[Testing of practical surgical teaching at a distance-Experiences with a hybrid OSCE in surgery]. / Prüfung praktisch-chirurgischer Lehre auf Distanz ­ Erfahrungen mit einem Hybrid-OSCE in der Chirurgie.

BACKGROUND: The COVID-19 pandemic has changed medical teaching worldwide. Digital teaching and examinations are successful for cognitive learning objectives, whereas practical skills had to be carried out predominantly in person under strict hygiene standards. AIM: This study presents the opportunities and challenges of using a presence objective structured clinical examination (OSCE) at a distance with digital support. METHOD: Following surgical practical teaching an OSCE was conducted in presence, where students demonstrated practical skills in one room while the examiners were connected via videoconference from another room. Students were surveyed about the OSCE and sustained learning via a standardized online questionnaire after completion of the surgical teaching. Additionally, examiners were surveyed on their experiences. RESULTS: In the online survey 40 students participated (25% of n = 157 students contacted) and 36 completed questionnaires were analyzed. Overall, the implementation of an OSCE even under pandemic conditions was perceived as very positive by the students (92% of students n = 33). In particular, the acquisition of practical skills was rated as very high. For 78% (n = 28) of the students, the acquisition of competencies through the practical examination was particularly sustainable. The vast majority of students and examiners felt safe regarding infection control because of the hygiene concept (92%, n = 33). Overall, 80 students achieved grade 1 (51%), 71 students grade 2 (45.2%) and 6 students grade 3 (3.8%) (grade 1 = very good, grade 6 = very bad). CONCLUSION: Practical examinations are essential for checking practical learning objectives and can be implemented at a distance with a well-developed hygiene concept and digital support.

Defibrillator generator replacements in patients with left ventricular assist device support: The risks of hematoma and infection.

BACKGROUND: The majority (89%) of left ventricular assist device (LVAD) patients have an implantable cardioverter-defibrillator (ICD) in place. Due to the advances of modern-day LVAD therapy, more patients are on support for longer. This inevitably leads to more LVAD patients facing ICD generator battery depletion. Until now, there are insufficient data regarding periprocedural risks of generator replacements in a high-risk group like the LVAD cohort. METHODS: A retrospective, single-center analysis of pocket-related outcomes of all ICD generator replacements in LVAD and Non-LVAD patients between January 2014 and December 2018. The primary outcome was the combined endpoint of clinically significant pocket hematoma and/or cardiac implantable electronic device (CIED) infection in the first 6 months after ICD generator exchange. The clinically significant hematoma was defined as hematoma requiring reoperation, prolongation of hospitalization, or interruption of anticoagulation. The cumulative incidence function was calculated for the primary endpoint. RESULTS: Two hundred seventy-seven patients underwent ICD generator exchange in our clinic in this time. Of these, 251 patients had a complete 6-month follow-up regarding clinically significant pocket hematomas and pocket infections. One hundred ninety patients had no LVAD, and 61 patients were on LVAD support. The rate of the primary combined endpoint clinically significant pocket hematoma and/or CIED infection was 3.5 times higher in LVAD patients compared to the non-LVAD cohort (event rate 39.14 vs 11.07 per 100 patient-years, p = 0.048). Clinically significant pocket hematomas necessitating revision occurred nearly 4 times more often in the LVAD group (p = 0.042). Pocket device infection rates were around 16 times higher in LVAD patients compared to non-LVAD patients (p = 0.002). CONCLUSIONS: Compared to Non-LVAD patients, LVAD patients exhibit a relevant higher rate of clinically significant pocket hematoma and CIED infection after ICD generator exchange. This information should additionally be considered in the decision-making process regarding the indication for ICD generator exchange.

[Chances and challenges of increasing digitalization of teaching in the discipline anesthesiology from the perspective of students]. / Chancen und Herausforderungen der zunehmenden Digitalisierung der Lehre im Fach Anästhesiologie aus Sicht der Studierenden.

