscopy, but all modalities had a low area under the curve, and in all clinical models more than half of all the lesions labeled as high risk were truly or likely benign. The studied risk model calculators overestimate the risk of malignancy compared to PAR, particularly in the subset in older patients, irregularly bordered nodules, and masses > 3 cm. Overall, the risk models perform only slightly better when confined to lung nodules

The Percepta Genomic Sequencing Classifier (GSC) was developed to up-classify as well as down-classify the risk of malignancy for lung lesions when bronchoscopy is non-diagnostic. We evaluated the performance of Percepta GSC in risk re-classification of indeterminate lung lesions. This multicenter study included individuals who currently or formerly smoked undergoing bronchoscopy for suspected lung cancer from the AEGIS I/ II cohorts and the Percepta Registry. The classifier was measured in normal-appearing bronchial epithelium from bronchial brushings. The sensitivity, specificity, and predictive values were calculated using predefined thresholds. The ability of the classifier to decrease unnecessary invasive procedures was estimated. A set of 412 patients were included in the validation (prevalence of malignancy was 39.6%). Overall, 29% of intermediate-risk lung lesions were down-classified to low-risk with a 91.0% negative predictive value (NPV) and 12.2% of intermediate-risk lesions were up-classified to high-risk with a 65.4% positive predictive value (PPV). In addition, 54.5% of low-risk lesions were down-classified to very low risk with >99% NPV and 27.3% of high-risk lesions were up-classified to very high risk with a 91.5% PPV. If the classifier results were used in nodule management, 50% of patients with benign lesions and 29% of patients with malignant lesions undergoing additional invasive procedures could have avoided these procedures. The Percepta GSC is highly accurate as both a rule-out and rule-in test. This high accuracy of risk re-classification may lead to improved management of lung lesions.

Annual screening with low dose chest tomography has been adopted for those at high risk to aid in the early detection of lung cancer. In addition to screening, it is recommended that such persons receive evidence-based smoking-cessation. However, both lung cancer screening and evidence-based smoking-cessation strategies are underutilized in the US. We review the impact of a dedicated Tobacco Treatment Clinic (TTC), delivering evidence-based smoking cessation strategies, on lung cancer screening enrollment. Patients of the TTC, aged 50 years or older, having a minimum 20-pack-year smoking history were included. All patients had records reviewed to see if they had received lung cancer screening; if their lung cancer screening was achieved through the TTC, this was documented as “initial screening” versus “continued screening or surveillance”. Sociodemographic variables were collected as well. As for results, between January 2019 to February 2020, 92 patients enrolled in the TTC and fulfilled criteria for lung cancer screening. The mean age was 65.7 ± 8.3 years old, with 58 (63.0%) of the patients being female. Seventy-five (81.5%) patients were African American. Of the 92, 68 (73.9%) patients had lung cancer screening, with 51 patients receiving their first lung cancer screening scan through the TTC. In conclusion, through enrollment in a dedicated TTC, a significant proportion of patients were able to access lung cancer screening for the first time. Further, many of these patients were of minority status. Having a dedicated TTC may improve current health equity gaps in lung cancer screenings in certain US populations.

