Gut dysbiosis has been associated with impaired outcomes in liver and kidney transplant recipients, but the gut microbiome of lung transplant recipients has not been extensively explored. We assessed ...the gut microbiome in 64 fecal samples from end-stage lung disease patients before transplantation and 219 samples from lung transplant recipients after transplantation using metagenomic sequencing. To identify dysbiotic microbial signatures, we analyzed 243 fecal samples from age-, sex-, and BMI-matched healthy controls. By unsupervised clustering, we identified five groups of lung transplant recipients using different combinations of immunosuppressants and antibiotics and analyzed them in relation to the gut microbiome. Finally, we investigated the gut microbiome of lung transplant recipients in different chronic lung allograft dysfunction (CLAD) stages and longitudinal gut microbiome changes after transplantation. We found 108 species (58.1%) in end-stage lung disease patients and 139 species (74.7%) in lung transplant recipients that were differentially abundant compared with healthy controls, with several species exhibiting sharp longitudinal increases from before to after transplantation. Different combinations of immunosuppressants and antibiotics were associated with specific gut microbial signatures. We found that the gut microbiome of lung transplant recipients in CLAD stage 0 was more similar to healthy controls compared to those in CLAD stage 1. Finally, the gut microbial diversity of lung transplant recipients remained lower than the average gut microbial diversity of healthy controls up to more than 20 years post-transplantation. Gut dysbiosis, already present before lung transplantation was exacerbated following lung transplantation.IMPORTANCEThis study provides extensive insights into the gut microbiome of end-stage lung disease patients and lung transplant recipients, which warrants further investigation before the gut microbiome can be used for microbiome-targeted interventions that could improve the outcome of lung transplantation.
Drug recalls occur frequently and have the potential to impact considerable numbers of patients and healthcare providers. However, in the absence of a comprehensive overview the extent of conducted ...recalls and their impact on patients remains unknown. To address this, we developed a comprehensive overview of drug recalls affecting patients. We compiled this overview based on the drug recall registrations from the Jeroen Bosch Hospital (JBZ), the University Medical Center Utrecht (UMCU), and the Royal Dutch Pharmacists Association (KNMP). A retrospective data analysis was conducted to identify drug recalls that affected patients. Specifically, we defined these as drug recalls that required patients to actively switch their drug to a different batch or brand of the same drug or to switch to a drug within the same or a different class of drugs. To quantify the impact, we used real‐world drug dispensing data. Between January 1, 2017, and December 31, 2021, we identified 48 drug recalls that necessitated patients to make active changes to their medications an estimated 855,000 times. Most of the affected patients (292,000) were required to switch to a different brand of the same drug, whereas in 95,000 cases patients had to switch to a drug from another drug class. Our study suggests that a significant number of patients are affected by drug recalls. Future efforts are needed to elucidate patients’ experiences and preferences regarding drug recalls, which could provide valuable insights to aid decision‐making by relevant (national) authorities concerning drug recalls.
•Real time EBUS-TBNA is effective & safe in diagnosing centrally located lung tumors.•EBUS-TBNA samples are highly adequate for molecular analysis.•EBUS can assess vascular/mediastinal tumor invasion ...(T4) and has added value to CT.
Tissue acquisition of lung tumors is crucial for diagnostic and treatment purposes. In patients with centrally located lung tumors without endobronchial abnormalities the yield of conventional bronchoscopy is poor. Objective of this study was to assess diagnostic yield of EBUS-TBNA in patients with lung tumors, located near or adjacent to the major airways.
International multicenter retrospective analysis (2013–2018) of linear EBUS databases in Bologna, Italy and Amsterdam, The Netherlands. Patients with a centrally-located lung tumor without endobronchial abnormalities who underwent lung tumor search with linear EBUS were included. Diagnostic yield, feasibility of EBUS guided tumor sampling, complication rate, adequacy of the aspirates for mutational analysis, and assessment of mediastinal/vascular invasion (T4) were evaluated.
Real-time EBUS-TBNA diagnostic yield to sample centrally located intrapulmonary tumor was 83% (136/163) and it was independent of tumor location (paratracheal, mainstem, lobar, segmental bronchus). The feasibility to sample the lung tumor was 89% (145/163). In 4 cases the tumor was not found with EBUS. In the other 14 cases, tumor sampling was not performed due to: loss of the echo window after needle insertion n = 3, interposition of a large vessel n = 7, switch to radial EBUS n = 1, switch and sampling through EUS or EUS-B n = 3. No major complications occurred. Mutational analysis was successful in 54/63 (86%) of samples. Using surgery as reference standard, EBUS proved more reliable than CT (24/24, 100% versus 22/24, 91.7%, respectively) in the assessment of mediastinal/vascular tumor invasion (T4 status). In conclusion: Lung tumors presenting without endobronchial abnormalities and located adjacent to the major airways can be safely sampled by EBUS-TBNA resulting in high diagnostic yield irrespective of tumor location. Successful molecular profiling and reliable assessment of mediastinal/vascular invasion (T4) in patients with advanced disease provide additional value to EBUS procedures in the setting of centrally-located lung lesions.
