Consensus for HER2 alterations testing in non-small-cell lung cancer.

Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. Its alterations, including mutation, amplification and overexpression, could result in oncogenic potential and have been detected in many cancers such as non-small-cell lung cancer (NSCLC). Such alterations are, in general, considered markers of poor prognosis. Anti-HER2 antibody-drug conjugates, e.g. trastuzumab deruxtecan (T-DXd, DS-8201) and disitamab vedotin (RC48), were recently approved for HER2-positive breast and gastric cancers. Meanwhile, several HER2-targeted drugs, such as T-DXd, neratinib, afatinib, poziotinib and pyrotinib, have been evaluated in patients with advanced NSCLC, with several of them demonstrating clinical benefit. Therefore, identifying HER2 alterations is pivotal for NSCLC patients to benefit from these targeted therapies. Recent guidelines on HER2 testing were developed for breast and gastric cancer, however, and have not been fully established for NSCLC. The expert group here reached a consensus on HER2 alteration testing in NSCLC with the focus on clinicopathologic characteristics, therapies, detection methods and diagnostic criteria for HER2-altered NSCLC patients. We hope this consensus could improve the clinical management of NSCLC patients with HER2 alterations.

NaPi2b expression in a large surgical Non-Small Cell Lung Cancer (NSCLC) cohort.

BACKGROUND: NaPi2b is a multi-transmembrane sodium-dependent phosphate transporter expressed at normal levels in several organs, including lung. High expression levels have been reported in various tumors including breast, thyroid, ovarian and non-small cell lung cancer. To date evaluation of NaPi2b expression has mostly been restricted to smaller lung cancer cohorts. METHODS: Analyses were performed on archival formalin fixed paraffin embedded primary tumor specimens from patients who had undergone curative intent resection at an Australian tertiary hospital. Tissue microarrays were constructed and stained with the chimeric anti-NaPi2b antibody, MERS67. Semi-quantitative H-scores (range 0 - 300) were calculated for each core tissue sample (H-score = % tumor cells staining for NaPi2b multiplied by staining intensity). An overall average H-score was reported for each specimen, with a cut-off score of 50 considered positive. RESULTS: Of 438 cases, high NaPi2b expression was observed in 151 (34.5%) overall, high expression in 137 of 208 (65.9%) adenocarcinoma cases, and 5 of 179 (2.8%) squamous cases (P < .0001). High NaPi2b expression was associated with female sex, EGFR or KRAS mutation, and TTF1 positivity (adenocarcinoma cases only). High NaPi2b expression was associated with improved overall survival (median 54 vs. 35 months, P = .029). CONCLUSION: High NaPi2b expression was noted in a significant subset of adenocarcinoma cases, and in particular amongst those who were TTF1+, or exhibited EGFR or KRAS mutations. This agrees with earlier reports and highlights the significance that NaPi2b may have a role as a possible target for delivery of cytotoxic agents via antibody-drug conjugate models for some patients with lung adenocarcinoma.

Whole-body [18F]-FDG-PET/MRI for staging of pediatric non-Hodgkin lymphoma: first results from a single-center evaluation.

AIM: In 2015, the revised International Pediatric Non-Hodgkin Lymphoma Staging System was published. It mentions [18F]-FDG-PET/MRI as the latest method to perform whole-body imaging. However, supporting data are pending. Our aim was to investigate the performance of whole-body [18F]-FDG-PET/MRI in pediatric non-Hodgkin lymphoma patients by using a limited number of MRI sequences. MATERIALS AND METHODS: Ten pediatric patients with histologically proven non-Hodgkin lymphoma underwent whole-body [18F]-FDG-PET/MRI at staging. The retrospective analysis included three steps: First, [18F]-FDG-PET and MR scans were evaluated separately by a nuclear medicine physician and a pediatric radiologist. Nineteen nodal and two extranodal regions as well as six organs were checked for involvement. Second, discrepant findings were reviewed together in order to reach consensus. Third, [18F]-FDG-PET/MRI findings were correlated with the results of other clinical investigations. RESULTS: Of the 190 lymph node regions evaluated, four were rated controversial. Consensus was reached by considering metabolic, functional and morphologic information combined. Concordantly, [18F]-FDG-PET and MRI detected Waldeyer's ring involvement in two patients whose Waldeyer's ring was negative on clinical assessment. In four patients MRI showed pleural effusion. However, in only two of them an increased glucose metabolism as a reliable sign of pleural involvement was detectable. In six patients [18F]-FDG-PET and MRI detected skeletal lesions although bone marrow biopsy was positive in only one of them. CONCLUSION: Despite the small number of cases evaluated, whole-body [18F]-FDG-PET turned out to be a valuable tool for staging of pediatric non-Hodgkin lymphoma.