Introduction: Checkpoint inhibitor pneumonitis (CIP) is a serious toxicity of anti–programmed death-(ligand) 1 immunotherapy. Whether pretreatment differences in pulmonary function exist in patients who develop CIP is unknown. We analyzed the pulmonary function tests (PFTs) of patients with NSCLC treated with immune checkpoint inhibitors (ICIs) to evaluate whether pretreatment lung function was associated with CIP development. Methods: Patients were included if they completed greater than or equal to 1 PFT within 2 years preceding ICI initiation. CIP status (CIP+: developed CIP, CIP−: did not develop CIP) was determined clinically. Generalized estimating equation–based linear regression was used to evaluate the effects of time and CIP on lung function. Primary outcomes included the following: percent-predicted forced expiratory volume in 1 second (FEV1pp), percent-predicted forced vital capacity (FVCpp), and FEV1/FVC. Results: A total of 43 patients (34 CIP−, 9 CIP+) with 79 PFTs (59 CIP−, 20 CIP+) were included. CIP+ patients had a 21.7% lower pretreatment FEV1pp compared with the CIP− group (95% confidence interval: −38.6 to −4.7). No statistically significant differences in FVCpp or FEV1/FVC were observed. The prevalence of obstructive lung disease was similar in both groups at 67% and 62% for the CIP+ and CIP− cohorts, as was the prevalence of current/former smoking at 100% and 93%, respectively. Conclusions: Pretherapy differences in lung function were evident between patients who did and did not develop CIP, though the prevalence of obstructive lung disease was similar. Prospective studies are needed to validate these findings, inform potential risk factors for CIP, and investigate the effects of ICI treatment and CIP on pulmonary function in patients with NSCLC.

Immune-related (IR)-pneumonitis is a rare and potentially fatal toxicity of anti-PD(L)1 immunotherapy. Expert guidelines for the diagnosis and management of IR-pneumonitis include multidisciplinary input from medical oncology, pulmonary medicine, infectious disease, and radiology specialists. Severe acute respiratory syndrome coronavirus 2 is a recently recognized respiratory virus that is responsible for causing the COVID-19 global pandemic. Symptoms and imaging findings from IR-pneumonitis and COVID-19 pneumonia can be similar, and early COVID-19 viral testing may yield false negative results, complicating the diagnosis and management of both entities. Herein, we present a set of multidisciplinary consensus recommendations for the diagnosis and management of IR-pneumonitis in the setting of COVID-19 including: (1) isolation procedures, (2) recommended imaging and interpretation, (3) adaptations to invasive testing, (4) adaptations to the management of IR-pneumonitis, (5) immunosuppression for steroid-refractory IR-pneumonitis, and (6) management of suspected concurrent IR-pneumonitis and COVID-19 infection. There is an emerging need for the adaptation of expert guidelines for IR-pneumonitis in the setting of the global COVID-19 pandemic. We propose a multidisciplinary consensus on this topic, in this position paper.

Background Pneumonitis from immune checkpoint inhibitors (ICI) is a potentially fatal immune-related adverse event (irAE) from antiprogrammed death 1/programmed death ligand 1 immunotherapy. Most cases of ICI pneumonitis improve or resolve with 4–6 weeks of corticosteroid therapy. Herein, we report the incidence, clinicopathological features and management of patients with non-small cell lungcancer (NSCLC) and melanoma who developed chronic ICI pneumonitis that warrants ≥12 weeks of immunosuppression.Methods Patients with ICI pneumonitis were identified from institutional databases of ICI-treated patients with advanced melanoma and NSCLC between January 2011 and July 2018. ICI pneumonitis was defined as clinical/radiographic evidence of lung inflammation without alternative diagnoses, adjudicated by a multidisciplinary team. Chronic ICI pneumonitis was defined as pneumonitis that persists or worsens with steroid tapering, and necessitates ≥12 weeks of immunosuppression, after ICI discontinuation. Serial chest CT was used to assess radiological features, and tumor response by Response EvaluationCriteria for Solid Tumors V.1.1. Bronchoalveolar lavage fluid (BALF) samples were assessed by cell differential. Lung biopsy samples were evaluated by H&E staining and multiplex immunofluorescence (mIF), where available.Results Among 299 patients, 44 developed ICI pneumonitis (NSCLC: 5/205; melanoma: 1/94), and of these, 6 experienced chronic ICI pneumonitis. The overall incidence of chronic ICI pneumonitis was thus 2%. Of those who developed chronic ICI pneumonitis: the majority had NSCLC (5/6), all sustained disease control from ICIs, and none had other concurrent irAEs. Timing of chronic ICI pneumonitis development was variable (range: 0–50 months), and occurred at a median of 12 months post ICI start. Recrudescence of ICI pneumonitis occurred at a median of 6 weeks after initial steroid start (range: 3–12 weeks), with all patients requiring steroid reintroduction when tapered to ≤10 mg prednisone/equivalent. The median total duration of steroids was 37 weeks (range: 16–43+weeks). Re-emergence of radiographic ICI pneumonitis occurred in the same locations on chest CT, in most cases (5/6). All patients who developed chronic ICI pneumonitis had BALF lymphocytosis on cell differential and organising pneumonia on lung biopsy at initial ICI pneumonitis presentation, with persistent BALF lymphocytosis and brisk CD8+ infiltration on mIF at pneumonitis re-emergence during steroid taper.Conclusions A subset of patients who develop pneumonitis from ICIs will develop chronic ICI pneumonitis, that warrants long-term immunosuppression of ≥12 weeks, and has distinct clinicopathological features.

