Invasive Diagnostics Research Articles

Acute angle closure : An ophthalmological emergency in the emergency room

HintergrundDie Symptome des akuten Winkelblocks, ein Notfallereignis, das ohne rechtzeitige Therapie zur irreversiblen Erblindung führen kann, sind vielfältig. Diese können initial als internistische oder neurologische Erkrankungen gedeutet werden, wenn Kopfschmerzen, Pupillenstarre oder Übelkeit im Vordergrund stehen. Ziel unserer Studie war es, die Rate belastender und invasiver Diagnostik durch primäre Vorstellung bei Nichtophthalmologen bei akutem primären Winkelblock zu erfassen.MethodeRetrospektive Single-Center-Studie von Patienten mit akutem primärem Winkelblock. Zur Identifizierung dieser wurden alle Patienten erfasst, bei denen im Universitätsklinikum Freiburg, Klinik für Augenheilkunde im Zeitraum 2014–2018 eine chirurgische Iridektomie (5-133.0) oder Iridotomie durch Laser (5-136.1) durchgeführt wurde. Anschließend erfolgte durch Akteneinsicht die Datenanalyse zur Prüfung der Ein- und Ausschlusskriterien sowie des Krankheitsverlaufs.ErgebnisseEingeschlossen wurden 91 Patienten mit akutem primären Winkelblock. Davon stellten sich 28 % (n = 25) initial bei nichtophthalmologischen Fachdisziplinen vor. In dieser Patientengruppe erhielten 56 % (n = 11) eine nichtzielführende Diagnostik, wobei bei 32 % (n = 8) eine kraniale Bildgebung und bei 8 % (n = 2) eine Lumbalpunktion durchgeführt wurde.SchlussfolgerungBei akutem primären Winkelblock zeigt sich eine hohe Rate an nicht wegweisender Diagnostik durch Nichtophthalmologen, weshalb dieses Krankheitsbild fächerübergreifend präsent sein sollte. Bei unspezifischen Symptomen, wie Kopfschmerzen, Übelkeit und Erbrechen sowie Pupillenstarre, muss an die Möglichkeit eines akuten Augeninnendruckanstiegs durch einen akuten Winkelblock gedacht und das frühzeitige Hinzuziehen eines Ophthalmologen erwogen werden.

A narrative review of invasive diagnostics and treatment of early lung cancer.

The diagnosis and treatment of early-stage lung cancer remains a clinical challenge. The broadening implementation of lung cancer screening has resulted in positive findings in numerous patients that are mostly non-malignant. Many other patients have indeterminate nodules that are difficult to assess through simple observation. The critical interpretation of such screening results remains a challenge for radiologists and multidisciplinary teams involved in screening for lung cancer. The evaluation and diagnosis of each participant suspected for malignancy should be based on the basic clinical principles such as a carefully collected medical history, physical examination, and detailed analysis of all imaging tests performed. Indeed, the decision to go ahead with more invasive diagnostics requires consideration of the both the risks and benefits, with reflection upon the complete clinical and radiological picture. Although transthoracic needle aspiration biopsy remains the first-choice method of diagnosis, several newer technologies have slowly begun to emerge as potential replacements. The guiding strategy for method selection is to choose the least harmful approach that offers the most relevant potential insights. Transthoracic biopsy is an effective method that allows the collection of cytological and tissue material from small, peripheral tumors, but it carries a moderate risk of complications. Bronchofiberoscopy, especially in combination with electromagnetic navigation, fluoroscopy or radial EBUS, also allows effective diagnosis of the peripheral pulmonary nodules. One of the most important diagnostic methods is the EBUS examination, which allows determining of staging in addition to diagnosis. Anatomical lung lobe resection and lymphadenectomy or sampling of the hilar and mediastinal lymph nodes is currently the treatment of choice for patients with stage I and II non-small cell lung cancer (NSCLC), but sublobar resections are recommended when a patient has limited pulmonary function or other significant comorbidities. Notably, several studies have highlighted the potential utility of more limited resections in small malignant lesions less than 2cm in diameter, with pure AIS histology, when more than 50% of the diameter of pulmonary nodule has ground-glass opacity (GGO) attenuation on CT, or long volume doubling time (VDT). Videothoracoscopy is the preferred surgical approach for resection of early-stage lung cancer. Patients who are not candidates for surgery or do not agree to surgery can be offered radical radiotherapy. Stereotactic body radiation therapy (SBRT) is a type of radical radiotherapy with proven effectiveness, a high rate of local control and an acceptable risk of the development of later complications. Future trials are expected to define the role of SBRT in the treatment of early lung cancer in healthy subjects.