BACKGROUND: The coronavirus pandemic caused a sudden change in medical education worldwide and induced a shift towards digital teaching. Previously, most courses were organized for students in physical presence on campus, while a few institutions already complemented these with blended learning methods, combining digital teaching with clinical presence; however, the use of digital teaching was heterogeneous, ranging from the use of PowerPoint slides to the application of virtual patients and telemedicine. OBJECTIVE: This study aimed to identify challenges and opportunities arising from the different tools used in digital teaching, such as recorded lectures or online seminars, and the role of hands-on clinical experience. In addition, the study examined student attitudes and experiences with the nearly all-digital semester beginning in spring 2020. These findings may help to better understand the impact of digital teaching on students and provide guidance on how to optimize digital medical teaching in the future. METHODS: A questionnaire with a 5-point Likert scale was developed to assess students' experiences with digital teaching at the onset of the COVID-19 pandemic in a cross-sectional study. The questionnaire was distributed to all medical students at the University of Mainz, Germany, who attended an anesthesiology course with asynchronously recorded lectures replacing traditional on-campus lectures during the pandemic. A total of 766 students in 4 courses met these criteria and received the online questionnaire for anonymous and voluntary response. RESULTS: A total number of 141 students responded, resulting in a response rate of 18.4%. Almost all students had access to the appropriate technology to participate in digital courses and 80.9% indicated seeing more recorded lectures compared to previous face-to-face lectures on campus. Moreover, 67.4% reported that they paused the asynchronous lectures to look up additional information and 95.7% stated that they appreciated the possibility to view lectures regardless of time and location. Hence, 84.3% said they would prefer digital lectures over face-to-face lectures in the future; however, 28.4% missed the interaction with teachers during lectures. Thus, 94.3% of the students appreciated the online seminars in terms of theoretical knowledge but the majority missed the practical aspects in the courses. Overall, 78.0% responded that the digital availability of material and digital teaching formats helped them to enhance their independent learning abilities. CONCLUSION: This study highlights several opportunities and challenges associated with digital teaching. The availability of prerecorded lectures at any time and place seems to facilitate access and increases student motivation. It also promotes individualization of student learning. Main disadvantages are the lack of communication with teachers and other students as well as the missing opportunity to reinforce the theoretical knowledge through application in practical courses, which, however, are essential for medical education. Therefore, a possible solution in the future could be the introduction of the "inverted classroom" concept, as it focuses on application and deepening of clinical skills in interactive classes, while the theoretical knowledge acquisition is taught in a digital teaching environment. The present study proposes the introduction of blended learning concepts to enhance the benefits of digital teaching while minimizing the identified disadvantages.

International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in completely resected stage II-IIIA non-small-cell lung cancer.

BACKGROUND: Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor. PATIENTS AND METHODS: Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator's choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS). RESULTS: Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T. CONCLUSION: In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm.

[Clinical Course of Typical and Atypical Carcinoids (bpNET): Evaluation of PneuNET Register Berlin Data for the Identification of Indicators for Prognosis Determination and Therapy Planning]. / Klinischer Verlauf typischer und atypischer Karzinoide (bpNET) ­ Auswertung von Registerdaten des PneuNET-Registers Berlin zur Identifikation von Indikatoren zur Prognosebestimmung und Therapieplanung.

