In Europe, pulmonary histoplasmosis is rarely diagnosed except in travelers. We report a probable autochthonous case of severe chronic pulmonary histoplasmosis in an immunocompetent man in ...Switzerland without travel history outside of Europe. Diagnosis was achieved by histopathology, fungal culture, and serology, but the source of the infection remains speculative.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Studies validating the prognostic accuracy of the tumor-node-metastases (TNM) classification in patients with lung cancer treated by neoadjuvant therapy are scarce. Tumor regression, particularly ...major pathological response (MPR), is an acknowledged prognostic factor in this setting. We aimed to validate a novel combined prognostic score. This retrospective single-center study was conducted on 117 consecutive patients with non-small cell lung cancer resected after neoadjuvant treatment at a Swiss University Cancer Center between 2000 and 2016. All cases were clinicopathologically re-evaluated. We assessed the prognostic performance of a novel prognostic score (PRSC) combining T-category, lymph node status, and MPR, in comparison with the eighth edition of the TNM classification (TNM8), the size adapted TNM8 as proposed by the International Association for the Study of Lung Cancer (IASLC) and MPR alone. The isolated ypT-category and the combined TNM8 stages accurately differentiated overall survival (OS, stage p = 0.004) and disease-free survival (DFS, stage p = 0.018). Tumor regression had a prognostic impact. Optimal cut-offs for MPR emerged as 65% for adenocarcinoma and 10% for non-adenocarcinoma and were statistically significant for survival (OS p = 0.006, DFS p < 0.001). The PRSC differentiated between three prognostic groups (OS and DFS p < 0.001), and was superior compared to the stratification using MPR alone or the TNM8 systems, visualized by lower Akaike (AIC) and Bayesian information criterion (BIC) values. In the multivariate analyses, stage III tumors (HR 4.956, p = 0.003), tumors without MPR (HR 2.432, p = 0.015), and PRSC high-risk tumors (HR 5.692, p < 0.001) had significantly increased risks of occurring death. In conclusion, we support 65% as the optimal cut-off for MPR in adenocarcinomas. TNM8 and MPR were comparable regarding their prognostic significance. The novel prognostic score performed distinctly better regarding OS and DFS.
Context:
Treatment of refractory adrenocortical carcinoma (ACC) is not established. Animal experiments pointed toward adrenal toxicity of sunitinib.
Objective:
The objective of the study was to ...determine the antitumor effects of sunitinib in refractory ACC.
Design:
This was a phase II, open-label trial using a two-stage accrual design.
Setting:
The study was conducted at two tertiary referral centers.
Patients:
Thirty-eight patients with refractory ACC progressing after mitotane and one to three cytotoxic chemotherapies participated in the study.
Intervention:
The intervention included sunitinib at a standard dose (50 mg/d, 4 wk on, 2 wk off).
Main Outcome Measure:
Response was defined as progression-free survival (PFS) of 12 wk or longer (first tumor evaluation).
Results:
Thirty-five patients could be evaluated for response. Five patients experienced stable disease, 24 had progressive disease, and six patients died from ACC before the first evaluation (naïve estimate five of 35 = 14.3%, median unbiased response rate 15.4%, 95% confidence interval 5.0–33.4%). The median PFS was 2.8 months. In responders, PFS ranged between 5.6 and 11.2 months and overall survival between 14.0 and 35.5 months. Of 36 serious adverse events, only nine were possibly related to sunitinib. Concomitant mitotane appeared to negatively impact on outcome. Furthermore, a negative correlation between the serum concentrations of sunitinib plus its active metabolite N-desethylsunitinib (SU12662) and mitotane (r = −0.650; P = 0.114) was observed in seven evaluable patients suggestive of a relevant drug interaction.
Conclusion:
Sunitinib has modest activity in advanced refractory ACC, which compares favorably with other targeted treatments in these patients. Sunitinib serum levels might have been profoundly reduced by mitotane induced cytochrome P450-3A4 activity attenuating its antitumor activity and adverse effects. Together these findings suggest that sunitinib deserves further investigation in mitotane-naïve ACC patients.
Abstract Purpose The goal of this prospective study was to evaluate the possible diagnostic benefits of contrast-enhanced digital mammography (CEDM) over conventional mammography. Materials and ...methods Our analysis included data from 70 patients with a total of 80 lesions (30 malignant and 50 benign). A series of contrast-enhanced images was acquired from each patient using a modified imaging system (GE Senographe 2000D with copper filter) suitable for displaying iodine contrast medium. After the mask image had been taken, the contrast medium was administered using a dosage of 1 ml/kg body weight at a rate of 4 ml/s. Three contrast-enhanced images in the cranio-caudal projection plane were then captured at intervals of 60 s. The mask image was logarithmically subtracted from the contrast-enhanced images. We performed a ROC analysis of diagnostic quality with three readers. Results On average, 5.66 more malignant lesions were detected with the addition of digital dynamic contrast mammography versus conventional mammography alone. The sensitivity was increased from an average of 0.43 in conventional mammography to an average of 0.62 with contrast mammography. Even in dense breast parenchyma, the sensitivity increased from an average of 0.35–0.59. In the multi-reader-ROC analyses of all readers, the differences in the AUC with p = 0.02 (BI-RADS) proved statistically significant in all cases. The Wilcoxon test showed that Readers I and II primarily used the CEDM to upgrade enhancing lesions to a higher BI-RADS category or a higher probability of malignancy. These two readers benefited most from the CEDM in the ROC analysis. Conclusion Overall, we conclude that the addition of dynamic digital subtraction mammography to conventional mammography can significantly improve diagnostic quality. The increased sensitivity is particularly pronounced in the case of dense breast tissue.