Safety and effectiveness of deep sedation in pediatric patients undergoing flexible fibroscopy in spontaneous breathing

Invasive diagnostics and minor surgical procedures with deep sedation on pediatric patients, such as fibroscopic examination, have increased over the past decade. The aim of this study was to evaluate the usefulness and safety of an anesthesiological technique, based on the use of midazolam and ketamine, conducted in spontaneous breathing on a population of pediatric patients with suspected tracheobronchial pathologies. Pediatric patients from birth to 18 years old who underwent sedation diagnostic fibroscopy between April 2018 and March 2019, were enrolled. The anesthesiological technique provided was the intravenous administration of midazolam 0.2 mg/kg and ketamine 2 mg/kg in spontaneous breathing using a face mask with support of O2 and air. Vital signs such as Heart rate (HR), Systolic and Diastolic blood pressure (PAS and PAD) and Arterial oxygen saturation were recorded at the beginning of the procedure, 10 minutes and 30 minutes from the start. Other parameter evaluated were patient’s level of consciousness, quality of the procedure, major and minor complications, adequate recovery of the waking state. Sixteen patients were enrolled, 12 males and 4 females aged between 2 days of life and 7 years. Laryngomalacia tracheomalacia, tracheoesophageal fistula, and congenital airway malformations were the most frequent diseases. As for vital signs: the HR has gone from an average value of 133.4 ± 16.26 bpm at T0 to an average value of 129.3 ± 16.55 bpm at T10 and 133.7 ± 17.35 bpm at T30; PAS and PAD had not significant variations. Among drugs available for the fibroscopic examinations, the combined use of intravenous midazolam 0.2 mg/kg and ketamine 2 mg/kg is safe and well tolerated, reducing the anxiety associated with the examination, without major complications. The current literature is lacking in studies that have included such small and low weight patients. It would be interesting to make a comparison between various sedation techniques in order to identify the safest for the pediatric population.

Transcriptomic analysis identifies a tumor subtype mRNA classifier for invasive non-functioning pituitary neuroendocrine tumor diagnostics.

Rationale: The invasive behavior of non-functioning pituitary neuroendocrine tumors (NF-PitNEts) presents obstacles for complete surgical resection and is indicative of poor prognosis. Therefore, developing reliable diagnostic tools for identifying invasive PitNEts would be helpful in guiding surgical decisions and, in particular, the follow-up treatment.Methods: We analyzed differential gene expression profiles between 39 non-invasive and 22 invasive NF-PitNEts by high-throughput sequencing, gene co-expression, and functional annotation. Twenty-one transcripts were further validated by Taqman-qPCR in another 143 NF-PitNEt samples. The histological expression and serum-exosomal mRNA of three candidate genes were examined by tissue microarray and droplet digital PCR.Results: Non-invasive and invasive NF-PitNEts were clustered into distinct groups with a few outliers because of their gonadotroph, corticotroph, or null cell lineages. The gene signature with strong invasive potential was enriched in 'Pathways in cancers' and 'MAPK pathway', with significantly higher in situ INSM1 and HSPA2 protein expression in invasive NF-PitNEts. Further integration of the 20 qPCR-validated differentially expressed genes and pituitary cell lineages provided a gene-subtype panel that performed 80.00-90.24% diagnostic accuracy for the invasiveness of NF-PitNEts.Conclusion: Our approach defined new characteristics in the core molecular network for patients at risk for invasive NF-PitNEt, representing a significant clinical advance in invasive PitNEt diagnostics.