AIM: Retrospective analysis of data from PneuNET registry to evaluate clinical follow up of patients with typical and atypical bronchopulmonary carcinoid (bpNET). METHOD: Three lung cancer centres in Berlin included patients in the registry between 2007 and 2016. Inclusion criteria were: diagnosis of typical or atypical carcinoid, age > 18 years, follow-up for not less than 2 years. Frequency, gender, functional status, smoking status, localisation of the tumour, biomarker, diagnostic and therapeutic procedures and follow-up were evaluated. RESULTS: Since 01. 01. 2007, 187 patients with bronchopulmonary carcinoid had been included in the registry. The ratio between TC and AC was 8:2. The median age was 65.4 years and 64 % of patients were women. 10.7 % of patients had pulmonary symptoms, 2 patients a carcinoid syndrome, no patient was detected with MEN-1-syndrome. 87.7 % of patients had undergone surgery, 69.5 % as lobectomy with systematic lymphadenectomy. Only 10 % of patients were diagnosed with Stage IV disease, with atypical carcinoid predominating Systemic therapies included chemotherapy, everolimus and somatostatin analogues. CONCLUSION: Bronchopulmonary carcinoids are well differentiated tumours of the lung. The early stage diagnosis offers the possibility of local therapy with excellent prognosis. We have improved systemic treatment options with mTOR-inhibitor everolimus and somatostatin analogues also in advanced stage of the disease. Because of the rareness of this heterogenous group of tumours, it is meaningful to collect data systematically in order to have a standardised algorithm of diagnostic procedures and therapy assessment.

Insight into the incidence of acute aortic dissection in the German region of Berlin and Brandenburg.

BACKGROUND: Stanford acute type A aortic dissection (ATAAD) is a potentially lethal condition. Epidemiology studies show a statistical incidence in Europe of approximately 2-16 cases/100,000 inhabitants/year. In Germany, the estimated incidence (here subsumed under "thoracic aortic dissection" with 4.63 cases/100,000 inhabitants/year) is mainly extracted from medical death certificates by the German Federal Statistical Office. The prehospital incidence of ATAAD deaths is largely unknown. Since patients often die in the pre-hospital setting, the incidence of ATAAD is therefore likely to be higher than current estimates. MATERIAL AND METHODS: For the period from 2010 to 2014, we retrospectively analyzed all in-hospital ATAAD data from two of the largest cardiac surgical centers that treat ATAAD in the Berlin-Brandenburg region. In addition, autopsy reports of all forensic medicine institutes and of one large pathological provider in the region were analyzed to identify additional non-hospitalized ATAAD patients. Based on these findings, the regional incidence of ATAAD was calculated. RESULTS: In addition to in-hospital ATAAD patients (n=405), we identified additional 145 lethal ATAAD cases among 14,201 autopsy reports. The total of 550 ATAAD cases led to an estimated incidence of 11.9 cases/100,000 inhabitants/year for the whole Berlin-Brandenburg region. Arterial hypertension, pre-existing aortic dilatation, and hereditary connective tissue disorder were found in, respectively, 62.7%, 10%, and 1.8% of patients. CONCLUSION: ATAAD is more frequent than previously reported. Our results show that when patients who die outside of cardiac surgery centers are included, the incidence of ATAAD significantly exceeds the rate reported by the Federal Statistical Office.

[Cross-sectional field pain medicine Q14 - the Mainz model : Development of the pain medicine curriculum in the standard study course at the University Medical School of the Johannes Gutenberg University Mainz]. / Querschnittsfach Schmerzmedizin Q14 ­ das Mainzer Modell : Die Entwicklung des Curriculums Schmerzmedizin im Regelstudiengang Humanmedizin an der Universitätsmedizin der Johannes Gutenberg-Universität Mainz.

BACKGROUND AND OBJECTIVES: Following the amendment of the Medical Licensure Act (ÄAppO) in 2012, pain medicine was introduced as a mandatory subject for students during undergraduate medical training. Medical schools were required to define and to implement adequate curricular and formal teaching structures based on interdisciplinary and multiprofessional requirements according to the curriculum for pain medicine of the German Pain Society. These aspects were considered in the new interdisciplinary curriculum for pain medicine, the so-called Mainz model. STUDY DESIGN AND METHODS: A new curriculum based on the Kern cycle was developed and implemented at the Medical Center of the Johannes Gutenberg University in Mainz. Different teaching methods (lectures, interprofessional tutorials and bedside coaching in small groups) were used to impart professional expertise in pain medicine to medical students in an interdisciplinary clinical context. RESULTS: The new curriculum was put into practice and evaluated starting from the winter semester 2014/2015. Before and after the first implementation, medical students were asked about the relevance of pain medicine and their perception of personal competence. CONCLUSION: The interdisciplinary course in pain medicine was successfully introduced into the degree program based on the curriculum of the German Pain Society and the Kern cycle. With educational support, interdepartmental and multiprofessional collaboration the process of implementation of new interdisciplinary courses can be facilitated. In the future, the question how to increase the amount of practical lessons without increasing the load on teaching resources has to be resolved. Blended learning modules, such as a combination of E­learning and practical lessons are currently being studied in smaller cohorts.

