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Introduction The sensitivity of suspicious lung nodules biopsied by currently available techniques is suboptimal. Robotic-assisted navigation bronchoscopy (RANB) is a novel method for biopsying lung nodules. Our study objective was to determine the sensitivity for malignancy and overall diagnostic accuracy for RANB when combined with cone beam CT (CBCT) for secondary confirmation. Methods 52 consecutive patients were prospectively enrolled. Demographic data, nodule characteristics, procedural information, and follow-up results were obtained. Results Mean patient age was 66, with the majority Caucasian (73%) females (65%) with a similar number of never (46%) and former (46%) smokers. 15 patients had a history of cancer and 3 had a prior thoracic surgery. 59 total nodules were included as 7 patients had two nodules biopsied. Mean nodule diameter was < 2 cm in all dimension with the majority solid (41, 70%) and located in the upper lobes (left: 22, 37%; right: 17, 29%). Bronchus sign was absent (32, 54%) or present (27, 46%) in a similar number. All nodules were successfully reached with nine (15%) requiring minor directional changes after initial cone beam CT. A tissue diagnosis was obtained in 83% (49/59) of biopsied nodules, with malignancy (31, 65%) most common. Including all biopsy results and follow-up imaging, we obtained an 84% (31/37) procedural sensitivity for malignancy and an overall 86% (51/59) diagnostic yield. Conclusion RANB with CBCT increases sensitivity for malignancy and diagnostic accuracy of lung nodule biopsies. Combining these modalities has the potential to shift the diagnostic approach to pulmonary nodules.

Background Children with nephrotic syndrome are exposed to alternate day steroids for prolonged periods and this poses the need for evaluation of adrenocortical suppression using the adrenocorticotropic hormone (ACTH) stimulation test. Methods This cross-sectional study enrolled children (2–18 years) both with steroid sensitive nephrotic syndrome (SSNS) ( n  = 27) and steroid resistant (SRNS) ( n  = 25); those on daily prednisolone or having serious bacterial infections or hospitalized were excluded. The primary objective was to determine prevalence of adrenocortical suppression in those on low dose alternate day steroids for more than 8 weeks or having received > 2 mg/kg/d for > 2 weeks in the past 1 year and currently in remission. A baseline morning fasting sample of serum cortisol was taken and 25 IU of ACTH (Acton Prolongatum*) injected intramuscularly and repeat serum cortisol sample taken after 1 h. All patients with 1 h post ACTH cortisol < 18.0 µgm/dl were diagnosed with adrenal insufficiency. Receiver operating characteristic curve was drawn to predict the prednisolone dose for adrenal insufficiency. Results Fifty-two (33 males) children were enrolled (mean age 9.4 years); proportion of adrenal insufficiency was 50% and 64% using baseline and post stimulation cutoffs. The total cumulative annual dose of prednisolone 0.22 mg/kg/day predicted adrenocortical suppression with AUC 0.76 (95% CI 0.63–0.89), with sensitivity of 63.9% and specificity of 81.3%. Conclusions A significant proportion of children with nephrotic syndrome were detected with adrenal insufficiency on ACTH stimulation test. A cumulative steroid intake of > 0.22 mg/kg/day on an alternate day basis emerged as a risk factor for predicting adrenocortical suppression. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Transbronchial cryobiopsies (TBCB) have recently been introduced as a promising and safer alternative to surgical lung biopsy in the diagnostic approach to diffuse parenchymal lung diseases (DPLD). Despite a substantial and expanding body of literature, the technique has not yet been standardized and its place in the diagnostic algorithm of DPLD remains to be defined. In part, this reflects concerns over the diagnostic yield and safety of the procedure, together with the rapid spread of the technique without competency and safety standards; furthermore, there is a substantial procedural variability among centers and interventional pulmonologists. We report this expert statement proposed during the third international conference on “Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease” (Ravenna, October 27–28, 2016), which formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure. The following 5 domains were reviewed: (1) what is the role of TBCB in the diagnostic evaluation of DPLD: patient selection; (2) pathological considerations; (3) contraindications and safety considerations; (4) how should TBCB be performed and in what procedural environment; and (5) who should perform TBCB. Finally, the existence of white paper recommendations may also reassure local hospital credentialing committees tasked with endorsing an adoption of the technique.

