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Introduction Recurrent pregnancy loss is usually associated with significant psychological distress for both partners of the couple. It may act as a traumatic experience resulting in a posttraumatic stress disorder. The object of this study is to examine the posttraumatic impact of recurrent pregnancy loss on men and women and their interdependencies. Methods Cross-sectional study. All couples referred to the special unit for recurrent pregnancy loss between March 2019 and October 2020 were asked to participate with a sample size of 105 couples and 17 women. They were invited to complete a questionnaire package estimating the prevalence of posttraumatic stress, with anxiety, depression, lack of social support and dysfunctional coping strategies as contributing risk factors. Couple data were analysed with the Actor Partner Interdependence Model, taking the couple as a dyad. Results The response rate was 82.3 percent, with posttraumatic stress being measured in 13.7% of the women versus 3.9% of the men (p = 0.017). For women, number of curettages, controlled for the number of losses, correlated with the severity of posttraumatic stress (p Conclusion The posttraumatic risks within a couple with recurrent pregnancy loss are interdependent. Recurrent pregnancy loss clinics should assess posttraumatic risks of both partners in their routine diagnostic process.

Background Prior spontaneous preterm birth is a strong risk factor for the recurrence of spontaneous preterm birth in a subsequent pregnancy and has been evaluated in prevention studies using progesterone (natural progesterone administered orally or vaginally, and 17-hydroxyprogesterone caproate [17-OHPC]) as a selection criterion. Based on the findings of a randomized, placebo-controlled study, 17-OHPC was approved for use in 2011 by the Food and Drug Administration in the USA for the prevention of recurrent preterm birth. The approval was granted with qualification that a subsequent confirmatory study would need to be carried out, the results of which have just been published (PROLONG trial). Method A systematic literature search for the period from 1970 to April 2020 using the search terms “preterm birth” and “17-OHPC” or “progesterone” was carried out. Only randomized, placebo-controlled studies of women with singleton pregnancies who received 17-OHPC to prevent recurrent preterm birth were included in the subsequent meta-analysis. The relative risk and associated 95% confidence intervals were calculated. The heterogeneity between studies was evaluated with I2 statistics. Results In addition to the original study used for the approval and the PROLONG trial, only one other study was found which met the inclusion criteria (total number of patients: 2221). With considerable heterogeneity between the studies, particularly with respect to the risk factors for preterm birth, the comparison between 17-OHPC and placebo showed no significant reduction in preterm birth rates before 37, 35 and 32 weeks of gestation and no significant differences with regard to the prevalence of miscarriage before 20 weeks of gestation or fetal deaths (antepartum or intrapartum) after 20 weeks of gestation and neonatal morbidity. Conclusion Based on the currently available data, 17-OHPC cannot be recommended for the prevention of recurrent preterm birth. Further randomized, placebo-controlled studies with clearly defined, comparable risk factors are required to identify the group of pregnant women which could benefit from the use of 17-OHPC to prevent preterm birth.

BACKGROUND/OBJECTIVES: Retinopathy of prematurity (ROP) is a severe neonatal complication potentially leading to visual impairment and blindness. Known risk factors include preterm birth, low birth weight and respiratory support. Limited and contradictory data exist on the risk of maternal smoking during pregnancy on the development of ROP. This study aims to investigate smoking as an independent risk factor for the development of severe ROP (≥stage 3). SUBJECTS/METHODS: This is a single centre retrospective case-control study of prospectively collected clinical data of infants born before 32 weeks of gestation between 2001 and 2012 at a tertiary care university hospital. The association between maternal smoking during pregnancy and the development of severe ROP was analyzed by multivariate logistic regression. RESULTS: In total, n = 751 infants born

Die Fruhgeburt tragt wesentlich zur perinatalen Morbiditat und Mortalitat bei und gilt als einer der Hauptrisikofaktoren fur „disability-adjusted life years“ (DALYs). Ihre Inzidenz liegt in Deutschland seit 2008 stabil bei etwas uber 8 %. Deutschland nimmt damit in Europa einen der hinteren Platze ein. Der Zustand nach Fruhgeburt ist der gewichtigste individuelle Risikofaktor fur eine erneute Fruhgeburt. Fur die Bitte ersetzen durch Gesamtfruhgeborenenrate einer Population sind allerdings die Nulliparitat und das mannliche fetale Geschlecht von deutlich groserer Bedeutung. Die Ursachen fur die erheblichen Unterschiede in der Fruhgeborenenrate zwischen einzelnen Landern gleicher Entwicklungsstufe sind zu grosen Teilen unklar. Durch den Einsatz verschiedener praventiver Masnahmen, z. B. Progesteron, Cerclage und Zervixpessar, lasst sich im individuellen Fall das Fruhgeburtsrisiko senken.

