Short-time mentoring - enhancing female medical students' intentions toward surgical careers.

BACKGROUND: Women pursuing a career in surgery or related disciplines are still in the minority, despite the fact that women compose at least half of the medical student population in most Western countries. Thus, recruiting and retaining female surgeons remains an important challenge to meet the need for surgeons and increase the quality of care. The participations were female medical students between their third and fifth academic year. In this study, we applied the well-established psychological theory of planned behavior (TPB) which suggests that the intention to perform a behavior (e.g. pursuing a career in surgery) is the most critical and immediate predictor of performing the behavior. We investigated whether a two-part short-mentoring seminar significantly increases students' intention to pursue a career in a surgical or related specialty after graduation. METHOD: The mentoring and role-model seminar was conducted at 2 days for 90 minutes by six inspiring female role models with a remarkable career in surgical or related disciplines. Participants (N = 57) filled in an online survey before (T0) and after the seminar (T1). A pre-post comparison of central TPB concept attitude towards the behavior, 2) occupational self-efficacy and 3) social norm) was conducted using a paired sampled t-test. A follow-up survey was administered 12 months later (T2). RESULTS: The mentoring seminar positively impacted female students' attitude towards a career in a surgical specialty. Female students reported a significantly increased positive attitude (p < .001) and significantly higher self-efficacy expectations (p < .001) towards a surgical career after participating in the mentoring seminar. Regarding their career intention after the seminar, female students declared a significantly higher intention to pursue a career in a surgical specialty after graduating (p < .001) and this effect seems to be sustainable after 1 year. CONCLUSION: For the first time we could show that short-mentoring and demonstrating role models in a seminar surrounding has a significant impact on female medical student decision´s to pursue a career in a surgery speciality. This concept may be a practical and efficient concept to refine the gender disparity in surgery and related disciplines.

Constrained Layer Assignment for the Protein Burial Folding Code Accounting for Chain Connectivity.

The connection between protein sequences and tertiary structures has intrigued investigators for decades. A plausible hypothesis for the coding scheme postulates that atomic burial information obtainable from the sequence could be sufficient for structural determination when combined to sequence-independent constraints. Accordingly, folding simulations using native burial information expressed by atomic central distances, discretized into a small number L of equiprobable burial layers, have indeed been successful in reaching and distinguishing the native structure of several globular proteins. Attempted predictions of layers from sequence, however, turned out to be insufficiently accurate for most proteins. Here we explore the possibility that a nonuniform assignment of layers, which is intended to account for constraints imposed by chain connectivity, might provide a more efficient burial encoding of tertiary structures. We consider the condition that adjacent Cα-atoms along the sequence cannot occupy nonadjacent layers, in which case the information required to specify sequences of burials would be smaller. It is shown that appropriate folding behavior can still be observed in this explicitly more constrained scenario with a structure-dependent assignment intended to produce the thinnest possible layers still compatible with the imposed burial constraint. This thinnest assignment turns out to be sufficiently restrictive for the observed examples and provides appropriately thinner layers or, equivalently, a larger number of layers, for examples previously observed to indeed require more restrictive constraints when compared to counterparts of similar size, as well as the appropriate increase in number of layers for larger proteins. Implications for the general understanding of the protein folding code are discussed.

Acute liver injury following acetaminophen administration does not activate atrophic pathways in the mouse diaphragm.

N-acetyl-para-amino phenol (APAP, usually named paracetamol), which is commonly used for its analgesic and antipyretic properties may lead to hepatotoxicity and acute liver damage in case of overdoses. Released cytokines and oxidative stress following acute liver damage may affect other organs' function notably the diaphragm, which is particularly sensitive to oxidative stress and circulating cytokines. We addressed this issue in a mouse model of acute liver injury induced by administration of APAP. C57BL/6J mice (each n = 8) were treated with N-acetyl-para-amino phenol (APAP) to induce acute drug caused liver injury and sacrificed 12 or 24 h afterwards. An untreated group served as controls. Key markers of inflammation, proteolysis, autophagy and oxidative stress were measured in diaphragm samples. In APAP treated animals, liver damage was proven by the enhanced serum levels of alanine aminotransferase and aspartate aminotransferase. In the diaphragm, besides a significant increase in IL 6 and lipid peroxidation, no changes were observed in key markers of the proteolytic, and autophagy signaling pathways, other inflammatory markers and fiber dimensions. The first 24 h of acute liver damage did not impair diaphragm atrophic pathways although it slightly enhanced IL-6 and lipid peroxidation. Whether longer exposure might affect the diaphragm needs to be addressed in future experiments.