Combined intraoperative navigation for RFA robotic surgical system

Background and purpose: Modern research shows that robotic systems for minimally invasive surgical operations significantly increase their quality and efficiency. In particular, this is due to the fact that modern robotic systems are able to achieve higher accuracy parameters than are allowed by natural human systems. Methods of minimally invasive diagnostics and local destruction of the affected tissues, such as radiofrequency ablation (RFA), require high precision at the operation stage. The movement and deformation of the organs in the abdominal zone, caused by breathing and other processes, leads to a deviation of the target neoplasm's position from the preliminary plan of the operation, built based on CT. In this regard, in the case of using robotic systems in minimally invasive surgery, there is a need for intraoperative navigation that provides operational data on the target's position for automated control of a medical instrument. Method: The project aims to develop an intraoperative navigation system for a robotic surgical system for minimally invasive surgery based on a combination of ultrasound, stereophotogrammetric navigation, and modern computer vision algorithms. It will allow for automatic tracking of the position of target areas of the patient's operating area in real-time, thus increasing the accuracy of novel robotic systems for minimally invasive surgery. Results and conclusion: Created RFA robotic surgical system integrates an automated ultrasonic needle localization system based on a vision system with stereotactic navigation.This approach involves the combined use of preoperative medical images based on CT / MRI and intraoperative ultrasound images to clarify the displacement of the target anatomical structures caused by breathing and other processes in the patient's body.

The impact of shared decision making on time consumption and clinical decisions. A prospective cohort study

ObjectiveConcerns of increased time consumption and of the impact on clinical decisions may restrain doctors from shared decision making (SDM). This paper evaluates consultation length and decisions made when using an in-consult patient decision aid (PtDA). MethodsThis prospective cohort study compared an unexposed cohort with a cohort exposed to SDM and a PtDA in two preference-sensitive decision situations: invasive lung cancer diagnostics and adjuvant treatment for early breast cancer. Outcome measures were consultation length and decisions made. ResultsThe study included 261 consultations, 115 were in the SDM-exposed cohort. Consultations were inconsiderably longer in the SDM cohort; 2 min, 11 s (p = 0.2217) for lung cancer diagnostics and 3 min, 57 s (p = 0.1128) for adjuvant breast cancer treatment. In lung cancer diagnostics, consultation length became more uniform and decisions tended to become conservative after introduction of SDM. For adjuvant breast cancer, slightly more patients in the SDM cohort chose to decline treatment. ConclusionShared decision making did not take significantly longer time and led to slightly more conservative decisions. Practice implicationsSDM may be implemented without considerable impact on consultation length. The impact on clinical decisions depends mainly on the clinical situation.

The Theoretical Basis of In Utero Hematopoietic Stem Cell Transplantation and Its Use in the Treatment of Blood Disorders

Since its conception, prenatal therapy has been successful in correction of mainly anatomical defects, although the range of application has been limited. Research into minimally invasive fetal surgery techniques and prenatal molecular diagnostics has facilitated the development of in utero stem cell transplantation (IUT)-a method of delivering healthy stem cells to the early gestation fetus with the hope of engraftment, proliferation, and migration to the appropriate hematopoietic compartment. An area of application that shows promise is the treatment of hematopoietic disorders like hemoglobinopathies. The therapeutic rationale of IUT with hematopoietic stem cells (HSCs) is based on the proposed advantages the fetal environment offers based on its unique physiology. These advantages include the immature immune system facilitating the development of donor-specific tolerance, the natural migration of endogenous hematopoietic cells providing space for homing and engraftment of donor cells, and the fetal environment providing HSCs with the same opportunity to survive and proliferate regardless of their origin (donor or host). Maternal immune tolerance to the fetus and placenta also implies that the maternal environment could be accepting of donor cells. In theory, the fetus is a perfect recipient for stem cell transplant. Clinically, however, IUT is yet to see widespread success calling into question these assumptions of fetal physiology. This review aims to discuss and evaluate research surrounding these key assumptions and the clinical success of IUT in the treatment of thalassemia.

Perspective of fibre-optical microendoscopy with microlenses.

Fibre-optical microendoscopy is based on fibre-optical confocal scanning microscopy, where optical fibres are introduced for delivery of the source and collection of the signal. Fibre-optical microendoscopy has led to innovations in imaging of freely moving animals, long-term imaging, minimally invasive diagnostics, and microsurgery. The lens system in fibre-optical microendoscopy is significant because of the imaging resolution and miniaturisation possibility. State-of-the-art fibre-optical microendoscopy based on various types of lens systems is introduced and compared. The lens system contains an objective lens, a gradient index microlens, and other novel lens systems fabricated by electric arc discharge or two-photon lithography.