Despite safety concerns, β2-sympathomimetics are still widely used as tocolytic agents. β-Blockers in turn are used to treat vasculo-proliferative diseases of the newborn such as retinopathy of prematurity (ROP), which may lead to visual impairment and blindness. The scope of this study was to investigate whether antenatal exposure to the β2-sympathomimetic fenoterol contributes to the development of ROP. For this single-center retrospective case–control study of prospectively collected clinical data, all infants born before 32 weeks of gestation between 2001 and 2012 were included. The association of prenatal exposure to fenoterol and the development of ROP were analyzed by multivariate logistic regression. n = 1134 infants

STUDY QUESTION When couples have to face recurrent pregnancy loss (RPL), what are the partners’ wishes and needs and what is their perception of helpful and unhelpful factors with regard to their own, their partners’ and their families’ and friends’ ways of dealing with the problem? SUMMARY ANSWER Women and men with repeated miscarriages want open communication about their losses, but expect a sensitive and empathetic attitude from others, not pity or trivialization. WHAT IS KNOWN ALREADY RPL not only causes the women affected and their partners considerable emotional distress; it also has an impact on the couples’ relationships and the way they relate to their families and friends. Studies suggest that women have a greater need than their male partners to talk about their losses and that these differences may lead to dissatisfaction and cause relational tension. In addition, men often assume a ‘mainstay’ role, supporting their partners and displaying fortitude in the face of distress. As yet, however, little research has been conducted so far on the question of what the members of couples with RPL expect from one another and from their families and friends. STUDY DESIGN, SIZE, DURATION The study sample consisted of 147 couples and 17 women with at least 2 miscarriages attending the special unit for RPL at the University Women’s Hospital in Heidelberg (Germany) for the first time between September 2018 and October 2020 (response rate: 82.7%). The patients were asked to participate in this combined qualitative and questionnaire study. PARTICIPANTS/MATERIALS, SETTING, METHODS In order to explore the wishes and needs of those affected in more detail, the free text responses obtained were examined in this study by using qualitative content analysis. Categories and subcategories were created inductively to summarize and systematize content. MAIN RESULTS AND THE ROLE OF CHANCE Patients affected by RPL want their partners and their families and friends to deal with the topic openly and empathically. In the partnership itself, acceptance of individual grieving modes and sharing a common goal are important factors. Men, in particular, want their partners to be optimistic in facing up to the situation. Regarding communication with family and friends, it transpired that ‘good advice’, playing the matter down, inquiries about family planning, pity and special treatment are explicitly not appreciated. LIMITATIONS, REASONS FOR CAUTION The sample was a convenience sample, so self-selection effects cannot be excluded. In addition, the level of education in the sample was above average. Accordingly, the sample cannot be regarded as representative. The results of the content analysis are based on the respondents’ written answers to open-ended questions in the questionnaire. Unlike qualitative interview studies, further questioning was not possible in the case of ambiguities or to request more details. WIDER IMPLICATIONS OF THE FINDINGS Frank and sincere communication about miscarriages and about one’s own emotions and needs should be promoted both in the partnership and among family members and friends in order to strengthen the potential of social support as a resource. Open communication about the different needs of both partners is necessary to create mutual understanding. The results show the importance not only of empathy and consideration for the couples concerned but also their desire not to be pitied. Striking a fine balance between fellow-feeling and pity may also lead to tension, and this potential dilemma should be addressed in psychosocial counselling. Overall, the study contributes to a better understanding of what couples want from their families and friends when they are attempting to come to terms with RPL and highlights potential challenges in the interaction between affected couples and their families and friends. STUDY FUNDING/COMPETING INTEREST(S) No funding was received for this study. None of the authors declared any conflicts of interest. TRIAL REGISTRATION NUMBER DRKS00014965.

Study question What are the psychological impacts of recurrent pregnancy loss (RPL) on men and women and their interdependencies? Summary answer Women show higher psychological risks than men, except for lack of social support. Avoidance behaviour of men correlates with higher posttraumatic stress of their partner. What is known already About 1-3% of all couples trying to conceive are affected by RPL. The loss of the unborn child can be the most traumatic experience in a woman’s life and is associated with significant psychological distress besides the instant grief. RPL can also be stressful for the partner, even though being at a lower risk for psychiatric morbidities. The man’s gender role expects him to support and not to show weakness which may result in a suppression of his feelings and a disenfranchised grief. Study design, size, duration Cross-sectional study. All women and men referred to the special unit for RPL between March 2019 and October 2020 were asked to participate voluntarily with a total sample size of 105 couples and 17 women. Exclusion criteria were less than two pregnancy losses, inadequate knowledge of the German language and incomplete data. Participants/materials, setting, methods Couples were invited to fill out a questionnaire package estimating their psychological risks (e.g. posttraumatic stress disorder, anxiety, depression, perceived social support) and coping strategies with established instruments. Clinical history was obtained from medical records. Couple data were analysed with the Actor Partner Interdependence Model, taking the couple as the unit of analysis. Main results and the role of chance The response rate was 82.3%. The following psychological risks were measured among women versus men: posttraumatic stress disorder (PTSD): 13.7% versus 3.9% (p = 0.017); anxiety: 50.4% versus 17.3% (p Limitations, reasons for caution The data show only correlations between the measured variables, as cross-sectional studies are not suitable to analyse causal relationships. The sample was obtained in a special unit for RPL at a university hospital, so the findings may not be generalizable to all couples with RPL. Wider implications of the findings Screening psychological risks in couples with RPL may be reasonable considering the high risks in both sexes and the extent of PTSD diagnoses in women, their interdependencies and the potential risk of chronification. Professionals should encourage affected couples to support each other and provide targeted information on mental health services. Trial registration number DRKS 00014965

