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BACKGROUND: Women with urgency/frequency predominant lower urinary tract symptoms (UF-LUTS) may have elevated pelvic floor muscle (PFM) position at rest and limited mobility with PFM contraction and bearing down, but this has not been quantified. OBJECTIVES: To compare PFM position and mobility using transperineal ultrasound (TPUS) at rest, maximal PFM contraction (perineal elevation), and bearing down (perineal descent) in women with and without UF-LUTS. We hypothesized that women with UF-LUTS would demonstrate elevated resting position and decreased excursion of pelvic landmarks during contraction and bearing down as compared to women without UF-LUTS. STUDY DESIGN: Case-control study METHODS: Women with UF-LUTS were matched 1:1 on age, body mass index and vaginal parity to women without UF-LUTS. TPUS videos were obtained during 3 conditions: rest, PFM contraction, and bearing down. Levator plate angle (LPA) and puborectalis length (PR length), were measured for each condition. Paired t-tests or Wilcoxon signed rank tests compared LPA and PR length between cases and controls. RESULTS: 21 case-control pairs (42 women): Women with UF-LUTS demonstrated greater LPA at rest (66.8 ± 13.2 degrees vs 54.9 ± 9.8 degrees; P=0.006), and less PR lengthening from rest to bearing down (0.2 ± 3.1 mm vs 2.1 ± 2.9 mm; P=.03). CONCLUSION: Women with UF-LUTS demonstrated more elevated (cranioventral) position of the PFM at rest and less PR muscle lengthening with bearing down. These findings highlight the importance of a comprehensive PFM examination and possible treatment for women with UF-LUTS to include PFM position and mobility.

OBJECTIVES: Task-specific movement training is a proposed intervention for patellofemoral pain aimed to optimise movement during daily tasks. Focused, progressive task practice emphasising optimal limb alignment may yield improvements in performance-based function and hip muscle strength, and transfer learnt movement patterns to untrained tasks. The purpose of this study was to determine if task-specific movement training improves performance-based function (composite score, movement, pain during movement) in an untrained task. Our secondary purpose was to test whether hip muscle strength improved following the movement training intervention. METHODS: This study was a secondary analysis of a prospective, non-randomised, within-group, double-baseline study. Twenty-three females with patellofemoral pain underwent task-specific movement training two times/week for 6 weeks. Outcomes were collected at three time points: enrolment (baseline), 6 weeks (preintervention) and 12 weeks (postintervention). A repeated measures analysis of variance tested whether the change during the intervention phase was greater than the change during the control phase. Y-balance composite score, hip and knee kinematics and pain during the Y-balance test were primary outcome measures; strength of the hip lateral rotator, abductor and extensor muscles was a secondary outcome measure. RESULTS: The change in composite score for the Y-balance test was not statistically significantly different between the intervention and control phases (p=0.16). The change during the intervention phase exceeded the change during the control phase for hip and knee kinematics and pain during the Y-balance test, with all variables improving (p

The goal of our research work is the development of a novel endoscopic anastomosis device for the colon. One of the main challenges in this context is the application of forces at the endoscope tip to rejoin the two bowel endings. Thus, we focus on a magnetic two-part compression implant approach. The implant halves are detached from the applicator units by means of electromagnets. In this contribution we present the results of our experiments to determine the implant design with special focus on tissue compression forces and the resultant electromagnet dimensioning to estimate size requirements of the application/detachment system. To achieve the targeted compression forces derived from literature, we used cubic N52 magnetized neodymium magnets1 with a side length of 5 mm and mild steel screws. For these magnets, we evaluated a required electromagnetic repulsion force of 4.1 N. For the electromagnetic detachment system this led to the need for 166 windings for the coils on oral side, and 146 windings for the coils at the aboral side. Based on these requirements, a colonoscope diameter (~14 mm) increase of 10.6 mm on the oral side and of 12 mm on the aboral side due to the application device must be assumed. Nevertheless, this diameter still remains within the size range of other colonoscopic tools, such as e.g., circular staplers.

For postmenopausal women with hormone-receptor-positive breast cancer, the most effective duration for adjuvant therapy with an aromatase inhibitor remains unclear.In this prospective, phase 3 trial, we randomly assigned postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy to receive the aromatase inhibitor anastrozole for an additional 2 years (2-year group, receiving a total of 7 years) or an additional 5 years (5-year group, receiving a total of 10 years). The primary end point was disease-free survival. The primary analysis included all the patients who were still participating in the trial and who had no recurrence 2 years after randomization (i.e., when treatment in the 2-year group had ended). Secondary end points were overall survival, contralateral breast cancer, second primary cancer, and clinical bone fracture.Among the 3484 women who were enrolled in the trial, 3208 remained in the trial without disease progression after the first 2 years of extended anastrozole treatment following randomization. Among these women, disease progression or death occurred in 335 women in each treatment group in the primary-analysis set at 8 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.90). No between-group differences occurred in most secondary end points, and subgroup analyses did not indicate differences in any particular subgroup. The risk of clinical bone fracture was higher in the 5-year group than in the 2-year group (hazard ratio, 1.35; 95% CI, 1.00 to 1.84).In postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy, extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture. (Funded by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group; ABCSG-16/SALSA ClinicalTrials.gov number, NCT00295620.).

Background Androgen receptor (AR) expression is a potential therapeutic target in breast cancer (BC) as it is frequently expressed in the luminal A and B subtypes and in approximately one third of basal-like cancers. As AR-positive BC displays a distinct biological behavior, we aimed to analyze AR expression in the particular context of BC brain metastases (BM). Materials and methods Patients with newly diagnosed BC BM treated with neurosurgical resection were identified from the Vienna Brain Metastasis Registry and clinical data including patient characteristics, biological tumor subtypes and overall survival were obtained by retrospective chart review. Formalin-fixed and paraffin-embedded specimen containing BM tissue were retrieved from the Neuro-Biobank. Immunohistochemical staining of AR was performed and AR expression in the tumor-cell nucleus was evaluated. Results Fifty-seven BM samples from 57 individual patients with BC were available for this analysis. AR expression of ≥1% tumor cells was evident in 20/57 (35.1%) BM specimens; the median AR-expression rate was 10% (range: 1% to 60%). AR expression was observed in 11/21 (52.4%) BM of the luminal/human epidermal growth factor receptor 2 (HER2)-negative subtype, 3/13 (23.1%) of the luminal/HER2-positive subtype, 2/7 (28.6%) of the HER2-positive subtype and 4/16 (25.0%) of the triple-negative subtype (P=0.247). Median survival from diagnosis of BM was 10 months (range: 0 to 104 mo) in the entire cohort. No significant association of overall survival and AR expression ≥1% was observed (15 vs. 13 mo; P>0.05). Conclusion AR is expressed in more than one third of BC BM with the highest rates among the luminal/HER2-negative BC subtype and may therefore be a potential prognostic and predictive biomarker in this particular BC population.

Summary Background The aim of the present study was to describe surgically induced astigmatism (SIA) and the coupling effect after conventional phacoemulsification cataract surgery (CPS) in relation to the incisional axis. Material and methods A total of 42 patients were included in the retrospective case series study. Corneal topography was obtained for patients with significant cataract before and 6 weeks after CPS with a main clear corneal incision size of 2.4 mm. Patients were grouped according to the relationship of the incisional axis to the position of the steep axis into a steep incisional group and a flat incisional group. Results In total, 46 eyes were included in the study. While the steep incisional group showed an SIA of −0.15 D (± 0.35), the flat incisional group had a significantly higher SIA of 0.20 D (± 0.51) (p = 0.03). The coupling ratio (CR) in the steep incisional group was −0.38 (± 1.41) and in the flat incisional group it was 0.16 (± 0.97). Correspondingly, a coupling constant (CC) of −0.25 was found for group 1 and a CC of 0.0 for group 2. Conclusion Our results suggest that the location of the main incision should be decided with consideration of the corneal astigmatism in order to minimize the SIA. The CR helps to understand the effect of induced astigmatism and the change in spherical equivalent.