In this work, the concept and mechanical design of a novel compact, lightweight, omnidirectional three-legged robot, featuring a hybrid serial–parallel topology including leg compliance is proposed. The proposal focusses deeply on the design aspects of the mechanical realisation of the robot based on its 3D-CAD assembly, while also discussing the results of multi-body simulations, exploring the characteristic properties of the mechanical system, regarding the locomotion feasibility of the robot model. Finally, a real-world prototype depicting a single robot leg is presented, which was built by highly leaning into a composite design, combining complex 3D-printed parts with stiff aluminium and polycarbonate parts, allowing for a mechanically dense and slim construction. Eventually, experiments on the prototype leg are demonstrated, showing the mechanical model operating in the real world.

In this study, a novel design for a compact, lightweight, agile, omnidirectional three-legged robot involving legs with four degrees of freedom, utilizing an spherical parallel mechanism with an additional non-redundant central support joint for the robot hip structure is proposed. The general design and conceptual ideas for the robot are presented, targeting a close match of the well-known SLIP-model. CAD models, 3d-printed prototypes, and proof-of-concept multi-body simulations are shown, investigating the feasibility to employ a geometrically dense spherical parallel manipulator with completely spherically shaped shell-type parts for the highly force-loaded application in the legged robot hip mechanism. Furthermore, in this study, an analytic expression is derived, yielding the calculation of stress forces acting inside the linkage structures, by directly constructing the manipulator hip Jacobian inside the force domain.

The burden of a number of pleural diseases continues to increase internationally. Although many pleural procedures have historically been the domain of interventional radiologists or thoracic surgeons, in recent years, there has been a marked expansion in the techniques available to the pulmonologist. This has been due in part to both technological advancements and a greater recognition that pleural disease is an important subspecialty of respiratory medicine. This article summarises the important literature relating to a number of advanced pleural interventions, including medical thoracoscopy, the insertion and use of indwelling pleural catheters, pleural manometry, point-of-care thoracic ultrasound, and image-guided closed pleural biopsy. We also aim to inform the reader regarding the latest updates to more established procedures such as chemical pleurodesis, thoracentesis and the management of chest drains, drawing on contemporary data from recent randomised trials. Finally, we shall look to explore the challenges faced by those practicing pleural medicine, especially relating to training, as well as possible future directions for the use and expansion of advanced medical interventions in pleural disease.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure originally performed using a 22-gauge (22G) needle. A recently introduced 21-gauge (21G) needle may improve the diagnostic yield and sample adequacy of EBUS-TBNA, but prior smaller studies have shown conflicting results. To our knowledge, this is the largest study undertaken to date to determine whether the 21G needle adds diagnostic benefit.Methods: We retrospectively evaluated the results of 1,299 patients from the American College of Chest Physicians Quality Improvement Registry, Education, and Evaluation (AQuIRE) Diagnostic Registry who underwent EBUS-TBNA between February 2009 and September 2010 at six centers throughout the United States. Data collection included patient demographics, sample adequacy, and diagnostic yield. Analysis consisted of univariate and multivariate hierarchical logistic regression comparing diagnostic yield and sample adequacy of EBUS-TBNA specimens by needle gauge.Results: A total of 1,235 patients met inclusion criteria. Sample adequacy was obtained in 94.9% of the 22G needle group and in 94.6% of the 21G needle group (P = .81). A diagnosis was made in 51.4% of the 22G and 51.3% of the 21G groups (P = .98). Multivariate hierarchical logistic regression showed no statistical difference in sample adequacy or diagnostic yield between the two groups. The presence of rapid onsite cytologic evaluation was associated with significantly fewer needle passes per procedure when using the 21G needle (P < .001).Conclusions: There is no difference in specimen adequacy or diagnostic yield between the 21G and 22G needle groups. EBUS-TBNA in conjunction with rapid onsite cytologic evaluation and a 21G needle is associated with fewer needle passes compared with a 22G needle. [ABSTRACT FROM AUTHOR]