The widespread adoption of renewable energy hinges on the efficient transportation of hydrogen. Reciprocating piston compressor technology in non-lubricated operation will play a key role, ensuring ...high flow rates and compression ratios. These systems rely on advanced high-strength sealing solutions for piston and rod packing rings utilizing advanced fiber-reinforced polymers. Polyphenylene sulfide (PPS) polymer matrix composites have seen use in tribological applications and promise high mechanical strength and wear resistance. The presented work describes carbon and glass fiber-reinforced PPS matrix polymers in comparison, which are characterized by complementary methods to investigate their properties and potential for application in reciprocating compressor under non-lubricated operation. Thermo-mechanical and tribological testing was supported by microstructure analysis utilizing advanced X-ray and electron imaging techniques. New insights in micromechanical deformation behavior in regard to fiber materials, interface strength and orientation in fiber-reinforced polymers are given. Conclusions on the suitability of different PPS matrix composites for high-pressure hydrogen compression applications were obtained.
Abstract Explainable artificial intelligence (XAI) has experienced a vast increase in recognition over the last few years. While the technical developments are manifold, less focus has been placed on ...the clinical applicability and usability of systems. Moreover, not much attention has been given to XAI systems that can handle multimodal and longitudinal data, which we postulate are important features in many clinical workflows. In this study, we review, from a clinical perspective, the current state of XAI for multimodal and longitudinal datasets and highlight the challenges thereof. Additionally, we propose the XAI orchestrator, an instance that aims to help clinicians with the synopsis of multimodal and longitudinal data, the resulting AI predictions, and the corresponding explainability output. We propose several desirable properties of the XAI orchestrator, such as being adaptive, hierarchical, interactive, and uncertainty-aware.
We report the case of a young patient treated with rituximab-containing chemotherapy who was infected with measles despite previous vaccination. Treatment with vitamin A, ribavirin, and ...immunoglobulins was started; nevertheless he developed severe pneumonitis and deceased. Broad vaccination coverage is crucial in protecting vulnerable subjects.
Précis:
Pregnancy-induced CS due to hCG-stimulated transformation of LHCGR-positive undifferentiated subcapsular cells into LHCGR-positive hyperplastic cortical cells with hCG-stimulated cortisol ...secretion.
Abstract
Context:
Elevated human choriogonadotropin (hCG) may stimulate aberrantly expressed luteinizing hormone (LH)/hCG receptor (LHCGR) in adrenal glands, resulting in pregnancy-induced bilateral macronodular adrenal hyperplasia and transient Cushing syndrome (CS).
Objective:
To determine the role of LHCGR in transient, pregnancy-induced CS.
Design, Setting, Patient, and Intervention:
We investigated the functional implications of LHCGRs in a patient presenting, at a tertiary referral center, with repeated pregnancy-induced CS with bilateral adrenal hyperplasia, resolving after parturition.
Main Outcome Measures and Results:
Acute testing for aberrant hormone receptors was negative except for arginine vasopressin (AVP)–increased cortisol secretion. Long-term hCG stimulation induced hypercortisolism, which was unsuppressed by dexamethasone. Postadrenalectomy histopathology demonstrated steroidogenically active adrenocortical hyperplasia and ectopic cortical cell clusters in the medulla. Quantitative polymerase chain reaction showed upregulated expression of LHCGR, transcription factors GATA4, ZFPM2, and proopiomelanocortin (POMC), AVP receptors (AVPRs) AVPR1A and AVPR2, and downregulated melanocortin 2 receptor (MC2R) vs control adrenals. LHCGR was localized in subcapsular, zona glomerulosa, and hyperplastic cells. Single adrenocorticotropic hormone–positive medullary cells were demonstrated in the zona reticularis. The role of adrenal adrenocorticotropic hormone was considered negligible due to downregulated MC2R. Coexpression of CYP11B1/CYP11B2 and AVPR1A/AVPR2 was observed in ectopic cortical cells in the medulla. hCG stimulation of the patient’s adrenal cell cultures significantly increased cyclic adenosine monophosphate, corticosterone, 11-deoxycortisol, cortisol, and androstenedione production. CTNNB1, PRKAR1A, ARMC5, and PRKACA gene mutational analyses were negative.
Conclusion:
Nongenetic, transient, somatic mutation-independent, pregnancy-induced CS was due to hCG-stimulated transformation of LHCGR-positive undifferentiated subcapsular cells (presumably adrenocortical progenitors) into LHCGR-positive hyperplastic cortical cells. These cells respond to hCG stimulation with cortisol secretion. Without the ligand, they persist with aberrant LHCGR expression and the ability to respond to the same stimulus.
•Reduction of APL antibodies by immunoadsorption may be a lifesaving therapy for the management of DAH with high titer of APL antibodies.•Autologous HSCT may be a valid treatment option in patients ...with primary APS and no response to standard immunosuppressive therapy.
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