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1.
Cureus ; 16(4): e57452, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38699125

RESUMO

Essential tremor (ET) is one of the most common adult movement disorders. As the worldwide population ages, the incidence and prevalence of ET is increasing. Although most cases can be managed conservatively, there is a subset of ET that is refractory to medical management. By virtue of being "reversible", deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is one commonly accepted intervention. As an alternative to invasive and expensive DBS, there has been a renaissance in treating ET with lesion-based approaches, spearheaded most recently by high-intensity focused ultrasound (HIFU), the hallmark of which is that it is non-invasive. Meanwhile, stereotactic radiosurgical (SRS) lesioning of VIM represents another time-honored lesion-based non-invasive treatment of ET, which is especially well suited for those patients that cannot tolerate open neurosurgery and is now also getting a "second look". While multiple SRS platforms have been and continue to be used to treat ET, there is little in the way of dosimetric comparison between different technologies. In this brief technical report we compare the dosimetric profiles of three major radiosurgical platforms (Gamma Knife, CyberKnife Robotic Radiosurgery, and Zap-X Gyroscopic Radiosurgery (GRS)) for the treatment of ET. In general, the GRS and Gamma Knife were shown to have the best theoretical dosimetric profiles for VIM lesioning. Nevertheless the relevance of such superiority to clinical outcomes requires future patient studies.

2.
J Appl Clin Med Phys ; : e14388, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38762906

RESUMO

BACKGROUND: The ZAP-X system is a novel gyroscopic radiosurgical system based on a 3 MV linear accelerator and collimator cones with a diameter between 4 and 25 mm. Advances in imaging modalities to detect small and early-stage pathologies allow for an early and less invasive treatment, where a smaller collimator matching the anatomical target could provide better sparing of surrounding healthy tissue. PURPOSE: A novel 3 mm collimator cone for the ZAP-X was developed. This study aims to investigate the usability of a commercial diode detector (microSilicon) for the dosimetric characterization of this small collimator cone; and to investigate the underlying small field perturbation effects. METHODS: Profile measurements in five depths as well as PDD and output ratio measurements were performed with a microSilicon detector and radiochromic EBT3 films. In addition, comprehensive Monte Carlo simulations were performed to validate the measurement observations and to quantify the perturbation effects of the microSilicon detector in these extremely small field conditions. RESULTS: It is shown that the microSilicon detector enables an accurate dosimetric characterization of the 3 mm beam. The profile parameters, such as the FWHM and 20%-80% penumbra width, agree within 0.1 to 0.2 mm between film and detector measurements. The output ratios agree within the measurement uncertainty between microSilicon detector and films, whereas the comparisons of the PDD results show good agreement with the Monte Carlo simulations. The analysis of the perturbation factors of the microSilicon detector reveals a small field correction factor of approximately 3% for the 3 mm circular beam and a correction factor smaller than 1.5% for field diameters above 3 mm. CONCLUSIONS: It could be shown that the microSilicon detector is well-suitable for the characterization of the new 3 mm circular beam of the ZAP-X system.

3.
Mutagenesis ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606763

RESUMO

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

4.
Chemosphere ; 356: 141819, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38575080

RESUMO

The comet assay allows the analysis of DNA damage caused by different genotoxins. This assay has recently gained interest because of its ease of studying the interactions of xenobiotics with different organisms. Chrysoperla externa (Hagen, 1861) is a species of great economic relevance because it is a predator of major agricultural pests during its larval stage. Neonicotinoids are the most important chemical class of insecticides introduced into markets. A previous imidacloprid toxicity assessment on C. externa showed that this neonicotinoid insecticide reduced the egg viability. The objective of this study was to analyze the genotoxicity of Confidor OD® (imidacloprid 20% a.i., LS, Bayer CropScience) on the biological control agent C. externa at DNA level using the comet assay as an ecotoxicological biomarker. A comet assay protocol has been developed for this species at first time. For the bioassays, the commercial product formulated Confidor OD® was used at two concentrations: 100 and 180 mg/l of the active ingredient. Selected eggs were dipped in a Confidor OD® solution for 15 s. Descriptors evaluated in the comet assay were damage index, % DNA damage, and tail length. The damage index did not show any significant differences between the different concentrations evaluated, but differences were observed for tail length, because at higher concentrations of Confidor OD®, there were greater DNA breaks. The DNA of the cells from treated eggs analyzed at 48 h and 96 h of development showed the same % DNA damage; that is, they had no recovery capacity. Application of Confidor OD® to C. externa eggs produced irreparable breaks at the DNA level. The technique adjusted for C. externa can be used in other beneficial insects to study pesticide genotoxicity using a comet assay.


