Quantification of Salmonella in asymptomatic carrier animals can be used to assess microbial risk and monitor the level of contamination in domestic animals used for food production. We examined the ...sensitivity, specificity and accuracy of real-time qPCR, without pre-enrichment or selective enrichment stages, for the quantification of S. enterica serovar Enteritidis in resistant mice, as a model of asymptomatic carrier animal. The results were compared with those obtained by traditional bacteriological culture methods, the gold standard test. Two hundred and forty-three samples, including spleen, liver, mesenteric lymph nodes, portions of intestine, intestinal content of the ileocecal portion, and feces, were collected from a group of 27 C57BL/6 mice, that had been intragastrically inoculated with high doses of S. enterica serovar Enteritidis. The real-time qPCR assay presented a consistent linearity of the standard curve (r(2) = 0.999), with very low differences between melting temperatures, and low coefficients of variation in intra- (< 1%) and interassay (< 2%) comparisons. The primers were highly specific; there was no amplification with other Salmonella serovars or with DNA from uninfected tissues and feces from mice. The detection limit of the technique was defined as 32 copies of S. enterica serovar Enteritidis. A sensitivity of 90%, a specificity of 77% and an accuracy of 79% were obtained. The higher sensitivity of PCR was reflected in a kappa coefficient of 0.41, showing moderate agreement between tests. We conclude that real-time qPCR is a good alternative for diagnostic scanning in asymptomatic carrier animals, due to its high sensitivity and rapidity.
Aims/hypothesis The Krüppel-like factor 11 (KLF11; TIEG2), a pancreas-enriched Sp1-like transcription factor, is a known negative regulator of pancreatic exocrine cell growth. A recent study ...indicated KLF11-induced activation of the human proinsulin promoter (hInsP). Materials and methods We investigated the functional role of KLF11 in pancreatic beta cells. Results Endogenous KLF11 mRNA expression was found in whole rat pancreas, human pancreatic islets and INS-1E beta cells and was profoundly reduced by high glucose in INS-1E. Cotransfections of INS-1E and beta-TC3 beta cells with a human (h)KLF11 expression plasmid and an hInsP-driven reporter plasmid resulted in a substantial dose-dependent and glucose-independent inhibition of proinsulin promoter activity. 5'-deletion of hInsP demonstrated that hKLF11 acts via DNA sequences upstream of -173 and requires the beta cell-specific transcription machinery, since hKLF11-mediated inhibition of promoter activity was abolished in HEK293 cells. Besides a previously described GC box, we further identified a CACCC box within the hInsP, both putative KLF11-binding motifs. Electrophoretic mobility shift analysis (EMSA) verified binding of in vitro translated hKLF11 to the GC box, but neither hKLF11-induced inhibition nor basal hInsP activity was altered by mutation or 5'-deletion of the GC box. In contrast, CACCC box mutation substantially reduced basal promoter activity and partially diminished hKLF11 inhibition, although binding of in vitro translated hKLF11 to the CACCC box could not be verified by EMSA. Conclusions/interpretation In rodent beta cell lines, we demonstrate hKLF11-overexpression of human proinsulin gene expression and characterise a prominent role for the CACCC box in maintaining basal proinsulin promoter activity.
We report on a pair of siblings with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) and a novel Thr462Lysfs mutation in the TANK-binding kinase 1 (TBK1) gene identified through ...the European Early-Onset Dementia Consortium. The patients presented at the age of 77 and 75 years and displayed dementia and bulbar symptoms as well as progressive paresis. After a progressive course, both of them died only a few months after diagnosis. Most recently, TBK1 mutations were identified in patients with FTD and ALS. A loss of expression of the mutant allele, leading to 50 % reduced TBK1 protein levels, seems to be causative. The occurrence of TBK1 mutations in FTD and ALS underlines the fact that FTD and ALS are part of the same disease spectrum. For future therapeutic trials, characterization of TBK1 mutation carriers in presymptomatic cohorts, such as the genetic frontotemporal dementia initiative (GENFI), is of great importance.