Numerous experimental studies indicate that natural progesterone, through various mechanisms, exerts an inhibitory effect on uterine contractility and sensitises the myometrium for tocolytics. It was therefore appropriate to investigate the possible benefits of oral/vaginal progesterone and the synthetic progesterone derivative 17-α-hydroxyprogesterone caproate, applied intramuscularly, in clinical studies on primary tocolysis, additively to established tocolytics (“adjunctive tocolysis”) and as maintenance treatment after successful tocolysis in cases of threatened preterm birth. Three studies with a small number of cases do not yield any sufficient evidence for recommending progesterone/17-α-hydroxyprogesterone caproate as primary tocolysis in women with preterm labour. There is also no evidence that progesterone or 17-α-hydroxyprogesterone caproate combined with commonly used tocolytics leads to a prolongation of pregnancy and a significant decrease in the rate of preterm birth. The data on the use of progesterone as maintenance treatment is controversial. While randomised, controlled studies with low quality showed promising results, studies with high quality did not reveal any significant differences with regard to the rate of preterm birth

Die S2k-Leitlinie der Deutschen (DGGG), Osterreichischen (OGGG) und Schweizerischen (SGGG) Gesellschaft fur Gynakologie und Geburtshilfe [1] hat evidenzbasiert die Diagnostik und Therapie des wiederholten Spontanaborts (WSA) anhand der aktuellen internationalen Literatur standardisiert. Dabei wurden die Empfehlungen und Statements in einem formalen Prozess erarbeitet und konsentiert. Insbesondere wurde auf die bekannten Risikofaktoren wie chromosomale, anatomische, endokrinologische, gerinnungsphysiologische, infektiologische und immunologische Storungen sowie die aktuellen Therapiemoglichkeiten eingegangen.

Background Availability of tumor material at baseline and disease progression is increasingly important for patient management in non-small-cell lung cancer (NSCLC), especially for the application of targeted therapies like tyrosine kinase inhibitors and for immune checkpoint inhibitor treatment. Here we report the experience of prospective biomaterial acquisition in advanced NSCLC from a pilot project. Methods Main objective was the longitudinal collection of high-quality, cryoconserved biopsies in addition to formalin-fixed paraffin-embedded (FFPE) biopsies required for routine diagnostics, along with blood samples and detailed clinical annotation using standardized questionnaires. Results Over five years, 205 patients were enrolled for the project, yielding 387 cryoconserved biopsies and 1,098 serum, plasma and buffy-coat samples. The feasibility of obtaining the cryoconserved biopsies in addition to the FFPE biopsies was 89% for newly diagnosed cases, but dropped down to 56% and 47% at first and second disease progression, respectively. While forceps biopsy was the preferred procedure for tissue acquisition, the highest tissue amounts were received using the cryobiopsy method. Biopsies had a median tumor cellularity of 34% and yielded in median 13.6 µg DNA and 12 µg RNA (median RIN =8). During the five-year project, a maximum of 38 follow-up blood samples per patient were assembled in up to four therapy lines. Conclusions Despite the poor condition and limited prognosis of most NSCLC patients, this serial biomaterial acquisition including routine collection of cryoconserved biopsies is feasible to support individualized management. The standardized collection of high-quality material has enabled and enriched several translational research studies that can advance therapeutic options.

Recurrent miscarriage (RM) and recurrent implantation failure (RIF) are unsolved challenges in reproductive medicine. Whether RIF patients share the same risk factors as RM patients is a matter of debate. Besides clinical factors, immune alterations are discussed in both conditions. The scope of this study was to compare the prevalence of clinical and immunological risk factors in a large cohort of RM and RIF patients. Between 11/2011 and 02/2019, 613 RM and 185 RIF patients were included. A screening for anatomical malformations, endocrine, autoimmune, prothrombotic and parental chromosomal disorders was performed. The immune status was assessed using flow cytometry analysis of peripheral lymphocyte subpopulations and uterine natural killer cells (uNK cells) using immunohistochemistry. RM patients showed a higher rate of intrauterine adhesions and elevated antinuclear antibodies ≥ 1:160 (p 0.05). A higher prevalence of submucous fibroids and increased factor VIII levels were observed in RIF patients (p 0.05). The prevalence of an antiphospholipid syndrome (APLS) was low and did not differ between the two groups. RIF patients had higher numbers of peripheral regulatory T-cells (p 0.05). Significant more RIF patients were diagnosed with elevated uNK cells (p 0.05). Differences in clinical and immunological risk factors of RM and RIF patients reflect different entities. Lower Tregs in RM and higher uNK cells in RIF patients might be related to the previous exposure of the immune system to fetal cells. The low prevalence of an APLS indicates a potential overestimation of this factor in the pathophysiology of RM and RIF.