Assuntos
Ensaio Cometa , Dano ao DNA , Insetos , Inseticidas , Neonicotinoides , Nitrocompostos , Animais , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Dano ao DNA/efeitos dos fármacos , Inseticidas/toxicidade , Insetos/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Mutagênicos/toxicidade , Larva/efeitos dos fármacos
5.
Phys Rev Lett ; 132(7): 075101, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38427884

RESUMO

Gyrokinetic simulations of the fishbone instability in DIII-D tokamak plasmas find that self-generated zonal flows can dominate the nonlinear saturation by preventing coherent structures from persisting or drifting in the energetic particle phase space when the mode frequency down-chirps. Results from the simulation with zonal flows agree quantitatively, for the first time, with experimental measurements of the fishbone saturation amplitude and energetic particle transport. Moreover, the fishbone-induced zonal flows are likely responsible for the formation of an internal transport barrier that was observed after fishbone bursts in this DIII-D experiment. Finally, gyrokinetic simulations of a related ITER baseline scenario show that the fishbone induces insignificant energetic particle redistribution and may enable high performance scenarios in ITER burning plasma experiments.

6.
Schmerz ; 2024 Feb 13.
Artigo em Alemão | MEDLINE | ID: mdl-38351150

RESUMO

BACKGROUND: The biopsychosocial model is fundamental for the understanding and treatment of chronic pain; however, little research has focused on whether those affected show a biopsychosocial understanding. The multidimensional questionnaire Biopsychosocial Pain Concept Matrix (BiPS matrix) is presented. The conception of the BiPS matrix is based on the biological, psychological and social areas as well as on the common sense model of self-regulation with five dimensions: (1) type of disorder, (2) assumptions on the causes, (3) consequences, (4) duration of the disease and (5) possibilities for control and treatment. OBJECTIVE: The present study aims to examine the content relevance and comprehension of the areas, dimensions and items, including the use of the BiPS matrix with children by interdisciplinary expert ratings. The questionnaire can be perspectively used by treating professionals for diagnostic purposes. METHOD: In an online study 17 experts were questioned. In addition to descriptive statistics, comments were evaluated using qualitative content analysis according to Mayring. RESULTS: All experts rated the assessment of pain concepts with the BiPS matrix as well as the areas and dimensions as very relevant. With respect to the items, suggestions were made mainly regarding the wording of the items and adjustments for children. DISCUSSION: From an expert point of view the BiPS matrix represents a relevant instrument. Further research on the psychometric properties of the BiPS matrix in adults and children is indicated. In addition, the BiPS matrix can also be used to investigate pain concepts of medical and psychotherapeutic professional groups to demonstrate the biopsychosocial understanding of pain and the associated treatment options.

7.
Scand J Rheumatol ; 53(3): 161-172, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38358097

RESUMO

OBJECTIVES: Our aim was to conduct a population-based projection to estimate the number of rheumatoid arthritis (RA) cases in Germany until 2040. METHOD: Data obtained from a report published in 2017 (doi:10.20364/VA-17.08) were used for future prediction analysis. The data were originally collected by the German Central Institute for Statutory Health Insurance. We used the illness-death model to estimate future numbers of RA cases, considering nine possible scenarios based on different incidence and mortality rates. RESULTS: In the baseline scenario, the number of women with RA is projected to increase by 417 000 cases and men by 179 000 cases by 2040, compared with 2015. Peak numbers of cases are concentrated in the 70-80-year-old age group, particularly among women. In the most favourable scenario (scenario 2), assuming a decreasing incidence, the total number of RA cases is projected to rise by 284 000 by 2040, reflecting a 38% relative increase from 2015 to 2040. The least favourable scenario (scenario 9), assuming an increasing incidence, projects a significant burden on the healthcare system. The total number of RA cases is expected to rise by 1.16 million by 2040, marking a substantial 158% relative increase from 2015 to 2040. CONCLUSIONS: Our research emphasizes a discernible trend: with an ageing society, improving treatment effectiveness, and declining all-cause mortality, we anticipate a rise in the absolute numbers of RA cases in Germany in the coming years. Our models robustly support this viewpoint, underscoring impending challenges for healthcare systems. Addressing these challenges demands multifaceted interventions.