Introduction Determining the cause of diffuse parenchymal lung disease (DPLD) is challenging. While surgical lung biopsy has been the standard approach, transbronchial lung cryobiopsy (TBLC) represents a minimally invasive alternative with an acceptable safety profile and reasonable accuracy. In this study, we prospectively assessed whether the use of cone beam CT (CBCT) coupled with a novel bronchoscope holder and prophylactic administration of vasoconstricting medications decreases potential complications and improves diagnostic accuracy when performing TBLC. Methods 33 patients presenting for evaluation of newly diagnosed DPLD were enrolled. Demographic data, pulmonary function values, chest imaging pattern, procedural information, and diagnosis were recorded. Results Mean patient age was 67, with the majority Caucasian ( n  = 26, 79%) and male ( n  = 20, 61%). Mean pulmonary function values revealed restrictive lung disease (76 ± 14% predicted) and diffusing capacity impairment (52 ± 16%). A non-usual interstitial pneumonia imaging pattern was commonly seen ( n  = 20, 61%). CBCT guided TBLC was performed in one lobe ( n  = 29, 88%) or two lobes ( n  = 4, 12%) with mean probe-to-pleura distance of 4.2 ± 1.3 mm. No peri or post procedural complications occurred. 32 patients (97%) received a histological diagnosis with a final multidisciplinary conference diagnosis possible for 32 (97%). Conclusion CBCT guided TBLC coupled with a novel articulating scope holder and prophylactic phenylephrine administration has the potential to increase safety and diagnostic yield for patients with newly identified DPLD. Future studies comparing different aspects of this approach in isolation and with other modalities have the potential to refine this procedure to improve patient care.

Background: Specimens from transbronchial lung biopsies lack sufficient quality due to crush artifact and are generally too small for diagnosis of diffuse lung diseases. Flexible cryoprobes have been shown to be useful in therapeutic bronchoscopy. We introduce a novel technique for obtaining lung biopsies bronchoscopically, using a flexible cryoprobe. Objectives: The purpose of this study was to show the feasibility of using a cryoprobe to obtain lung biopsies during flexible bronchoscopy. Methods: Forty-one patients with radiographic signs of diffuse lung disease were selected for transbronchial biopsy. During flexible bronchoscopy, conventional transbronchial biopsies using forceps were done first. Then a flexible cryoprobe was introduced into the selected bronchus under fluoroscopic guidance. Once brought into position, the probe was cooled and then retracted with the frozen lung tissue being attached on the probe’s tip. The tissue was processed for histology. After establishing a diagnosis, the specimen area was measured using a digital morphometry system. Results: We evaluated the biopsy samples of 41 patients. The mean specimen area was 5.82 mm 2 (0.58–20.88 mm 2 ) taken by forceps compared to 15.11 mm 2 obtained using the cryoprobe (2.15–54.15 mm 2 , p < 0.01). Two patients had a pneumothorax which resolved with tube thoracostomy. Biopsy-associated bleeding did not require any intervention. Transbronchial cryobiopsy contributed in a substantial number of cases to a definitive diagnosis. Conclusions: Transbronchial cryobiopsy is a novel technique which allows to obtain large biopsy samples of lung parenchyma that exceed the size and quality of forceps biopsy samples. Prospective trials are needed to compare this technique with surgical lung biopsy for diagnosis of diffuse lung diseases.

Purpose While there is significant mortality and morbidity with lung cancer, early stage diagnoses carry a better prognosis. As lung cancer screening programs increase with more pulmonary nodules detected, expediting definitive treatment initiation for newly diagnosed patients is imperative. The objective of our analysis was to determine if the use of a dedicated interventional pulmonology practice decreases time delay from new diagnosis of lung cancer or metastatic disease to the chest to treatment initiation. Methods Retrospective chart analysis was done of 87 consecutive patients with a new diagnosis of primary lung cancer or metastatic cancer to the chest from our interventional pulmonology procedures. Demographic information and time intervals from abnormal imaging to procedure and to treatment initiation were recorded. Results Patients were older (mean age 69) and former or current smokers (72%). A median of 27 days (1–127 days) passed from our diagnostic biopsy to treatment initiation. A median of 53 total days (2–449 days) passed from abnormal imaging to definitive treatment. Endobronchial ultrasound-guided transbronchial needle aspiration was the most commonly used diagnostic procedure (59%), with non-small cell lung cancer the majority diagnosis (64%). For surgical patients, all biopsy-negative lymph nodes from our procedures were cancer-free at surgical excision. Conclusions Compared to prior reports from international and United States cohorts, obtaining a tissue biopsy diagnosis through a gatekeeper interventional pulmonology practice decreases median delay from abnormal imaging to treatment initiation. This finding has the potential to positively impact patient outcomes and requires further evaluation.

Film cooling as applied to rocket nozzles is analyzed numerically with emphasis on the assessment of the effect of the mixing of coolant with the hot stream. Cooling performance, as characterized by cooling effectiveness, is studied for three different coolants in the three-dimensional, turbulent flow field of a supersonic convergent-divergent nozzle operating with a hot stream temperature of 2500 K over a range of blowing ratios. The coolant stream is injected tangentially into the mainstream using a diffuser-type injector. Parameters influencing the effectiveness, such as coolant injector configuration and mixing layer, are analyzed. Thermal and species mixing between the coolant and the mainstream are investigated with regard to their impact on cooling effectiveness. The results obtained provide insight into the film cooling performance of the gases and the heat transfer characteristics associated with these three gases. An injector taper angle of 30° results in the most effective cooling among the configurations considered (0°, 15°, 30° and 45°). Mixing of the coolant with the hot stream is examined based on the distributions of velocity, temperature and species. The higher values of cooling effectiveness for Helium are attributed to its thermophysical properties and the reduced rate of mixing with the hot stream. The results further indicate that through optimization of the blowing ratio and the coolant injector configuration, the film cooling effectiveness can be substantially improved.

