AZ Turnhout

Introduction: Aspiration of foreign bodies is relatively uncommon in adults but may cause significant morbidity because of the formation of granulation tissue. This granulation tissue can cause complications, for example, airway obstruction, hemoptysis, and post-obstructive infections. Case Report: We present the case of a 63-year-old man with dyspnoea and hemoptysis. Computed tomography (CT) thorax showed a foreign body in the bronchus intermedius. Upon removal of the foreign body, extensive granulation tissue was found, causing bronchial obstruction. The granulation tissue was successfully treated with cryotherapy and coagulation. After cryotherapy, the patient was admitted because of a post-obstructive pneumonia caused by airway obstruction due to necrotic tissue. This necrotic tissue was removed during repeat bronchoscopy. Conclusion: Granulation tissue should only be removed when bronchial obstruction occurs. A stepwise approach is advised after removal of a foreign body when residual granulation tissue is present. Our case highlights this stepwise approach of conservative management with active follow-up. When bronchial obstruction is present, the granulation tissue should be removed. Interventional techniques such as cryotherapy or coagulation are effective. Cryotherapy causes necrotic tissue that will heal over time. However, this necrotic tissue can cause airway obstruction which can lead to post-obstructive pneumonia. This is a known delayed complication of cryotherapy and needs immediate re-intervention to clear the airways. Our case highlights the potential delayed complication of cryotherapy as well.

Voriconazole (VRC), a triazole antifungal agent, is recommended as primary treatment for invasive aspergillosis. Due to its unpredictable dose-exposure relationship, therapeutic drug monitoring (TDM) is recommended. Despite TDM, the probability of achieving therapeutic targets is only approximately 50%. This highlights the need for new dosing strategies. Calculating the metabolic ratio (MR) of NOX, the principal N-oxide metabolite of voriconazole primarily formed by the genetically polymorphic CYP2C19 enzyme, to VRC concentrations could serve as a surrogate for phenotype information. This is particularly relevant since the CYP2C19 genotype is often unavailable in acute clinical settings. Moreover, genotype may be less informative during inflammation due to a phenomenon known as 'phenoconversion', where inflammation masks genotype effects through downregulation of CYP450 enzymes. However, before integrating NOX in population PK models and/or as an adjunct in voriconazole TDM flowcharts, it is important to understand the factors impacting NOX exposure, and hence the MR. The objective of this narrative review is therefore to summarise recent literature on patient- and drug-related covariates impacting NOX exposure. A comprehensive search was conducted in PubMed and Embase for articles published from 2003 to 2025 focusing on factors impacting NOX or the MR. Twenty-one articles were included, predominantly involving adult patients from an Asian or white ethnicity. Studies were mainly set up as pharmacokinetic (PK) studies, in which associations between NOX or MR were assessed in uni- or multivariate analyses. Key covariates identified were as follows: (1) voriconazole dose (6/11 studies)-higher doses increasing NOX, although this relationship was complicated by saturated metabolism; (2) C-reactive protein (CRP) (8/9)-higher inflammation levels correlated with reduced metabolic capacity due to CYP450 enzyme downregulation; (3) age (7/12)-children exhibited higher MR, probably driven by higher clearance due to increased CYP2C19 and FMO3 expression, while older adults (> 60 years) showed decreased MR due to a decline in CYP2C19 activity; (4) CYP2C19 genotype (10/13)-poor metabolizers had lower MR and lower NOX, supporting the utility of genotyping, if available with acceptable turnaround time. A CRP threshold of 100 mg/L has been found in some studies and may serve as a crucial indicator for clinicians in optimising dosage adjustments. Although hepatic impairment is recognised as a significant covariate for voriconazole, its influence on NOX or the MR was found limited in this review. This is likely due to the exclusion of patients with hepatic impairment from most studies, which resulted in lower interindividual variation in liver function test results. While renal function does not affect voriconazole exposure, it may impact NOX or MR, as some studies suggest a higher renal clearance of NOX compared to voriconazole. However, only one of the included studies suggested that impaired renal function resulted in a higher MR, indicating NOX accumulation. Further research is however needed. VRC dose, CRP, age and CYP2C19 genotype are the primary covariates affecting NOX or MR, and renal and liver function should also be considered in future population pharmacokinetic models and TDM protocols.