[S2k Guideline - Recommendations for Inpatient Therapy of Patients with COVID-19]. / S2k-Leitlinie ­ Empfehlungen zur stationären Therapie von Patienten mit COVID-19.

Since December 2019, the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - Corona Virus-2) has been spreading rapidly in the sense of a global pandemic. This poses significant challenges for clinicians and hospitals and is placing unprecedented strain on the healthcare systems of many countries. The majority of patients with Coronavirus Disease 2019 (COVID-19) present with only mild symptoms such as cough and fever. However, about 6 % require hospitalization. Early clarification of whether inpatient and, if necessary, intensive care treatment is medically appropriate and desired by the patient is of particular importance in the pandemic. Acute hypoxemic respiratory insufficiency with dyspnea and high respiratory rate (> 30/min) usually leads to admission to the intensive care unit. Often, bilateral pulmonary infiltrates/consolidations or even pulmonary emboli are already found on imaging. As the disease progresses, some of these patients develop acute respiratory distress syndrome (ARDS). Mortality reduction of available drug therapy in severe COVID-19 disease has only been demonstrated for dexamethasone in randomized controlled trials. The main goal of supportive therapy is to ensure adequate oxygenation. In this regard, invasive ventilation and repeated prone positioning are important elements in the treatment of severely hypoxemic COVID-19 patients. Strict adherence to basic hygiene, including hand hygiene, and the correct wearing of adequate personal protective equipment are essential when handling patients. Medically necessary actions on patients that could result in aerosol formation should be performed with extreme care and preparation.

[Perception of the COVID-19 Pandemic among Pneumology Professionals in Germany]. / Wahrnehmung der COVID-19-Pandemie unter pneumologischen Fachkräften in Deutschland.

The COVID-19 pandemic represents a huge burden on global health systems. Although far-reaching prevention measures such as the increase of intensive care capacities and drastic restrictions of public life have so far been able to avert an overload of the German health care system, the current situation implies an exceptionally high burden on medical professionals. The current study presents the results of an opinion evaluation among 513 pneumology specialists in Germany in the period from March 27th to April 11th, 2020. While the majority of respondents stated that Germany was "well" prepared for the pandemic, this assessment was significantly worse among participants from the outpatient sector compared to the hospital sector (p < 0.001). Furthermore, a lack of medical protective equipment was reported significantly more frequently by respondents from the outpatient sector (p < 0.001). The importance of telemedicine approaches during the COVID-19 pandemic was rated "high" (35.2 %) or "very high" (17.2 %) by most pneumology professionals, with participants from the hospital sector giving a higher rating (p < 0.001). Finally, 45.8 % of the respondents expressed a "negative" influence of the COVID-19 pandemic on their personal mood and 58.3 % expressed "strong" or "very strong" concerns about the health of their fellow human beings. This assessment was significantly stronger among female participants and participants from the nursing sector (p < 0.001). In summary, the current study analyses for the first time the professional and personal impact of the COVID-19 pandemic on pneumology professionals in Germany. The results could help to identify first starting points to better support health professionals during the current and future challenges.

Recommendations for treatment of critically ill patients with COVID-19 : Version 3 S1 guideline.

Since December 2019 a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The immense challenges for clinicians and hospitals as well as the strain on many healthcare systems has been unprecedented.The majority of patients present with mild symptoms of coronavirus disease 2019 (COVID-19); however, 5-8% become critically ill and require intensive care treatment. Acute hypoxemic respiratory failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to intensive care unit (ICU) admission. At this point bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS).So far, remdesivir and dexamethasone have shown clinical effectiveness in severe COVID-19 in hospitalized patients. The main goal of supportive treatment is to ascertain adequate oxygenation. Invasive mechanical ventilation and repeated prone positioning are key elements in treating severely hypoxemic COVID-19 patients.Strict adherence to basic infection control measures (including hand hygiene) and correct use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be carried out with utmost precaution and preparation.

Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial.