Evidence related to physical therapist-led intervention for patients with chronic hip-related groin pain (HRGP) is limited. The purpose was to assess sustainability of treatment effects for people with HRGP undergoing two physical therapist-led interventions. We completed an ancillary analysis of a pilot multicenter, randomized clinical trial (RCT). Forty-six patients with chronic HRGP, 15-40 years, were enrolled. Patients were randomized to participate in 10 sessions over 12 weeks of either movement pattern training (MoveTrain) or traditional strength/flexibility (Standard). Participants completed self-report questionnaires before treatment and 6 and 12 months after treatment completion. Outcome measures included Hip disability and Osteoarthritis Outcome Score (HOOS), Patient Specific Functional Scale (PSFS) and Numeric Pain Rating Scale (NPRS) for average and worst pain. Continuous data were analyzed with mixed model repeated measures analysis of variance (RM-ANOVA) within each group. NPRS was analyzed using multinomial generalized estimating equations (GEE) with a cumulative logit. Reported p-values are from statistical contrasts within the RM-ANOVAs and GEEs testing a priori hypotheses regarding change from pretest to month 6, and pretest to month 12. 43/46 (93.5%) participants completed treatment, 40 (87.0%) completed 6 and 38 (82.6%) completed 12 month questionnaires. At 6 and 12 months, both groups demonstrated clinically significant improvements, compared to pretest, in all subscales of HOOS (P

The programme for combatting venereal diseases in the Soviet Occupation Zone of Germany (SOZ), the German Democratic Republic (GDR) and the Polish Peoples’ Republic (PPR) after the Second World War was adopted from the Soviet healthcare model. In order to maintain the spread of infections, both countries introduced specific legislation. The analysis of the regulations shows several similarities, such as establishment of easy access to anti-venereal health services, interruption of the chain of infection, and special treatment of individuals who constituted a danger of spreading the infection through compulsory hospitalisation. However, some differences are also visible. In the PPR, the decision about compulsory hospitalisation was left to individual evaluation of the attending physician. Closed venereology facilities or reformatories for treatment of venereal diseases, which existed in the GDR, were not established through legal regulations in the PPR. Since 1964, Polish law specifically targeted prostitutes and alcoholics as sources of spreading venereal diseases. These groups were not mentioned in the German legal acts. Analysis of praxis of compulsory commitment in the SOZ and GDR shows that mostly young women characterized as “drifters” were sent to closed venereology wards with breach of legal regulations. The number of prostitutes constituted only a very small fraction. In the PPR, the data from contemporary literature also indicates a considerable number of young women, the so-called “drifters”, committed to venereology ward.

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on practical activities and didactic teaching of residents and fellows. This survey aimed to propose long-term changes for ophthalmology training based on the changes experienced by trainees and their perception of new training opportunities. Methods: An online survey was distributed to ophthalmology trainees in multiple countries. Descriptive statistics were used to analyse the data. Results: A total of 504 analyzable responses were collected from 32 different countries. The current impact of COVID-19 pandemic was described as “severe” by most trainees (55.2%); however, the future perspective was more optimistic as demonstrated by the greater number of responses reporting a presumed “moderate” (37.3%), “mild” (14.1%) or “slight” (4.2%) long-term impact. The vast majority of trainees reported a decrease ≥50% of clinical activity (76.4%) and >75% of surgical activity (74.6%). Although an initial gap in didactic teaching has been experienced by many (55.4%), regular web-based teaching was reportedly attended by 67.7% of the respondents. A strong agreement was found regarding the worthwhile role of web-based case-presentations in clinical training (91.7%), web-based discussion of edited surgical videos (85.7%) and simulation-based practice (86.9%) in surgical training. Conclusions: This survey, focusing on trainees’ perspective, strongly reinforces the need to promptly include new technology-based training tools, such as web-based teaching, virtual surgical simulators, and telementoring, in long-term reorganisation of ophthalmology training to ensure its continuity and effectiveness, which would remain available even in the face of another unpredictable crisis within the health system.

Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.

Bei der Installation von Erdwarmesonden ist die Vermeidung hydrogeologischer Schadensfalle mit einer adaquaten Hinterfullung essenziell. In dieser Studie wurde ein magnetisches Suszeptibilitatsmesssystem zur Hinterfullkontrolle im Labormasstab untersucht. An mit Magnetit dotierten Verfullbaustoffproben wurde die Sensoreindringtiefe und Sensitivitat ermittelt sowie die unbekannten Messwerte des Messsystems nachvollzogen. Zudem wurde das Potenzial hinsichtlich der Fullstands- und Fehlstellenkontrolle sowie der Einfluss moglicher Storstellen betrachtet. Die Messwerte entsprechen magnetischen Volumensuszeptibilitaten im SI-System, die vom Messsystem mit dem Faktor 350 in ubersichtlichere Dezimalzahlen von 0 bis 11 [–] uberfuhrt werden. Dies wurde durch Vergleichsmessungen mit einem anderen Suszeptibilitatssensor validiert, und hat den Hintergrund der benutzerfreundlicheren Baustellenanwendung. Mit einer Eindringtiefe von 20–35 mm und einer Sensitivitat von nur noch 10 % bei > 20 mm ist das Messsystem ausreichend fur die Fullstandskontrolle, jedoch nicht ausreichend, um alle potenziell kritischen Fehlstellen zu erfassen. Schwachungen des Suszeptibilitatssignals durch Sondenrohre, Abstandshalter und Hohlraume sind kaum voneinander zu unterscheiden. Auserdem konnen bestimmte Gesteine Signalstorungen verursachen. Optimierungen der Sensoreindringtiefe, des Messprozederes sowie der Verfullbaustoffsuszeptibilitat konnen Beitrage zu einer verbesserten Qualitatssicherung sein. Neben der Schadensfallvermeidung konnen diese moglicherweise auch eine Ausweitung der Erdwarmesondentechnologie in wasserrechtlich noch unzulassigen Regionen zukunftig zulassen.

The ongoing COVID-19 pandemic constitutes not only a danger for public health, but may also threaten civil liberties. Looking at the examples of recent events in Poland and Hungary, the authors argue that governments may misuse pandemic for their political advantage, thus endangering public health. Political decisions taken to stem the spread of pandemics should be limited and strictly proportionate to the situation., publishedVersion

Background: Trastuzumab targets the extracellular domain of the HER2 protein. Adding trastuzumab to chemotherapy for patients with early-stage, HER2-positive breast cancer reduces the risk of recurrence and death, but is associated with cardiac toxicity. We investigated the long-term benefits and risks of adjuvant trastuzumab on breast cancer recurrence and cause-specific mortality. Methods: We did a collaborative meta-analysis of individual patient data from randomised trials assessing chemotherapy plus trastuzumab versus the same chemotherapy alone. Randomised trials that enrolled women with node-negative or node-positive, operable breast cancer were included. We collected individual patient-level data on baseline characteristics, dates and sites of first distant breast cancer recurrence and any previous local recurrence or second primary cancer, and the date and underlying cause of death. Primary outcomes were breast cancer recurrence, breast cancer mortality, death without recurrence, and all-cause mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, oestrogen receptor (ER) status, and trial yielded first-event rate ratios (RRs). Findings: Seven randomised trials met the inclusion criteria, and included 13 864 patients enrolled between February, 2000, and December, 2005. Mean scheduled treatment duration was 14·4 months and median follow-up was 10·7 years (IQR 9·5 to 11·9). The risks of breast cancer recurrence (RR 0·66, 95% CI 0·62 to 0·71; p Interpretation: Adding trastuzumab to chemotherapy for early-stage, HER2-positive breast cancer reduces recurrence of, and mortality from, breast cancer by a third, with worthwhile proportional reductions irrespective of recorded patient and tumour characteristics.