[Simulation-based training and OR apprenticeship for medical students : A prospective, randomized, single-blind study of clinical skills]. / Simulationsbasiertes Training und Lehre im OP für Studierende : Eine prospektive randomisierte, einfach verblindete Studie klinischer Fertigkeiten.

BACKGROUND: Simulation-based training (SBT) has developed into an established method of medical training. Studies focusing on the education of medical students have used simulation as an evaluation tool for defined skills. A small number of studies provide evidence that SBT improves medical students' skills in the clinical setting. Moreover, they were strictly limited to a few areas, such as the diagnosis of heart murmurs or the correct application of cricoid pressure. Other studies could not prove adequate transferability from the skills gained in SBT to the patient site. Whether SBT has an effect on medical students' skills in anesthesiology in the clinical setting is controversial. To explore this issue, we designed a prospective, randomized, single-blind trial that was integrated into the undergraduate anesthesiology curriculum of our department during the second year of the clinical phase of medical school. OBJECTIVES: This study intended to explore the effect of SBT on medical students within the mandatory undergraduate anesthesiology curriculum of our department in the operating room with respect to basic skills in anesthesiology. MATERIALS AND METHODS: After obtaining ethical approval, the participating students of the third clinical semester were randomized into two groups: the SIM-OR group was trained by a 225 min long SBT in basic skills in anesthesiology before attending the operating room (OR) apprenticeship. The OR-SIM group was trained after the operating room apprenticeship by SBT. During SBT the students were trained in five clinical skills detailed below. Further, two clinical scenarios were simulated using a full-scale simulator. The students had to prepare the patient and perform induction of anesthesia, including bag-mask ventilation after induction in scenario 1 and rapid sequence induction in scenario 2. Using the five-point Likert scale, five defined skills were evaluated at defined time points during the study period. 1) application of the safety checklist, 2) application of basic patient monitoring, 3) establishment of intravenous access, 4) bag-and-mask ventilation, and 5) adjustment of ventilatory parameters after the patients' airways were secured. A cumulative score of 5 points was defined as the best and a cumulative score of 25 as the worst rating for a defined time point. The primary endpoint was the cumulative score after day 1 in the operating room apprenticeship and the difference in cumulative scores from days 1 to 4. Our hypothesis was that the SIM-OR group would achieve a better score after day 1 in the operating room apprenticeship and would gain a larger increase in score from day 1 to day 4 than the OR-SIM group. RESULTS: 73 students were allocated to the OR-SIM group and 70 students to the SIM-OR group. There was no significant difference between the two groups after day 1 of the operating room apprenticeship and no difference in increase of the cumulative score from day 1 to day 4 (median of cumulative score on day 1: 'SIM-OR' 11.2 points vs. 'OR-SIM' 14.6 points; p = 0.067; median of difference from day 1 to day 4: 'SIM-OR' -3.7 vs. 'OR-SIM' -6.4; p = 0.110). CONCLUSION: With the methods applied, this study could not prove that 225 min of SBT before the operating room apprenticeship increased the medical students' clinical skills as evaluated in the operating room. Secondary endpoints indicate that medical students have better clinical skills at the end of the entire curriculum when they have been trained through SBT before the operating room apprenticeship. However, the authors believe that simulator training has a positive impact on students' acquisition of procedural and patient safety skills, even if the methods applied in this study may not mirror this aspect sufficiently.

