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ABSTRACT Antibiotic Resistance (ABR) is a global concern and while many students are aware of this issue, many of them are unclear on the mechanisms by which ABR may emerge. The mechanism of horizontal gene transfer is something many students are not familiar with. In this curriculum contribution we present 2 versions of an ‘interrupted case study’ that is designed as an introduction to horizontal gene transfer for early major students and as a review case for advanced major students in biology and life sciences. The case is based on an authentic patient who developed infections with both methicillin resistant Staphylococcus aureus and vancomycin resistant S. aureus. The interrupted case study is appropriate for small and large groups and engages students while content is introduced in a highly structured way. This type of case study can be done by novice and seasoned instructors and lead to considerable learning gains in both introductory and intermediate microbiology courses.

A digitally enabled environment is a setting which incorporates sensors coupled with reporting and analytics tools for understanding, observing or managing that environment. Large scale data collection and analysis are a part of the emerging digitally enabled approach for the characterisation and understanding of our environment. It is recognised as offering an effective methodology for addressing a range of complex and interrelated social, economic and environmental concerns. The development and construction of the approach requires advances in analytics control linked with a clear definition of the issues pertaining to the interaction between elements of these systems. This paper presents an analysis of selected issues in the field of analytics control. It also discusses areas of progress, and areas in need of further investigation as sensing networks evolve. Three case studies are described to illustrate these points. The first is a physical analytics test kit developed as a part of the “Reinvent the Toilet Challenge” (RTTC) for process control in a range of environments. The second case study is the Cranfield Urban Observatory that builds on elements of the RTTC and is designed to allow users to develop user interfaces to monitor, characterise and compare a variety of environmental and infrastructure systems plus behaviours (e.g., water distribution, power grids). The third is the Data and Analytics Facility for National Infrastructure, a cloud-based high-performance computing cluster, developed to receive, store and present such data to advanced analytical and visualisation tools.

Control of the reproduction of domesticated stocks is considered a prerequisite for aquaculture development of pikeperch. However, knowledge about the physiology of the captive pikeperch male reproductive system and the biology of semen is very limited, especially regarding protein characteristics. The aims of our study were to characterize pikeperch sperm quantity and quality parameters and to analyze changes in the proteome of the same males spawned for the first and second times. Moreover, attempts were made to generate the first proteomic library of seminal plasma proteins. Semen collected during the first spawning season was characterized by lower sperm concentration and volume than for the second season. Using mass spectrometry-based label-free quantitative proteomics, we identified 850 proteins in the seminal plasma of pikeperch from both spawning seasons, and 65 seminal proteins were found to be differentially abundant between the first and second spawning seasons. The majority of differentially abundant proteins were involved in stress and immune responses, developmental processes, cofactor metabolic processes, proteolysis, cellular oxidant detoxification and organization of the extracellular matrix (ECM). In addition, several proteins unique to pikeperch seminal plasma were identified, including antifreeze proteins, hibernation-specific plasma proteins, lectins and vitellogenin. In summary, our results indicate that males that spawned for the first time were characterized by incompletely mature gonads and the expression of proteins associated with the early phase of spermatogenesis and ECM organization. On the other hand, males that spawned for the second time exhibited advanced gonadal maturation and expression of proteins related to the late stage of spermatogenesis and sperm maturation, including regulation of reactive oxygen species generation, bicarbonate production, sperm elongation and separation. The identification of a large number of seminal plasma proteins provides a valuable resource for understanding the functions of seminal plasma and the molecular mechanisms involved in testicular development and maturation in domesticated fish, which is a prerequisite for better control of reproduction in captivity.

Society relies on infrastructure, but as infrastructure systems are often collocated and interdependent, they are vulnerable to cascading failures. This study investigated cross-infrastructure and societal impacts of burst water mains, with the hypothesis that multi-infrastructure failures triggered by burst water mains are more common in sandy soils. When water mains in sandy soils burst, pressurised water can create subsurface voids and abrasive slurries, contributing to further infrastructure failures. Three spatial data investigations, at nested scales, were used to assess the influence that soil sand content has on the frequency and damage caused by burst water mains (1) to roads in the county of Lincolnshire, (2) to other proximal water mains in East Anglia and (3) to other proximal infrastructure and wider society across England and Wales. These investigations used infrastructure network and failure data, media reports and soil maps, and were supported by workshop discussions and structured interviews with infrastructure industry experts. The workshop, interviews and media reports produced a greater depth of information on the infrastructure and societal impacts of cascading failures than the analysis of infrastructure data. Cross-infrastructure impacts were most common on roads, built structures and gas pipes, and they occurred at a higher rate in soils with very high sand contents.

Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as a pigmented polymer. In an observational study carried out by National AKU Centre (NAC) in Liverpool, a total of thirty-nine AKU patients attended yearly visits in varying numbers. At each visit a mixture of clinical, joint and spinal assessments were carried out and the results calculated to yield an AKUSSI (Alkaptonuria Severity Score Index), see “Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre” (Ranganath at el., 2018). The aim of this data article is to produce visual representation of the change in the components of AKUSSI over 3 years, through radar charts. The metabolic effect of nitisinone is shown through box plots.

In this study, the quality of northern pike eggs collected by the traditional method (hand stripping) and the pneumatic method (air stripping) was compared. Additionally, different activation solutions (Billard solution, hatchery water, and Woynarovich solution) were tested for their effects on egg fertilization under artificial conditions. After the eggs were collected, the Pseudo-Gonado-Somatic Index (PGSI) was measured. Although the values of the PGSI in the samples obtained with use of air stripping were lower (13.8 ± 3.9%), they did not differ statistically from those obtained by hand stripping (16.5 ± 5.4%). Hatchery water and Woynarovich solution were found to be the most suitable solutions for sperm activation using the Computer-Assisted Sperm Analysis (CASA) system as compared to the Billard solution. Hand stripping was found to negatively affect the percentage of fertilized eggs and the percentage of hatched larvae in samples fertilized in hatchery water and Woynarovich solution. When the traditional method of egg collection was used, there were no differences in the percentage of fertilization and the percentage of hatched larvae between Billard solution (54.0 ± 21.5% and 44.1 ± 21.9%, respectively), hatchery water (60.0 ± 22.5% and 55.9 ± 22.8%, respectively), and Woynarovich solution (72.0 ± 25.8% and 69.0 ± 23.9%, respectively) treatments. Air stripped eggs showed a higher fertilization rate when hatchery water or Woynarovich solution was applied (86.2 ± 9.3% and 92.4 ± 3.9%, respectively). Also hatching rate was the highest in these samples (83.0 ± 8.4% and 88.3 ± 6.2%). The application of the pneumatic method and Woynarovich solution to northern pike artificial fertilization resulted in higher fertilization and hatching rates as compared to other techniques. Because this was successful in northern pike, the use of air stripping is a promising option for artificial reproduction in other fish species.

The drier parts of the Mediterranean biome of southwest Australia contain the largest remaining Mediterranean woodlands and shrublands on Earth. Despite this, there has been no formal, comprehensive assessment of their biodiversity. The region abuts the southwest Australian floristic region which has received much scientific attention. The aim of this paper is to provide the first general overview of the biodiversity of part of this intact, yet relatively unknown, Mediterranean ecosystem. We do this by synthesizing data from State Government agencies and published research. We found that, like other parts of southwest Australia, the region has globally significant levels of plant species diversity. More than 2400 plant species, including 291 species considered threatened, have been recorded, representing one-sixth of all Australia’s vascular plant species. Eleven of Australia’s 23 major vegetation groups are represented even though the region covers less than 1% of continental Australia. We documented 170 vertebrate species, including 31 threatened species, with a particularly high richness of reptile species (n = 46). We highlight how little is known about this region. For example, 116 vertebrate species not recorded in the region probably occur there based on their habitat requirements and known distributions. An examination of plant and vertebrate diversity in the region, using a half degree latitude and longitude grid cells, showed a highly heterogeneous pattern of species richness and vulnerability, with a general decline in species richness from southwest to northeast. Conservation strategies that rely on capturing the highest levels of biodiversity in a series of protected areas are unlikely to guarantee protection for all species given these high levels of heterogeneity. Instead, a region-wide conservation plan should involve targeted ecological research, consideration of ecological processes and stakeholder consultation.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) among animals and humans are a public health threat. This study analyzed the occurrence of ESBL-E in a high-risk environment in a companion animal clinic and two animal patients’ households. In an intensive care unit (ICU), rectal swabs from 74 dogs and cats, 74 hand swabs from staff and 298 swabs from surfaces were analyzed for ESBL-E. Seventeen hospitalized patients (23%) and ten (3%) surfaces in the ICU tested ESBL-E positive. Transmission chains for Klebsiella pneumoniae ST307 blaCTX-M-15 and Escherichia coli ST38 blaCTX-M-14, ST88 blaCTX-M-14 and ST224 blaCTX-M-1 were observed over extended periods of time (14 to 30 days) with similar strains isolated from patients and the clinical environment. After discharge, two colonized dogs (dogs 7 and 12) and their household contacts were resampled. Dog 7 tested repeatedly positive for 77 days, dog 12 tested negative; six (24%) surfaces in the household of the persistently colonized dog tested ESBL-E positive. The owner of dog 7 and one of the owners of dog 12 were colonized. Based on whole genome sequencing, isolates from the owners, their dogs and other ICU patients belonged to the same clusters, highlighting the public health importance of ESBL-E in companion animal clinics.

Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat low-risk women with endometrial cancer prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 2 of this short version of the guideline provides recommendations on the treatment of precancerous lesions and early-stage endometrial cancer, surgical treatment, radiotherapy and drug-based therapy, follow-up, recurrence, and metastasis of endometrial cancer as well as the state of psycho-oncological care, palliative care, patient education, rehabilitative and physiotherapeutic care., Competing Interests: Conflict of Interest/Interessenkonflikt The conflicts of interest of the authors are listed in the long German-language version of the guideline. Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie aufgelistet., (Thieme. All rights reserved.)

Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat women with endometrial cancer of low risk prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 1 of this short version of the guideline provides recommendations on epidemiology, screening, diagnosis, and hereditary factors. The epidemiology of endometrial cancer and the risk factors for developing endometrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer. The use of geriatric assessment is considered and existing structures of care are presented., Competing Interests: Conflict of Interest/Interessenkonflikt The conflicts of interest of the authors are listed in the long German-language version of the guideline./Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie aufgelistet., (© Thieme Medical Publishers.)

Background: Trauma related deaths remain a relevant public health problem, in particular in the younger male population. A significant number of these deaths occur prehospitally without transfer to a hospital. These patients, sometimes termed "the forgotten cohort", are usually not included in clinical registries, resulting in a lack of information about prehospitally trauma deaths. The aim of the present study was to compare patients who died prehospital with those who sustained life-threatening injuries in order to analyze and potentially improve prehospital strategies., Methods: This cohort study included all primary operations carried out by Switzerland's largest helicopter emergency medical service (HEMS) between January 1, 2011, and December 31, 2021. We included all adult trauma patients with life-threatening or fatal conditions. The outcome of this study is the vital status of the patient at the end of mission, i.e. fatal or life-threatening. Injury, rescue characteristics, and interventions of the forgotten trauma cohort, defined as patients with a fatal injury (NACA score of VII), were compared with life-threatening injuries (NACA score V and VI)., Results: Of 110,331 HEMS missions, 5534 primary operations were finally analyzed, including 5191 (93.8%) life-threatening and 343 (6.2%) fatal injuries. More than two-thirds of patients (n = 3772, 68.2%) had a traumatic brain injury without a significant difference between the two groups (p > 0.05). Thoracic trauma (44.6% vs. 28.7%, p < 0.001) and abdominal trauma (22.2% vs. 16.1%, p = 0.004) were more frequent in fatal missions whereas pelvic trauma was similar between the two groups (13.4% vs. 12.9%, p = 0.788). Pneumothorax decompression rate (17.2% vs. 3.7%, p < 0.001) was higher in the forgotten cohort group and measures for bleeding control (15.2% vs. 42.7%, p < 0.001) and pelvic belt application (2.9% vs. 13.1% p < 0.001) were more common in the life-threating injury group., Conclusion: Chest decompression rates and measures for early hemorrhage control are areas for potential improvement in prehospital care., (© 2023. Norwegian Air Ambulance Foundation.)

Recurrent stroke is a dreaded complication of symptomatic internal carotid artery occlusion (ICAO). Transcranial Duplex (TCD)-derived increased flow velocity in the ipsilateral posterior cerebral artery (PCA)-P2 segment indicates activated leptomeningeal collateral recruitment and hemodynamic impairment. Leptomeningeal collaterals are pial vascular connections between the anterior and posterior vascular territories. These secondary collateral routes are activated when primary collaterals via the Circle of Willis are insufficient. Our goal was to test the TCD parameter PCA-P2 flow for prediction of ipsilateral ischemia recurrence. We retrospectively analyzed clinical and ultrasound parameters in patients with ICAO. Together with clinical variables, we tested systolic PCA-P2 flow velocity as predictor of a recurrent ischemic event using logistic regression models. Of 111 patients, 13 showed a recurrent ischemic event within the same vascular territory. Increased flow in the ipsilateral PCA-P2 on transcranial ultrasound (median and interquartile range [IQR]: 60 cm/s [IQR 26] vs. 86 cm/s [IQR 41], p  = <0.001), as well as previous transient ischemic attack (TIA) and low NIHSS were associated with ischemia recurrence. Combined into one model, accuracy of these parameters to predict recurrent ischemia was 89.2%. Our data suggest that in patients with symptomatic ICAO, flow increases in the ipsilateral PCA-P2 suggest intensified compensatory efforts when other collaterals are insufficient. Together with the clinical variables, this non-invasive and easily assessable duplex parameter detects ICAO patients at particular risk of recurrent ischemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jud, Klövekorn, van Niftrik, Herzog, Sebök, Schweizer, Luft, Fierstra and Wegener.)