The diagnosis and staging of lung cancer critically depends on surgical procedures. Endoscopic ultrasound (EUS) -guided fine-needle aspiration (FNA) is an accurate, safe, and minimally invasive ...technique for the analysis of mediastinal lymph nodes (LNs) and can additionally detect tumor invasion (T4) in patients with centrally located tumors. The goal of this study was to assess to what extent EUS-FNA could prevent surgical interventions.
Two hundred forty two consecutive patients with suspected (n = 142) or proven (n = 100) lung cancer and enlarged (> 1 cm) mediastinal LNs at chest computed tomography were scheduled for mediastinoscopy/tomy (94%) or exploratory thoracotomy (6%). Before surgery, all patients underwent EUS-FNA. If EUS-FNA established LN metastases, tumor invasion, or small-cell lung cancer (SCLC), scheduled surgical interventions were cancelled. Surgical-pathologic verification occurred when EUS-FNA did not demonstrate advanced disease. Cancelled surgical interventions because of EUS findings was the primary end point.
EUS-FNA prevented 70% of scheduled surgical procedures because of the demonstration of LN metastases in non-small-cell lung cancer (52%), tumor invasion (T4) (4%), tumor invasion and LN metastases (5%), SCLC (8%), or benign diagnoses (1%). Sensitivity, specificity, and accuracy for EUS in mediastinal analysis were 91%, 100% and 93%, respectively. No complications were recorded.
EUS-FNA qualifies as the initial staging procedure of choice for patients with (suspected) lung cancer and enlarged mediastinal LNs. Implementation of EUS-FNA in staging algorithms for lung cancer might reduce the number of surgical staging procedures considerably.
The data transmission capabilities of silicon avalanche mode light-emitting diodes (AMLEDs) were investigated, and the results are correlated with the multiplication noise and leakage current. The ...incoming data were modulated using pulse-position modulation, and the bit error rate (BER) and jitter in the transmitted data were measured. The results indicate an intrinsically low speed in terms of BER and jitter. From various size AMLEDs, temperature variations, and optical excitations, it is shown that the speed can be improved by using AMLEDs with a: 1) relatively high multiplication noise; 2) relatively high leakage current; and 3) higher charge-per-bit. Design recommendations for the high-speed AMLEDs are discussed.
With ongoing CMOS evolution, the gate-oxide thickness steadily decreases, resulting in an increased radiation tolerance of MOS transistors. Combined with special layout techniques, this yields ...circuits with a high inherent robustness against X-rays and other ionizing radiation. In bandgap voltage references, the dominant radiation-susceptibility is then no longer associated with the MOS transistors, but is dominated by the diodes. This paper gives an analysis of radiation effects in both MOS devices and diodes and presents a solution to realize a radiation-hard voltage reference circuit in a standard CMOS technology. A demonstrator circuit was implemented in a standard 0.13 mum CMOS technology. Measurements show correct operation with supply voltages in the range from 1.4 V down to 0.85 V, a reference voltage of 405 mV plusmn 7.5 mV ( sigma = 6 mV chip-to-chip statistical spread), and a reference voltage shift of only plusmn1.5 mV (around 0.8%) under irradiation up to 44 Mrad (Si).
A deep understanding of people's support for road pricing may help policymakers to design more practical pricing schemes that are effective in abating congestion but lead to less public opposition. ...This study adds to the rich body of road pricing acceptability literature by taking a different approach that focuses on the underlying pattern of the arguments, beliefs and attitudes, which largely determine the viewpoint of individuals with respect to road pricing. We apply Q-methodology to find these viewpoints by asking respondents to rank order subjective arguments that are subtracted from the public debate on road pricing and to identify shared viewpoints that are called frames. Analysis revealed four frames: The polluter should pay, Focus on fair alternatives, What's in it for me? and Don't interfere. Only the Polluter should pay frame is positive about road pricing. The other three frames are negative about road pricing, which suggests that there is not just one single block of citizens opposed to road pricing, but that quite different arguments are used in the various frames. We discuss how these frames can be used by policy-makers that intend to implement road pricing, to fine-tune the design, communication and implementation process of road pricing schemes.
•Four frames are found: The polluter should pay, Focus on fair alternatives, What’s in it for me?, and Don’t interfere.•Different arguments are used in the frames which means that there is not just one block of citizens opposing road pricing.•A person-centred approach can provide fresh insights into the coherence of underlying beliefs, motives and arguments.
PDF