Salivary Raman Spectroscopy: Standardization of Sampling Protocols and Stratification of Healthy and Oral Cancer Subjects.

Minimally invasive cancer detection using bio-fluids has been actively pursued due to practical limitations, though there are better suited noninvasive and online invivo methods. Saliva is one such clinically informative bio-fluid that offers the advantages of easy and multiple sample collection. Despite its potential in cancer diagnostics, saliva analysis is challenging due to its heterogeneous composition.Recently, there has been an upsurge in saliva exploration using optical techniques. Forms of saliva such as precipitate and supernatant have been monitored, but this sampling method needs to be standardized due to the obvious loss of analytes in processing. In that context, present work details the comparison of four different saliva sampling methodologies, i.e., air-dried, lyophilized, pellet, and supernatant using Raman spectroscopy collected from 10 healthy samples. Composition-driven spectral features of all forms were compared and classified using principal component analysis and linear discriminant analysis. Analysis was carried out on all four groups in the first step. In the second step, groups of pellet and supernatant , and air-dried and lyophilized were analyzed. Findings suggest that pellet and supernatant exhibit discrete spectroscopic features and demonstrate high classification efficiency, which is indicative of their distinctive biochemical composition. On the other hand, air-dried and lyophilized forms showed overlapping spectral features and low classification, suggesting these forms retain majority spectroscopic features of whole saliva and are less prone to sampling losses. Thus, this study indicates air-dried and lyophilized forms may be more appropriate for saliva sampling using Raman spectroscopy providing the comprehensive information required for cancer diagnosis. Furthermore, the method was also tested for the classification of oral cancer and healthy subjects (n = 27) which yielded 90% stratification. The findings of the study indicate the utility of minimally invasive salivary Raman-based diagnostics in oral cancers.

The Role of the Liquid Biopsy in Decision-Making for Patients with Non-Small Cell Lung Cancer.

Liquid biopsy is a rapidly emerging tool of precision oncology enabling minimally invasive molecular diagnostics and longitudinal monitoring of treatment response. For the clinical management of advanced stage lung cancer patients, detection and quantification of circulating tumor DNA (ctDNA) is now widely adopted into clinical practice. Still, interpretation of results and validation of ctDNA-based treatment decisions remain challenging. We report here our experience implementing liquid biopsies into the clinical management of lung cancer. We discuss advantages and limitations of distinct ctDNA assay techniques and highlight our approach to the analysis of recurrent molecular alterations found in lung cancer. Moreover, we report three exemplary clinical cases illustrating the complexity of interpreting liquid biopsy results in clinical practice. These cases underscore the potential and current limitations of liquid biopsy, focusing on the difficulty of interpreting discordant findings. In our view, despite all current limitations, the analysis of ctDNA in lung cancer patients is an essential and highly versatile complementary diagnostic tool for the clinical management of lung cancer patients in the era of precision oncology.

Aspherical microlenses enabled by two-photon direct laser writing for fiber-optical microendoscopy

Fiber-optical microendoscopy has made significant improvements to in vivo neural imaging, minimally invasive diagnostics, and microsurgery. However, high resolution, miniaturization, and low complexity cannot be simultaneously achieved together in the lens system for fiber-optical microendoscopy because current lens systems are in shape and dimensions restricted by limitations of manufacturing. Recently, two-photon direct laser writing (DLW) has been implemented in the fabrication of low-resolution micro-optics structures. Here, we demonstrate a high-resolution miniaturized singlet aspherical microlens fabricated on the fiber facet using DLW. The microlens has a high numerical aperture (NA), of 0.9, in air with only one aspherical surface, and is 10–20 times smaller in diameter than a typical gradient refractive index (GRIN) microlens. The designs of aspherical microlenses with NAs of 0.3, 0.6, and 0.9 in air are aberration-free at three wavelengths (561, 590, and 630 nm). The full width at half maximum of the effective intensity point spread function of a 0.9 NA aspherical microlens is 0.85 μm. We demonstrate fiber-optical microendoscopy imaging with a 0.6 NA aspherical microlens. The proposed aspherical microlens can potentially be applied to the development of a high-resolution, extremely miniaturized fiber-optical microendoscope.