Diagnosing myocarditis relies on multimodal data including magnetic resonance imaging (MRI), clinical symptoms, and blood values. The correct interpretation and integration of MRI findings requires ...radiological expertise and knowledge. We aimed to investigate the performance of Generative Pre-trained Transformer 4 (GPT-4), a large language model, for report-based medical decision-making in the context of cardiac MRI for suspected myocarditis.
This retrospective study includes MRI reports from 396 patients with suspected myocarditis and eight centers, respectively. MRI reports and patient data including blood values, age, and further clinical information were provided to GPT-4 and to radiologists with 1 (Resident 1), 2 (Resident 2), and 4 years (Resident 3) of experience in cardiovascular MRI and knowledge of the 2018 Lake Louise Criteria. The final impression of the report regarding the radiological assessment of whether myocarditis is present or not was not provided. The performance of GPT-4 and of the human readers were compared to a consensus reading (two board-certified radiologists with 8 and 10 years of experience in cardiovascular MRI). Sensitivity, specificity, and accuracy were calculated.
GPT-4 yielded an accuracy of 83%, sensitivity of 90%, and specificity of 78%, which was comparable to the physician with 1 year of experience (R1: 86%, 90%, 84%, p=.14) and lower than that of more experienced physicians (R2: 89%, 86%, 91%, p=.007 and R3: 91%, 85%, 96%, p<.001). GPT-4 and human readers showed a higher diagnostic performance when results from T1- and T2-mapping sequences were part of the reports, for Residents 1 and Resident 3 with statistical significance (p=.004 and p=.02, respectively).
GPT-4 yielded good accuracy for diagnosing myocarditis based on MRI reports in a large dataset from multiple centers and therefore holds the potential to serve as a diagnostic decision supporting tool in this capacity, particularly for less experienced physicians. Further studies are required to explore the full potential and elucidate educational aspects of the integration of large language models in medical decision-making.
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Abstract
Background:
Administered either alone or in combination with various cytostatic, endocrine
or targeted therapies, trastuzumab significantly improves the prognosis of patients with
...HER2-positive breast cancer. As trastuzumab is effective across multiple lines of therapy in the
metastatic setting (treatment beyond progression: TBP), it is often administered over a long
period of time. The aim of this study was to evaluate the tolerability and clinical practice of
long-term trastuzumab administration (> 1 year) in metastatic breast cancer patients treated
in a large university breast center.
Methods:
Metastatic breast cancer patients who
received at least 18 cycles of trastuzumab administered every three weeks at the University
Gynecological Hospital of Tuebingen between 1999 and 2012 were included in this retrospective
study. Typical combination drugs, side effects, and the impact of administration on left
ventricular ejection fraction (LVEF) were investigated.
Results:
72 patients were
eligible for inclusion in the study. The mean number of administrations was 50.14 (SD: 27.51).
In 53 patients the principle of TBP was followed across an average of 2.4 therapy lines. Classic
cardiac risk factors were present at the beginning of trastuzumab treatment in 34 patients
(47 %). Seven patients (10 %) experienced a decrease in LVEF during treatment, 9 patients (13 %)
had hypersensitivity reactions. Treatment was discontinued in two patients due to side effects
(1 × progressive LVEF decrease, 1 × intolerance).
Summary:
The administration of
trastuzumab across multiple lines of therapy was generally tolerated well. Cardiac risk factors
were not a limiting factor. If regular cardiac monitoring is done, trastuzumab appears not only
to improve survival but also helps preserve the quality of life of patients with HER2-positive
metastatic breast cancer.
•Deep learning-based photon-counting artificial intelligence-derived fractional flow reserve evaluation improves the diagnostic capabilities of coronary CT angiography in pre-TAVR work-up for the ...diagnosis of coronary artery stenosis ≥ 50%.•Implementation of artificial intelligence-derived fractional flow reserve evaluation reduces the need for invasive coronary angiography in pre-TAVR work-up.•Integration of photon-counting artificial intelligence-derived fractional flow reserve evaluation can streamline coronary artery disease evaluation in clinical pre-TAVR work-up.