Assuntos
Artrite Reumatoide , Masculino , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/epidemiologia , Incidência , Previsões , Alemanha/epidemiologia
8.
Mar Pollut Bull ; 201: 116141, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401386

RESUMO

The loggerhead turtle (Caretta caretta) has been suggested as a bio-indicator species for plastic pollution. However, detailed investigations in the eastern Mediterranean are limited. Here, we present data from loggerhead turtles (2012-2022; n = 131) of which 42.7 % (n = 57) had ingested macroplastic (pieces ≥ 5 mm). Frequency of occurrence (%) was not found to have changed over time, with body size (CCL cm), between stranded or bycaught turtles, or with levels of digesta present. The characteristics of ingested plastic (n = 492) were largely sheetlike (62 %), clear (41 %) or white (25 %) and the most common polymers identified were Polypropylene (37 %) and Polyethylene (35 %). Strong selectivity was displayed towards certain types, colours and shapes. Data are also presented for posthatchling turtles (n = 4), an understudied life stage. Much larger sample sizes will be needed for this species to be an effective bio-indicator, with the consideration of monitoring green turtles (Chelonia mydas) for the eastern Mediterranean recommended allowing a more holistic picture to be gathered.


Assuntos
Tartarugas , Animais , Conteúdo Gastrointestinal , Plásticos , Poluição Ambiental , Monitoramento Ambiental
9.
J Vet Cardiol ; 52: 14-18, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342049

RESUMO

Feline arterial thromboembolism has been reported to be secondary to various feline cardiomyopathies; however, it has not been described in cats with transient myocardial thickening. A previously healthy, one-year-old, castrated male cat presented with acute paraparesis and congestive heart failure. Echocardiography revealed asymmetric left ventricular free wall thickening and left atrial enlargement. Antithrombotic treatment and cardiac medication resulted in reperfusion and mobility on day seven in one limb and on day 10 in the other. Different complications were managed successfully, including worsening acute kidney injury, inflammation, pleural effusion, and anemia. After three weeks, the cat was discharged and prescribed oral antithrombotic drugs (clopidogrel and rivaroxaban) and cardiac medication. Within five months, echocardiographic findings normalized, and medical treatment was gradually discontinued. To date, the cat remains healthy at 1735 days after the initial diagnosis and 1494 days after the last antithrombotic medication. To the best of our knowledge, this is the first case report on feline arterial thromboembolism combined with transient myocardial thickening, with favorable long-term survival.


Assuntos
Doenças do Gato , Tromboembolia , Gatos , Animais , Masculino , Doenças do Gato/tratamento farmacológico , Doenças do Gato/patologia , Doenças do Gato/diagnóstico por imagem , Doenças do Gato/diagnóstico , Tromboembolia/veterinária , Tromboembolia/tratamento farmacológico , Ecocardiografia/veterinária , Cardiomiopatias/veterinária , Cardiomiopatias/complicações
10.
J Patient Rep Outcomes ; 8(1): 4, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38285076