The equilibrium structures of cis- and trans-1,2-difluoroethylene and 1,1-difluoroethylene, C2H2F2, have been determined with high-level coupled cluster techniques combined with large basis sets, explicit consideration of core/valence, and scalar relativistic and higher order correlation effects. Excellent agreement was found with new semiexperimental structures, increasing the level of confidence in both approaches. Differences in bond lengths among ethylene and the fluoroethylenes are discussed. [ABSTRACT FROM AUTHOR]

Geometry parameters, frequencies, heats of formation, and bond dissociation energies are predicted for the simple alkaline earth (Be, Mg and Ca) fluorides, chlorides, oxides, and hydroxides at the coupled cluster theory [CCSD(T)] level including core−valence correlation with the aug-cc-pwCVnZ basis sets up to n= 5 in some cases. Additional corrections (scalar relativistic effects, vibrational zero-point energies, and atomic spin−orbit effects) were necessary to accurately calculate the total atomization energies and heats of formation. The calculated geometry parameters, frequencies, heats of formation, and bond dissociation energies are compared with the available experimental data. For a number of these alkaline earth compounds, the experimental geometries and energies are not reliable. MgF2and BeF2are predicted to be linear and CaF2is predicted to be bent. BeOH is predicted to be bent, whereas MgOH and CaOH are linear. The OBeO angle in Be(OH)2is not linear, and the molecule has C2symmetry. The heat of formation at 298 K for MgO is calculated to be 32.3 kcal/mol, and the bond dissociation energy at 0 K is predicted to be 61.5 kcal/mol. [ABSTRACT FROM AUTHOR]

High level ab initio calculations, utilizing coupled cluster theory with quasi-perturbative triple excitations and augmented quadruple ζ level basis sets, have been used to determine the structures and relative energies of the four stationary points on the 1,3-butadiene torsional potential curve. Corrections were applied in order to minimize the residual basis set error, as well as account for core/valence correlation and scalar relativistic effects. Higher order correlation recovery was also included to improve our estimate of the relative energies. The transition state separating the transand gaucherotamers lies 26.8 kJ/mol above the transglobal minimum. The gaucherotamer lies 12.6 kJ/mol above the transrotamer and the s-cisform is a transition state 2.0 kJ/mol higher than the gaucherotamer (excluding zero point energies). [ABSTRACT FROM AUTHOR]

The article presents an assessment of pleural pressure in the evaluation of pleural effusions. Pleural manometry provides data to enhance understanding of the underlying pleural pathophysiology when an effusion is present and aids the physician in both diagnostic and therapeutic decisions. The measurement of pleural pressure helps differentiate lung entrapment and trapped lung, allows for the safe removal of large effusions, and is a useful tool to select appropriate patients for pleurodesis.