First Infection with Absidia Corymbifera in a CLL Patient - Ibrutinib As Risk Factor?

Introduction Targeted therapy as ibrutinib, alone or in combination, is the new standard of care in CLL and has improved the clinical outcome. However, the rate of infectious side effects in the "real world" is still under debate. Several retrospective trials have observed a significant risk of invasive fungal infections (IFD) in this patient group, mostly caused by Aspergillus sp., Cryptococcus sp. or Pneumocystisjiroveci and often occurring early after initiation of the drug. Here we report the first case of an invasive infection with Absidia corymbifera, a member of the zygomyces group, in a CLL patient. The life-threatening infection occurred six years after initiation of ibrutinib treatment infiltrating and destroying the left kidney. Invasive infections with Absidia corymbifera are extremely rare and mostly reported from patients with acute leukemia or severe immunosuppression after organ transplantation. This species is not sensitive to echinoncandins and azoles with the exception of posaconazol. Thus, uncommon IFD has to be suggested in patients treated with ibrutinib treatment and invasive diagnostics should be performed early. Patient characteristics The patient, a 70 years old male, was diagnosed in 2005 with B-CLL harbouring high risk cytogenetics (deletion 17p). CLL was treated since 2005 with R-CHOP, R-bendamustine and ofatumumab before ibrutinib was started in 2014. Due to secondary antibody deficiency, the patient was substituted with IVIG every 4 weeks. At the beginning of 2020 the patient suffered three weeks from cough, fever and abdominal pain before he was admitted to our ward. We found elevated CRP (362 mg/l, normal range: < 5) and procalcitonin (2.02 µg/l, normal range: < 0.5), leukocytosis dominated by CLL cells, mild neutropenia (> 1000 mm3) and an IgG level of 4 g/l (normal range: 7-16). A CT scan showed a barely vascularized tumor at the left kidney, peri-renal inflammation, atypical pneumonic infiltrates and multiple enlarged abdominal lymph nodes. Clinical outcome: The patient was initially treated with antibiosis and caspofungin without success. A fine-needle biopsy of the renal tumor was performed, where fungal structures were identified. Since a renal scintigraphy showed loss of function of the infected kidney, a nephrectomy was conducted to reduce the fungal load while the anti-mycotic treatment was changed to liposomal amphotericin B for three weeks. The molecular analysis of the infected kidney showed an infection with Absidia corymbifera. The patient recovered from fever and all other signs of infection under this treatment, so that he could be discharged after 4 weeks but oral posaconazole was given for additional 6 weeks. Conclusion: Here we report the first infection of a CLL patient with Absidia corymbifera, a germ only found in heavily immunosuppressed patients so far. However, ibrutinib should be considered as risk factor for uncommon invasive fungal infection. Thus, in all cases with fever of unknown origin in this patient group, lesions suspicious for IFD has to be carefully investigated and a biopsy should be taken to characterize the infectious agent. Treatment has to combine surgery and long-term antimycotic treatment. Disclosures No relevant conflicts of interest to declare.

Characterization of B-Cell and Plasma Cell Compartment By Eight-Color Multiparameter Flow Cytometry in Patients with Waldenstrom Macroglobulinemia Prospectively Enrolled in the Fondazione Italiana Linfomi (FIL) BIO-WM Trial

Characterization of B-Cell and Plasma Cell Compartment By Eight-Color Multiparameter Flow Cytometry in Patients with Waldenstrom Macroglobulinemia Prospectively Enrolled in the Fondazione Italiana Linfomi (FIL) BIO-WM Trial

Predicting human health from biofluid-based metabolomics using machine learning

Biofluid-based metabolomics has the potential to provide highly accurate, minimally invasive diagnostics. Metabolomics studies using mass spectrometry typically reduce the high-dimensional data to only a small number of statistically significant features, that are often chemically identified—where each feature corresponds to a mass-to-charge ratio, retention time, and intensity. This practice may remove a substantial amount of predictive signal. To test the utility of the complete feature set, we train machine learning models for health state-prediction in 35 human metabolomics studies, representing 148 individual data sets. Models trained with all features outperform those using only significant features and frequently provide high predictive performance across nine health state categories, despite disparate experimental and disease contexts. Using only non-significant features it is still often possible to train models and achieve high predictive performance, suggesting useful predictive signal. This work highlights the potential for health state diagnostics using all metabolomics features with data-driven analysis.