BACKGROUND: The preterm birth rate in Germany has remained unchanged at 8–9% since 2009. Preterm birth is the most common cause of neonatal morbidity and mortality. In the absence of a causal treatment, it is important to lower the risk of preterm birth by preventive measures in prenatal outpatient care. METHODS: This review is based on pertinent publications from the years 2000–2019 that were retrieved by a selective search in PubMed. RESULTS: The clinical risk factors for preterm birth—known mainly from retrospective cohort studies—include previous preterm birth (adjusted odds ratio [aOR]: 3.6), multiple pregnancy (relative risk [RR]: 7.7), nicotine consumption (aOR: 1.7), and a short uterine cervix, i.e.

Trotz modernster Verfahren der Reproduktionsmedizin inklusive der Praimplantationsdiagnostik gelingt in manchen Fallen auch bei wiederholtem Transfer eines morphologisch und genetisch unauffalligen Embryos keine Einnistung. Man spricht von rezidivierendem Implantationsversagen (RIF). Daruber hinaus sind etwa 1–3 % aller Paare von wiederkehrenden Spontanaborten (WSA) betroffen. Lediglich bei etwa der Halfte dieser Paare lasst sich ein ursachlicher Faktor ermitteln. In den letzten Jahren sind infektiologische und immunologische Aspekte in den Fokus der Ursachensuche geruckt. Neben autoimmunologischen Faktoren wie dem Antiphospholipidsyndrom wird insbesondere die Rolle der peripheren und uterinen naturlichen Killerzellen bei der Implantation und dem Abortgeschehen beleuchtet. Neueste Daten weisen zudem auf eine Bedeutung der chronischen Endometritis als Risikofaktor sowohl fur RIF als auch fur WSA hin. Inwieweit sich die Pathogenese bei RIF und WSA uberschneidet, ist unklar.

β2-sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the β2-sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other β2-mimetic tocolytic agents like fenoterol. Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups. N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619–1.384) or in a subgroup of neonates

Etwa 1–3 % aller Paare im reproduktiven Alter sind von habituellen Aborten betroffen. Ihre Betreuung stellt besondere Herausforderungen an den behandelnden Arzt, insbesondere da die Ursachen multifaktoriell sein konnen. Daher ist eine zielgerichtete Diagnostik von groser Bedeutung. Einordnung der verschiedenen diagnostischen Verfahren in evidenzbasierte und nichtevidenzbasierte Masnahmen. Anhand der bestehenden Literatur, die auch in der Neufassung der S2k-Leitlinie der AWMF (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften), „Diagnostik und Therapie beim wiederholten Spontanabort“ (015/50), und in der ESHRE(European Society of Human Reproduction and Embryology)-Leitlinie, „Guideline on the management of recurrent pregnancy loss“, berucksichtigt wurde, soll eine evidenzbasierte Diagnostik beschrieben werden. Die Diagnostik bei Paaren mit habituellen Aborten umfasst den Ausschluss von genetischen, anatomischen, infektiologischen, psychologischen, hamostaseologischen und immunologischen Risikofaktoren. Eine Vielzahl weiterer moglicher Risikofaktoren wird derzeit unter Studienbedingungen untersucht. Die Abklarung habitueller Aborte sollte im Rahmen eines standardisierten diagnostischen Vorgehens erfolgen. Aufgrund vieler neuer Risikofaktoren, die in der internationalen Literatur beschrieben werden, ist eine Abgrenzung zu evidenzbasiertem Vorgehen notwendig. Eine besondere Bedeutung kommt dem arztlichen Gesprach zu; es muss mogliche diagnostische Schritte erlautern und auch uberhohte Erwartungen an eine nichtevidenzbasierte Diagnostik, welche innerhalb von Studien stattfinden sollte, einordnen.