RESUMO

BACKGROUND: Patient-reported outcomes (PROs) play a crucial role in assessing rheumatic diseases, offering insights into disease evaluation and treatment efficacy. This study focuses on PRO assessment in large vessel vasculitides, including Takayasu Arteritis and Giant Cell Arteritis (GCA). METHODS: We retrospectively analyzed routine data from patients treated at our rheumatology clinic over a 10-year span. Patient and physician-rated global disease activity scale (G-DAS) scores, measured on a numeric rating scale (0-10 points), were collected at each visit. Clinical variables like age, sex, body mass index (BMI), disease duration, lab values, pain perception, and questionnaire responses were recorded. Linear regression and generalized additive linear regression (GAM analysis) examined associations between PROs and these factors. RESULTS: The study included 138 patients, primarily diagnosed with GCA (94.4%). Mean follow-up was 2.5 years (0-7.7). Patient and physician G-DAS exhibited a moderate correlation (Pearson R 0.19, CI 0.14-0.24, p < 0.001). Higher patient G-DAS correlated with younger age (CI -3.4 - -1.5, p < 0.001), increased pain (CI 3.5-4, p < 0.001), functional limitations (HAQ, CI 0.5-0.6, p < 0.001), reduced physical (CI 2.3-2.7, p ≤ 0.001) and psychological well-being (CI 2.1-2.5, p < 0.001), and higher BMI (CI 1.3-2.4, p < 0.001). Physician G-DAS correlated with Birmingham Vasculitis Activity Score (V3.0; R 0.42, p 0.046) and were significantly linked to serum CRP elevations (ß = 0.04, CI 0.0-0.08, p 0.028). CONCLUSIONS: These findings underscore the need to integrate PRO measures into vasculitis disease management strategies, enhancing the understanding of disease activity from the patient's perspective.


Assuntos
Arterite de Células Gigantes , Arterite de Takayasu , Humanos , Estudos Retrospectivos , Arterite de Células Gigantes/diagnóstico , Arterite de Takayasu/diagnóstico , Medidas de Resultados Relatados pelo Paciente , Instituições de Assistência Ambulatorial
11.
J Clin Virol ; 171: 105637, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38218116

RESUMO

BACKGROUND: Reliable and fast detection and quantification of human cytomegalovirus (CMV) DNA in various diagnostic specimens is essential for care of immunocompromised or congenitally infected individuals. OBJECTIVES: To evaluate the analytical and clinical performance of the Panther Aptima® CMV (Hologic) quantitative real-time transcription mediated amplification (TMA) assay. STUDY DESIGN: Performance of the TMA assay run on the Hologic Panther Fusion was analysed for 32 proficiency testing samples and 21 quantitative reproducibility panel samples; additionally, we compared results of TMA assay and routine quantitative real-time PCR assays ("PCR-A"= Biomérieux CMV R-gene® or "PCR-B"= Laboratory-developed CMV-PCR) in 518 diagnostic specimens (254 plasma, 120 EDTA whole blood, 43 urine, 45 amniotic fluid and 56 breast milk) at two university hospital laboratories. RESULTS: All proficiency panel samples were correctly identified and quantified by the TMA assay; replicate testing of the reproducibility panel samples showed good reproducibility within and between the two laboratories. Sensitivity in plasma and WB was higher for the TMA assay detecting low-level CMV-DNAemia in samples tested negative by routine PCR. Quantitative CMV-DNAemia values correlated well between TMA and real-time PCR. Similarly, urine, AF and BM specimens showed a high rate of concordant results (91%, 98% and 98%, respectively) among TMA and PCR with good correlation of quantitative values. CONCLUSION: The performance of the Aptima® CMV TMA assay for viral blood load testing compared well to established real-time PCRs. In addition, it can be useful for diagnostics in urine, amniotic fluid and breast milk specimens.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Feminino , Humanos , Citomegalovirus/genética , Sensibilidade e Especificidade , Reprodutibilidade dos Testes , Infecções por Citomegalovirus/diagnóstico , DNA Viral/genética , Carga Viral
12.
Nat Commun ; 14(1): 7046, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37949859

RESUMO

Large laser facilities have recently enabled material characterization at the pressures of Earth and Super-Earth cores. However, the temperature of the compressed materials has been largely unknown, or solely relied on models and simulations, due to lack of diagnostics under these challenging conditions. Here, we report on temperature, density, pressure, and local structure of copper determined from extended x-ray absorption fine structure and velocimetry up to 1 Terapascal. These results nearly double the highest pressure at which extended x-ray absorption fine structure has been reported in any material. In this work, the copper temperature is unexpectedly found to be much higher than predicted when adjacent to diamond layer(s), demonstrating the important influence of the sample environment on the thermal state of materials; this effect may introduce additional temperature uncertainties in some previous experiments using diamond and provides new guidance for future experimental design.