16p11.2 Locus modulates response to satiety before the onset of obesity.

BACKGROUND: The 600 kb BP4-BP5 copy number variants (CNVs) at the 16p11.2 locus have been associated with a range of neurodevelopmental conditions including autism spectrum disorders and schizophrenia. The number of genomic copies in this region is inversely correlated with body mass index (BMI): the deletion is associated with a highly penetrant form of obesity (present in 50% of carriers by the age of 7 years and in 70% of adults), and the duplication with being underweight. Mechanisms underlying this energy imbalance remain unknown. OBJECTIVE: This study aims to investigate eating behavior, cognitive traits and their relationships with BMI in carriers of 16p11.2 CNVs. METHODS: We assessed individuals carrying a 16p11.2 deletion or duplication and their intrafamilial controls using food-related behavior questionnaires and cognitive measures. We also compared these carriers with cohorts of individuals presenting with obesity, binge eating disorder or bulimia. RESULTS: Response to satiety is gene dosage-dependent in pediatric CNV carriers. Altered satiety response is present in young deletion carriers before the onset of obesity. It remains altered in adolescent carriers and correlates with obesity. Adult deletion carriers exhibit eating behavior similar to that seen in a cohort of obesity without eating disorders such as bulimia or binge eating. None of the cognitive measures are associated with eating behavior or BMI. CONCLUSIONS: These findings suggest that abnormal satiety response is a strong contributor to the energy imbalance in 16p11.2 CNV carriers, and, akin to other genetic forms of obesity, altered satiety responsiveness in children precedes the increase in BMI observed later in adolescence.

[Tension pneumomediastinum and tension pneumothorax following tracheal perforation during cardiopulmonary resuscitation]. / Spannungspneumomediastinum und -pneumothorax nach Trachealperforation während Reanimation.

Tension pneumothorax can occur at any time during cardiopulmonary resuscitation (CPR) with external cardiac massage and invasive ventilation either from primary or iatrogenic rib fractures with concomitant pleural or parenchymal injury. Airway injury can also cause tension pneumothorax during CPR. This article presents the case of a 41-year-old woman who suffered cardiopulmonary arrest after undergoing elective mandibular surgery. During CPR the upper airway could not be secured by orotracheal intubation due to massive craniofacial soft tissue swelling. A surgical airway was established with obviously unrecognized iatrogenic tracheal perforation and subsequent development of tension pneumomediastinum and tension pneumothorax during ventilation. Neither the tension pneumomediastinum nor the tension pneumothorax were decompressed and accordingly resuscitation efforts remained unsuccessful. This case illustrates the need for a structured approach to resuscitate patients with ventilation problems regarding decompression of tension pneumomediastinum and/or tension pneumothorax during CPR.

[Models of communication to integrate early palliative care in thoracic oncology]. / Kommunikationsmodell zur frühen Integration der Palliativmedizin in der thorakalen Onkologie.

The recent development in optimising palliative care standards in thoracic oncology is associated with an increased demand in specialized communication skills. Standardised and integrated assessments of the palliative care need of the patient is met by limited health care resources. The model of communication described in this article emphasizes the need to structure palliative distress assessment of the patient. Communication pathways are shown as a platform to evaluate and support patient and caregivers. Standards to establish algorithms of communication in palliative care will improve the very important interaction between patient and caregivers.

Detection of respiratory viruses and Bordetella bronchiseptica in dogs with acute respiratory tract infections.