The purpose of this study was to evaluate the capabilities of photon-counting (PC) CT combined with artificial intelligence-derived coronary computed tomography angiography (PC-CCTA) stenosis quantification and fractional flow reserve prediction (FFRai) for the assessment of coronary artery disease (CAD) in transcatheter aortic valve replacement (TAVR) work-up.
Consecutive patients with severe symptomatic aortic valve stenosis referred for pre-TAVR work-up between October 2021 and June 2023 were included in this retrospective tertiary single-center study. All patients underwent both PC-CCTA and ICA within three months for reference standard diagnosis. PC-CCTA stenosis quantification (at 50% level) and FFRai (at 0.8 level) were predicted using two deep learning models (CorEx, Spimed-AI). Diagnostic performance for global CAD evaluation (at least one significant stenosis ≥ 50% or FFRai ≤ 0.8) was assessed.
A total of 260 patients (138 men, 122 women) with a mean age of 78.7 ± 8.1 (standard deviation) years (age range: 51–93 years) were evaluated. Significant CAD on ICA was present in 126/260 patients (48.5%). Per-patient sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 96.0% (95% confidence interval CI: 91.0–98.7), 68.7% (95% CI: 60.1–76.4), 74.3 % (95% CI: 69.1–78.8), 94.8% (95% CI: 88.5–97.8), and 81.9% (95% CI: 76.7–86.4) for PC-CCTA, and 96.8% (95% CI: 92.1–99.1), 87.3% (95% CI: 80.5–92.4), 87.8% (95% CI: 82.2–91.8), 96.7% (95% CI: 91.7–98.7), and 91.9% (95% CI: 87.9–94.9) for FFRai. Area under the curve of FFRai was 0.92 (95% CI: 0.88–0.95) compared to 0.82 for PC-CCTA (95% CI: 0.77–0.87) (P < 0.001). FFRai-guidance could have prevented the need for ICA in 121 out of 260 patients (46.5%) vs. 97 out of 260 (37.3%) using PC-CCTA alone (P < 0.001).
Deep learning-based photon-counting FFRai evaluation improves the accuracy of PC-CCTA ≥ 50% stenosis detection, reduces the need for ICA, and may be incorporated into the clinical TAVR work-up for the assessment of CAD.
Most school counseling site supervisors have not received training in clinical supervision despite regularly serving as supervisors for school counseling students. In this article, we describe how ...one university has created a clinical faculty supervision training program for school counselors to address this need. The program infrastructure, training activities, session content, and evaluation methods are described. We present informal program evaluation data (N = 19) assessing participants' perspectives of the program and discuss implications for supervision training.
Abstract Background New-onset diabetes mellitus after organ transplantation (PTDM) significantly impairs patient and organ survival. Published rates of PTDM range from 2% to 54%, depending on the ...definition. Objectives To analyze incidence of PTDM after renal transplantation according to recent guidelines and to evaluate implementation of a prospective standardized screening protocol. Patients and Methods Data for all consecutive patients who underwent transplantation from 2000 to 2006 were analyzed retrospectively for PTDM. In a prospective pilot trial all candidates for living related donor transplantation underwent a 75-g oral glucose tolerance test at evaluation prior to renal transplantation and at 3, 6, and 12 months thereafter. Results Data for 181 out of 271 consecutive patients were analyzed. Of these patients, 36 (19.9%) developed PTDM. Age, body mass index, pretransplantation fasting glucose concentration, and number of HLA mismatches were significant predictive risk factors. Posttransplantation diabetes mellitus occurred more frequently in patients receiving a cadaver organ compared with a living donor organ and in those receiving tacrolimus therapy vs cyclosporine therapy. Preliminary results demonstrated a 55.5% incidence of PTDM at 3 months in patients who received a living donor organ, much higher than expected. Conclusions With an incidence of approximately 20%, PTDM is a frequent complication of transplantation. Prospective screening using oral glucose tolerance testing is a more sensitive method for detection of impaired glucose metabolism and PTDM. Relevance and therapeutic consequences must be determined in large-scale prospective studies.
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