Nach der standardisierten diagnostischen Abklarung von Frauen mit habituellen Aborten (wiederkehrende Spontanaborte, WSA) sollte eine spezifische risikofaktoradaptierte Therapie eingeleitet werden. Bislang gibt es jedoch wenige evidenzbasierte Daten, welche eine klare Indikationsstellung fur eine Therapieeinleitung bedingen. Welche therapeutischen Konzepte gibt es derzeit zur Behandlung von Frauen mit WSA? Anhand der bestehenden Literatur, der aktuellen ESHRE(European Society of Human Reproduction and Embryology)-Leitlinie, „Guideline on the management of recurrent pregnancy loss“, und der S2k-Leitlinie der AWMF (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften), „Diagnostik und Therapie beim wiederholten Spontanabort“ (015/50), werden mogliche therapeutische Konzepte bei WSA dargelegt. Eine Septumresektion sollte ebenso wie die Optimierung der Schilddrusenfunktion (Zielwert TSH, Thyreoidea-stimulierendes Hormon

Background The advanced lung cancer inflammation index [ALI: body mass index × serum albumin/neutrophil-to-lymphocyte ratio (NLR)] reflects systemic host inflammation, and is easily reproducible. We hypothesized that ALI could assist guidance of non-small-cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICIs). Patients and methods This retrospective study included 672 stage IV NSCLC patients treated with programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy in 25 centers in Greece and Germany, and a control cohort of 444 stage IV NSCLC patients treated with platinum-based chemotherapy without subsequent targeted or immunotherapy drugs. The association of clinical outcomes with biomarkers was analyzed with Cox regression models, including cross-validation by calculation of the Harrell's C-index. Results High ALI values (>18) were significantly associated with longer overall survival (OS) for patients receiving ICI monotherapy [hazard ratio (HR) = 0.402, P < 0.0001, n = 460], but not chemo-immunotherapy (HR = 0.624, P = 0.111, n = 212). Similar positive correlations for ALI were observed for objective response rate (36% versus 24%, P = 0.008) and time-on-treatment (HR = 0.52, P < 0.001), in case of ICI monotherapy only. In the control cohort of chemotherapy, the association between ALI and OS was weaker (HR = 0.694, P = 0.0002), and showed a significant interaction with the type of treatment (ICI monotherapy versus chemotherapy, P < 0.0001) upon combined analysis of the two cohorts. In multivariate analysis, ALI had a stronger predictive effect than NLR, PD-L1 tumor proportion score, lung immune prognostic index, and EPSILoN scores. Among patients with PD-L1 tumor proportion score ≥50% receiving first-line ICI monotherapy, a high ALI score >18 identified a subset with longer OS and time-on-treatment (median 35 and 16 months, respectively), similar to these under chemo-immunotherapy. Conclusions The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-L1 inhibitors alone, but not in combination with chemotherapy. Its association with outcomes appears to be stronger than that of other widely used parameters. For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy., Highlights • ALI is prognostic and predictive for patients with advanced NSCLC treated with immunotherapy monotherapy, but not chemo-immunotherapy. • Its association with outcomes is stronger than that of other parameters (PD-L1 TPS, NLR, lung immune prognostic index, EPSILoN). • For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.

The prevention and treatment of preterm birth remains one of the biggest challenges in obstetrics. Worldwide, 11% of all children are born prematurely with far-reaching consequences for the children concerned, their families and the health system. Experimental studies suggest that progesterone inhibits uterine contractions, stabilises the cervix and has immunomodulatory effects. Recent years have seen the publication of numerous clinical trials using progestogens for the prevention of preterm birth. As a result of different inclusion criteria and the use of different progestogens and their methods of administration, it is difficult to draw comparisons between these studies. A critical evaluation of the available studies was therefore carried out on the basis of a search of the literature (1956 to 09/2018). Taking into account the most recent randomised, controlled studies, the following evidence-based recommendations emerge: In asymptomatic women with singleton pregnancies and a short cervical length on ultrasound of ≤ 25 mm before 24 weeks of gestation (WG), daily administration of vaginal progesterone (200 mg capsule or 90 mg gel) up until 36 + 6 WG leads to a significant reduction in the preterm birth rate and an improvement in neonatal outcome. The latest data also suggest positive effects of treatment with progesterone in cases of twin pregnancies with a short cervical length on ultrasound of ≤ 25 mm before 24 WG. The study data for the administration of progesterone in women with singleton pregnancies with a previous preterm birth have become much more heterogeneous, however. It is not possible to make a general recommendation for this indication at present, and decisions must therefore be made on a case-by-case basis. Even if progesterone use is considered to be safe in terms of possible long-term consequences, exposure should be avoided where it is not indicated. Careful patient selection is crucial for the success of treatment.

Die Prognose des Lungenkarzinoms bleibt trotz Fortschritten in der Therapie weiterhin ernst. Die Behandlung hangt dabei entscheidend vom Tumorstadium und von individuellen Faktoren der Patienten ab. Dieser Beitrag gibt Ihnen ein Update zur stadienabhangigen Therapie des Lungenkarzinoms.

βClinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups.N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619-1.384) or in a subgroup of neonates 32 weeks of gestation or with a birth weight 1500 g (OR 1.127, 95% CI 0.709-1.791). In the total matched population, prenatal exposure to glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI 0.332-0.964) and neonates with IH showed a prolonged total hospital stay compared to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were confirmed by our large study cohort and included female gender, low birth weight, preterm birth and multiple gestations (all p 0.005).Exposure to fenoterol during pregnancy does not increase the occurrence of IH. Further studies are needed to explore differences in the risk profiles of different β

Item does not contain fulltext Communication and the care of patients with advanced cancer are a dynamic, interactive and challenging process, often characterised in every day practice by discontinuity and lack of coordination. The objective of this study was to explore the patients' and family-caregivers' needs and preferences regarding communication, quality of life and care over the trajectory of disease. The second aim was to assess health professionals' views on a longitudinally structured, forward-thinking communication approach based on defined milestones. A qualitative approach was chosen incorporating semi-structured interviews with nine patients with metastatic lung cancer and nine relatives, and focus groups with 15 healthcare providers from different professions involved in the care of these patients. Patients and relatives described a situation of shock and coping deficits with moments of insufficient communication and lack of continuity in care. Healthcare providers reported the strong need for improvement in communication within the team and between patients and professionals and welcomed the implementation of a longitudinal communication approach. Requirements for the implementation of a longitudinal communication approach include specific communication training with focus on the process that patients and relatives are involved in. Team-building measures and the necessary flexibility to respect individuality in life should be incorporated.

Angesichts der demographischen Entwicklung der kommenden Jahrzehnte wird der Anteil der alteren Lungenkrebs-Patienten bei einem aktuellen Altersmedian von 68 Jahren weiter ansteigen. Dabei ist hoheres Lebensalter grundsatzlich kein alleiniger Ausschlussgrund fur eine Therapiemodalitat, vielmehr mussen individuell Allgemeinzustand und Komorbiditatsstatus berucksichtigt werden. In den fruhen Stadien besteht in Hinsicht auf den Therapieerfolg eine leichtgradige Uberlegenheit fur die Lobektomie gegenuber einer sublobaren Resektion, im Falle einer funktionellen Inoperabilitat steht die stereotaktische Radiotherapie als sinnvolle Alternative zur Verfugung. Patienten in lokoregionar fortgeschrittenen Stadien werden wenn moglich radio-/chemotherapiert. Bei Einschrankungen wird auf eine kurativ dosierte alleinige Radiotherapie zuruckgegriffen. Im fernmetastasierten Stadium kommen Carboplatin-haltige Kombinationsschemata oder Monotherapien zur Anwendung. Hier sind im Besonderen stratifizierbare zielgerichtete Therapien bei der Detektion von pradiktiven Biomarkern zu berucksichtigen. Nicht zu vernachlassigen ist im fortgeschrittenen Stadium die fruhzeitige palliativmedizinische Versorgung im Hinblick auf Symptomkontrolle und psychosozialer Begleitung.

Background Osimertinib is the preferable therapeutic option for many epidermal growth factor receptor (EGFR)+ non-small cell lung cancer (NSCLC) patients failing other tyrosine kinase inhibitors (TKI), but implementation of EGFR TKI sequencing is often problematic. Methods We retrospectively studied the clinical course of EGFR+ NSCLC patients that received first-/second-generation TKI at our institutions and had their last follow-up after osimertinib approval (02/2016). Results A total of n = 283 EGFR+ NSCLC patients received erlotinib (45%), gefitinib (19%) and/or afatinib (36%) in the 1st-4th treatment lines with a median age of 66 years, a median ECOG performance status of 0 (137/266 patients with available data) and a predominance of female (183/283=65%) never-/light-smokers (177/283=63%). Median overall survival (OS) from treatment start was 32.7 months (95% confidence interval [CI] 28.1 – 37.3) with 2.2 treatment lines on average (standard deviation 1.4). EGFR T790M testing was performed for 139/203 (68%) patients after TKI failure, with a positive result in 77/139 (55%) and subsequent treatment with osimertinib in 50/77 (65%). Overall, 50/203 (25%) of patients received osimertinib, with a median OS of 44.9 (27.9 – 62.1) months, significantly longer than the 30.4 (20.6 – 40.3) months for patients with alternative or no subsequent therapies (logrank p = 0.053, Breslow p = 0.002). Among the 134 deceased patients with complete follow-up, 84 (63%) received additional systemic treatment (37% chemotherapy, 16% osimertinib, 8% only alternative EGFR inhibitors, 2% only immunotherapy), while 50/134 (37%) died without next-line therapy. For patients that subsequently received chemotherapy, median time to start of chemotherapy was 11.6 (8.9 – 14.3) months. Conclusions Sequential treatment with osimertinib after first- or second-generation EGFR inhibitors significantly prolongs OS, but in the real-world setting a considerable fraction of patients will not be able to benefit from that. Main obstacles in our cohort were lack of EGFR T790M testing (32% of total cases), T790M-negative progression (45% of tested cases), and rapid clinical deterioration without the chance of next-line therapy (about one-third of patients). Legal entity responsible for the study Thoraxklinik at Heidelberg University Hospital. Funding Thoraxklinik at Heidelberg University Hospital AstraZeneca. Disclosure P. Christopoulos: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Chugai; Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Boehringer; Research grant / Funding (institution): Takeda. F. Bozorgmehr: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self): MSD. J.B. Kuon: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Cellgene. V. Endris: Honoraria (self), Advisory / Consultancy: ThermoFisher; Honoraria (self), Advisory / Consultancy: AstraZeneca. T. Bochtler: Honoraria (institution), Research grant / Funding (institution): Roche. F.J.F. Herth: Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Boehringer; Honoraria (self), Research grant / Funding (institution): Chiesi; Honoraria (self), Research grant / Funding (institution): Teva; Honoraria (self): Pulmonx BTG; Honoraria (self): Olympus. C. Heussel: Honoraria (self), Honoraria (institution): Novartis, Basilea, Bayer, Grifols, Boehringer, Pierre Fabre, Covidien, Siemens, Chiesi, Intermune, MEDA Pharma, Bracco, Pfizer, MSD, Roche, Lilly, AstraZeneca, Schering-Plough, Essex, Gilead, MeVis, Fresenius, Astellas; Shareholder / Stockholder / Stock options: GSK. T. Muley: Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Roche. J.R. Fischer: Advisory / Consultancy: Boehringer, Roche, Celgene and AstraZeneca. A. Stenzinger: Honoraria (self), Advisory / Consultancy: Novartis, AstraZeneca, ThermoFisher, BMS; Honoraria (self): BMS, Illumina, AstraZeneca, Novartis, ThermoFisher, MSD, Roche; Research grant / Funding (institution): Chugai; Honoraria (self): Illumina, AstraZeneca, Novartis, ThermoFisher . M. Thomas: Honoraria (self), Advisory / Consultancy: Novartis, Lilly, BMS, MSD, Roche, Celgene, Takeda, AbbVie, Boehringer, Lilly, MSD, Takeda; Research grant / Funding (institution): AstraZeneca, BMS, Celgene, Novartis, Roche, Takeda. All other authors have declared no conflicts of interest.