Background Following the PACIFIC trial, durvalumab has been approved by the European Medicines Agency (EMA) for consolidation of locally advanced PD-L1-positive NSCLC after chemoradiotherapy (CRT). Patients were treated with durvalumab in the EAP from 22.11.2017 to 15.10.2018 allowing analysis of its efficacy and safety. Methods Data from 56 centres were analysed for adverse events (AE), progression-free survival (PFS), overall survival (OS). Results 126 patients actually received at least 1 cycle durvalumab. Compared to the PACIFIC trial, the EAP population had more advanced stage and included “oligometastatic” stage IV patients and patients with autoimmune disease. PFS (20.1 months) and OS (not reached) were similar in the EAP and the PACIFIC trial. 42.9 % completed 12 months of durvalumab without deaths during FU. Stage IV patients (n = 7) had encouraging OS (not reached at 27 months). Autoimmune disease did not affect survival. PFS and OS were similar in PD-L1-negative patients (n = 32) and PD-L1-positive patients (n = 79). Conclusions Survival in the EAP was comparable to the PACIFIC trial. Selected stage IV patients and patients with autoimmune disease may benefit from durvalumab consolidation and should be included in future immuno-oncological trials. PD-L1 did not predict survival challenging the exclusion of PD-L1-negative patients from durvalumab consolidation. In summary, durvalumab consolidation is safe and effective in a European real-world setting.

The present study aimed at analysing the effect of Khat plant extract on rat testicular development. Thirty-two weaned male albino rats (4 weeks old) were divided into four groups consisting of eight animals each. While control animals received normal saline, rats of groups I, II and III received 100, 200 and 300 mg Khat extract per kg body weight dissolved in distilled water by oral gavage daily for 8 weeks, respectively. Blood samples were collected in separate heparinized tubes by cardiac puncture from each rat and processed for measuring plasma levels of reproductive hormones LH, FSH, testosterone and prolactin. Five-µm sections were stained with haematoxylin and eosin and examined by light microscope. Some sections were immunostained for protamine-1 representing a biomarker for intact sperm differentiation. The present study clearly demonstrated that Khat extract has a pronounced effect on testicular maturation of developing albino rats at both the morphological and functional levels. Khat-treated groups revealed a significantly low serum testosterone level and severe impairment of spermatogenesis when compared with control animals. The current findings also verified, for the first time, that the final stages of sperm maturation (spermiogenesis) were strongly impaired after administration of Khat extract to experimental rats particularly at a higher dose (300 mg/kg body weight). This was proved by the very weak, if any, expression of protamine-1 in the maturing spermatids in Khat-treated rats.

Context:Patients with anterior cruciate ligament (ACL) tears are likely to have deficient dynamic postural stability compared with healthy sex- and age-matched controls.Objectives:To test the hypothesis that patients undergoing ACL reconstruction have decreased dynamic postural stability compared with matched healthy controls.Design:Prospective case-control study.Setting:Orthopedic sports medicine and physical therapy clinics.Patients or Other Participants:Patients aged 20 years and younger with an ACL tear scheduled for reconstruction were enrolled prospectively. Controls were recruited from local high schools and colleges via flyers.Interventions:Patients underwent double-stance dynamic postural stability testing prior to surgery, recording time to failure and dynamic motion analysis (DMA) scores. Patients were then matched with healthy controls.Main Outcome Measures:Demographics, time to failure, and DMA scores were compared between groups.Results:A total of 19 females and 12 males with ACL tears were matched with controls. Individuals with ACL tears were more active (Marx activity score: 15.7 [1.0] vs 10.8 [4.9],P P P Conclusions:Patients undergoing ACL reconstruction had worse global dynamic postural stability compared with well-matched controls. This may represent the effect of the ACL injury or preexisting deficits that contributed to the injury itself. These differences should be studied further to evaluate their relevance to ACL injury risk, rehabilitation, and return to play.

Zusammenfassung Gegenstand und Ziel Die Prävalenz von antibiotikaresistenten Bakterien bei Zier-, Zoo- und falknerisch gehaltenen Greifvögeln ist noch weitgehend unbekannt. Daher sollten retrospektiv Antibiogramme schnellwachsender aerober Bakterienarten ausgewertet werden. Material und Methoden Im Auswertungszeitraum von 2007 bis 2016 standen 1036 Antibiogramme zur Verfügung. Die Bakterienisolate stammten vorzugsweise aus Süddeutschland und von 811 Vögeln aus 20 zoologischen Ordnungen (am häufigsten Papageienvögel [61,8 %] und Sperlingsvögel [14,5 %]) sowie aus Proben von klinischen Patienten und Sektionsmaterial. Die phänotypische In-vitro-Empfindlichkeit wurde mittels Plattendiffusionstest ermittelt. Ergebnisse Die meisten Antibiogramme lagen für E. coli (n = 386 Isolate) vor, gefolgt von Staphylococcus (S.). aureus (n = 150), Enterobacter cloacae (n = 122), Klebsiella pneumoniae (n = 86) und Pseudomonas aeruginosa (n = 64). Resistenzen gegen mindestens einen antibiotischen Wirkstoff zeigten 53,1 % der E. coli-Isolate, dabei am häufigsten gegen Doxycyclin (50,3 %) und Ampicillin (46,1 %). Bei 78,0 % der S. aureus-Isolate und bei 95,9 % der Enterococcus faecalis-Isolate wurden Resistenzen gegenüber mindestens einem Wirkstoff nachgewiesen. Multiresistenzen (Resistenz gegenüber ≥ 3 Antibiotikagruppen) traten bei 37,3 % der Isolate von S. aureus auf. Bei Isolaten von Zier- und Greifvögeln wurden höhere Resistenzraten festgestellt als bei Isolaten von Zoovögeln und bei Papageienvögeln höhere Resistenzraten als bei Sperlingsvögeln. Im Untersuchungszeitraum zeigte sich bei E. coli ein tendenzieller Anstieg der Resistenzrate für Fluorchinolone (Minimum von 0 % im Jahr 2013 und Maximum von 27,3 % im Jahr 2015) und bei S. aureus eine tendenzielle Abnahme der Resistenzraten für Tetrazykline (Maximum von 39,4 % im Jahr 2007 und Minimum von 0 % in den Jahren 2014 und 2015). Schlussfolgerung und klinische Relevanz Die Resistenzsituation von Bakterien aus Zier-, Zoo- und falknerisch gehaltenen Greifvögeln ist als problematisch zu bewerten und verdeutlicht die Wichtigkeit der Empfindlichkeitsprüfung für eine gewissenhafte Therapie. Im Fall einer Infektion mit S. aureus bei Zier-, Zoo- oder falknerisch gehaltenen Greifvögeln kann es zu einem Therapienotstand kommen.

Zusammenfassung Ziel In der DDR konnten auch Männer in geschlossene Venerologische Stationen zwangseingewiesen werden. Während zum Umgang mit Frauen in geschlossenen Venerologischen Stationen zahlreiche Forschungsergebnisse vorliegen, ist über den Umgang mit Männern in diesen Stationen kaum etwas bekannt. Methoden Es wurden ungedruckte Quellen im Bundesarchiv und Landesarchiv Berlin und in den Stadtarchiven von Erfurt und Zwickau recherchiert und historisch-kritisch ausgewertet. Zudem wurden in Datenbanken gedruckte Quellen recherchiert und ausgewertet. Ergebnisse In der DDR wurden Männer in geschlossene Venerologische Stationen zwangseingewiesen. Diese Stationen waren Teil von geschlossenen Venerologischen Einrichtungen, zu denen jeweils auch eine Station für Frauen gehörte. Die Männer wurden getrennt von den Frauen untergebracht. Die Anzahl der Betten und durchgeführten Zwangseinweisungen war in den Stationen für Männer erheblich geringer als in Stationen für Frauen. Gründe für Einweisungen von Männern waren zu behandelnde Geschlechtskrankheiten, HwG-Verdacht und Disziplinarmaßnahmen. Die medizinische Versorgung der Männer entsprach dem zeitgenössischen medizinischen Standard. Schlussfolgerung Die Anzahl der Betten und der Zwangseinweisungen war auf den Stationen für Männer deutlich geringer als auf den Stationen für Frauen. Die Männer wurden überwiegend zwangseingewiesen, weil sie eine Geschlechtskrankheit hatten oder als HwG-Person galten, während mehr als 50 % der Frauen wegen Herumtreiberei eingewiesen wurden. Darüber hinaus galten Männer als zuverlässige Patienten in der medizinischen Versorgung, während Frauen als säumig und unzuverlässig angesehen wurden. In dieser Hinsicht unterscheidet sich die Situation der Männer grundlegend von der der Frauen.