Abstract Background An urgent need remains for antiviral therapies to treat patients hospitalized with COVID-19. PF-07304814—the prodrug (lufotrelvir) and its active moiety (PF-00835231)—is a potent inhibitor of the SARS-CoV-2 3CL protease. Method Eligible participants were 18 to 79 years old and hospitalized with confirmed COVID-19. This first-in-human phase 1b study was designed with 2 groups: single ascending dose (SAD) and multiple ascending dose (MAD). Participants could receive local standard-of-care therapy. In SAD, participants were randomized to receive a 24-hour infusion of lufotrelvir/placebo. In MAD, participants were randomized to receive a 120-hour infusion of lufotrelvir/placebo. The primary endpoint was to assess the safety and tolerability of lufotrelvir. The secondary endpoint was to evaluate the pharmacokinetics of lufotrelvir and PF-00835231. Results In SAD, participants were randomized to receive 250 mg lufotrelvir (n = 2), 500 mg lufotrelvir (n = 2), or placebo (n = 4) by continuous 24-hour infusion. In MAD, participants were randomized to receive 250 mg lufotrelvir (n = 7), 500 mg lufotrelvir (n = 6), or placebo (n = 4) by continuous 120-hour infusion. No adverse events or serious adverse events were considered related to lufotrelvir. At doses of 250 and 500 mg, concentrations for the prodrug lufotrelvir and active moiety PF-00835231 increased in a dose-related manner. Unbound concentrations of the lufotrelvir active metabolite reached steady state approximately 2- and 4-fold that of in vitro EC90 following 250- and 500-mg doses, respectively. Conclusions These safety and pharmacokinetic findings support the continued evaluation of lufotrelvir in clinical studies. Clinical Trials Registration. ClinicalTrials.gov NCT04535167. Single and multiple ascending PF-07304814 (lufotrelvir) infusions were generally safe and well tolerated in participants hospitalized with COVID-19. Unbound concentrations of the lufotrelvir active metabolite reached steady state approximately 2- and 4-fold that of in vitro EC90 following 250 and 500 mg/d, respectively.

Energy, a basic need of human life, has been playing significant role behind many technological developments. Most of the world’s commercial energy requirements are fulfilled by using fossil fuels. Combustion of fossil fuels releases toxic gases which in further turns as a source of pollution for the environment, globally. The present research work focused on minimizing the emissions that emerges during combustion in an IC engine through Reactivity Controlled Compression Ignition (RCCI) mode. The performance and emission characteristics of a single-cylinder CI engine are analyzed with 3 different fuels; biodiesel, butanol-gasoline (1:4 ratio), and biogas. The operational loads taken for the present study falls in the range from 5 N-m to 20 N-m at the engine speed of 1800 RPM. The influence of biogas on the emission characteristics is exclusively carried out with two different flow rates; 12lpm and 16lpm. The injection timings for butanol-gasoline blend are varied from 0 to 8ms. Fuel properties such as Viscosity, Vapor pressure, Density, Cloud point, Pour point, and Flashpoint are estimated. Engine parameters such as Brake Thermal Efficiency (BTE), Volumetric Efficiency (VE), HC, CO, NOx and smoke emissions, Peak pressure, Heat Release Rate (HRR), Ignition Delay, are analyzed. It is observed from the experiments that increasing injection time of pilot fuel - increases the HC and CO emissions; reduces the NOx emissions; decreases the smoke level with increase in biogas flow rate; and decreases the BTE, VE, and HRR

In this experimental investigation, a varied CR (CR) diesel engine is fuelled with palmyra biodiesel B20 (20% palmyra methyl ester + 80% diesel) and emulsified palmyra biodiesel (85% B20 + 10% water + 5% surfactant), with span 80 and tween 80 (hlb of 6.43) used as surfactants. The study aims to evaluate the performance, emissions and combustion characteristics of the engine at varying CR of 17, 17.5 and 18 with the standard CR set at 17.5. Results show that increasing the CR leads to an improvement in Brake Thermal Efficiency (BTE), with a 3.89% higher BTE observed at a CR of 18 compared to 17. Additionally, higher CRs result in significant reductions in emissions, including hydrocarbons by 25.49%, carbon monoxide by 28.35% and smoke by 11.82%) compared to running on neat diesel. These findings highlight the potential of emulsified palmyra biodiesel at higher CRs to improve the engine efficiency and reduce emissions, emphasizing its viability as a sustainable alternative fuel.