Male breast cancer is an unknown field for many practitioners. Patients often see different doctors before the correct diagnosis is made - often too late. This article is intended to point out risk factors, initiation of diagnostics and therapy. In the dawning age of molecular medicine, we will also take a look at genetics., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein. Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein. Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Background/aim: Smaller, earlier-stage breast tumors are being found in breast cancer screening, and neoadjuvant chemotherapy is the gold standard when chemotherapy is indicated. Precise marking and localization of the tumor are thus becoming increasingly important. Wire-free localization techniques are under investigation in order to reduce presurgical radiography, pain, the risk of wire dislocation, and allow scheduling flexibility for patients and surgery departments., Patients and Methods: This single-center observational study from June 2020 to October 2021 included 15 patients with mammographically or sonographically detected nonpalpable breast lesions. Radiofrequency identification (RFID) tags were placed preoperatively under ultrasound or radiologic guidance to localize lesions for planned surgery. All patients underwent breast conservation surgery, including one bilateral and one targeted axillary dissection., Results: Histology identified two benign and 13 malignant lesions, including three ductal carcinomas in situ and 11 invasive breast cancers. Placement, control radiography, and handling of the RFID tag were feasible in everyday routine for different radiologists and surgeons and managed cost-effectively. All of the RFID tags were found in the specimen radiographs., Conclusion: The feasibility and cost-effectiveness of this non-wire localization method were demonstrated in this rather small cohort of patients. Further studies including larger numbers of patients are needed to confirm the method's accuracy., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Endosymbiont-conferred resistance to parasitoids is common in aphids, but comes at a cost to the host in the absence of parasitoids. In black bean aphids ( Aphis fabae ), costs in terms of reduced lifespan and lifetime reproduction were demonstrated by introducing 11 isolates of the protective symbiont Hamiltonella defensa into previously uninfected aphid clones. Transfection of H .  defensa isolates into a common genetic background allows to compare the costs of different endosymbiont isolates unconfounded by host genetic variation, but has been suggested to overestimate the realized costs of the endosymbiont in natural populations, because transfection creates new and potentially maladapted host-symbiont combinations that would be eliminated by natural selection in the field. In this experiment, we show that removing H .  defensa isolates from their natural host clones with antibiotics results in a fitness gain that is comparable to the fitness loss from their introduction into two new clones. This suggests that estimating cost by transfecting endosymbiont isolates into a shared host genotype does not lead to gross overestimates of their realized costs, at least not in the two recipient genotypes used here. By comparing our data with data reported in previous publications using the same lines, we show that symbiont-induced costs may fluctuate over time. Thus, costs estimated after extended culture in the laboratory may not always be representative of the costs at the time of collection in the field. Finally, we report the accidental observation that two isolates from a distinct haplotype of H .  defensa could not be removed by cefotaxime treatment, while all isolates from two other haplotypes were readily eliminated, which is suggestive of variation in susceptibility to this antibiotic in H .  defensa ., Competing Interests: The authors declare no competing interests., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Introduction: Oncological second opinions are becoming increasingly important in the era of complex treatments and established certified cancer centers. Oncological guidelines with the highest levels of evidence are available, but these can only be effective to the extent that they are implemented. Therefore, we analyzed the effects of second opinions with regard to their agreement with first opinions and conformity with guidelines., Methods: In 164 patients with a diagnosis of breast cancer or gynecological malignancy who requested a second opinion, the first and second opinions, established at the interdisciplinary tumor conference, and conformity with the guidelines were evaluated., Results: The first opinion was not in agreement with the guidelines in 34.8% (15.2% diagnosis, 12.8% surgical therapy, 13.4% systemic therapy, and 5.5% radiotherapy), and the recommendations were optimized in the second opinion in 56.7% (28.7% diagnosis, 15.9% surgical therapy, 30.5% systemic therapy, and 8.5% radiotherapy)., Conclusions: Oncological second opinions showed significant effects and one-third of first opinions were not in conformity with the guidelines. In a significant proportion of cases, the existing treatment plan was changed or supplemented to allow modern and individualized treatment approaches., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