Background Considering the increasing number of chemical peeling applications, also the interest in the history of chemical peelings and agents, has grown in dermatology. Research ascribes the first use of phenol as a chemical peeling agent to William Tilbury Fox (1836-1879) in 1871. Furthermore, Ferdinand von Hebra (1847-1902) is said to describe the properties of various peeling agents in 1874, and Paul Gerson Unna (1850-1929) adds resorcinol and trichloroacetic acid in 1882. Objective To identify the first mentions of chemical peeling applications and agents in 19th-century dermatology. Methods Nineteenth-century dermatologists were identified by an examination of literature of the last 30 years on the history of chemical peeling. Systematic examination of the medical textbooks of Hebra, Fox and Unna was conducted. It was proved whether the mentioned agents were used for chemical peeling applications. Results The skin peeling property of phenol was already discovered by its first describer, the chemist Friedlieb Ferdinand Runge (1795-1867) in 1834. The Viennese dermatologist Hebra described phenol as a chemical peeling agent in 1860. Hebra and his associate Moriz Kaposi (1837-1902) stated that 'Lotio carbolica' was already used in London. Fox used phenol mostly as a disinfectant and not for chemical peelings since 1869. Unna described the chemical peeling property of salicylic acid in 1882 and gave the most comprehensive account of chemical peels of the 19th century in 1899. Unna also introduced the Gutta-percha plaster with salicylic acid and phenol. Around 1900, Unna was famous for his peeling paste with resorcinol in Germany. Conclusions A new chronology of the introduction of chemical peeling in dermatology can be drawn from the results. The German-speaking dermatology pioneered the treatment of skin diseases with chemical peelings as well as for aesthetical purposes 21 years earlier than hitherto known.

Reliable determination of Ki67 labeling index (Ki67-LI) on core needle biopsy (CNB) is essential for determining breast cancer molecular subtype for therapy planning. However, studies on agreement between molecular subtype and Ki67-LI between CNB and surgical resection (SR) specimens are conflicting. The present study analyzed the influence of clinicopathological and sampling-associated factors on agreement. Molecular subtype was determined visually by Ki67-LI in 484 pairs of CNB and SR specimens of invasive estrogen receptor (ER)–positive, human epidermal growth factor (HER2)–negative breast cancer. Luminal B disease was defined by Ki67-LI > 20% in SR. Correlation of molecular subtype agreement with age, menopausal status, CNB method, Breast Imaging Reporting and Data System imaging category, time between biopsies, type of surgery, and pathological tumor parameters was analyzed. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. CNB had a sensitivity of 77.95% and a specificity of 80.97% for identifying luminal B tumors in CNB, compared with the final molecular subtype determination after surgery. The correlation of Ki67-LI between CNB and SR was moderate (ROC-AUC 0.8333). Specificity and sensitivity for CNB to correctly define molecular subtype of tumors according to SR were significantly associated with tumor grade, immunohistochemical progesterone receptor (PR) and p53 expression (p p = 0.22 for both). The identified factors likely mirror intratumoral heterogeneity that might compromise obtaining a representative CNB. Our results challenge the robustness of a single CNB-driven measurement of Ki67-LI to identify luminal B breast cancer of low (G1) or intermediate (G2) grade.

Aims The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter-Defibrillators (EU-CERT-ICD), a prospective investigator-initiated, controlled cohort study, was conducted in 44 centres and 15 European countries. It aimed to assess current clinical effectiveness of primary prevention ICD therapy. Methods and results We recruited 2327 patients with ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and guideline indications for prophylactic ICD implantation. Primary endpoint was all-cause mortality. Clinical characteristics, medications, resting, and 12-lead Holter electrocardiograms (ECGs) were documented at enrolment baseline. Baseline and follow-up (FU) data from 2247 patients were analysable, 1516 patients before first ICD implantation (ICD group) and 731 patients without ICD serving as controls. Multivariable models and propensity scoring for adjustment were used to compare the two groups for mortality. During mean FU of 2.4 ± 1.1 years, 342 deaths occurred (6.3%/years annualized mortality, 5.6%/years in the ICD group vs. 9.2%/years in controls), favouring ICD treatment [unadjusted hazard ratio (HR) 0.682, 95% confidence interval (CI) 0.537–0.865, P = 0.0016]. Multivariable mortality predictors included age, left ventricular ejection fraction (LVEF), New York Heart Association class Conclusion In contemporary ICM/DCM patients (LVEF ≤35%, narrow QRS), primary prophylactic ICD treatment was associated with a 27% lower mortality after adjustment. There appear to be patients with less survival advantage, such as older patients or diabetics.

Background STEPAUT, an Austrian non-interventional study, evaluated the safety and efficacy of everolimus plus exemestane in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) recurring/progressing on/after nonsteroidal aromatase inhibitors (NSAIs) in routine clinical practice. Methods Postmenopausal women with HR+, HER2− ABC progressing on/after NSAIs receiving everolimus plus exemestane in accordance with routine practice and the current version of Summary of Product Characteristics were eligible. Planned individual observation period corresponded to the duration of treatment until formal study end. Results Overall, 236 patients (median age: 65 years) were enrolled at 17 sites across Austria. The median progression-free survival (mPFS) in the overall population was 9.5 months (95% confidence interval [CI]: 8.6–10.7 months). The mPFS (95% CI) in patients who received everolimus 10 and 5 mg was 9.9 months (7.3–11.5 months) and 8 months (4.7–10.7 months), respectively. The median time to progression was numerically longer in patients who had a therapy break (11.9 months, 95% CI: 10.0–14.6 months) versus those who did not have any therapy break (10.7 months, 95% CI: 8.9–12.6 months). Patients experienced grade 1 (53.7%), grade 2 (35.9%), grade 3 (9.9%), grade 4 (0.2%) adverse events (AEs). The most common AEs of any grade were stomatitis, mucositis (53.8%), rash, exanthema (29.7%), loss of appetite, nausea (28.4%). Conclusions Real-world safety and efficacy data from STEPAUT were consistent with results from BOLERO-2, supporting everolimus plus exemestane as a suitable treatment option for HR+, HER2− ABC recurring/progressing on/after NSAIs., Highlights • STEPAUT, an Austrian non-interventional study, evaluated everolimus plus exemestane. • The median progression-free survival in the overall population was 9.5 months. • Majority of the patients had grade 1 (53.7%) to grade 2 (35.9%) adverse events. • Real-world data from STEPAUT were consistent with results from the BOLERO-2., Trial registration: BASG, AGES, NIS002843

PURPOSE: To describe prevalence of subscapularis and long head of biceps tendon (LHB) pathology in relation to presence and severity of degenerative posterosuperior (PS) rotator cuff disease in a prospective cohort. METHODS: Subjects with asymptomatic rotator cuff tears were enrolled for this prospective longitudinal study (n=354) and followed annually with shoulder ultrasonography and clinical evaluations to assess for presence of subscapularis, LHB, and PS rotator cuff pathology and pain development. RESULTS: Subscapularis pathology developed in 14% of shoulders over a median follow-up of 5 years, with partial-thickness tearing occurring most commonly (83%). Age, gender, and hand dominance were not associated with subscapularis pathology. A greater proportion of concomitant full-thickness PS cuff tears was observed in shoulders that developed subscapularis tears (76% vs. 50%;p=0.002). PS cuff tear width (10mm vs. 14mm,p=0.01) at time of enrollment and both tear width (10mm vs. 15mm,p=0.003) and length (12mm vs. 15.5mm,p=0.02) at time of diagnosis of subscapularis pathology were greater in subscapularis-torn shoulders. LHB pathology was prevalent in 34% of shoulders, with dislocation/subluxation occurring in 63%, and higher prevalence in subscapularis-torn shoulders (71% vs. 12%;p

Zusammenfassung Hintergrund Der Hexenglaube beeinflusste im 16. Jahrhundert das medizinische Denken und Handeln. Der Ulmer Stadtarzt Wolfgang Reichart (1486–1547) hat in einem bisher unbekannten Traktat die Impotenz eines Patienten mit medizinischen Konzepten rational erklärt. Material und Methode Der Traktat wurde transkribiert, übersetzt und hinsichtlich seiner Quellen, Struktur und des Inhalts analysiert. Die Ergebnisse wurden mit Johann Weyers (1515–1588) Konzepten verglichen. Ergebnisse Reichart erklärt die Impotenz seines Patienten als erworbene Erkrankung, an der Dämonen beteiligt waren. Da Dämonen nur auf natürliche Weise auf den menschlichen Körper wirken, sei die Krankheit auf natürlichem Weg heilbar. Grundlage der Therapie ist ein mittelalterliches pathophysiologisches Konzept, das antike Elemente kombinierte. Schlussfolgerungen Reicharts Therapie unterscheidet sich von derjenigen zeitgenössischer Ärzte, weil er den Patienten selbst behandelt und nicht an einen Theologen überweist. Im Gegensatz zu Weyer bietet er ein detailliertes pathophysiologisches Konzept zur medizinischen Erklärung der Impotenz.