Canine infectious respiratory disease (CIRD) is an acute, highly contagious disease complex caused by a variety of infectious agents. At present, the role of viral and bacterial components as primary or secondary pathogens in CIRD is not fully understood. The aim of this study was to investigate the prevalence of canine parainfluenza virus (CPIV), canine adenovirus type 2 (CAV-2), canine influenza virus (CIV), canine respiratory coronavirus (CRCoV), canine herpes virus-1 (CHV-1), canine distemper virus (CDV) and Bordetella bronchiseptica in dogs with CIRD and to compare the data with findings in healthy dogs. Sixty-one dogs with CIRD and 90 clinically healthy dogs from Southern Germany were prospectively enrolled in this study. Nasal and pharyngeal swabs were collected from all dogs and were analysed for CPIV, CAV-2, CIV, CRCoV, CHV-1, CDV, and B. bronchiseptica by real-time PCR. In dogs with acute respiratory signs, 37.7% tested positive for CPIV, 9.8% for CRCoV and 78.7% for B. bronchiseptica. Co-infections with more than one agent were detected in 47.9% of B. bronchiseptica-positive, 82.6% of CPIV-positive, and 100% of CRCoV-positive dogs. In clinically healthy dogs, 1.1% tested positive for CAV-2, 7.8% for CPIV and 45.6% for B. bronchiseptica. CPIV and B. bronchiseptica were detected significantly more often in dogs with CIRD than in clinically healthy dogs (P < 0.001 for each pathogen) and were the most common infectious agents in dogs with CIRD in Southern Germany. Mixed infections with several pathogens were common. In conclusion, clinically healthy dogs can carry respiratory pathogens and could act as sources of infection for susceptible dogs.

[Malignant pleural mesothelioma: new aspects of medical therapy]. / Neue Aspekte der medikamentösen Therapie des malignen Pleuramesothelioms.

Malignant pleural mesothelioma, a typical long-term consequence of exposure to asbestos, represents a therapeutic challenge. In the early stages of the disease, trimodal therapy combining surgery, radiation and chemotherapy is used as standard care. In advanced stages, the combination of cisplatin and pemetrexed has been approved as first-line therapy, but there is a lack of randomised controlled drug trials for second-line treatment. Monotherapy with pemetrexed, vinorelbine or gemcitabine may provide some survival benefit compared to treatment aiming at symptom control only. Immunotherapy seems to be a promising new concept. The so-called frustrated phagocytosis, with continuing antigen presentation leading to persisting local inflammation and antigen tolerance, can be interrupted by blocking the T-cell surface protein CTLA-4. The monoclonal antibodies ipilimumab and tremelimumab that block CTLA-4 can stimulate immune response and thus increase the number of tumor-infiltrating lymphocytes. Clinical studies exploring this avenue of treatment are being awaited with great excitement.

Phase I study of weekly nab-paclitaxel + weekly cetuximab + intensity-modulated radiation therapy (IMRT) in patients with stage III-IVB head and neck squamous cell carcinoma (HNSCC).

BACKGROUND: There is a clinical need to improve the efficacy of standard cetuximab + concurrent intensity-modulated radiation therapy (IMRT) for patients with locally and/or regionally advanced HNSCC. Taxanes have radiosensitizing activity against HNSCC, and nab-paclitaxel may offer therapeutic advantage in comparison with other taxanes. PATIENTS AND METHODS: This was a single-institution phase I study with a modified 3 + 3 design. Four dose levels (DLs) of weekly nab-paclitaxel were explored (30, 45, 60, and 80 mg/m(2)), given with standard weekly cetuximab (450 mg/m(2) loading dose followed by 250 mg/m(2) weekly) and concurrent IMRT (total dose, 70 Gy). RESULTS: Twenty-five eligible patients (20 M, 5 F) enrolled, with median age 58 years (range, 46-84 years). Primary tumor sites were oropharynx, 19 (10 human papillomavirus [HPV] pos, 8 HPV neg, 1 not done); neck node with unknown primary, 2; larynx 2; and oral cavity and maxillary sinus, 1 each. Seven patients had received prior induction chemotherapy. Maximum tolerated dose (MTD) was exceeded at DL4 (nab-paclitaxel, 80 mg/m(2)) with three dose-limiting toxicities (DLTs) (grade 3 neuropathy, grade 3 dehydration, with grade 3 mucositis grade 3 anemia) among five assessable patients. There was only one DLT (grade 3 supraventricular tachycardia) among six patients at DL3 (nab-paclitaxel, 60 mg/m(2)), and this was deemed the MTD. Among 23 assessable patients, the most common ≥ g3 AEs were lymphopenia 100%, functional mucositis 65%, and pain in throat/oral cavity 52%. At a median follow-up of 33 months, 2-year failure-free survival (FFS) is 65% [95% confidence interval (CI) 42% to 81%] and 2-year overall survival (OS) is 91% (95% CI 69-97). CONCLUSION: The recommended phase II dose for nab-paclitaxel is 60 mg/m(2) weekly when given standard weekly cetuximab and concurrent IMRT. This regimen merits further study as a nonplatinum alternative to IMRT + cetuximab alone. CLINICALTRIALSGOV ID: NCT00736619.