BACKGROUND: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for extended adjuvant treatment in early-stage HER2-positive breast cancer based on the phase III ExteNET study. In that trial, in which no antidiarrheal prophylaxis was mandated, grade 3 diarrhea was observed in 40% of patients and 17% discontinued due to diarrhea. The international, open-label, sequential-cohort, phase II CONTROL study is investigating several strategies to improve tolerability. PATIENTS AND METHODS: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year plus loperamide prophylaxis (days 1-28 or 1-56). Sequential cohorts evaluated additional budesonide or colestipol prophylaxis (days 1-28) and neratinib dose escalation (DE; ongoing). The primary end point was the incidence of grade ≥3 diarrhea. RESULTS: Final data for loperamide (L; n = 137), budesonide + loperamide (BL; n = 64), colestipol + loperamide (CL; n = 136), and colestipol + as-needed loperamide (CL-PRN; n = 104) cohorts, and interim data for DE (n = 60; completed ≥six cycles or discontinued; median duration 11 months) are available. No grade 4 diarrhea was observed. Grade 3 diarrhea rates were lower than ExteNET in all cohorts and lowest in DE (L 31%, BL 28%, CL 21%, CL-PRN 32%, DE 15%). Median number of grade 3 diarrhea episodes was one; median duration per grade 3 episode was 1.0-2.0 days across cohorts. Most grade 3 diarrhea and diarrhea-related discontinuations occurred in month 1. Diarrhea-related discontinuations were lowest in DE (L 20%, BL 8%, CL 4%, CL-PRN 8%, DE 3%). Decreases in health-related quality of life did not cross the clinically important threshold. CONCLUSIONS: Neratinib tolerability was improved with preemptive prophylaxis or DE, which reduced the rate, severity, and duration of neratinib-associated grade ≥3 diarrhea compared with ExteNET. Lower diarrhea-related treatment discontinuations in multiple cohorts indicate that proactive management can allow patients to stay on neratinib for the recommended time period. CLINICALTRIALS.GOV: NCT02400476.

Preoperative cisplatin, fluorouracil, and docetaxel with or without radiotherapy after poor early response to cisplatin and fluorouracil for resectable oesophageal adenocarcinoma (AGITG DOCTOR): results from a multicentre, randomised controlled phase II trial.

BACKGROUND: Patients with oesophageal/gastro-oesophageal junction adenocarcinoma (EAC) not showing early metabolic response (EMR) to chemotherapy have poorer survival and histological response rates <5%. We investigated whether tailoring neoadjuvant therapy can improve outcomes in these patients. PATIENTS AND METHODS: Patients with resectable EAC were enrolled and randomised into two single-arm, multicentre phase II trials. After induction cisplatin and 5-fluorouracil (CF), all were assessed by day 15 positron emission tomography (PET). Patients with an EMR [maximum standardised uptake values (SUVmax) ≥35% reduction from baseline to day 15 PET] received a second CF cycle then oesophagectomy. Non-responders were randomised 1 : 1 to two cycles of CF and docetaxel (DCF, n = 31) or DCF + 45 Gy radiotherapy (DCFRT, n = 35) then oesophagectomy. The primary end point was major histological response (<10% residual tumour) in the oesophagectomy specimen; secondary end points were overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LR). RESULTS: Of 124 patients recruited, major histological response was achieved in 3/45 (7%) with EMR, 6/30 (20%) DCF, and 22/35 (63%) DCFRT patients. Grade 3/4 toxicities occurred in 12/45 (27%) EMR (CF), 13/31 (42%) DCF, and 25/35 (71%) DCFRT patients. No treatment-related deaths occurred. LR by 3 years was seen in 5/45 (11%) EMR, 10/31 (32%) DCF, and 4/35 (11%) DCFRT patients. PFS [95% confidence interval (CI)] at 36 months was 47% (31% to 61%) for EMR, 29% (15% to 45%) for DCF, and 46% (29% to 61%) for DCFRT patients. OS (95% CI) at 60 months was 53% (37% to 67%) for EMR, 31% (16% to 48%) for DCF, and 46% (29% to 61%) for DCFRT patients. CONCLUSIONS: EMR is associated with favourable OS, PFS, and low LR. For non-responders, the addition of docetaxel augmented histological response rates, but OS, PFS, and LR remained inferior compared with responders. DCFRT improved histological response and PFS/LR outcomes, matching the EMR group. Early PET/CT has the potential to tailor therapy for patients not showing an early response to chemotherapy. TRIAL REGISTRATION: ACTRN12609000665235.

The impact and indications for Oncotype DX on adjuvant treatment recommendations when third-party funding is unavailable.