Purpose: Second opinions in oncology are becoming increasingly important in an era of more complex treatments and a growing demand for information by patients. Therefore, we analyzed their effects and influencing factors like patients' motives, subjective extent of information and satisfaction with communications., Methods: This prospective study evaluated second opinions for patients with breast cancer or gynecological malignancy. The patients received a questionnaire before and two months after, which inquired expectations, reasons, and satisfaction with the second opinion and the attending physicians., Results: A total of 164 patients were included and the majority had breast cancer (75.0%). Receiving the second opinion made 89.7% feel better informed, their need for information decreased (from 75.3% to 39.2%, P < 0.0001), and satisfaction with doctor-patient communications increased (from 61.9 to 91.8%, P = 0.0002). There were various reasons for requesting a second opinion, e.g., the extremely stressful situation of a cancer diagnosis, hope for change in the treatment recommendation or dissatisfaction with the initial physicians., Conclusions: Second opinions can lead to significantly greater patient satisfaction, meeting the need for information and leading to better management of patients in the extremely stressful situation of a cancer diagnosis. Doctor-patient communications play a key role.

Introduction: Oncological second opinions are becoming increasingly important given more complex treatment strategies, simultaneously more patients use complementary and alternative medicine (CAM), and many comprehensive cancer centers initiate integrative medicine programs. The present study focuses on analyzing the effects of a second opinion in relation to attitudes toward CAM., Methods: In this prospective study patients (n = 97) with a diagnosis of breast cancer or gynecological malignancies who had requested a second opinion received a questionnaire before and after the second opinion concerning their attitudes toward CAM., Results: The majority of patients had breast cancer (72.2%, n = 70). Only 6.2% (n = 6) stated that they had been informed about CAM by the doctors who treated them first, 21.6% (n = 21) had received information about it when seeking the second opinion. After the first opinion, 42.3% (n = 41) wanted to try CAM, the same proportion trusted orthodox medicine alone. After the second opinion, 24 patients (24.7%) wanted to try CAM, while 38.1% (n = 37) relied exclusively on orthodox medicine. There was a significant correlation between an increased patients' need for information and interest in CAM (p = 0.02)., Conclusions: Today, aspects of CAM still are very often no part of oncological first and second opinions. This might hence lead to discouraging patients to try out CAM and therefore integrative medicine programs in comprehensive cancer centers might be problem-solving., (© 2020 S. Karger AG, Basel.)

Background: The interaction of our immune system with breast cancer (BC) cells prompted the investigation of tumor-infiltrating lymphocytes (TILs) and targeted, tumor antigen-specific immunotherapy., Objectives: Correlation between TILs and pathological complete response (pCR) after neoadjuvant systemic therapy (NACT). Tumor-specific antigens (TSAs) in HER2+ and triple negative BC and establishment of TSA-specific therapies within the interdisciplinary TILGen study., Methods: Illustration of the TILGen study design. Assessment of TILs and correlation with pCR within this BC study., Results: pCR was achieved in 38.4% (56/146) and associated with estrogen receptor/progesterone receptor negative (ER-/PR-) and HER2+ tumors. Lymphocytic predominant BC (LPBC) was found in 16.4% (24/146), particularly in ER-/PR- (ER-: 27.3% vs. ER+: 9.9%, PR-: 22.3% vs. PR+: 8.2%), large, and poorly differentiated BC. TILs were significantly correlated with pCR in multivariate analysis. In LPBC, pCR was achieved in 66.7%, whereas it was 32.8% in non-LPBC., Conclusions: First results confirm the influence of the human immune system on the response to NACT in HER2+ and triple negative BC. TSA-specific immunotherapy might improve the outcome in BC patients but there is an urgent need for comprehensive studies to further investigate this issue.