Orthotopic mouse liver transplantation (MLTx) is an established model for immunological studies of graft rejection and tolerance induction after solid organ transplantation. Since its introduction in mice by Qian et al. (1991) in 1991, the mouse model has been frequently used to study immunological responses (Qian et al. 1994, 1997, 1996; Li et al. 2001; Klein and Crispe 2006). The model is also suitable to analyze the pathways of hepatic regeneration after prolonged ischemia time and/or partial liver transplantation (Conzelmann et al. 2003; Tian et al. 2011).

Purpose: This phase II study determined the efficacy of lacnotuzumab added to gemcitabine plus carboplatin (gem-carbo) in patients with advanced triple-negative breast cancer (TNBC). Patients and Methods: Female patients with advanced TNBC, with high levels of tumor-associated macrophages not amenable to curative treatment by surgery or radiotherapy were enrolled. Lacnotuzumab was dosed at 10 mg/kg every 3 weeks, ± a dose on cycle 1, day 8. Gemcitabine (1,000 mg/m2) and carboplatin (dose in mg calculated by area under the curve [mg/mL/min] × (glomerular filtration rate [mL/min] + 25 [mL/min]) were dosed every 3 weeks. Treatment continued until unacceptable toxicity, disease progression, or discontinuation by physician/patient. Results: Patients received lacnotuzumab + gem-carbo (n = 34) or gem-carbo (n = 15). Enrollment was halted due to recruitment challenges owing to rapid evolution of the therapeutic landscape; formal hypothesis testing of the primary endpoint was therefore not performed. Median progression-free survival was 5.6 months [90% confidence interval (CI), 4.47–8.64] in the lacnotuzumab + gem-carbo arm and 5.5 months (90% CI, 3.45–7.46) in the gem-carbo arm. Hematologic adverse events were common in both treatment arms; however, patients treated with lacnotuzumab experienced more frequent aspartate aminotransferase, alanine aminotransferase, and creatine kinase elevations. Pharmacokinetic results showed that free lacnotuzumab at 10 mg/kg exhibited a typical IgG pharmacokinetic profile and target engagement of circulating colony-stimulating factor 1 ligand. Conclusions: Despite successful target engagement and anticipated pharmacokinetic profile, lacnotuzumab + gem-carbo showed comparable antitumor activity to gem-carbo alone, with slightly poorer tolerability. However, the data presented in this article would be informative for future studies testing agents targeting the CSF1–CSF1 receptor pathway in TNBC.

In this case report, we describe two cases of gastric mucosa- associated lymphoid tissue (MALT) lymphoma. The first patient, who presented with complaints of indigestion, nausea and epigastralgy, had a solid ulcer on endoscopy. Biopsies showed, next to MALT, presence of Helicobacter Pylori. The second patient was admitted with hematemesis. The multiple ulcerations in his stomach were thought to be cocaine-induced. Only after multiple biopsies the diagnosis of MALT was made. No presence of Helicobacter Pylori could be detected. The first patient was successfully treated with Helicobacter Pylori eradication therapy. Localized radiotherapy resulted in complete remission in our second patient. Hence, in absence of Helicobacter Pylori, more aggressive treatment modalities are needed.

ObjectiveIn response to the COVID-19 pandemic, strict hygiene and containment measures have been instituted in the clinical ophthalmological examination to prevent virus transmission. The aim of this study is to assess the effects of these protective measures on the quality of the examination with an emphasis on gender-specific differences.Methods and analysisAn online survey was sent to ophthalmologists in 10 countries. The collected data included demographics, place of work, current professional status, COVID-19 protective measures and their impact on the quality of the examination. Descriptive statistics were used to analyse the data. Fisher’s exact test was used to analyse gender differences.ResultsA total of 120 responses were collected. 54.0% of the respondents identified as female and 43.4% as male. Over 75% agreed that protective measures made the examination conditions more difficult. The major problems were fogging of the lenses (87.6%) or slit lamp oculars (69.9%), reduced operability of the slit lamp due to protective barriers (60.2%) and time delay due to disinfection measures (68.1%). Significantly more women than men reported that they used filtering face piece (FFP2) instead of surgical masks (p=0.02). More male participants reported that they removed their mask to prevent fogging (p=0.01). 31% of all participants felt that the COVID-19 protective measures reduced the overall quality of slit lamp examination and 43.4% reported a reduced quality of fundoscopic examination.ConclusionCOVID-19 related safety measures reduce the feasibility of the clinical ophthalmological examination. Practicable solutions are required to maintain good examination quality without compromising personal safety.

Background The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade ≥3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.

Background If a COVID-19 patient develops a so-called severe course, he or she must be taken to hospital as soon as possible. This proves difficult in domestic isolation, as patients are not continuously monitored. The aim of our study was to establish a telemonitoring system in this setting. Methods Oxygen saturation, respiratory rate, heart rate and temperature were measured every 15 minutes using an in-ear device. The data was transmitted to the Telecovid Centre via mobile network or internet and monitored 24/7 by a trained team. The data were supplemented by daily telephone calls. The patients´ individual risk was assessed using a modified National Early Warning Score. In case of a deterioration, a physician initiated the appropriate measures. Covid-19 Patients were included if they were older than 60 years or fulfilled at least one of the following conditions: pre-existing disease (cardiovascular, pulmonary, immunologic), obesity (BMI >35), diabetes mellitus, hypertension, active malignancy, or pregnancy. Findings 153 patients (median age 59 years, 77 female) were included. Patients were monitored for 9 days (median, IQR 6–13 days) with a daily monitoring time of 13.3 hours (median, IQR 9.4–17.0 hours). 20 patients were referred to the clinic by the Telecovid team. 3 of these required intensive care without invasive ventilation, 4 with invasive ventilation, 1 of the latter died. All patients agreed that the device was easy to use. About 90% of hospitalised patients indicated that they would have delayed hospitalisation further if they had not been part of the study. Interpretation Our study demonstrates the successful implementation of a remote monitoring system in a pandemic situation. All clinically necessary information was obtained and adequate measures were derived from it without delay.

The ocular surface vascular system plays a key role in corneal and conjunctival inflammatory, infectious and neoplastic pathology. Angiographic vessel analysis using intravenous dyes and optical coherence tomography technology allow both the quantitative and functional assessment of conjunctival vasculature and corneal neovessels. Based on a thorough understanding of vascular alterations in ocular surface disease, angiographic assessment facilitates the clinical management of corneal neovascularisation, the grading of ocular surface inflammation and the identification of tumour angiogenesis in dysplastic or malignant lesions. This review summarises key aspects of the clinical application of corneal and conjunctival angiography as presented at the 2021 virtual Bowman Club meeting.

Background Recurrent ventricular tachycardia (VT) can occur after left ventricular assist device (LVAD) implantation. In this case, medical treatment might be insufficient. We report a case of a left-sided thoracoscopic sympathectomy as a feasible treatment escalation in intractable VT. Case report A 72-year-old patient underwent an internal cardioverter defibrillator (ICD) implantation as primary prophylaxis for VTs in the setting of staged heart failure therapy. Afterwards, due to a progressive dilative cardiomyopathy he underwent a minimal-invasive LVAD implantation (HeartWare, Medtronic). After an uneventful minimal-invasive LVAD-implantation the patient was discharged to a rehabilitation program. However, after 7 weeks he developed recurrent VTs which were successfully terminated by ICD shocks deliveries leading to severe discomfort and frequent hospitalizations. Eventually, the patient was admitted with an electrical VT storm. Successful endocardial catheter ablation of all inducible VTs were performed combined with multiple rearrangements of his oral antiarrhythmic medication. However, all these treatments could not suppress further occurrence of VTs. After an interdisciplinary discussion the patient agreed to a left-sided video-assisted thoracoscopic sympathectomy. After a follow up of 150 days the patient was free from VTs apart from one short event. Conclusion We believe video-assisted thoracoscopic sympathectomy might be a surgical treatment option in patients with intractable recurrent VTs after catheter ablation of VT reentrant substrate even after minimal-invasive LVAD implantation.

