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ALK fusions were first described by Morris et al1 in 1994. Several studies have reported genetic alterations of the ALK gene in various tumor types since then, consisting of mutations, amplifications, and fusions.1-3 Fusion proteins have an active C-terminal tyrosine kinase domain in common.3 Here, we describe an STRN-ALK fusion in malignant peritoneal mesothelioma (MPM), which has previously been documented in other neoplasms, including thyroid cancer, renal carcinoma, leukemia, lymphoma, colon adenocarcinoma, head and neck adenocarcinoma, pericardial and peritoneal mesothelioma, and cutaneous squamous cell carcinoma.4-6 MPM is a rare disease with an incidence of approximately seven per million people per year.7 Patients' life expectancy is low (on average 12 months) because of the late clinical presentation with abdominal or pelvic pain or lymphadenopathy.8,9 Recently, ALK rearrangements have gained attention, especially in young female patients with MPM. Hung et al10 identified three ALK fusions in 88 consecutively screened patients with MPM. Fusion partners were ATG16L1, TPM1, and STRN. In another study by Mian et al,11 among 32 patients ��� 40 years old with mesothelioma (of which 25 were MPM), an ALK rearrangement was detected by fluorescence in situ hybridization in two patients (6%). One of the cases harbored an STRN-ALK fusion as described in the current case. Argani et al12 described additional five cases of ALK fusions in pediatric MPM. Subsequently, three more cases of STRN-ALK rearrangements in MPM have been published individually.6,13,14 In non���small-cell lung cancer (NSCLC), the discovery of specific drugs targeting ALK rearrangements led to significant therapeutic advances. Currently, various ALK inhibitors, namely, ceritinib, crizotinib, and alectinib, are used as first-line treatment in adult ALK-positive advanced NSCLC. Although crizotinib as a first-generation ALK inhibitor has already proven superiority over chemotherapy,15 next-generation ALK inhibitors such as ceritinib yielded even better survival rates.16 Moreover, both brigatinib and alectinib demonstrated superior effectiveness when directly compared with crizotinib.17,18 Unfortunately, resistance is frequently observed following an initial response in all these agents.19 Mechanisms of resistance, which often include ALK mutations, are in general universal although variable mutational frequencies are observed depending on the inhibitor.20 Despite this large base of knowledge for lung cancer, the evaluation of ALK fusions in other entities remains challenging because of limited available data.

Die Zahl der Patientinnen, die einer onkologischen Nachsorge bedurfen, ist stark angestiegen. Dies liegt am demografischen Wandel durch die zunehmende Zahl alterer Menschen in der Bevolkerung, aber auch an der wachsenden Effektivitat onkologischer Therapien. Zu den Aufgaben onkologischer Nachsorge gehoren das fruhzeitige Erkennen eines Lokalrezidivs oder Zweitkarzinoms mit potenziell kurativer Behandlungsintention zur Verbesserung der Uberlebenschancen. Davon abzugrenzen ist die Detektion von Fernmetastasen, die meist nicht mehr heilbar sind und i. d. R. nur die Moglichkeit symptomatischer oder palliativer Therapie zur Verbesserung der Lebensqualitat bieten. Ein weiterer Bestandteil der Nachsorge ist die Erkennung und Behandlung physischer und psychischer Folgen der Tumorerkrankung und der vorausgegangenen Therapien. Dieser Beitrag gibt einen Uberblick uber die derzeitigen Empfehlungen zur Nachsorge von Patientinnen mit gynakologischen Malignomen und Mammakarzinom.

Studies have shown that hearing preservation is possible in the context of reimplantation, but residual hearing could not be predicted or expected in these cases. We describe a case in which a patient with mild to profound sensorineural hearing loss who underwent cochlear implantation with a lateral wall array and had hearing preserved postoperatively. She developed facial nerve stimulation which was unresponsive to reprogramming. Using electrocochleography to measure intracochlear trauma during the insertion process, the patient underwent reimplantation with a perimodiolar electrode and hearing was preserved postoperatively. This case demonstrates the potential to use electrocochleography for hearing preservation during reimplantation. Laryngoscope, 131:2348-2351, 2021.