Background Since its introduction in clinical practice, patient selection and procedural technique for transcatheter aortic valve implantation (TAVI) have continued to evolve. Methods We investigated temporal trends in patient profiles, procedural, 30-day and 1-year clinical outcomes in all consecutive patients undergoing TAVI at our centre from March 2008 to February 2024 (n = 1000). Patients were stratified into eight consecutive 2-year calendar cohorts. Outcomes were reported according to VARC-III criteria. Results Median age was 82 y (53% male). Over the consecutive cohorts, we observed significant decreases in STS score (8.1 ± 3.1 to 4.4 ± 2.6%) and EuroSCORE II (10.2 ± 8.0 to 6.4 ± 7.0; p < 0.001 for both). In-hospital death rates decreased significantly (9.4% to 1.3%; p = 0.030). The incidence of major vascular complications, life-threatening bleeding, and cardiac tamponade decreased significantly over time (p < 0.05 for all). Enhanced learning and a shift to a minimalist approach resulted in reduced need for intensive care (from 4 [3–5] to 0 days) and shorter hospital stay (from 13 [8–19] to 2 [2–4] days) (p < 0.001 for both). Overall 30-day survival was 96.4%, with significant improvement across cohorts (93.4% to 98.7%), while 1-year survival was 88.1% with a similar gradual increase (81.3% to 90.2%). Composite VARC-III endpoints demonstrated high technical success and significant improvements in device success and early safety across the eight 2-year cohorts. Conclusions Over 15 years we observed a shift from very high-risk towards predominantly intermediate- to high-risk patients, together with substantial procedural simplification and a marked reduction in in-hospital complications and length of stay. These improvements translated into a significant increase in 30-day and 1-year survival.

BackgroundPatients with pancreatic ductal adenocarcinoma face a poor prognosis, with radical resection being the only potential cure. Because symptoms typically appear late, many patients are diagnosed with advanced disease. Locally advanced pancreatic tumours are characterised by extensive vascular involvement, which precludes R0 resection. Systemic therapy is therefore indicated, not only for palliation but also for reducing the risk of metastatic disease. Locoregional control remains paramount, irrespective of distant metastases as progressive tumours can cause considerable morbidity, negatively affecting patients’ quality of life. Previous studies investigating conventionally fractionated (chemo)radiotherapy have yielded mixed results, indicating opportunities for further research to optimise treatment outcomes. The TORPEDO study aims to prospectively assess whether adding stereotactic body radiation therapy (SBRT) to standard chemotherapy can improve outcomes in patients with initially inoperable, non-metastasized pancreatic ductal adenocarcinoma.MethodsThis study is a multicentre randomised phase II trial. While it primarily targets locally advanced lesions, patients with borderline resectable tumours who are either medically inoperable or decline surgery are also eligible. After twelve weeks of induction chemotherapy (modified FOLFIRINOX or gemcitabine/nab-paclitaxel), patients without development of distant metastases are randomised 1:1 to receive either continued chemotherapy alone (arm A) or one month of chemotherapy followed by SBRT (5 × 8 Gy) (arm B). Resectability is evaluated through a multidisciplinary tumour board. The primary endpoint is the 2-year progression-free survival. Secondary endpoints include overall survival, local progression-free survival, metastasis-free survival, objective response rate, resectability, R0 resection rates, surgical morbidity, toxicity, quality of life, and the impact of radiation doses on outcomes.DiscussionWe evaluate the efficacy and safety of SBRT following induction chemotherapy in patients with inoperable, non-metastasized pancreatic ductal adenocarcinoma. We hypothesize that adding SBRT enhances outcome by improving local control and increasing overall survival. Effective control of the pancreatic primary tumor may help reduce pain and thereby improve quality of life.Trial registrationThe ethics committee of the GZA Hospitals approved this study on April 8, 2024. It was registered on ClinicalTrials.gov (NCT06691425) on November 15, 2024.