Introduction: Surgical treatment of primary spontaneous pneumothorax (PSP) usually consists of bullectomy and any form of pleurodesis to reduce risk of disease recurrence. Whether pleurectomy is superior to pleural abrasion is still a matter of debate with recurrence rates especially high when performed with a video-assisted thoracoscopic (VATS) approach. Aim of this study was to compare the efficacy of the two methods in prevention of recurrence of pneumothorax in a minimally invasive setting., Materials and Methods: Between 01/2005 and 12/2015, 107 patients younger than 40 years with PSP underwent VATS bullectomy and either partial pleurectomy or pleural abrasion. Medical records of patients were reviewed retrospectively., Results: Pleural abrasion was performed in 34/107 patients, 73/107 patients underwent partial pleurectomy. There were no statistically significant differences in age, sex, body mass index or smoking history at time of surgery. There was no significant difference in major postoperative complications (p = 0.3022). Nine (8.4%) patients had a recurrence of pneumothorax during follow-up. Incidence of recurrence in those undergoing pleural abrasion was significantly higher than those undergoing apical pleurectomy (8/34 vs. 1/73, p < 0.001). Surgical technique was the only factor associated with a recurrence of PSP after surgical intervention., Discussion: In our analysis, a VATS partial pleurectomy proved to be effective for prevention of recurrent PSP. Recurrence rates were low despite a minimally invasive approach and significantly lower than in the pleural abrasion group. According to these findings, VATS pleurectomy might be considered as the primary choice for surgical pleurodesis in patients with PSP.

Background: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study., Methods: Neoadjuvantly treated HER2-positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype 'lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading., Results: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01)., Conclusion: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach.

Background: The assessment of circulating tumor cells (CTCs) has been shown to enable monitoring of treatment response and early detection of metastatic breast cancer (MBC) recurrence. The aim of this study was to compare a well-established CTC detection method based on immunomagnetic isolation with a new, filtration-based platform., Methods: In this prospective study, two 7.5 ml blood draws were obtained from 60 MBC patients and CTC enumeration was assessed using both the CellSearch® and the newly developed filtration-based platform. We analyzed the correlation of CTC-positivity between both methods and their ability to predict prognosis. Overall survival (OS) was calculated and Kaplan-Meier curves were estimated with thresholds of ≥1 and ≥5 detected CTCs., Results: The CTC positivity rate of the CellSearch® system was 56.7% and of the filtration-based platform 66.7%. There was a high correlation of CTC enumeration obtained with both methods. The OS for patients without detected CTCs, regardless of the method used, was significantly higher compared to patients with one or more CTCs (p < 0.001). The median OS of patients with no CTCs vs. ≥ 1 CTC assessed by CellSearch® was 1.83 years (95% CI: 1.63-2.02) vs. 0.74 years (95% CI: 0.51-1.52). If CTCs were detected by the filtration-based method the median OS times were 1.88 years (95% CI: 1.74-2.03) vs. 0.59 years (95% CI: 0.38-0.80)., Conclusions: The newly established EpCAM independently filtration-based system is a suitable method to determine CTC counts for MBC patients. Our study confirms CTCs as being strong predictors of prognosis in our population of MBC patients.

Interferon-α (IFNα) was the first effective drug therapy for hairy cell leukemia (HCL). Nowadays, it is used as an alternative treatment in selected patients. Due to unlimited treatment time, monitoring and early prediction of response are important. Moreover, IFNα is used in the therapy of chronic hepatitis C, where a single nucleotide polymorphism of interleukin-28B gene (IL28B) correlates with therapy response. The role of this polymorphism in therapy response of IFNα-treated patients with HCL is unknown. Thirty-seven HCL patients treated between 1978 and 2014 were included in this study. Treatment strategy and response parameters (blood cell counts, soluble interleukin-2 receptor (sIL2R), and bone marrow examination) have been assessed. Relative decrease of sIL2R was correlated with outcome parameters. Response parameters of IFNα-treated patients were correlated with IL28B polymorphism. Twenty-one patients were analyzed for the correlation of sIL2R ratio and outcome. After 1 and 3 months of therapy (IFNα or cladribine (CDA)), the median sIL2R level showed a relative decrease of 79 and 91%. These decreases significantly correlate with time to complete remission (CR, p = 0.029 and p = 0.018). Correlation analyses of IL28B genotype with outcome parameters are not significant. Six patients (16%) were diagnosed with secondary malignancies, and one death was registered (median follow-up time 14 years). IFNα is a safe, effective, and well-tolerated long-term treatment in HCL. Relative decreases of sIL2R levels correlate with time to CR and are useful as early predictor for response. There is no significant correlation between IL28B polymorphism and treatment response to IFNα. Graphical abstract.