OBJECTIVES: Industry-supported decision impact studies demonstrate that Oncotype Dx (ODX) changes treatment recommendations (TR) in 24-40% of hormone receptor+/HER2- patients. ODX is not reimbursed by third-party payers in Australia, potentially resulting in more selective use. We sought to evaluate the impact of self-funded ODX on TRs. METHODS: Data collected included demographics, tumor characteristics, indication for ODX and pre- and post-recurrence score (RS) TR. Primary endpoint was frequency of TR change and associations with TR change were sought. RESULTS: Eighteen physicians contributed 382 patients (median age 54). A total of 232 (61%) of tumors were T1 and were grade 1, 2 and 3 in 49 (13%), 252 (66%) and 79 (21%). A total of 257 (67%) were node negative. Assay indications were: confirm need for chemotherapy (CT) (36%), confirm omission of CT (40%) and genuine equipoise (24%). RS was low (≤17) in 55%, intermediate (18-31) in 36% and high (≥32) in 9%. Thirty-eight percent of patients had TR change post-ODX. Sixty-five percent of patients recommended CT pre-ODX changed to hormone therapy alone (HT)-more likely if lower grade and if ER and/or PR > 10%. Fourteen percent of patients with pre-ODX TR for HT added CT-more likely if ER and/or PR ≤10% and if Ki67 > 15% Overall, TR for CT decreased from 47% to 24%. CONCLUSION: Patient-funded ODX changed TRs in 38% of patients, de-escalating 65% from CT to HT and adding CT to 14% of those recommended HT. These changes were greater than an industry-funded study suggesting that physicians can identify situations where the assay may influence decisions.

Urine neutrophil gelatinase-associated lipocalin predicts outcome and renal failure in open and endovascular thoracic abdominal aortic aneurysm surgery.

Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been evaluated as a biomarker for AKI detection and adverse outcome in open and endovascular thoracoabdominal aortic aneurysm surgery. This observational, retrospective study included 52 patients. UNGAL was measured peri-operatively (48 h) and correlated with AKI requiring dialysis, tracheotomy and adverse outcome. Mean patients' age was 64.5 years. A total of 26.9% (n = 14) developed AKI, and 21.1% (n = 11) required dialysis, tracheotomy rate was 19.2% (n = 10) and in-hospital mortality rate was 7.6% (n = 4). uNGAL levels were related to AKI requiring dialysis at ICU (p = 0.0002), need for tracheotomy at baseline and admission on ICU (p = 0.0222, p = 0.0028, respectively), as well as adverse discharge modality (p = 0.0051, p = 0.0048, respectively). Diagnostic quality was good for uNGAL levels at admission to ICU regarding AKI requiring dialysis (sensitivity: 81.8% [48.2-97.7]; specificity: 87.8% [73.8-95.9]; area under the curve (AUC): 0.874 [0.752-0.949]). The diagnostic quality of uNGAL was favorable for the prediction of tracheotomy (sensitivity: 70.0% [34.8-93.3]; specificity: 83.3% [68.6-93.0]; AUC: 0.807 [0.674-0.903]) and adverse discharge (sensitivity: 77.8% [40.0-97.2]; specificity: 83.7% [69.3-93.2]; AUC: 0.817 [0.685-0.910]). uNGAL may be valuable as an post-operative predictor of AKI and adverse outcome after open and endovascular TAAA repair.

[Sense of Coherence Scale according to Antonovsky as a possible predictor for return to work for cardiac surgery intensive care patients]. / "Sense-of-coherence"-Skala nach Antonovsky als möglicher Prädiktor für den Wiedereinstieg in das Berufsleben für herzchirurgische Intensivpatienten.

BACKGROUND: For cardiac surgery patients who were employed prior to surgery, the return to their professional life is of special importance. In addition to medical reasons, such as pre-existing conditions, the success of the operation or postoperative course and patient-intrinsic reasons, which can be assessed with the Sense of Coherence (SOC) scale by Antonovsky, may also play a role in the question of a possible return into working life. METHODS: In this study 278 patients (invasive coronary artery bypass graft surgery and/or surgery on heart valves, age < 60 years, employed) were questioned postoperatively via post with the SOC questionnaire. The SOC questionnaire was used in addition to questions about return to work. The cohort was stratified according to the time of return to work. Subsequently, the point of maximum sensitivity and specificity was determined for the total SOC score and the prediction power was considered. RESULTS: Of the 278 patients, 61 questionnaires (22%) were considered as eligible and included in the analysis. Of these, 47 participants had returned to work after undergoing cardiac surgery and 14 participants had not. We observed significant differences in SOC values between both groups (146.07 ± 29.76 versus 124.29 ± 28.8, p = 0.020). Patients that returned to work within the first 6 months after surgery showed even higher SOC scores (148.56 ± 28.98, p = 0.034). CONCLUSION: Patients with an SOC score < 130 are at greater risk not to return to their professional life after cardiac surgery. The SOC is an easily obtainable score that reliably predicts the probability of return to work after cardiac surgery.

Fission of Polyanionic Metal Clusters.