Purpose The effectiveness of a pathway with quality of life (QoL) diagnosis and therapy has been already demonstrated in an earlier randomized trial (RCT) in patients with breast cancer. We refined the pathway by developing and evaluating an electronic tool for QoL assessment in routine inpatient and outpatient care. Methods In a single-arm study, patients with breast cancer with surgical treatment in two German hospitals were enrolled. QoL (EORTC QLQ-C30, QLQ-BR23) was measured with an electronic tool after surgery and during aftercare in outpatient medical practices (3, 6, 9, 12, 18, and 24 months) so that results (QoL-profile) were available immediately. Feedback by patients and physicians was analyzed to evaluate feasibility and impact on patient-physician communication. Results Between May 2016 and July 2018, 56 patients were enrolled. Physicians evaluated the QoL pathway as feasible. Patients whose physician regularly discussed QoL-profiles with them reported significantly more often that their specific needs were cared for (p p p Conclusion The QoL pathway with electronic QoL assessments is feasible for inpatient and outpatient care. QoL results should be discussed directly with the patient. Clinical trial information NCT04334096, date of registration 06.04.2020

ZusammenfassungDie Evaluation von Interventionseffekten ist eine wichtige Domäne der Versorgungsforschung. Die vom Deutschen Netzwerk Versorgungsforschung (DNVF) ins Leben gerufene Ad hoc Kommission zur Nutzung versorgungsnaher Daten beschäftigt sich in diesem zweiten Teil des Manuals deshalb mit der Nutzung dieser Daten zur Evaluation von Interventionseffekten. Zunächst erfolgt dabei eine Aufarbeitung der Begriffsbestimmung und Diskussion zur Bedeutung von Kontextfaktoren. Anschließend werden sowohl allgemeine Anforderungen an Planung, Datenerhebung und Auswertung sowie konkrete Beispiele zur Evaluation von Interventionseffekten für die 3 Anwendungsfelder Arzneimitteltherapie, nicht-medikamentöse Maßnahmen sowie komplexe Interventionen herausgearbeitet. Dabei werden sowohl Szenarien betrachtet, bei denen bisher keine Informationen aus direkt vergleichenden randomisierten kontrollierten Studien (RCTs) vorliegen bzw. bereits RCTs vorhanden sind, jedoch eine Erweiterung der Fragestellung erforderlich ist. Im Zentrum steht bei allen Beispielen an erster Stelle immer die Frage, ob die Datenquelle für die entsprechende Forschungsfrage geeignet ist und zwar unabhängig davon, ob eine Studie mit oder ohne Randomisierung durchgeführt wird. Die gewählten Beispiele stammen größtenteils aus der Onkologie, weil die hierfür notwendigen Daten zumindest in Ansätzen bereits für Deutschland vorliegen. Abschließend diskutiert das Manual mögliche Herausforderungen für eine zukünftige Nutzung dieser Daten.

Since 2008, guidelines recommend that patients with HER2-positive early breast cancer (BC) should receive adjuvant chemotherapy in combination with trastuzumab in Germany. However, recent studies highlight that a substantial share of patients do not receive trastuzumab. We investigate which patient characteristics are associated with a tumor board recommendation for trastuzumab in Breast Cancer Centers (BCC) certified by the German Cancer Society (DKG) and the German Society for Senology, and if the recommendation differs between BCCs. Multi-level modeling was performed using quality assurance data based on 3052 HER2-positive, operated patients with a first diagnosis of early BC treated between 2006 and 2019 in 17 BCCs in Germany to investigate whether trastuzumab recommendation varies with patient sex, age, and disease characteristics, as well as over time and across BCCs. Tumor board recommendations for trastuzumab differ substantially between BCCs (intraclass correlation coefficient [ICC] null model: 0.11). Our final model (ICC 0.17, Akaike Information Criterion [AIC], 1328.0, R2 0.69) shows that physicians in BCCs more often recommend trastuzumab to patients who are younger than 60 years and those with a recommendation for any additional therapy (chemotherapy, radiation or endocrine therapy) (all p