Hintergrund: Die Pravention und Behandlung der Fruhgeburt gehort auch heute noch zu den ungelosten Problemen der Geburtshilfe. Progesteron entfaltet eine Vielzahl von Wirkungen auf Myometrium und Zervix, u. a. eine Hemmung der Myometriumkontraktion und eine zervixstabilisierende Wirkung durch Inhibition proinflammatorischer Zytokine und konsekutiv der Produktion von Prostaglandinen sowie durch die Reduktion der Expression von Proteinen, die fur die Wehentatigkeit von Bedeutung sind. Daher ist Progesteron ein vielversprechender Kandidat zur Pravention der Fruhgeburt. Material und Methode: In PubMed wurde eine Literaturrecherche des Zeitraumes 1956–August 2014 durchgefuhrt, der folgende Suchbegriffe zugrunde lagen: Fruhgeburt und Progesteron oder 17-OHPC oder Progestin. Ergebnisse: (i) Frauen mit Einlingsschwangerschaften sollten nach vorangegangener Fruhgeburt taglich vaginales Progesteron (200 mg Kapsel oder 90 mg Gel) von der 16+0 bis 36+0 SSW erhalten (alternativ: 250 mg 17-OHPC intramuskular wochentlich): Level of Evidence Ia, Empfehlungsgrad ++ . Die prophylaktische Applikation von Progesteron fuhrt zu einer signifikanten Senkung der Rate an Fruhgeburten Diskussion: Die prophylaktische Gabe von Progesteron ist eine evidenzbasierte Masnahme zur Pravention der Fruhgeburt bei Frauen mit Einlingsschwangerschaft nach vorangegangener Fruhgeburt und bei Schwangeren mit sonografisch verkurzter Zervix (≤ 25 mm) vor der 24. SSW. Die vaginale Applikation von Progesteron ist der intramuskularen Injektion von 17-OHPC insbesondere aufgrund der geringeren Rate maternaler NW vorzuziehen. Ob Progesteron zur primaren oder adjunktiven Tokolyse oder zur Erhaltungstherapie nach initialer Tokolyse mit Sistieren der Wehen eine effektive Option zur Behandlung der Fruhgeburt darstellt, muss in weiteren gut konzipierten randomisierten klinischen Studien mit ausreichender statistischer Power geklart werden.

Five hundred and three elective repeat caesarean sections were analysed to examine the impact of timing of delivery between 37 and 40 weeks' gestation on foetal and maternal short-term outcome. Gestational age, Apgar scores and admission to the neonatal intensive care unit (NICU)-based foetal outcome. Maternal complications were comparatively evaluated. Due to the increasing incidence of gestational diabetes a subgroup analysis on this issue was performed. Neonates born by elective repeat caesarean in early term had a 3.2 times increased risk of being admitted to the NICU due to foetal adaption disorders in the early post-natal phase. Overall maternal peri-operative risks were low and did not differ significantly between 37 and 41 weeks' gestation. Maternal gestational diabetes constituted an additional independent risk factor in early term. In summary, elective early-term caesarean delivery appears to negatively impact immediate neonatal outcome. Waiting at least until 38 completed weeks' gestation improves foetal outcome, especially in diabetic patients.