Size-selected dianionic lead clusters Pb_{n}^{2-}, n=34-56, are stored in a Penning trap and studied with respect to their decay products upon photoexcitation. Contrary to the decay of other dianionic metal clusters, these lead clusters show a variety of decay channels. The mass spectra of the fragments are compared to the corresponding spectra of the monoanionic precursors. This comparison leads to the conclusion that, in the cluster size region below about n=48, the fission reaction Pb_{n}^{2-}→Pb_{n-10}^{-}+Pb_{10}^{-} is the major decay process. Its disappearance at larger cluster sizes may be an indication of a nonmetal to metal transition. Recently, the pair of Pb_{10}^{-} and Pb_{n-10}^{-} were observed as pronounced fragments in electron-attachment studies [S. König et al., Int. J. Mass Spectrom. 421, 129 (2017)IMSPF81387-380610.1016/j.ijms.2017.06.009]. The present findings suggest that this combination is the fingerprint of the decay of doubly charged lead clusters. With this assumption, the dianion clusters have been traced down to Pb_{21}^{2-}, whereas the smallest size for the direct observation was as high as n=28.

Performance on a 1-week delayed recall task is associated with medial temporal lobe structures in neurologically normal older adults.

OBJECTIVE: Traditional episodic memory tests employ a delayed recall length ranging from 10 to 30 min. The neurobiological process of memory consolidation extends well beyond these time intervals, however, raising the possibility that these tests might not be fully sensitive to the subtle neurocognitive changes found in early disease or age-related decline. We aimed to determine the sensitivity of a 1-week delayed recall paradigm to medial temporal lobe (MTL) structure among neurologically normal older adults. METHODS: One hundred and forty functionally intact, older adults (mean age = 75.8) completed a story recall test in which participants learned to 90% criterion. Recall was tested after 30-min and 1-week. Participants also completed a standardized list learning task with a 20-min delay (n = 129) and a structural brain MRI. The MTL, including the parahippocampal gyrus, hippocampus, and entorhinal, was our primary region of interest. RESULTS: Controlling for age, education, gender and total intracranial volume, the standard 20- and 30-min recalls showed no significant relationship with MTL. In contrast, 1-week recall was uniquely associated with MTL structure (partial r = .24, p = .006), specifically entorhinal (partial r = .27; p = .001) and hippocampal (partial r = .21, p = .02) volumes. CONCLUSION: Memory paradigms that utilize 1-week delays are more sensitive than standard paradigms to MTL volumes in neurologically normal older adults. Longer delay periods may improve detection of memory consolidation abilities associated with age-related, and potentially pathological, neurobehavioral change.

[Diaphragm dysfunction : Facts for clinicians]. / Diaphragmale Dysfunktion : Fakten für den Kliniker.

Diaphragm function is crucial for patient outcome in the ICU setting and during the treatment period. The occurrence of an insufficiency of the respiratory pump, which is predominantly formed by the diaphragm, may result in intubation after failure of noninvasive ventilation. Especially patients suffering from chronic obstructive pulmonary disease are in danger of hypercapnic respiratory failure. Changes in biomechanical properties and fiber texture of the diaphragm are further cofactors directly leading to a need for intubation and mechanical ventilation. After intubation and the following inactivity the diaphragm is subject to profound pathophysiologic changes resulting in atrophy and dysfunction. Besides this inactivity-triggered mechanism (termed as ventilator-induced diaphragmatic dysfunction) multiple factors, comorbidities, pharmaceutical agents and additional hits during the ICU treatment, especially the occurrence of sepsis, influence diaphragm homeostasis and can lead to weaning failure. During the weaning process monitoring of diaphragm function can be done with invasive methods - ultrasound is increasingly established to monitor diaphragm contraction, but further and better powered studies are in need to prove its value as a diagnostic tool.

[Weaning ward-different from the ICU?] / Weaningstation ­ was ist anders als auf der ICU?

Weaning from mechanical ventilation is generally not the most urgent topic on many ICUs, because acutely endangered patients are usually the staff's main focus. Nevertheless, even these patients whose underlying problem has been mostly solved-whether it was neurologic, internal or surgical-are in need of a structured weaning strategy. The aim of this weaning "road map" is ventilator independence, decannulation and regaining of muscular strength. Achieving of these aims needs a well-educated team of physicians, nurses, respiratory/physical therapists, logopedists and pychologists. Assessment of patient health status, including respiratory muscle function must be part of the overtaking procedure to be able to focus on the main problem that may be causative for the inability to wean so far. Every weaning unit must be able to organize the future treatment of patients (different ward inside the hospital, rehabilitation) or the transfer into a (ventilated) home care situation.