Purpose In Dec 2019, COVID-19 was first recognized and led to a worldwide pandemic. The German government implemented a shutdown in Mar 2020, affecting outpatient and hospital care. The aim of the present article was to evaluate the impact of the COVID-19 shutdown on patient volumes and surgical procedures of a Level I trauma center in Germany. Methods All emergency patients were recorded retrospectively during the shutdown and compared to a calendar-matched control period (CTRL). Total emergency patient contacts including trauma mechanisms, injury patterns and operation numbers were recorded including absolute numbers, incidence proportions and risk ratios. Results During the shutdown period, we observed a decrease of emergency patient cases (417) compared to CTRL (575), a decrease of elective cases (42 vs. 13) and of the total number of operations (397 vs. 325). Incidence proportions of emergency operations increased from 8.2 to 12.2% (shutdown) and elective surgical cases decreased (11.1 vs. 4.3%). As we observed a decrease for most trauma mechanisms and injury patterns, we found an increasing incidence proportion for severe open fractures. Household-related injuries were reported with an increasing incidence proportion from 26.8 to 47.5% (shutdown). We found an increasing tendency of trauma and injuries related to psychological disorders. Conclusion This analysis shows a decrease of total patient numbers in an emergency department of a Level I trauma center and a decrease of the total number of operations during the shutdown period. Concurrently, we observed an increase of severe open fractures and emergency operations. Furthermore, trauma mechanism changed with less traffic, work and sports-related accidents.

OBJECTIVE: As humans age, compressive nonlinearity –a hallmark of healthy cochlear function– changes. The nonlinear distortion-component of the distortion product otoacoustic emission (DPOAE) provides a noninvasive gauge of cochlear nonlinearity. Earlier published work has suggested that weakened nonlinearity begins in middle-age; the current work extends this investigation into the 8(th) decade of life using advanced DPOAE data collection and analysis methods as well as multiple metrics of nonlinearity including a test of loudness scaling. DESIGN: The 2f(1)-f(2) DPOAE was recorded in 20 young-adults, 25 middle-aged adults and 32 older-adults from f(2) = 0.78 to 9.4 kHz with primary tones (f(2)/f(1) = 1.22) swept upward at a rate of 0.5 octave/sec. Only frequencies with audiometric thresholds ≤20 dB HL were included in the analysis and to the extent possible, ears were audiometrically matched to eliminate hearing threshold as a contributing factor to the observed age effects. Input/Output functions were generated for the separated distortion-component of the DPOAE to probe compressive nonlinearity of the cochlea, and ipsilateral suppression of the DPOAE was conducted to probe two-tone suppression. To investigate the perceptual effects of weakening nonlinearity on loudness perception, the same subjects performed categorical loudness scaling. Age effects on both DPOAE and loudness scaling variables were assessed, and correlations were conducted between key OAE and perceptual metrics. RESULTS: Age × Frequency ANOVAs revealed that the compression knee of the DPOAE I/O function occurred at higher stimulus levels in both groups of older adults compared to young adults, suggesting an expanded linear range with aging; also, the compressive slope (growth beyond the knee point) was steeper in older- compared to young adults. These results were most notable at high-frequencies. ANOVAs including age and auditory threshold as factors confirmed that the age effect observed was independent of threshold. Additionally, in smaller subsets of subjects with audiometrically matched data, these same trends persisted, further rulilng out hearing threshold as an influential factor. The growth of DPOAE ipsilateral suppression was shallower near 4 kHz in middle-aged and older adults compared to young-adults and elevated suppression thresholds were observed. Results of categorical loudness scaling showed steeper growth of loudness for older adults and, at fixed sensation levels (dB SL), the older-adult group rated tones as louder than did their young-adult counterparts, suggesting abnormal loudness growth and perception. Several correlations between the compression knee of the DPOAE I/O function and key metrics of loudness scaling were significant and accounted for up to one-third of the variance. CONCLUSIONS: Results indicate that the aging cochlea begins to show weakened nonlinearity in middle age and it progressively weakens further into senescence. The perceptual impact of weakened nonlinearity during aging is manifest as abnormal loudness judgements; that is, in older-adult ears, a tone considered comfortable or medium in young-adult ears can be considered loud in older adults. The biophysical origin of this weakened nonlinearity is not known. It is hypothesized to reflect aging-related damage to, or loss of, outer hair cells and their stereocilia. More work is warranted to better define the perceptual impact of a linearized cochlear response in older adults and to consider how this deficit might impact the fitting of hearing aids and other intervention strategies.