Fruhgeborene (unterhalb von 30 SSW) Kinder sind in besonderem Mas von perinatalen Hirnschaden betroffen. Typische Lasionen sind periventrikulare Hirnblutungen (PIVH) und periventrikulare Leukomalazien (PVL), die infolge einer Ischamie, aber auch einer aszendierenden intrauterinen Infektion auftreten konnen. Beide Insulte betreffen v. a. die Pyramidenbahnen und fuhren zu einer beinbetonten spastischen Zerebralparese. Viele der so geschadigten Kinder sind schwerbehindert. Ihre Versorgung stellt eine enorme Belastung fur Familien, Arzte, Pflegekrafte und Kostentrager dar. Ziel der Arbeit ist es, den Stand der Neuroprotektion bei fruhgeborenen Kindern darzustellen. Eine Vermeidung der Fruhgeburt, aber auch eine fruhzeitige Intervention bei drohender intrauteriner Infektion reduziert die Inzidenz fruhkindlicher Hirnlasionen. Eine hoch dosierte intravenose Gabe von Magnesium bei drohender Fruhgeburt fuhrt zu einer signifikanten Reduktion der kindlichen Zerebralparese sowie schwerwiegender grobmotorischer Beeintrachtigungen. Ein spates Abnabeln bei Geburt senkt die Hirnblutungsrate bei diesen Kindern um bis zu 50 %. Mesenchymale Stammzellen zeigen in tierexperimentellen Untersuchungen ein erhebliches neuroprotektives Potenzial, sie verbessern die Regeneration der geschadigten zerebralen Areale nach Insult signifikant. Eine klinische Testung dieser therapeutischen Intervention scheint sich anzubahnen. Im letzten Trimester der Schwangerschaft steigt die Serumkonzentration von Ostradiol und Progesteron sehr stark an, bis auf das 100-fache des Ausgangwertes. Fruhgeborene werden diesem Milieu abrupt entzogen. Ostradiol und Progesteron schutzen im Tierexperiment das unreife Gehirn vor hypoxisch-ischamischen Lasionen. Es liegt deshalb nahe, fruhgeborene Kinder nach Partus mit Ostradiol und Progesteron zu substituieren. Die antenatale Applikation von Magnesium sowie spates Abnabeln bei Geburt reduziert die Inzidenz von Hirnschaden bei fruhgeborenen Kindern.

Mithilfe vieler technischer Erneuerungen im IVF-Labor und durch die Optimierung der Stimulationsbehandlung ist es in den letzten Jahren gelungen, die Schwangerschaftsrate nach einer IVF/ICSI-Behandlung deutlich zu steigern. Dennoch bleiben etwa 20–30 % der Paare kinderlos. Einen moglichen Faktor stellen dabei immunologische Storungen dar, welche im Bereich des Endometriums bzw. im peripheren Blut Einfluss auf die Implantation nehmen. Die Vielzahl an immunkompetenten Gegenspielern umfasst sowohl periphere und uterine naturliche Killerzellen als auch Zytokine, T- und B-Zellen sowie weitere (Auto-)Immunzellen. Bislang ist es nicht moglich, eine spezifische immunologische Diagnostik einer gezielten Therapie zuzuordnen, auch wenn eine Vielzahl an immunmodulatorischen Medikamenten zur Verfugung steht. In einzelnen Studien konnte teilweise ein Benefit hinsichtlich der Lebendgeburtenrate beim Einsatz von Immuntherapeutika in der Reproduktionsmedizin gezeigt werden. Bislang sind die Fallzahlen jedoch noch relativ klein, weshalb diese Therapieformen v. a. in klinischen Studien angewandt werden sollten. Dieser Ubersichtsartikel fasst die aktuelle Datenlage der in der Reproduktionsmedizin verwendeten immunmodulatorischen Therapien wie TNF-Inhibitoren, Granulozyten-Kolonie-stimulierender Faktor (G-CSF), Immunglobuline und Lipidemulsionen zusammen.

Das Hormon Progesteron entfaltet eine Vielzahl von Wirkungen auf Myometrium und Zervix, u.a. eine Hemmung der Myometriumkontraktion und einen zervixstabilisierende Effekt. Es ist daher ein vielversprechender Kandidat zur Pravention der Fruhgeburt. Die prophylaktische Gabe von Progesteron ist eine evidenzbasierte Masnahme zur Pravention der Fruhgeburt bei Frauen mit Einlingsschwangerschaft nach vorangegangener Fruhgeburt sowie bei Schwangeren mit Einlingsschwangerschaft und Verkurzung der Zervix vor der 24. SSW. Inwieweit weitere Anwendungsmoglichkeiten bestehen (u.a. bei vorzeitiger Wehentatigkeit), wird derzeit in klinischen Studien uberpruft.