13.
Rev Sci Instrum ; 94(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37955555

RESUMO

A methodology for measuring x-ray continuum spectra of inertial confinement fusion (ICF) implosions is described. The method relies on the use of ConSpec, a high-throughput spectrometer using a highly annealed pyrolytic graphite crystal [MacDonald et al., J. Instrum. 14, P12009 (2019)], which measures the spectra in the ≃20-30 keV range. Due to its conical shape, the crystal is sagittally focusing a Bragg-reflected x-ray spectrum into a line, which enhances the recorded x-ray emission signal above the high neutron-induced background accompanying ICF implosions at the National Ignition Facility. To improve the overall measurement accuracy, the sensitivity of the spectrometer measured in an off-line x-ray laboratory setting was revised. The error analysis was expanded to include the accuracy of the off-line measurements, the effect of the neutron-induced background, as well as the influence of possible errors in alignment of the instrument to the ICF target. We demonstrate how the improved methodology is applied in the analysis of ConSpec data with examples of a relatively low-neutron-yield implosion using a tritium-hydrogen-deuterium mix as a fuel and a high-yield deuterium-tritium (DT) implosion producing high level of the background. In both cases, the shape of the measured spectrum agrees with the exponentially decaying spectral shape of bremsstrahlung emission to within ±10%. In the case of the high-yield DT experiment, non-monotonic deviations slightly exceeding the measurement uncertainties are observed and discussed.

14.
Phys Rev Lett ; 131(15): 156701, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37897745

RESUMO

Spin-wave amplification techniques are key to the realization of magnon-based computing concepts. We introduce a novel mechanism to amplify spin waves in magnonic nanostructures. Using the technique of rapid cooling, we create a nonequilibrium state in excess of high-energy magnons and demonstrate the stimulated amplification of an externally seeded, propagating spin wave. Using an extended kinetic model, we qualitatively show that the amplification is mediated by an effective energy flux of high energy magnons into the low energy propagating mode, driven by a nonequilibrium magnon distribution.

16.
Mov Ecol ; 11(1): 50, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37550738

RESUMO

BACKGROUND: Fish migration has severely been impacted by dam construction. Through the disruption of fish migration routes, freshwater fish communities have seen an incredible decline. Fishways, which have been constructed to mitigate the problem, have been shown to underperform. This is in part due to fish navigation still being largely misunderstood. Recent developments in tracking technology and modelling make it possible today to track (aquatic) animals at very fine spatial (down to one meter) and temporal (down to every second) scales. Hidden Markov models are appropriate models to analyse behavioural states at these fine scales. In this study we link fine-scale tracking data of barbel (Barbus barbus) and grayling (Thymallus thymallus) to a fine-scale hydrodynamic model. With a HMM we analyse the fish's behavioural switches to understand their movement and navigation behaviour near a barrier and fishway outflow in the Iller river in Southern Germany. METHODS: Fish were tracked with acoustic telemetry as they approached a hydropower facility and were presented with a fishway. Tracking resulted in fish tracks with variable intervals between subsequent fish positions. This variability stems from both a variable interval between tag emissions and missing detections within a track. After track regularisation hidden Markov models were fitted using different parameters. The tested parameters are step length, straightness index calculated over a 3-min moving window, and straightness index calculated over a 10-min window. The best performing model (based on a selection by AIC) was then expanded by allowing flow velocity and spatial velocity gradient to affect the transition matrix between behavioural states. RESULTS: In this study it was found that using step length to identify behavioural states with hidden Markov models underperformed when compared to models constructed using straightness index. Of the two different straightness indices assessed, the index calculated over a 10-min moving window performed better. Linking behavioural states to the ecohydraulic environment showed an effect of the spatial velocity gradient on behavioural switches. On the contrary, flow velocity did not show an effect on the behavioural transition matrix. CONCLUSIONS: We found that behavioural switches were affected by the spatial velocity gradient caused by the attraction flow coming from the fishway. Insight into fish navigation and fish reactions to the ecohydraulic environment can aid in the construction of fishways and improve overall fishway efficiencies, thereby helping to mitigate the effects migration barriers have on the aquatic ecosystem.