Due to insufficient and conflicting prospective evidence, the recommendations on when to apply adjuvant radiochemotherapy in early-stage cervical cancer vary between international guidelines. In this population-based study, we evaluated the outcome of patients with early-stage cervical cancer based on risk factors and the adjuvant therapy they received. The effect of primary therapy (surgery and radiochemotherapy RCT, surgery and radiotherapy RT, and surgery alone) on overall survival (OS) and recurrence-free survival (RFS) was evaluated in the complete cohort of 442 patients and in subgroups according to risk profile and nodal status. In low-risk patients, there was no difference in OS (p = 0.276) depending on whether patients received adjuvant therapy or not. Concerning RFS, patients with RT (including one patient with RCT) exhibited a significantly worse outcome compared to the group with surgery alone (p = 0.015). In intermediate-risk patients, the administration of adjuvant RT significantly benefited RFS when compared to surgery only in multivariate analysis (p = 0.031). Concerning OS, no significant influence for adjuvant treatment could be seen (p = 0.354). Though trends towards better OS and RFS could be observed in patients of the high-risk group—both in RCT and RT groups compared to surgery alone—the effects did not prove to be significant. Our study reaffirms the evidence against the use of adjuvant radio(chemo)therapy in low-risk early-stage cervical cancer. In intermediate-, and less pronounced in high-risk patients, however, it seems to be beneficial. The role of adjuvant radio(chemo)therapy in early cervical cancer should be further investigated in prospective randomized trials.

Die Nationale Dekade gegen Krebs (NDK) wurde 2019 vom Bundesministerium fur Bildung und Forschung (BMBF) gemeinsam mit dem Bundesministerium fur Gesundheit (BMG) und vielen Partnern ins Leben gerufen, um die Krebsforschung in Deutschland zu starken. Das Ziel des Bundnisses ist u. a., neue innovative Moglichkeiten der Fruherkennung, Diagnose, Therapie und Nachsorge zu erforschen und moglichst schnell zu den Betroffenen zu bringen. Fur drei Themenfelder – onkologische Grundlagenforschung, Praventionsforschung, Vernetzungsstrategien – hat der Strategiekreis der NDK Arbeitsgruppen (AGs) eingesetzt: AG „Grose ungeloste Fragen der Krebsforschung“, AG „Pravention“, AG „Wissen generieren durch Vernetzung von Forschung und Versorgung“. Hier diskutieren Expert(inn)en der Krebsforschung zentrale Forschungsaufgaben und entwickeln Losungsstrategien. In diesem Beitrag stellen die Themenpaten der AGs den aktuellen Stand vor. Auf Basis der von den AGs erarbeiteten wissenschaftlich drangenden Forschungsfragen hat das BMBF entsprechende Forderrichtlinien erarbeitet. Diese und weitere BMBF-Masnahmen werden dargestellt.