Retinitis pigmentosa: rapid neurodegeneration is governed by slow cell death mechanisms.

For most neurodegenerative diseases the precise duration of an individual cell's death is unknown, which is an obstacle when counteractive measures are being considered. To address this, we used the rd1 mouse model for retinal neurodegeneration, characterized by phosphodiesterase-6 (PDE6) dysfunction and photoreceptor death triggered by high cyclic guanosine-mono-phosphate (cGMP) levels. Using cellular data on cGMP accumulation, cell death, and survival, we created mathematical models to simulate the temporal development of the degeneration. We validated model predictions using organotypic retinal explant cultures derived from wild-type animals and exposed to the selective PDE6 inhibitor zaprinast. Together, photoreceptor data and modeling for the first time delineated three major cell death phases in a complex neuronal tissue: (1) initiation, taking up to 36 h, (2) execution, lasting another 40 h, and finally (3) clearance, lasting about 7 h. Surprisingly, photoreceptor neurodegeneration was noticeably slower than necrosis or apoptosis, suggesting a different mechanism of death for these neurons.

[Interdisciplinary management of a large Legionella outbreak in Germany]. / Interdisziplinäres Management eines länderübergreifenden Legionellenausbruchs.

Between December 2009 and the end of January 2010, the largest hitherto known outbreak of Legionella in Germany took place in the cities of Ulm and Neu-Ulm. Of a total of 64 patients involved, 60 patients had to be hospitalized, and 5 patients died from the infection. This event was caused by a wet cooling tower of a large air conditioning system in the city center of Ulm. The search for the source of the Legionella emission was extremely difficult, since these plants are neither notifiable nor subject to authorization in Germany. We report about the search for the source and the measures to control the outbreak. We also discuss communication and coordination during these investigations. Regulatory measures as proposed by the World Health Organization (WHO) and the European Network for Legionellosis (EWGLI) and already implemented in numerous other European countries would be desirable to prevent such outbreaks in the future.

ReSTOR diffractive versus Array 2 zonal-progressive multifocal intraocular lens: a contralateral comparison.

PURPOSE: To evaluate near and distance visual performance after implantation of a diffractive multifocal intraocular lens (MIOL) (AcrySof ReSTOR) or a refractive MIOL (Array 2) in bilateral cataract surgery. METHODS: In this prospective, comparative trial, 18 patients with bilateral cataract were selected to have lens surgery with asymmetric MIOL implantation. Eighteen eyes received ReSTOR MIOL and the 18 fellow eyes were implanted with Array 2. Five months after second lens implantation, main postoperative outcomes were uncorrected and distance corrected near visual acuities (VA). Secondary outcomes were distance VA and near acuity with power add, contrast sensitivity with and without glare (Pelly-Robson Contrast Sensitivity Chart, CSV 1000 HGT). Quality of vision was measured by comparing the severity of visual symptoms as referred to a masked interviewer. RESULTS: Patients reported similar postoperative distance visual acuities for both eyes. ReSTORimplanted eyes showed better uncorrected and distance corrected near acuity than eyes with Array 2 (p=0.002 and p=0.003, respectively). Intermediate VA with distance correction was slightly higher with the Array 2 MIOL (p=0.058). No important difference was observed in contrast sensitivity, glare disability, and subjective rating of light sensations. Severe photic phenomena were reported only for one Array 2-implanted eye. CONCLUSIONS: The diffractive MIOL showed better uncorrected and distance corrected near VA. The refractive Array 2 MIOL had a tendency to better value for intermediate distance. Disturbing photic phenomena were observed only in one case with the Array 2 MIOL.