Osteoarthritis is a common disease, with a prevalence of symptomatic disease of 8.9%. One treatment option is radiotherapy. Most published samples were treated with an orthovoltage technique or with a telecobalt device. A lot of radiotherapy institutions are nowadays using linear accelerators for treatment of osteoarthritis. There is a discussion on whether the treatment results achieved with a linear accelerator are comparable to those with the orthovoltage technique. The aim of this study is to analyze the results of radiotherapy for osteoarthritis with a linear accelerator and compare the results with reference to different joints. The analysis was performed in patients of two German radiotherapy institutions and included 295 irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 65 years, with 39.0% male and 61.0% female patients. Most frequently, osteoarthritis of the knee (34.6%) or the finger (15.9%) was treated. We could find a significant response to radiotherapy. Median pain for the whole sample was 7 on the NRS before radiotherapy, 4 after 6 weeks, and 3 after 12 and 24 months. The percentage of patients with 0 or 1 on the NRS was 33.8% 12 months after radiotherapy. All investigated subgroups had a significant reduction of pain. Radiotherapy of osteoarthritis with a linear accelerator is an effective treatment which is very well tolerated. All analyzed subgroups show a good response to radiotherapy for at least 24 months. Orthovoltage therapy seems to be superior to treatment with a linear accelerator in a case-related analysis of the published samples. Further investigations should be performed for a definitive answer to this question.

In March 2019, the German Gemeinsamer Bundesausschuss (G‑BA; Federal Joint Committee) presented the result of the method assessment process on non-invasive prenatal testing (NIPT). The aim of this method assessment process was to decide whether NIPT should become a publicly funded procedure of routine prenatal care. The G‑BA decided in favor of NIPT, making the implementation of NIPT very likely, provided that other healthcare and political institutions also agree. This development could be interpreted as empowering from the perspective of reproductive autonomy, since NIPT allows pregnant women to obtain valuable information on the health of the fetus in a fast and easy manner and without the risks of invasive methods. However, the routinization of NIPT also implies ethical challenges. Will the routinization lead to a normalization of prenatal quality control? Will it lead to an expansion to women outside the high-risk group? What would be the ethical implications of such a development? How should physicians, geneticists, and patients deal with the increased amount of obtainable information? What are the implications for choice and decision-making in the prenatal care context? In this paper, we analyze the ethical aspects of the routinization of NIPT, focusing on information and the counseling process, the burden of choice, and the threats to reproductive autonomy by societal interests linked to NIPT.

Introduction: Myelosuppresion is a common side effect of chemotherapy and granulocyte-colony stimulating factor (G-CSF) is often used to reduce the risk of neutropenic events. The purpose of this e...

Background No consensus regarding the best post-operative treatment option for air leak has been established. In this study, we evaluate the use of intra-pleural fresh frozen plasma (FFP) as a promising treatment method. Methods Treatment for a sustained air leak (3 days) was warranted in approximately 12% of the lung surgeries at our institution. Fifty-two patients were treated with FFP by application of 250 mL daily. The patients were divided into two cohorts: cohort 1 consisted of 35 patients undergoing anatomical lung resections and cohort 2 consisted of 17 patients after miscellaneous types of lung surgery. Successfulness of the procedure as well as the potential influential factors was evaluated statistically and validated by a bootstrapping. Area under receiver operating characteristic curve was used to establish a cut-off value of the predictor. Results In the first cohort, air leakage was successfully treated in 28 (80%), while in seven (20%) it was still present after third treatment with FFP. The success rate in cohort 2 was 76.5%. The only covariate which appeared to remain significant in both cohorts was flow as displayed on the digital suction device prior to application of FFP. Flow ≤375 mL/min was indicative of successful aerostasis. Conclusion Intra-pleural instillation of FFP seems to be a feasible method for the treatment of post-operative air leakage. Although the optimum strategy regarding its application as well as its limitations is yet to be established, an absence of complications or undesirable events makes this (off label) method a safe and promising alternative to existing options.

Purpose of the study To discuss the ethical challenges for the therapeutic team when dealing with a young savior sibling as a potential tissue donor. Basic procedures Savior siblings are children that are created to serve a sibling as a donor of umbilical cord blood, bone marrow, or peripheral blood from which hematopoietic stem cells are derived. These cells are used for hematopoietic stem cell therapy, which is the only curative treatment for certain hemoglobinopathies. We used a case including a 19-year-old thalassemia patient and his two and a half year old sister from our practice as ethics consultants. Our methodological basis is the principlism approach by Beauchamp and Childress, consisting of four principles: autonomy, non-maleficence, beneficence, and justice. Main findings We found that the main conflict arises between the autonomy of the savior sibling as well as the non-maleficence regarding her and the beneficence of the thalassemia patient. Principal conclusions Decision-making is complex when decisions within the family are concerned, especially when non-competent young children are involved. The therapeutic team does not only have to recognize the principal vulnerability of children but also the different scales of vulnerability depending on their age.

Ionizing radiation is able to cause severe damage to cardiac implantable electronic devices (CIED). In Germany, the DEGRO/DGK guideline recommends close monitoring of patients with CIEDs undergoing radiotherapy (RT). Nevertheless, especially in the era of intensity-modulated techniques and predominant use of 6 MV photons, errors of CIEDs are rare events. Therefore, we performed daily CIED controls and hypothesized that no relevant device interaction would occur in our cohort. From 2014 to 2018, we collected data of 51 patients (62 courses) with daily interrogation (n = 1046) of CIED. The dose to the skin above the CIED was measured by semiconductor or ion chamber dosimetry at least once per RT course. In many cases the dose was also calculated. The prescribed dose to the planning target volume (PTV) ranged from 7.5 to 78.0 Gy (IQR 27.8–61.0 Gy). The median measured cumulative dose to the skin above the CIED was 0.17 Gy, whereas the median calculated dose was 1.03 Gy. No error occurred in the group with maximum beam energy >10 MeV. Three events without clinical relevance could be recognized in the group with an intensity-modulated technique at 6 MV. None of the three concerned devices were located directly within the PTV. Errors of CIEDs during RT are rare events. The approach according to the DEGRO/DGK guideline is safe, but also consumes resources. In our cohort it was not compulsory to relocate any CIED. Clinically relevant events are uncommon, so it remains debatable which procedure is necessary. Daily controls could be avoided in some selected cases without compromising patient safety.