In the management of patients with decompensated liver cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) insertion is well-established but common recommendations in the follow up management are inconsistent. Doppler sonography is commonly used for detection for TIPS dysfunction whilst data on the impact of elective invasive examinations are scarce. The aim of this retrospective analysis is to evaluate potential benefits of elective invasive examinations in the follow up management of patients after TIPS insertion METHODS: Data of all patients receiving TIPS at the university hospitals of Muenster and Bonn between 2013 and 2018 (n = 534) were collected. The impact of performance of elective invasive examinations at 12 months after TIPS insertion on the occurrence of liver related events (LREs) and frequency of TIPS revisions within 24 months after TIPS insertion was analyzed. No significant differences were found concerning occurrence of liver related events after 24 months depending on whether an elective invasive examination was performed. Occurrence of hepatic encephalopathy, relapse of initial indication for TIPS, as well as death or liver transplantation all did not differ. These findings were verified by a subgroup analysis including only patients who did not experience a LRE or TIPS revision within the first 12 months after TIPS procedure. The analyzed data suggest no evidence for a beneficial impact due to implementation of an elective invasive examination program after TIPS insertion. Invasive examinations should remain reserved to patients with suspected TIPS dysfunction. Die Anlage eines transjugulären intrahepatischen portosystemischen Shunts ist ein etabliertes Verfahren in Patienten mit dekompensierter Leberzirrhose, es fehlen jedoch einheitlich Empfehlungen in der Patientennachsorge. Die Doppler-Sonografie wird regelhaft zur Kontrolle des Shunts genutzt. Aktuell gibt es keine Daten in Bezug auf elektive invasive Kontrollen. ZIEL: Ziel dieser retrospektiven Arbeit ist die Evaluation des Einflusses elektiver invasiver TIPS-Kontrollen in der Patientennachsorge. Es wurden Daten aller Patienten, die eine TIPS Implantation an den Universitätskliniken Münster und Bonn zwischen 2013 und 2018 erhalten haben, erhoben. Der Einfluss elektiver invasiver Kontrollen zwölf Monate nach TIPS Implantation bezüglich des Auftretens leber-assoziierter Ereignisse sowie der Häufigkeit von Shunt-Revisionen wurde analysiert. Es zeigten sich keine signifikanten Unterschiede bezüglich Leber-assoziierter Ereignisse nach 24 Monaten. Unterschiede bezüglich der Häufigkeit von Episoden hepatischer Enzephalopathien, einer Rekurrenz der initialen TIPS-Indikation, sowie Todesfällen oder Lebertransplantationen konnten nicht nachgewiesen werden. In einer Subgruppen-Analyse wurden nur Patienten, die innerhalb der ersten zwölf Monate kein leber-assoziiertes Ereignis oder eine TIPS-Revision hatten, analysiert: Auch hier wurden keine Unterschiede festgestellt. Unsere Daten zeigen keinen Vorteil für Patienten durch die Implementierung elektiver invasiver Kontrollen. Invasive Kontrollen sollten Patienten mit Hinweisen auf eine Shunt-Dysfunktion vorbehalten werden.

The usage of radioactive Technetium99m (Tc99m) colloid for the purpose of sentinel lymph node biopsy (SLNB) in early breast cancer is considered the gold standard in Germany. However, new tracers, such as near-infrared (NIR) imaging agents like indocyanine green (ICG) could offer an alternative in future, as they overcome drawbacks associated with radioactive Technetium99m (Tc99m) like limited availability, high costs and radioactivity exposure for both patients and surgeons. In this double-arm retrospective study, we sought to establish the usefulness of indocyanine green as an alternative or an addition to the conventional Technetium99m (Tc99m) in the identification of the SLN in early breast cancer. Among the 161 patients who underwent primary SLNB, 34 patients had at least 1 SLN with metastasis. Among these patients with SLN metastasis, 33 had the SLN detected by ICG; while 31 had the SLN detected by Tc99m. The conventional Technetium99m radiotracer failed to detect 2 patients with metastasis in this Arm of the study. Among the 87 patients who underwent SLNB after NACT, 13 patients had at least 1 SLN with metastasis. Among these 13 patients with SLN metastasis, ICG and Tc99m had detected the SLN among 12 patients, while 1 patient had been detected by ICG alone. Our results show that ICG is as effective as the radioisotope for SLNB even among patients who have undergone NACT. This trial is registered with the German Clinical Trial Register, ID: DRKS00013606.