Spleen but not tumor infiltration by dendritic and T cells is increased by intravenous adenovirus-Flt3 ligand injection.

Dendritic cell (DC) expansion is regulated by the hematopoietic growth factor fms-like tyrosine kinase 3 ligand (Flt3L). DCs are critical to the control of tumor growth and metastasis, and there is a positive correlation between intratumoral DC infiltration and clinical outcome. In this report, we first demonstrate that single intravenous (i.v.) injections of adenovirus (Adv)-Flt3L significantly increased splenic dendritic, B, T and natural killer (NK) cell numbers in both normal and mammary tumor-bearing mice. In contrast, the numbers of DCs and T cells infiltrating the tumors were not increased. Consistent with the minimal effect on immune cell infiltration, i.v. Adv-Flt3L injections had no therapeutic activity against orthotopic mammary tumors. In addition, we noted tumor and Adv-Flt3L expansion of Gr1(+)CD11b(+) immature myeloid suppressor cells (IMSCs), which may inhibit the therapeutic efficacy of Adv-Flt3L-expanded DCs.

Epidemiological and health economical evaluation of intraoperative antibiosis as a protective agent against endophthalmitis after cataract surgery.

OBJECTIVE: To evaluate risk factors for endophthalmitis after cataract surgery and to retest recent findings on the protective effect of intraoperative antibiosis and the promoting effect of the clear corneal as compared to sclerocorneal incision. In addition, the economics of intraocular intraoperative antibiosis as a prophylaxis in cataract surgery are asketched. DESIGN: Survey study. PARTICIPANTS: Five hundred thirty-eight ophthalmosurgical centres in Germany. MAIN OUTCOME MEASURE: epidemiological evaluation: responder specific endophthalmitis incidence in year 2000; economical evaluation: direct cost analysis based on incidence data and local cost estimates (health service's perspective). RESULTS: A total of 310 (58%) questionnaires were computed resulting in an overall count of 404,356 cataract surgeries and 291 self-reported endophthalmitis cases (crude rate 0.072%). The risk of postoperative endophthalmitis for sclerocorneal versus clear corneal incisions was not significantly reduced (relative risk 0.97, 99% confidence interval 0.69-1.38). The hypothesis of a protective effect of intraocular antibiosis could be confirmed by a significantly decreased risk ratio of 0.69 (99% confidence interval 0.48-0.99) indicating a significant benefit from intraoperative intraocular antibiosis. A similar tendency was observed for an intraoperative periocular antibiosis with a significantly reduced risk ratio of 0.68 (99% confidence interval 0.49-0.96). These risk estimates had been adjusted for the size of the surgical centre: a significantly reduced risk ratio of 0.70 (99% confidence interval 0.49-0.98) for postoperative endophthalmitis was observed for local centres. Cost evaluation for the prophylactic use of intraocular intraoperative antibiosis in cataract surgery revealed an economically relevant decrease in direct endophthalmitis associated costs. CONCLUSIONS: Whereas this 2000 appraisal of a recent survey in 1996 could not reproduce the benefit of sclerocorneal incision, the protective effect of intraoperative intraocular antibiotic prophylaxis could be confirmed. However, the results of this survey have to be interpreted with care, since it is not based on individual case information, but rather on aggregate questionnaire data.