[When emergency physician and tele-emergency physician save life together : A case description on the application of prehospital telemedicine for ventricular tachycardia with hemodynamic instability]. / Wenn Notarzt und Telenotarzt gemeinsam Leben retten : Eine Fallbeschreibung für die Anwendung der prähospitalen Telemedizin bei einer kreislaufinstabilen ventrikulären Tachykardie.

Telemedicine has already entered the rescue service in some regions of Germany. This case description is about a telemedical emergency physician case where an emergency doctor was also at the scene of the emergency. The patient had a life-threatening ventricular tachycardia and became hemodynamically unstable. The emergency physician was still inexperienced and overwhelmed by the complex situation. She decided to contact the tele-emergency medical services (tele-ems) and could then be instructed to perform intraosseous access, drug treatment and electrical cardioversion in the unstable patient. The cooperation with the tele-ems physician enabled the still inexperienced emergency physician to perform a guideline-compliant treatment and to transport the stabilized patient to the hospital in a timely manner.

[Differential diagnosis of cystic abdominal masses in children]. / Differenzialdiagnosen zystischer abdominaler Raumforderungen im Kindesalter.

BACKGROUND: Cystic abdominal masses are a common main or incidental finding in daily radiological practice; however, differentiation is not always trivial. OBJECTIVES: In children, cystic abdominal masses represent a special feature compared to adults, since the spectrum of congenital lesions must be taken into consideration. The article gives a structured overview of the most common entities. MATERIALS AND METHODS: The standard methods in abdominal imaging in pediatric radiology are ultrasound and MRI. Based on a literature review, the most important differential diagnoses with their characteristics in ultrasound and MRI were compiled. RESULTS AND DISCUSSION: With anatomical classification, presence or absence of solid components as well as the contrast agent behavior in the MRI, the cystic masses can be well differentiated and classified into three groups: congenital and acquired cysts as well as neoplasms.

European Society of Paediatric Radiology 2019 strategic research agenda: improving imaging for tomorrow's children.

The European Society of Paediatric Radiology (ESPR) research committee was established to initiate, drive forward and foster excellence in paediatric imaging, paediatric image-guided intervention and radiation protection research, by facilitating more evidence-based standards, protocols and multi-institutional collaborations. The ESPR Strategic Research Agenda outlines our current research approach, highlighting several areas of paediatric imaging where the society can help guide current and future research, and emphasizing those areas where early research ("seed") funding may need to be allocated by this and other societies as precursors to larger grant applications. The key aims are to evaluate normal variation in order to be able to confidently diagnose disease states, develop robust image-based classification systems to aid diagnosis and treatment monitoring, and help develop evidence-based clinical guidelines using current literature and experience to identify knowledge gaps. For this reason, the development of evidence-based imaging pipelines, broken down step-by-step to include diagnosis, classification and clinical effectiveness, should be the end goal for each disease entity for each affected child. Here, we outline the 2019 ESPR Strategic Research Agenda along three points in the clinical imaging pipeline: clinical referral, disease diagnosis and evolution, and clinical therapeutic evaluation and effectiveness. Through multicentre trials, using existing high-level experience and expertise, and nurturing the next generation of researchers, we will be able to achieve these aims.

HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib.

BACKGROUND: Effective targeted therapy for non-small-cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) mutations remains an unmet need. This study investigated the antitumor effect of an irreversible pan-HER receptor tyrosine kinase inhibitor, pyrotinib. PATIENTS AND METHODS: Using patient-derived organoids and xenografts established from an HER2-A775_G776YVMA-inserted advanced lung adenocarcinoma patient sample, we investigated the antitumor activity of pyrotinib. Preliminary safety and efficacy of pyrotinib in 15 HER2-mutant NSCLC patients in a phase II clinical trial are also presented. RESULTS: Pyrotinib showed significant growth inhibition of organoids relative to afatinib in vitro (P = 0.0038). In the PDX model, pyrotinib showed a superior antitumor effect than afatinib (P = 0.0471) and T-DM1 (P = 0.0138). Mice treated with pyrotinib displayed significant tumor burden reduction (mean tumor volume, -52.2%). In contrast, afatinib (25.4%) and T-DM1 (10.9%) showed no obvious reduction. Moreover, pyrotinib showed a robust ability to inhibit pHER2, pERK and pAkt. In the phase II cohort of 15 patients with HER2-mutant NSCLC, pyrotinib 400 mg resulted in a objective response rate of 53.3% and a median progression-free survival of 6.4 months. CONCLUSION: Pyrotinib showed activity against NSCLC with HER2 exon 20 mutations in both patient-derived organoids and a PDX model. In the clinical trial, pyrotinib showed promising efficacy. CLINICAL TRIAL REGISTRATION: NCT02535507.

Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer.

Background: Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs. Design: Randomized trials of EGFR-directed mAbs cetuximab and necitumumab in combination with chemotherapy, immunotherapy, or antiangiogenic therapy in patients with advanced NSCLC, including SqCLC, were searched in the literature. Results of associations of potential biomarkers and outcomes were summarized. Results: Data from phase III clinical trials indicate that patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein (H-score of ≥200) and/or gene copy numbers of EGFR (e.g. ≥40% cells with ≥4 EGFR copies as detected by fluorescence in situ hybridization; gene amplification in ≥10% of analyzed cells) derive greater therapeutic benefits from EGFR-directed mAbs. Biomarker data are limited for EGFR mAbs used in combination with immunotherapy and are absent when used in combination with antiangiogenic agents. Conclusions: Therapy with EGFR-directed mAbs in combination with chemotherapy is associated with greater clinical benefits in patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein and/or have increased EGFR gene copy number. These data support validating the role of these as biomarkers to identify those patients who derive the greatest clinical benefit from EGFR mAb therapy. However, data on biomarkers for EGFR-directed mAbs combined with immunotherapy or antiangiogenic agents remain limited.

Early Regression of Carotid Intima-Media Thickness after Bariatric Surgery and Its Relation to Serum Leptin Reduction.

PURPOSE: Bariatric surgery (BS) promotes carotid intima-media thickness (C-IMT) regression as early as 6 months post-surgery. To verify whether C-IMT regression occurs even earlier, we aimed at the effect of Roux-en-Y gastric bypass (RYGBP) and biliopancreatic diversion (BPD) on C-IMT 1-2 months and 12 months post-surgery. SUBJECTS/METHODS: Prospective trial. BS was performed on 109 patients either with (RYGBP = 42; BDP = 40) or without type 2 diabetes (RYGBP = 27). Healthy volunteers served as control group. FOLLOW-UP: baseline, 1-2 months, 12 months post-surgery. ENDPOINTS: changes (∆) in C-IMT, weight, body mass index, fat mass, waist and neck circumferences, blood pressure, HbA1c, glucose, insulin, insulin sensitivity [HOMA-IR; OGIS, from meal tolerance test], lipids, C-reactive protein, leptin, adiponectin, MCP-1. RESULTS: All surgery subgroups had similar levels of ∆-C-IMT. C-IMT in the pooled surgery group reduced from [mean (95% confidence interval)] 0.81 (0.77-0.84) mm to 0.66 (0.63-0.69) mm, p < 0.001 [-17.1 (-20.4 to -13.8)%] at 1-2 months, and to 0.63 (0.59-0.66) mm, p < 0.001 [-21.8 (-25.3 to -18.4)%] at 12 months post-surgery. ∆-C-IMT 1-2 months and 12 months post-surgery correlated to baseline C-IMT, and with ∆-leptin at 1-2 months, but not at 12 months post-surgery. In linear regression analysis, ∆-leptin and baseline C-IMT were predictors of ∆-C-IMT 1-2 months post-surgery. CONCLUSIONS: A remarkable C-IMT regression occurred as early as 1-2 months after BS in obese patients either with or without type 2 diabetes, which was associated to the early reduction in leptin, (at least partially) independent of weight loss. Whether this is a causative or correlative association needs further investigation.

[Consensus-Based Guidelines for Diagnosis, Prevention and Treatment of Tuberculosis in Children and Adolescents - A Guideline on Behalf of the German Society for Pediatric Infectious Diseases (DGPI)]. / S2k-Leitlinie zur Diagnostik, Prävention und Therapie der Tuberkulose im Kindes- und Jugendalter.

Recently, epidemiological data shows an increase of childhood tuberculosis in Germany. In addition to this, drug resistant tuberculosis becomes more frequent. Therefore, diagnosis, prevention and therapy in childhood and adolescence remain a challenge. Adult guidelines do not work for children, as there are age specific differences in manifestation, risk of progression and diagnostic as well as therapeutic pathways.The German Society for Pediatric Infectious Diseases (DGPI) has initiated a consensus-based (S2k) process and completed a paediatric guideline in order to improve and standardize care for children and adolescents with tuberculosis exposure, infection or disease.Updated dosage recommendations take age dependant pharmacokinetics in the treatment of drug sensitive but also drug resistant tuberculosis in account. In addition to this, there is a detailed chapter on perinatal exposure and disease as well as extrapulmonary manifestations.