Humeral epicondylitis is a common elbow disease. The prevalence is about 1.7%. One of the most effective treatment options is radiotherapy. Some authors mention that they apply a second or third course of radiation for recurrent pain or partial or no response to the initial course. As the results of a re-irradiation have not been systematically analyzed, the aim of this study was to document the results of repeated radiation treatment and to identify those patients who will benefit.The analysis was performed on patients from three German radiotherapy institutions and included 99 re-irradiated elbows. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy as well as for the follow-up of 24 months. The median age of the patients was 51 years with 48.8% male and 51.2% female patients. Repeated radiation was indicated because the initial radiotherapy resulted in 39.7% of no response, in 41.0% of partial response and in 19.3% of recurrent pain.A significant response to re-irradiation was found. For the whole sample the median pain score was 6 before re-irradiation, 3 after 6 weeks, 2 after 12 months and 1 after 24 months. The percentage of patients being free of pain or with very little pain was 50.9% 24 months after re-irradiation. All subgroups, notably those with no response, partial response and recurrent pain had a significant reduction of pain.Re-irradiation of humeral epicondylitis is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months.HINTERGRUND: Die Epicondylitis humeri ist eine der häufigsten Erkrankungen des Ellenbogens. Die Prävalenz liegt bei etwa 1,7 %. Eine der wirkungsvollsten Therapieoptionen stellt die Strahlentherapie dar. Dabei beschreiben viele Autoren die Durchführung einer oder mehrerer weiterer Bestrahlungsserien bei rezidivierten Schmerzen bzw. unzureichendem oder keinem Ansprechen auf die initiale Bestrahlungsserie. Da eine strukturierte Auswertung der Rebestrahlung bisher nicht existiert, war das Ziel dieser Arbeit, die Ergebnisse einer wiederholten Strahlenbehandlung zu dokumentieren und Patienten zu identifizieren, die von einer Rebestrahlung profitieren.Ausgewertet wurden Patienten aus drei strahlentherapeutischen Institutionen. Insgesamt konnten 99 rebestrahlte Ellenbogen analysiert werden. Die Schmerzintensität wurde mit Hilfe der numerischen Ratingskala (NRS) quantifiziert und zu den Zeitpunkten vor Bestrahlungsbeginn, direkt nach Radiatio, 6 und 12 Wochen sowie 6, 12 und 24 Monate nach Bestrahlung erfasst. Von den Patienten waren 48,8% männlich und 51,2% weiblich, bei einem medianen Alter von 51 Jahren. Grund der Rebestrahlung war in 39,7% kein Ansprechen und in 41,0% ein unzureichendes Ansprechen auf die erste Bestrahlungsserie sowie in 19,3% rezidivierte Schmerzen.Es zeigte sich für das Gesamtkollektiv eine signifikante Schmerzreduktion. Die mediane Schmerzintensität war 6 vor der Rebestrahlung, 3 nach 6 Wochen und 2 bzw. 1 nach 12 und 24 Monaten. Nach 24 Monaten waren 50,9% der Patienten schmerzfrei oder nahezu schmerzfrei. Alle Subgruppen, insbesondere Patienten ohne und Patienten mit unzureichendem Ansprechen auf die initiale Bestrahlung bzw. Patienten mit rezidivierten Schmerzen verzeichneten eine signifikante Schmerzreduktion.Zusammenfassend zeigt diese Arbeit, dass die Rebestrahlung bei der Epicondylitis humeri eine effektive und sichere Therapie darstellt. Alle Patientengruppen profitieren über mindestens 24 Monate von der Rebestrahlung.

Purpose:Brain metastases (BMs) are a rare but devastating condition in estrogen receptor (ER)–positive metastatic breast cancer (MBC). Although endocrine therapy (ET) is the mainstay of treatment in this disease subtype, only case reports have been published concerning the activity of ET in BMs henceforth. Therefore, we aimed to systematically investigate the impact of ET after diagnosis of BM on outcome and clinical course of disease in patients with ER-positive MBC.Experimental Design:Patient characteristics, detailed information about BMs including diagnosis-specific graded prognostic assessment class (DS-GPA), and clinical outcome were obtained by retrospective chart review for all patients treated for ER-positive breast cancer BMs between 1990 and 2017 at an academic care center. Overall survival (OS) was measured as the interval from diagnosis of BM until death or last date of follow-up.Results:Overall, 198 patients [female: 195/198 (98.5%); male: 3/198 (1.5%)] with ER-positive breast cancer BMs were available for this analysis. Eighty-eight of 198 patients (44.4%) received ET after diagnosis of BM including aromatase inhibitors (AIs; letrozole, anastrozole, exemestane), tamoxifen, and fulvestrant. Median OS was significantly longer in patients receiving ET after diagnosis of BM compared with patients who did not (15 vs. 4 months, P < 0.001; log-rank test). No significant difference in terms of OS was observed between patients receiving AIs, tamoxifen, or fulvestrant. In patients with concomitant leptomeningeal carcinomatosis (LC), ET prolonged median OS significantly as well (7 vs. 3 months, P = 0.012; log-rank test). In a multivariate analysis including DS-GPA and ET, only treatment with ET after diagnosis of BM (HR, 0.69; 95% confidence interval, 0.48–0.99; P = 0.046) was associated with prognosis (Cox regression model).Conclusions:Continuing ET after BM diagnosis was associated with a significantly prolonged OS in this large single-center cohort. No substantial differences between substances were observed. These findings should be validated in a prospective cohort.

The aim was to evaluate the incidence of stroke in the setting of cardiac surgery with or without hemodynamically relevant asymptomatic carotid stenosis contralateral to the occlusion. We designed a historical cohorts study, focused on patients with unilateral totally occluded internal carotid arteries who were referred for any cardiac surgery at our center. Isolated unilateral occlusions were assigned to group 1 (n = 60), and those with a contralateral stenosis grade ≥ 60% were included in group 2 (n = 51). A total of 111 patients operated in our center from 1997 to 2016 were included. Patients in group 2 had an asymptomatic contralateral internal carotid artery stenosis with a mean stenosis grade of 71 ± 20%. Simultaneous carotid endarterectomy (CEA) was performed in 22 patients from group 2. The overall mortality was 8/111 (7.2%). Carotid-associated mortality was not observed, whereas an overall stroke incidence of 8/111 (7.2%) was detected. The group-related outcome showed comparable results for mortality (group 1: 4/60 (6.7%) vs. group 2: 4/51 (7.8%); p = 1.0). Regarding stroke incidence, group 2 had a higher incidence of overall strokes (2/60 (3.3%) vs. 6/51 (11.8%); p = 0.14) with more contralateral (0/60 (0%) vs. 2/51 (3.9%); p = 0.209) and ipsilateral strokes (2/60 (3.3%) vs. 4/51 (7.8%); p = 0.411). Stroke rate peaked in patients with simultaneous carotid and cardiac surgery (n = 22; 18.2%; p = 0.048). Performing simultaneous CEA during cardiac surgery in the presence of a contralateral occlusion may promote stroke. Asymptomatic contralateral carotid stenosis is a risk factor for stroke in patients with carotid occlusion prior to cardiac surgery.

Der weltweit erste Mitochondrien-Transfer, auch als Erzeugung eines „Drei-Eltern-Kindes“ bezeichnet, hat 2016 eine intensive Debatte ausgelost. Hinsichtlich des Verfahrens, das bisher nur in Grosbritannien zugelassen ist, werden auch verschiedene ethische Aspekte angesprochen. Dazu gehoren die Risikoabwagung, die reproduktive Selbstbestimmung und die psychosoziale Entwicklung eines Kindes, das von drei Individuen abstammt. Dabei fallt auf, dass zentrale konzeptuelle Fragen hinsichtlich des Mitochondrien-Transfers nicht geklart sind. Ist der Mitochondrien-Transfer eine genetische Intervention in die Keimbahn? Handelt es sich bei dem Verfahren um eine medizinisch indizierte Therapie oder um eine elektive Behandlung assistierter Reproduktion? Welche Konzepte von Identitat und Elternschaft liegen der Auffassung eines „Drei-Eltern-Kindes“ zugrunde? Im Kontext dieser konzeptuellen Fragen muss eine ethische Analyse des Mitochondrien-Transfers durchgefuhrt werden. In den meisten Fallen zeigt sich allerdings, dass die ethische Analyse zu stark auf Einzelaspekte fokussiert ist, wodurch diese konzeptuellen Fragen aus dem Blick geraten. Daher verbinden wir in unserem Beitrag die ethische Analyse mit konzeptuellen Uberlegungen. Dabei ist es von zentraler Bedeutung, auch die biomedizinischen Grundlagen des Verfahrens eingehend zu erortern, um die konzeptuellen Aspekte angemessen einordnen zu konnen. In einem ersten Schritt erlautern wir die unterschiedlichen Verfahren des Mitochondrien-Transfers. In einem zweiten Schritt schlagen wir eine konzeptuelle Klarung der drei genannten Fragen vor. Diese konzeptuelle Klarung dient als Grundlage, um die ethischen Aspekte der reproduktiven Selbstbestimmung, Risikoabwagung sowie Elternschaft und Identitatskonzeption zu analysieren. In einem dritten Schritt fassen wir die Ergebnisse zusammen.