Background: Baricitinib (Bari) is an oral, selective and reversible Janus kinase 1 and 2 inhibitor approved for the treatment of adults with active RA. In addition to long-term safety which has been disclosed previously with data up to 7 years [1], an important clinical consideration is whether treatment efficacy can be maintained over the long term. Objectives: To evaluate the long-term efficacy of once-daily Bari 4 mg in patients with active rheumatoid arthritis (RA) who were either naïve to or who had inadequate response (IR) to methotrexate (MTX) Methods: Post hoc analyses of data from two phase 3 studies, RA-BEGIN (MTX-naïve) and RA-BEAM (MTX-IR) for 52 weeks, and one long-term extension (LTE) study (RA-BEYOND) for an additional 96 weeks were conducted (148 weeks in total). At week 52, MTX-naïve patients initially treated with MTX monotherapy, Bari 4 mg monotherapy, or Bari 4 mg +MTX in RA-BEGIN were switched to open-label Bari 4 mg monotherapy for treatment in the LTE. Similarly, at week 52, MTX-IR patients initially treated with Bari 4 mg [+ background MTX noted as (+MTX) for RA-BEAM] or adalimumab (ADA) (+MTX) in RA-BEAM were switched to open-label Bari 4 mg (+MTX) for treatment in the LTE. Patients who received placebo (+MTX) were switched to open-label Bari 4 mg (+MTX) at week 24. The analyses of efficacy (SDAI) and physical function (HAQ-DI) were conducted on all patients who were randomized into the RA-BEGIN and RA-BEAM studies and had received ≥1 dose of study drug after randomization (mITT population). The proportion of patients who reached low disease activity (LDA), as measured by SDAI ≤11, was evaluated along with change from baseline in HAQ-DI. The non-responder imputation (NRI) method was used for the categorical analysis. Results: By week 24 in RA-BEGIN (N=584), 62% of patients treated with Bari 4 mg monotherapy or Bari 4 mg +MTX achieved SDAI LDA in comparison to 40% of pts in the MTX monotherapy group; response rates seen at week 24 in the Bari treatment groups were maintained through week 148 (Fig 1A). Similarly, by week 24 in RA-BEAM (N=1,305), 52% of patients treated with Bari 4 mg (+MTX) and 50% of patients treated with ADA (+MTX) achieved a SDAI LDA in comparison to 26% of patients from the PBO (+MTX) group. The response rate seen at week 24 with Bari 4 mg and ADA were maintained through week 148, even after patients switched from ADA to Bari 4 mg at week 52 (Fig 1B). Similar improvement and maintenance patterns in physical function measured by HAQ-DI were demonstrated. The overall discontinuation rate across treatment groups from RA-BEGIN (19.5%) and RA-BEAM (14.2%) have been published. In the LTE, the discontinuation rate from Bari treatment was 13.7% for patients originating from RA-BEGIN (1.1% due to lack of efficacy, 6.4% due to safety) and 12.6% for patients originating from RA-BEAM (1.8% due to lack of efficacy, 5.9% due to safety).

Uber die Halfte aller peri- und postmenopausaler Frauen leiden an klimakterischen Beschwerden. Am haufigsten sind dabei vasomotorische Symptome wie Hitzewallungen. Die Hormonersatztherapie (HRT) ist die effektivste Therapie zur Beseitigung solcher Beschwerden. Zudem kann sie die Risiken von Erkrankungen mindern, die mit einem niedrigeren Ostrogenspiegel einhergehen. So wird durch die HRT das osteoporoseassoziierte Frakturrisiko deutlich reduziert. Jedoch hat sie auch eine Reihe von Risiken, wie eine Steigerung des thromboembolischen Risikos. Auch eine mogliche Steigerung des zerebrovaskularen und des kardialen Risikos in Abhangigkeit des Alters und der Vorerkrankungen der Patientin sollte berucksichtigt werden. Studien zeigen eine mogliche Erhohung des Malignomrisikos in Abhangigkeit verschiedener Therapieregime und Applikationsformen. Eine sorgfaltige Anamnese mit Erhebung von moglichen relevanten Vorerkrankungen und Eruierung der belastenden Symptome ist daher essenziell fur die adaquate Beratung und Festlegung der geeigneten Therapieform.

Molecular investigations are crucial for further developments in precision medicine. RNA sequencing, alone or in combination with further omic-analyses, resulted in new therapeutic strategies. In this context, biobanks represent infrastructures to store tissue samples and body fluids in combination with clinical data to promote research for new predictive and prognostic biomarkers as well as therapeutic candidate molecules. Until today, the optimal storage conditions are a matter of debate especially with view to the storage temperature. In this unique approach we compared parallel samples from the same tumour, one half stored at − 80 °C and one half in the vapor phase of liquid nitrogen, with almost identical pre-analytical conditions. We demonstrated that RNA isolated from breast cancer samples revealed significantly higher RINe-values after 10 years of storage in the vapor phase of liquid nitrogen compared to storage at − 80 °C. In contrast, no significant difference was found regarding the DIN-values after DNA isolation. Morphological changes of the nucleus and cytoplasm, especially in the samples stored at − 80 °C, gave insights to degenerative effects, most possibly due to the storage protocol and its respective peculiarities. In addition, our results indicate that exact point-to point documentation beginning at the sample preparation is mandatory.