The use of chromosomal microarray analysis for diagnostics of chromosomal pathology in fetal central nervous system malformations

Introduction. The prevalence of congenital malformations (CMFs) in fetal central nervous system (CNS) ranges from 1.5 to 3 % and covers around 29 % among all malformations, whereas percentage in the structure of perinatal and infant mortality reaches 25–26 %.Aim: to estimate frequency of pathogenic copy number variations (CNVs) in fetuses with congenital malformations of CNS and normal karyotyping cytogenetic analysis.Materials and Methods. There were enrolled 42 pregnant women underwent invasive prenatal diagnostics in 2013–2019 due to ultrasound detection of congenital CNS defect in fetus. Fetal samples were studied by using chromosome microarray analysis (CMA).Results. Various pathogenic CNVs were detected in 7 (16.6 %) fetuses with prenatally diagnosed congenital CNS malformations. Non-syndrome pathogenic CNVs were detected in 85.7 %.Conclusion. Thus, performing chromosome microarray analysis as the first-line assay allows to diagnose not only aneuploidy, but also microdeletion/microduplication, the size of which below resolution threshold for standard cytogenetic karyotyping

Analysis of Reciprocally Dysregulated miRNAs in Eutopic Endometrium Is a Promising Approach for Low Invasive Diagnostics of Adenomyosis.

Endometriosis is a chronic disease characterized by the growth of endometrial tissue outside of the uterine cavity. Endometriosis affects up to 10% of women of reproductive age and has great social impact. The diagnostics of endometriosis are based on clinical appearance, ultrasound, and magnetic resonance imaging (MRI); however, a diagnosis is frequently hampered by the absence of objective criteria. Adenomyosis (AM) is a particular type of endometriosis wherein the spread of the ectopic endometrial gland is limited by the uterine myometrium. Alteration of the microRNA expression profile in the eutopic endometrium can be associated with AM, and may be assayed for diagnostic purposes. In the presented study, we aimed to explore the diagnostic potency of this approach. Eutopic endometrium specimens were collected from patients (n = 33) and healthy women (n = 30). The microRNA expression was profiled to select individual microRNAs with AM-associated expression alterations. A new method of two-tailed RT-qPCR microRNA analysis was applied to assay potential markers. The expression ratios of reciprocally dysregulated microRNAs were calculated, and the diagnostic potency of these parameters was evaluated by receiver operation curve (ROC) analysis. Mir-10b, miR-200c and miR-191 were significantly dysregulated in the eutopic endometrium of AM patients. The expression ratio of reciprocally dysregulated microRNAs allowed us to diagnose AM with a range of sensitivity from 65% to 74%, and of specificity from 72% to 86%. The analysis of microRNAs from the eutopic endometrium might present a promising low-invasive method of AM diagnostics.

Powered Versus Manual Scalers, The Competition Ends with Wins or Failures

A novel coronavirus (COVID-19) is associated with human to human transmission. The COVID-19 was recently identified saliva of infected patients. The possibilities of transmission by the saliva of this virus are discussed in this article. The dental clinical procedures are expected to transmit COVID-19 through contact with droplets and aerosols. In order to improve efficient strategies for prevention, especially for dentists and health professionals performing aerosol generation procedures, it is essential strategies that more investigation into the detection and impact of COVID-19 in oral fluids be made – savior which can play a crucial role in human to human transmission, can be convenient and economic health care platform for quick and early detection of COVID-19 infection through non- invasive salivation diagnostics.

Benefit and burden in the Dutch cytology-based vs high-risk human papillomavirus-based cervical cancer screening program