In postmenopausal women with hormone receptor-positive, early-stage breast cancer, treatment with adjuvant aromatase inhibitors is the standard of care, but it increases risk for osteoporosis and fractures. Results from the ABCSG-18 trial showed that use of denosumab as an adjuvant to aromatase inhibitor therapy significantly reduced clinical fractures. Disease-free survival outcomes from ABCSG-18 have not yet been reported.Postmenopausal patients with early, hormone receptor-positive, non-metastatic adenocarcinoma of the breast, who had completed their initial adjuvant treatment pathway (surgery, radiotherapy, or chemotherapy, or a combination) and were receiving adjuvant aromatase inhibitors, were enrolled at 58 trial centres in Austria and Sweden into this prospective, double-blind, placebo-controlled, phase 3 trial. With permuted block randomisation (block sizes 2 and 4, stratified by previous aromatase inhibitor use, total lumbar spine bone mineral density score at baseline, and type of centre), patients were assigned (1:1) to receive subcutaneous denosumab (60 mg) or matching placebo every 6 months during aromatase inhibitor therapy. The primary endpoint (previously reported) was the time to first clinical fracture after randomisation. The secondary endpoint reported here is disease-free survival (defined as time from randomisation to first evidence of local or distant metastasis, contralateral breast cancer, secondary carcinoma, or death from any cause) in the intention-to-treat population. This study is registered with EudraCT (number 2005-005275-15) and ClinicalTrials.gov (number NCT00556374), and is ongoing for long-term follow-up.Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled and randomly assigned; 1711 to the denosumab group and 1709 to the placebo group (with five others withdrawing consent). After a median follow-up of 73 months (IQR 58-95), 240 (14·0%) patients in the denosumab and 287 (16·8%) in the placebo group had disease-free survival events. Disease-free survival was significantly improved in the denosumab group versus the placebo group (hazard ratio 0·82, 95% CI 0·69-0·98, Cox p=0·0260; descriptive analysis, without controlling for multiplicity). In the denosumab group, disease-free survival was 89·2% (95% CI 87·6-90·8) at 5 years and 80·6% (78·1-83·1) at 8 years of follow-up, compared with 87·3% (85·7-89·0) at 5 years and 77·5% (74·8-80·2) and 8 years in the placebo group. No independently adjudicated cases of osteonecrosis of the jaw or confirmed atypical femoral fractures were recorded. The total number of adverse events was similar in the denosumab group (1367 [including 521 serious] adverse events) and the placebo group (1339 [515 serious]). The most common serious adverse events were osteoarthritis (62 [3·6%] of 1709 in the denosumab group vs 58 [3·4%] of 1690 in the placebo group), meniscus injury (23 [1·3%] vs 24 [1·4%]), and cataract (16 [0·9%] vs 28 [1·7%]). One (0·1%) treatment-related death (due to pneumonia, septic kidney failure, and cardiac decompensation) occurred in the denosumab group.Denosumab constitutes an effective and safe adjuvant treatment for patients with postmenopausal hormone receptor-positive early breast cancer receiving aromatase inhibitor therapy.Amgen.

This abstract was withdrawn by the authors. Citation Format: Minichsdorfer C, Bergen E, Steger GG, Pfeiler G, Frantal S, Greil R, Fohler H, Egle D, Balic M, Fitzal F, Wette V, Exner R, Bartsch RA, Gnant M. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-21-02.

Background: Therapeutic recommendations for adjuvant treatment of hormone-receptor positive breast cancer patients depend on the individual recurrence risk. A number of genomic assays introduced to achieve this goal, but it's still questioned if they actually offer superior risk assessment compared to traditional risk evaluation by experienced clinicians. This study was designed to compare the prognostic accuracy of PAM-50 to clinical judgment. Methods: Based on the real data of a large adjuvant trial cohort (ABCSG-8, postmenopausal HR positive breast cancer patients), we created online-questionnaires including demographic, histological, and local-therapy details, with and without results of PAM50 ROR score. Out of 14 international breast cancer experts asked for individual patient's risk evaluation (low, intermediate, high) and therapy recommendations, 9 completed the questionnaire. Patient data were described by Kaplan-Meier estimates of distant disease free survival (DDFS) stratified by risk group. Cox regression models were compared using the Akaike Information Criterion (AIC). Results: 10 years DDFS and hazard ratios for distant recurrences stratified by risk-group as estimated giving in Table 1: 10 years DDFS and hazard ratios for distant recurrences stratified by risk-group as estimated Low riskIntermediate riskHigh risk n (%)10y DDFS,%(95%CI)n (%)10y DDFS,%(95%CI)n (%)10y DDFS, %(95%CI) HR(95% CI) HR(95% CI) HR(95% CI)Clinical only: AIC 817.6269 (43)93.0(89.8-96.2)289 (46)89.7(85.9-93.5)73 (11)76.6(66.1-87.1) 0.68(0.39,1.20) 1 2.57(1.41,4.65)PAM50 ROR: AIC 804.8241 (34)96.5(93.1-99.1)210 (33)89.2(84.7-93.7)207 (33)82.5(76.9-88.2) 0.27(0.11,0.62) 1 1.66(0.99,2.78)Combined: AIC 813.4232 (37)95.7(93.0-98.5)282 (45)87.8(83.7-92.0)117 (18)81.7(74.2-89.2) 0.42(0.22,0.84) 1 1.90(1.11,3.24) Adding genomic information to clinical risk factors leads to escalation of therapeutic recommendations (i.e. additional chemotherapy, extended adjuvant endocrine) in 20% of patients, and de-escalation in 13% of patients. Conclusions: Clinical judgment accurately identified the patients at high risk of relapse, but was clearly inferior to multi-genomic testing using the PAM-50 ROR score in differentiating low from intermediate risk. Particularly when avoiding unnecessary escalated therapy is the strategic goal, the addition of PAM-50 testing to clinical judgment offers improved accuracy in predicting low vs. intermediate risk of breast cancer recurrence. Citation Format: Devyatko Y, Filipits M, Greil R, Balic M, Bago-Horvath Z, Singer C, Fitzal F, Steger G, Gray B, Ferree S, Fesl C, Soelkner L, von Minckwitz G, Gnant M. The impact of clinical risk assessment versus PAM-50 ROR score on prognosis and therapeutic decision making in patients with hormone-receptor positive early stage breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-05.

Lamellar keratoplasty is fast becoming the most popular form of corneal transplantation. The adoption of Descemet membrane endothelial keratoplasty (DMEK) in the management of Fuchs endothelial dystrophy and pseudophakic bullous keratopathy is partly responsible for this shift in the paradigm of management of corneal pathology. The learning curve of DMEK, however, has been proven to be much steeper than previous endothelial keratoplasty procedures. To ease the procedure, experts have proposed multiple innovative techniques from tissue preparation to graft unfolding to aid the more novice surgeon. Here, we collate and share tips and tricks from our collective experiences to support the learning curve and outcomes in DMEK for both the novice and more experienced corneal transplant surgeons.

Purpose It is well reported that dry eye symptoms can increase after many refractive surgery procedures. This study aims to provide a clinical understanding of the correlation of fluorescein tear film breakup time (FTBUT) with quality of vision (QoV) and dry eye symptoms following small incision lenticule extraction surgery (SMILE). Methods Patients electing to have SMILE surgery were subdivided into 2 groups: Group 1 included short preoperative FTBUTs of 3 to 6 seconds (s); Group 2 included long FTBUTs of ≥ 8 s. Uncorrected distance visual acuity, corrected distance visual acuity, manifest refraction, FTBUT, QoV and Ocular Surface Disease Index (OSDI) questionnaires were recorded 1 and 6 months postoperatively. Results Thirty-nine subjects were included in each group. There was no significant difference in visual outcomes between the 2 groups at both the 1- and 6-month postoperative assessments. FTBUT remained significantly lower in group 1. Oxford staining was initially higher for group 1 at 1 month (P = 0.007), but there was no significant difference at 6 months (P = 0.180). There was no significant difference in QoV or OSDI scores between the 2 groups at both postoperative visits. Conclusions Low preoperative FTBUT (3–6 s) does not appear to negatively affect postoperative visual outcomes or results in a greater likelihood of dry eye symptoms and poor ocular surface compared to eyes with a longer preoperative FTBUT. These results suggest that a low preoperative FTBUT does not necessarily increase the likelihood of poor visual acuity, dry eyes symptoms, or poor ocular surface outcomes following SMILE surgery.