Background: Patellar tendinopathy (PT) is a highly prevalent injury among jumping athletes. The long-term prognosis of athletes with PT following physical therapy is unknown. Purpose: To assess self-perceived recovery rate and the 5-year change in pain levels, disability, and sports participation, and to explore the prognostic factors associated with self-perceived recovery. Study Design: Cohort study; Level of evidence, 3. Methods: Athletes with PT who were previously enrolled in a randomized trial and received education, load management advice, and exercise therapy instructions at baseline were eligible. An online questionnaire was sent 5 years after inclusion. Self-perceived recovery was assessed by a dichotomized 7-point global rating of change (recovery was defined as “significantly improved” to “completely recovered”). Pain levels during sports (0-10 points) and disability assessed by the Victorian Institute of Sport Assessment–Patellar (VISA-P) score were recorded at baseline and 5 years. Sports participation was categorized into return to performance, return to sport, return to participation, and quitting sports. Nonparametric tests were performed to compare scores at baseline and 5 years. Logistic regression models were used to identify prognostic factors. Results: Of 76 eligible participants, 58 (76%) responded (mean age, 30 years [SD, 4 years]; 28% female). At a mean follow-up of 5 years, 76% of participants felt recovered. Pain levels during sports (median, 7 points [IQR, 7-8 points] to 2 points [IQR, 1-4 points]) and VISA-P score (median, 57 [IQR, 45-66] to 82 [IQR, 74-97] points) significantly improved from baseline to 5 years (all P < .001). In total, 41 participants (71%) returned to their desired sports (68% to performance and 32% below preinjury level), 12 participants (21%) returned to participation in other sports, and 5 (9%) completely ceased sports participation. Participants who felt unrecovered had higher levels of pain and disability and lower return to performance (all P < .05). No prognostic factors were identified that were associated with self-perceived recovery. Conclusion: Athletes with PT after physical therapy can expect a generally acceptable long-term prognosis. However, almost one-quarter did not feel recovered and perceived worse patient-reported outcomes. Clinicians treating athletes with PT may use these findings to estimate the average prognosis.

Two distinct stx2f-carrying Escherichia coli (E. coli) strains, isolated from a child with uncomplicated diarrhea fifteen weeks apart, were characterized by combining short- and long-read sequencing to compare their genetic relatedness. One strain was characterized as Shiga toxin-producing E. coli (STEC)/typical enteropathogenic E. coli (tEPEC) O63:H6 with a repertoire of virulence genes including stx2f, eae (α2-subtype), cdt, and bfpA. The other STEC with serotype O157:H16, reported for the first time as stx2f-carrying Escherichia coli in this study, possessed, in addition, eae (ε-subtype) and cdt, amongst other virulence-related genes. BLAST comparison showed that the stx2f-harboring prophage sequences of both strains were highly homologous (99.6% identity and 96.1% coverage). These results were corroborated by core Stx2f phage Multilocus Sequence Typing (cpMLST) as the stx2f-harboring prophages of both isolates clustered together when compared to those of 167 other human stx2f-carrying Escherichia coli. Overall, the stx2f-harboring prophages of the two distinct E. coli strains isolated from the present case were highly similar, suggesting that the stx2f-harboring phage might have been transferred from the STEC/tEPEC O63:H6 strain to the atypical EPEC (aEPEC) O157:H16 strain in the gut of the child.

A metal 3D-printed high performance multi-jet impingement cooling solution for enabling thermal management of power electronics is presented for integration in electric vehicles. In this paper, we describe the concept, metal additive manufacturing and assembling to demonstrate the proof-of-concept of direct liquid jet impingement cooling of mock-up power modules dissipating heat loss up to 400 W (~230 W/cm<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup>).

Adsorben berupa pektin berhasil diekstraksi dari kulit pisang menggunakan larutan asam kuat dan telah digunakan untuk menyisihkan ion Fe3+ dalam air. Pengaruh berbagai parameter terhadap proses adsorbsi, seperti waktu kontak, pH larutan, dosis adsorben, dan temperatur adsorbsi diinvestigasi dalam suatu sistem batch. Konsentrasi ion Fe3+ dalam larutan air diukur menggunakan Atomic Absorption Spectrometry . Efisiensi adsorbsi terbaik diperoleh pada waktu kontak selama 4 jam, pH larutan 2, dosis adsorben sebesar 3 g, dan temperatur 20oC. Mekanisme proses adsorbsi dan perubahan energi bebas Gibbs, entalpi, serta entropi telah dievalusi. Model isoterm Freundlich dan Temkin paling sesuai untuk menggambarkan mekanisme adsorbsi ion Fe3+ pada pektin dengan R2 berturut-turut 0,9871 dan 0,9591. Data parameter termodinamika membuktikan bahwa adsorpsi ion Fe3+ bersifat eksotermis dan berlangsung secara tidak spontan pada rentang temperatur 20 hingga 60ᵒC. Penelitian ini menunjukkan bahwa kulit pisang dapat dimanfaatkan sebagai adsorben murah yang menjanjikan untuk menghilangkan ion Fe3+ dalam air.