In recent years complementary and alternative medicine (CAM) has increasingly been the focus of international research. Numerous subsidised trials (7903) and systematic reviews (651) have been published, and the evidence is starting to be integrated into treatment guidelines. However, due to insufficient evidence and/or insufficient good quality evidence, this has mostly not translated to practice recommendations in reviews by the Cochrane collaboration gynaecology group. There is nevertheless a not insignificant number of CAM providers and users. The percentage of oncology patients who use CAM varies between 5 and 90 %. Doctors have been identified as the main providers of CAM. Half of gynaecologists offer CAM because of personal conviction or on suggestion from colleagues. This must be viewed in a critical light, since CAM is mostly practiced without appropriate training, often without sufficient evidence for a given method - and where evidence exists, practice guidelines are lacking - and lack of safety or efficacy testing. The combination of patient demand and lucrativeness for doctors/alternative medicine practitioners, both based on supposed effectiveness CAM, often leads to its indiscriminate use with uncertain outcomes and significant cost for patients. On the other hand there is published, positive level I evidence for a number of CAM treatment forms. The aim of this article is therefore to review the available evidence for CAM in gynaecological oncology practice. The continued need for research is highlighted, as is the need to integrate practices supported by good evidence into conventional gynaecological oncology.

Introduction: Stereotactically-guided core needle biopsies (CNB) of breast tumours allow histological examination of the tumour without surgery. Touch imprint cytology (TIC) of CNB promises to be useful in providing same-day diagnosis for counselling purposes and for planning future surgery. Having addressed the issue of accuracy of immediate microscopic evaluation of TIC, we wanted to re-examine the usefulness of this procedure in light of the present health care climate of cost containment by incorporating the surgical 15-year follow-up data and outcome. Patients and Methods: From January until December 1996 we performed TIC in core needle biopsies of 173 breast tumours in 169 patients, consisting of 122 malignant and 51 benign tumours. Histology of core needle biopsies was proven by surgical histology in all malignant and in 5 benign tumours. Surgical breast biopsy was not performed in 46 patients with 46 benign lesions, as the histological result from the core needle biopsy and the result of the TIC were in agreement with the suspected diagnosis from the complementary breast diagnostics. A 15-year follow-up of these patients followed in 2013 and follow-up data was collected from 40 women. Results: In the 15-year follow-up of the 40 benign lesions primarily confirmed using CNB and TIC, a diagnostic sensitivity, specificity, positive and negative predictive value and accuracy of 100 % was found. Conclusion: TIC and stereotactically guided CNB showed excellent long-term follow-up in patients with benign breast lesions. The use of TIC to complement CNB can therefore provide immediate cytological diagnosis of breast lesions.

Introduction: The potential of sonography in the examination of lung tissue is extremely limited by the air-filled alveoles of the lung. Only in special circumstances like pleural adhesion lesions, atelectasis or pneumonia can lung tissue be visualized by B-mode sonography. Real-time elastography was primarily applied to detect and visualize pulmonary lesions., Methods and Patients: 8 patients with a total of 18 histologically proven metastases of the lung were included. All pulmonary lesions were detected by computed tomography. Sonographic examination was performed with a 7.5 MHz linear transducer (Acuson Antares premium edition, Siemens, Erlangen, Germany), including B-mode and real-time elastography (RTE). The mean distance between pleura and the lesions ranged from 0 to 2.5 cm. Two lesions were located in the upper right lobe, eleven lesions in the lower right and five in the lower left lobe., Results: RTE was able to detect and visualize all 18 pulmonary lesions in contrast to B-mode. The size and distance of the lesions from the pleura correlated with the CT findings., Conclusion: In contrast to B-mode sonography, RTE is able to detect and visualize peripheral, non-pleural adherent pulmonary lesions., (© Georg Thieme Verlag KG Stuttgart · New York.)

Breast cancer centres - certified in accordance with the criteria of the German Cancer Association and the German Mastology Association - are established throughout Germany. Although the setting up of centres and the subsequent need for certification are associated with a marked increase in costs, initial data show positive effects on quality. Certified centres are cost-effective from the point of view of health economics - they lead to improved quality in processes and results without creating any increase in costs for the funding bodies. However, the organization of the necessary structures, with interdisciplinary treatment, documentation and quality-assurance measures, requires considerable resources. Increasing consolidation of inpatient services is also involved, while shortening of the patients' hospitalization periods is leading to reduced remuneration from the funding bodies. The current cost deficits, which have resulted from the increased resources required, need to be recouped through additional charges. It will only be possible to maintain the high quality achieved if additional charges become available to cover the centres' added costs. Good data are increasingly becoming available as a basis for negotiations on charges - e.g., with regard to the quality of results and the National Cancer Plan - as well as clear support from patients.