Modern four-factor prothrombin complex concentrate was designed originally for rapid targeted replacement of the coagulation factors II, VII, IX and X. Dosing strategies for the approved indication of vitamin K antagonist-related bleeding vary greatly. They include INR and bodyweight-related protocols as well as fixed dose regimens. Particularly in the massively bleeding trauma and cardiac surgery patient, four-factor prothrombin complex concentrate is used increasingly for haemostatic resuscitation. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology performed a systematic literature review on four-factor prothrombin complex concentrate. The available evidence has been summarised for dosing, efficacy, drug safety and monitoring strategies in different scenarios. Whereas there is evidence for the efficacy of four-factor prothrombin concentrate for a variety of bleeding scenarios, convincing safety data are clearly missing. In the massively bleeding patient with coagulopathy, our group recommends the administration of an initial bolus of 25 IU.kg-1 . This applies for: the acute reversal of vitamin K antagonist therapy; haemostatic resuscitation, particularly in trauma; and the reversal of direct oral anticoagulants when no specific antidote is available. In patients with a high risk for thromboembolic complications, e.g. cardiac surgery, the administration of an initial half-dose bolus (12.5 IU.kg-1 ) should be considered. A second bolus may be indicated if coagulopathy and microvascular bleeding persists and other reasons for bleeding are largely ruled out. Tissue-factor-activated, factor VII-dependent and heparin insensitive point-of-care tests may be used for peri-operative monitoring and guiding of prothrombin complex concentrate therapy.

OBJECTIVES: Assess trends in inpatient acute gastroenteritis (AGE) management across children’s hospitals and identify elements of AGE management associated with resource use. METHODS: We examined inpatient stays for children 6 months to 18 years hospitalized with AGE from 2009 to 2018 using the Pediatric Health Information System database. We characterized demographics, hospital-level resource use (ie, medications, laboratories, and imaging), and outcomes (ie, cost per case, 14-day revisit rates, and length of stay [LOS]). We compared demographic characteristics and resource use between 2009 to 2013 and 2014 to 2018 using χ2 and Wilcoxon rank-sum tests. We grouped hospitals on the basis of 2009 use of each resource and trended use over time using logistic regression. Annual change in mean cost and LOS were estimated by using models of log-transformed data. RESULTS: Across 32 354 hospitalizations at 38 hospitals, there was a high use of electrolyte testing (85.4%) and intravenous fluids (84.1%) without substantial changes over time. There were significant reductions in the majority of laboratory, medication, and imaging resources across hospitals over the study period. The most notable reductions were for rotavirus and stool testing. Many hospitals saw a decrease in LOS, with only 3 noting an increased revisit rate. Reductions in cost per case over time were most associated with decreases in imaging, laboratory testing, and LOS. CONCLUSIONS: Significant variation in resource use for children hospitalized with AGE coupled with high use of resources discouraged in AGE guidelines highlights potential opportunities to improve resource use that may be addressed in future AGE guidelines and quality improvement initiatives.

Purpose Mutations in the genes BRCA1 and BRCA2 represent a significant risk factor for ovarian and breast cancer. With increasing number and success rates, fertility protection and treatment are gaining importance also for BRCA1/2 mutation carriers. However, the effect on primary cancer risk and risk for recurrence remains unclear. This review analyses the published data on fertility treatment and risk of ovarian and breast cancer in BRCA1/2 mutation carriers. Methods In this review, we included all relevant articles published in English from 1995 to 2018. Literature was identified through a search on PubMed and Cochrane Library. Results We identified one retrospective cohort and one case–control study regarding the association of fertility treatments and ovarian cancer risk in BRCA mutation carriers. The studies show no increase in ovarian cancer risk. Furthermore, one case–control study on the association between fertility treatment and breast cancer risk in BRCA mutation carriers and one prospective cohort study on the long-term safety of medication used for fertility preservation in women with a history of breast cancer were identified. One of the studies shows a possible adverse effect for gonadotropin-containing medication. Conclusion Possible increases in cancer risk associated with fertility treatments in BRCA1/2 mutation carriers cannot be excluded at this time. Based on the existing studies, BRCA1/2 mutation carriers should not be generally excluded from fertility treatments. However, they have to be informed about limited data and possible increases in cancer risk.