17.
Int J Surg Case Rep ; 105: 108028, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36966719

RESUMO

INTRODUCTION: Synchronous visceral malignancy is rare especially for esophagogastric junction adenocarcinoma combined with malignancy in the pancreas. So far only 7 cases of combined partial pancreatoduodenectomy and esophagectomy for synchronous malignancy have been described in the literature and none for combined total pancreatectomy and esophagectomy. PRESENTATION OF CASE: We report the case of a 67-year-old male patient, who underwent multi-modality treatment including two-stage total pancreatoduodenectomy and subsequent Ivor-Lewis esophagectomy for synchronous adenocarcinoma of the distal esophagus and pancreatic multilocal metastases of a renal cell carcinoma after nephrectomy 17 years ago. Pathology revealed R0 resections for both malignancies and there were no postoperative complications. A 12 months follow-up showed no signs of recurrence and a good quality of life. CONCLUSION: Curative-intent, combined oncological two-stage open total pancreatoduodenectomy and esophagectomy with several days interval is safe and feasible in selected cases when performed by an experienced interdisciplinary team in a high-volume surgical center.

18.
Antioxidants (Basel) ; 12(2)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36830000

RESUMO

Idiopathic pulmonary fibrosis (IPF) has a detrimental prognosis despite antifibrotic therapies to which individual responses vary. IPF pathology is associated with oxidative stress, inflammation and increased activation of SRC family kinases (SFK). This pilot study evaluates individual responses to pirfenidone, nintedanib and SFK inhibitor saracatinib, markers of redox homeostasis, fibrosis and inflammation, in IPF-derived human bronchial epithelial (HBE) cells. Differentiated HBE cells from patients with and without IPF were analyzed for potential alterations in redox and profibrotic genes and pro-inflammatory cytokine secretion. Additionally, the effects of pirfenidone, nintedanib and saracatinib on these markers were determined. HBE cells were differentiated into a bronchial epithelium containing ciliated epithelial, basal, goblet and club cells. NOX4 expression was increased in IPF-derived HBE cells but differed on an individual level. In patients with higher NOX4 expression, pirfenidone induced antioxidant gene expression. All drugs significantly decreased NOX4 expression. IL-6 (p = 0.09) and IL-8 secretion (p = 0.014) were increased in IPF-derived HBE cells and significantly reduced by saracatinib. Finally, saracatinib significantly decreased TGF-ß gene expression. Our results indicate that treatment responsiveness varies between IPF patients in relation to their oxidative and inflammatory status. Interestingly, saracatinib tends to be more effective in IPF than standard antifibrotic drugs.

19.
J Neurooncol ; 161(1): 147-153, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36609807

RESUMO

PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Feminino , Temozolomida/uso terapêutico , Lomustina/uso terapêutico , Prognóstico , Dacarbazina/efeitos adversos , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Antineoplásicos Alquilantes/efeitos adversos
20.
Arch Orthop Trauma Surg ; 143(7): 4019-4029, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36399163

RESUMO

BACKGROUND: Boxer elbow and handball goalkeeper elbow are causes of impingement characterized by osteophytes formation at the olecranon and coronoid tip as well as their corresponding fossae. Herein, we present another distinct pathology in these patients: the formation of an exostosis at the posterolateral aspect of the elbow. METHODS: Between April 2016 and May 2020, 12 athletes with boxer elbow and handball goalkeeper elbow (mean age of 22 years) suffering from elbow pain were enrolled in the present study. Plain radiography, magnetic resonance imaging (MRI), and computer tomography (CT) scans were used to evaluate the bone conformation of the posterolateral aspect of the elbow. Assessment and staging of the ossification was performed by two independent fellowship-trained elbow surgeons. RESULTS: Bone marrow edema of the posterior aspect of the elbow at the origin of the anconeus muscle was initially detected in MRI scans. With the progression of the condition, imaging revealed an ossification posterior to the capitellum with bony bridges. In the advanced stage of the disease, the exostoses was unstable as the ossification had no adherence to the posterior capitellum during surgical excision. Plain radiographs are limited in their ability to detect the condition, whereas MRI and CT scans allow to identify a signal enhancement at the posterolateral aspect of the elbow. CONCLUSION: In patients without history of elbow trauma, bony irregularities of the posterior aspect of the capitellum may indicate ossification of the posterolateral aspect of the elbow, most likely caused by repetitive hyperextensions.


Assuntos
Articulação do Cotovelo , Artropatias , Humanos , Adulto Jovem , Adulto , Osteogênese , Cotovelo , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/cirurgia , Radiografia
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