Purpose: To evaluate complication rates associated with total laparoscopic hysterectomy (TLH) using the Hohl instrument in women with benign indications for hysterectomy, a prospective cohort study was conducted in a university teaching hospital., Methods: A total of 567 women with benign indications for hysterectomy underwent the TLH procedure using the Hohl instrument between January 2005 and July 2009. The laparoscopic approach was used when the patient had undergone more than one previous pelvic abdominal operation, when an adnexal finding was present, and/or if the patient had reduced vaginal capacity., Results: One ureteral injury (0.18%), four bladder injuries (0.71%), one small-bowel injury (0.18%), one vaginal injury (0.18%), and one conversion to abdominal hysterectomy (0.18%) occurred. The general complication rate during surgery was 1.42%, whereas in the postoperative period was 3.19%. The mean loss of hemoglobin was 1.47 g/dL (SD 1.06), the mean operating time was 103.87 min (SD 43.89), and the mean uterus weight was 241.41 g (SD 196.73)., Conclusions: Total laparoscopic hysterectomy using the Hohl instrument simplifies the surgical procedure. The technique reported here is safe and effective in preventing ureteral complications during TLH, even in a university training program.

Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER- tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10(-18)), rs3803662 (16q12) (P = 3.7 × 10(-5)), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10(-6) and P = 4.1 × 10(-4), respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ≤ 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.

Sensory gain (i.e., hyperalgesia) and sensory loss (ie, hypoalgesia) are key features of neuropathic pain syndromes. Previously, we showed that conditioning electrical stimuli may provoke either sensory gain or decline in healthy subjects, depending on the stimulation frequencies applied. In the present study we sought to determine whether sensory decline induced by 20-Hz electrical stimulation preferentially of peptidergic C-nociceptors induces antihyperalgesic effects in a transdermal electrical pain model. Twelve healthy volunteers underwent 0.5-Hz noxious electrical stimulation of the right volar forearm for 35minutes, leading to secondary mechanical hyperalgesia. In 5 sessions the 0.5-Hz stimulus was applied either alone (Stim1) or with concurrent noxious 20-Hz stimulation at different sites (Stim2: ipsilateral 5 cm distance; Stim3: ipsilateral 10 cm distance; Stim4: contralateral arm; Stim5: contralateral dorsal foot). Close concurrent 20-Hz stimulation (Stim2) inhibited the development of hyperalgesia, as measured using the mechanical pain threshold, while remote and contralateral 20-Hz stimulation had no impact on mechanical pain threshold. However, after ipsilateral (stim2, stim3) and contralateral (stim4) forearm stimulation the area of hyperalgesia around the 0.5-Hz stimulation site was significantly reduced. Thus, antihyperalgesia was induced in a homotopic and in a heterotopic ipsisegmental manner. Underlying mechanisms may include neuroplastic changes of pro- and antinociceptive systems at the spinal or supraspinal level. We conclude that 20-Hz noxious electrical stimulation may represent a neurostimulatory paradigm with antihyperalgesic properties. These findings may thus be of relevance for the future therapy of neuropathic pain syndromes as well. Sensory decline induced by 20-Hz electrical stimulation of peptidergic C-nociceptors induces antihyperalgesic effects in a transdermal electrical pain model., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Introduction: The proliferation biomarker Ki-67 is a prognostic factor for breast cancer that has been investigated in several retrospective studies and a few prospective ones. The aims of the present study were to examine interactions between Ki-67 and other biomarkers in breast cancer patients and to assess the relationship of Ki-67 to histological grading., Patients and Methods: Patients with uniform immunohistochemical staining of Ki-67 by MIB-1 were identified from the database of the University Breast Center for Franconia. Data were available for 1232 of 2523 patients with invasive breast cancer who had been treated between 1998 and 2005. Ki-67 index was determined during routine work-up of the breast cancers by several surgical pathologists according to a standardized procedure. The Ki-67 proliferation index was correlated with hormone receptor status, HER2/neu status, age, tumor staging, and prognosis. In routine clinical practice, the grading was assessed according to Elston and Ellis, along with all other parameters., Results: Ki-67 proliferation index>or=20% was found to be associated with all of the prognostic factors that were tested. However, it also maintained statistical significance relative to poor overall survival in a multivariate Cox proportional hazards model (hazards ratio 1.81; 95% CI, 1.17-2.78). The hazards ratio for disease-free survival did not reach statistical significance (HR 1.41; 95% CI, 0.95-2.09; P=0.086). However, in both models the grade was not an independent prognostic factor., Conclusions: For routine clinical purposes, grading appears to add only limited information about the prognosis in comparison with Ki-67 expression. Further investigation of quality assurance for grading and of Ki-67 as a prognostic and predictive factor is warranted.