Die Beratung und Behandlung von Menschen mit erblichen Tumorerkrankungen stellen besondere Herausforderungen dar. Es gilt hier, sowohl die erkrankten Personen als auch die gesunden Familienangehorigen zu betreuen. In der Gynakologie sind erbliche Tumorerkrankungen von besonderer Bedeutung. Wir kennen erbliche Formen von Brust- und Eierstockkrebs sowie von Gebarmutterschleimhauttumoren. Die bisher bekannten Genveranderungen, die fur die Gynakologie relevant sind, haben zum Teil prognostischen und pradiktiven Aussagewert hinsichtlich einzelner Therapieverfahren und konnen damit zum Teil therapiemodifizierend sein. Das Management des Risikos von gesunden Tragerinnen pathogener Mutationen stellt eine besondere Herausforderung dar. Daraus resultieren komplexe Informationen, die fur die Beratung von Patientinnen und deren Angehorigen berucksichtigt werden mussen.

Background/Aims Robotic assisted devices are increasingly used in neurological rehabilitation for improving upper extremity function. The new hand therapy device Manovo Power of the Armeo Power provides integrated assessment of grip strength measurement. Reliability and validity of the grip strength measurement are unknown. The aim of this study was to evaluate the reliability and validity of grip strength measurement with the hand module of the Manovo Power robot-assisted device compared with a Biometrics E-Link hand-grip dynamometer. Methods This was a cross-sectional study design with grip strength measurements taken once a day for a total of 3 days, with a 2-day interval in between each test. Participants of the study were patients 0.8. Absolute reliability was evaluated using limits of agreement (LoA). Validity was supported if the correlation between measures with the two devices was >0.6. Results The robotic device had good intra-rater reliability (ICC=0.89, 95% confidence interval [CI] 0.81–0.94, LoA 1.23–1.16) and inter-rater reliability (ICC=0.91, 95% CI 0.85–0.95, LoA 1.01–1.23). Intra-rater reliability of the Biometrics E-Link grip strength dynamometer was higher compared with the robotic device (ICC=0.98, 95% CI 0.96–0.99, LoA 3.94–4.42). Validity was confirmed by a correlation between devices of 0.76 (95% CI 0.60–0.85). Conclusions Measurement of grip strength with the robotic device was reliable and valid in patients with stroke and impaired hand function. There was no absolute measurement error that might have indicated a learning effect. Reliability was higher for the Biometrics E-Link grip strength dynamometer compared with the robotic-assisted device. Using the robotic device for grip strength measurement in patients who exercise with that device saves time and increases efficiency.

Eine Hormonersatztherapie kann effektiv klimakterische Beschwerden lindern. Daruber hinaus hat sie Wirkungen, die sich positiv auf die Gesundheit auswirken, aber auch die Anwendung limitieren konnen. Unbestritten ist der positive Effekt auf die Knochenstruktur mit der Folge einer substanziellen Senkung der Frakturraten. Bezuglich hormonabhangiger Tumoren sind die Effekte gering und gegensatzlich, sodass eine Hormonersatztherapie nicht zur onkologischen Vorsorge geeignet ist. Das gilt auch fur die Pravention der koronaren Herzkrankheit, zumal eine Erhohung des Thrombose- und Schlaganfallrisikos nur durch transdermale Applikation vermieden werden kann. Dadurch werden wiederum gunstige Wirkungen auf das Lipidprofil und den Glukosestoffwechsel mitigiert, die zusammen mit einem individuell unterschiedlichen Effekt auf den Blutdruck nach jeweiliger Veranlagung positiv genutzt werden konnen.