IR and Raman spectra are reported for 1,1-difluorocyclopropane-d0, -d2, and -d4, and complete assignments of vibrational fundamentals are given for these species. These assignments are consistent with predictions of frequencies, intensities, and Raman depolarization ratios computed with the B3LYP/cc-pVTZ quantum chemical (QC) model. Ground state rotational constants for five 13C and deuterium isotopomers, obtained from published microwave spectra, were “corrected” into equilibrium rotational constants. The needed vibration−rotation interaction constants were computed with QC models after scaling the force constants. A semi-experimental equilibrium structure, fitted to the equilibrium moments of inertia, is rC1C1.470(1) Å, rCC1.546(1) Å, rCF1.343(1) Å, rCH1.078(1) Å, FCF109.5(1), FCC119.4(1)°, HCH116.7(1)°, C1CH117.4(1)°, and CCH117.1(1)°. This structure agrees within the indicated uncertainties with the ab initio structure obtained from an extrapolated set of CCSD(T)/aug-cc-pVnZ calculations except for rCC1.548 Å. The F2C−CH2bonds are significantly shortened and strengthened; the H2C−CH2bond is significantly lengthened and weakened. [ABSTRACT FROM AUTHOR]

SUMMARY: OBJECTIVE To determine the safety and efficacy of photodynamic therapy (PDT) in patients with endobronchial tumors using the flexible bronchoscope for light application and debridement bronchoscopy without general anesthesia or the rigid bronchoscope.METHOD Thirty-seven consecutive cases with inoperable cancer, either primary or metastatic to the lung, were treated with PDT. PDT was performed using Photofrin® infusion at 2 mg/kg followed by illumination after 48-72 hours. 630 nm laser light was delivered with a cylindrical light diffusing fiber passed through a flexible bronchoscope. Pulmonary hygiene flexible bronchoscopy was performed 48 hours later and as needed to remove necrotic debris. Repeat illumination was done as needed to a maximum of three treatments.RESULTS There were 32 complete or partial responders and five treatment failures. There was no treatment-related mortality. Major postoperative complications included respiratory failure requiring short-term intubation in one patient. All illumination and debridement bronchoscopies were performed with the flexible bronchoscope and conscious sedation onlyCONCLUSIONS PDT is effective for palliation of inoperable advanced lung cancer. PDT and hygiene bronchoscopy can be performed safely and effectively with the flexible bronchoscope alone. General anesthesia and rigid bronchoscopy are not mandatory for effective PDT. [ABSTRACT FROM AUTHOR]

The bond length of a carbon−carbon sp2−sp2-bond without the perturbing effects of -interactions has been estimated by high level calculations on two prototypical systems:  a 90°-twisted form of butadiene and the tub conformer of cyclooctatetraene. The former system yields a value of 1.4818 Å, considerably longer than previous estimates. The corresponding bond length in the latter is slightly shorter due to some -electron delocalization. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer is still the leading cause of cancer among cancer patients. Although there are novel therapies as second line treatment for NSCLC, there is an issue for elderly patients. Patients and Methods: We collected retrospectively data from 60 patients >75 years of age. Thirty of these patients received nab-paclitaxel and first line treatment and were compared to thirty patients that received only best supportive care. Results: The median life of patients at the date of disease progression, although increased by the administration of the drug (92 days versus 70) was not confirmed statistically significantly (Mann-Whitney test: W = 280, p = 0.138). The administration of drug seems to keep stable the biological condition of patients (McNemar's test: χ 2 = 0.033, p = 0.99). Patients with chemotherapy the death rate was increased by 50% as compared to those with best supportive care (12 vs 8), the median life until the unfortunate event surpassed statistically significantly the latter (150 days of life as compared to 108, Mann-Whitney test: W = 57.5, p = 0.045). Discussion: Nab-paclitaxel as a monotherapy could be considered as a first line treatment option for patients > 75 years of age without any previous cardiological medical history when compared to best supportive care., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.