In 2017, the Dutch cervical cancer screening program had replaced the primary cytology-based screening with primary high-risk human papillomavirus-based screening, including the opportunity to participate through self-sampling. Evaluation and balancing benefit (detection of high-grade cervical intraepithelial neoplasia) and burden of screening (unnecessary referrals, invasive diagnostics, and overtreatment) is needed. This study aimed to compare the referral rates, detection of high-grade cervical intraepithelial neoplasia, overdiagnosis, and overtreatment in the new high-risk human papillomavirus-based screening program, including physician-sampled and self-sampled material, with the previous cytology-based screening program in the Netherlands. A retrospective cohort study was conducted within the Dutch population-based cervical cancer screening program. Screenees with referrals for colposcopy between 2014 and 2015 (cytology-based screening) and 2017 and 2018 (high-risk human papillomavirus-based screening) were included. Data were retrieved from the Dutch Pathology Registry (PALGA) and compared between the 2 screening programs. The main outcome measures were referral rate, detection of high-grade cervical intraepithelial neoplasia or worse, overdiagnosis (cervical intraepithelial neoplasia grade 1 or less in the histologic specimen), and overtreatment (cervical intraepithelial neoplasia grade 1 or less in the treatment specimen). Of the women included in the study, 19,109 received cytology-based screening, and 26,171 received high-risk human papillomavirus-based screening. Referral rates increased from 2.5% in cytology-based screening to 4.2% in high-risk human papillomavirus-based screening (+70.2%). Detection rates increased to 46.2% for cervical intraepithelial neoplasia grade 2 or worse, 32.2% for cervical intraepithelial neoplasia grade 3 or worse, and 31.0% for cervical cancer, and overdiagnosis increased to 143.4% with high-risk human papillomavirus-based screening. Overtreatment rates were similar in both screening periods. The positive predictive value of referral for detection of cervical intraepithelial neoplasia grade 2 or worse in high-risk human papillomavirus-based screening was 34.6% compared with 40.2% in cytology-based screening. Women screened through self-sampling were at higher risk of cervical intraepithelial neoplasia grade 2 or worse detection (odds ratio, 1.38; 95% confidence interval, 1.20-1.59) and receiving treatment (odds ratio, 1.31; 95% confidence interval, 1.16-1.48) than those screened through physician-sampling. Compared with cytology-based screening, high-risk human papillomavirus-based screening increases detection of high-grade cervical intraepithelial neoplasia, with 462 more cervical intraepithelial neoplasia grade 2 or worse cases per 100,000 women but at the expense of 850 more cases per 100,000 women with invasive diagnostics indicating cervical intraepithelial neoplasia grade 1 or less.

Troponin elevation in acute ischemic stroke-unspecific or acute myocardial infarction? : Diagnostics and clinical implications

Routine determination of troponin levels is recommended for all patients with acute ischemic stroke. In 20-55% of these patients the troponin levels are elevated, which may be caused by ischemic as well as non-ischemic myocardial damage and particularly neurocardiogenic myocardial damage. In patients with acute ischemic stroke, the prevalence of previously unknown coronary heart disease is reported to be up to 27% and is prognostically relevant for these patients; however, relevant coronary stenoses are less frequently detected in stroke patients with troponin elevation compared to patients with non-ST elevation myocardial infarction. The risk of secondary intracerebral hemorrhage due to the necessity for dual platelet aggregation inhibition illustrates the challenging indication for invasive coronary diagnostics and revascularization. Therefore, adiagnostic work-up and interdisciplinary risk evaluation appropriate to the urgency are necessary in order to be able to determine areasonable treatment approach with timing of the intervention, type and duration of blood thinning. In addition to conventional examination methods, multimodal cardiac imaging is increasingly used for this purpose. This review article aims to provide apragmatic and clinically oriented approach to diagnostic and therapeutic procedures, taking into account the available evidence.

Biomedical Micro-/Nanomotors: From Overcoming Biological Barriers to In Vivo Imaging.

Self-propelled micro- and nanomotors (MNMs) have shown great potential for applications in the biomedical field, such as active targeted delivery, detoxification, minimally invasive diagnostics, and nanosurgery, owing to their tiny size, autonomous motion, and navigation capacities. To enter the clinic, biomedical MNMs request the biodegradability of their manufacturing materials, the biocompatibility of chemical fuels or externally physical fields, the capability of overcoming various biological barriers (e.g., biofouling, blood flow, blood-brain barrier, cell membrane), and the in vivo visual positioning for autonomous navigation. Herein, the recent advances of synthetic MNMs in overcoming biological barriers and in vivo motion-tracking imaging techniques are highlighted. The challenges and future research priorities are also addressed. With continued attention and innovation, it is believed that, in the future, biomedical MNMs will pave the way to improve the targeted drug delivery efficiency.