Products of the Propargyl Self-Reaction at High Temperatures Investigated by IR/UV Ion Dip Spectroscopy.

The propargyl radical is considered to be of key importance in the formation of the first aromatic ring in combustion processes. Here we study the bimolecular (self-) reactions of propargyl in a high-temperature pyrolysis flow reactor. The aromatic reaction products are identified by IR/UV ion dip spectroscopy, using the free electron laser FELIX as mid-infrared source. This technique combines mass selectivity with structural sensitivity. We identified several aromatic reaction products based on their infrared spectra, among them benzene, naphthalene, phenanthrene, indene, biphenyl, and surprisingly a number of aromatic compounds with acetylenic (ethynyl) side chains. The observation of benzene confirms that propargyl is involved in the formation of the first aromatic ring. The observation of compounds with acetylenic side chains shows that, in addition to a propargyl- and phenyl-based mechanism, the HACA (hydrogen abstraction C2H2 addition) mechanism of polycyclic aromatic hydrocarbons formation is present, although no acetylene was used as a reactant. On the basis of the experimental results we suggest a mechanism that connects the two pathways.

Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin plus necitumumab versus gemcitabine-cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer.

BACKGROUND: SQUIRE demonstrated addition of necitumumab to gemcitabine and cisplatin significantly improved survival in patients with stage IV sq-NSCLC. Here, we report additional outcomes for the subpopulation of patients with tumor epidermal growth factor receptor (EGFR) protein expression. PATIENTS AND METHODS: Patients with pathologically confirmed stage IV sq-NSCLC were randomized 1:1 to receive a maximum of six 3-week cycles of gemcitabine (1250 mg/m(2) i.v., days 1 and 8) and cisplatin (75 mg/m(2) i.v., day 1) chemotherapy with or without necitumumab (800 mg i.v., days 1 and 8). Patients in the chemotherapy plus necitumumab group with no progression continued on necitumumab alone until disease progression or intolerable toxicity. SQUIRE included mandatory tissue collection. EGFR protein expression was detected by immunohistochemistry (IHC) in a central laboratory. Exploratory analyses were pre-specified for patients with EGFR protein expressing (EGFR > 0) and non-expressing (EGFR = 0) tumors. RESULTS: A total of 982 patients [90% of intention-to-treat (ITT)] had evaluable IHC results. The large majority of these patients (95%) had tumor samples expressing EGFR protein; only 5% had tumors without detectable EGFR protein. Overall survival (OS) for EGFR > 0 patients was significantly longer in the necitumumab plus gemcitabine-cisplatin group than in the gemcitabine-cisplatin group {stratified hazard ratio (HR) 0.79 [95% confidence interval (CI) 0.69, 0.92; P = 0.002]; median 11.7 months (95% CI 10.7, 12.9) versus 10.0 months (8.9, 11.4)}. Additionally, an OS benefit was seen in all pre-specified subgroups in EGFR > 0 patients. However, OS HR for EGFR = 0 was 1.52. Adverse events of interest with the largest difference between treatment groups in EGFR > 0 patients (Grade ≥3) were hypomagnesemia (10% versus <1%) and skin rash (6% versus <1%). CONCLUSIONS: In line with SQUIRE ITT, addition of necitumumab to gemcitabine-cisplatin significantly prolonged OS and was generally well tolerated in the subpopulation of patients with EGFR-expressing advanced sq-NSCLC. The benefit from addition of necitumumab to chemotherapy was not apparent in this analysis for the small subgroup of patients with non-EGFR-expressing tumors. CLINICAL TRIAL: NCT00981058.

[Accident or maltreatment? Radiographic X­ray patterns in non­accidental trauma : The concept of sentinel injuries]. / Unfall oder Misshandlung? Radiologische Befunde beim nichtakzidentiellen Trauma : Das Konzept der "sentinel injuries".

The focus of this review article is on child abuse and the radiographic pattern of X­ray findings. The radiologist should be able to recognize typical injuries resulting from child abuse. In some cases the findings are highly specific for abuse and these include metaphyseal corner fractures of the long bones in children aged up to 24 months. In other cases the fractures are not specific but highly indicative of child abuse: rib fractures, for example can be associated with child abuse in more than 50 % of the cases; however, maltreatment is difficult to diagnose without taking the entire pattern of skeletal findings into consideration so that a radiological screening of the entire skeleton is often necessary. The concept of sentinel injuries might be helpful for deciding in which cases a complete skeletal screening should be performed. In the age group up to 24 months old a complete skeletal status (with some exceptions) is recommended if one of the three sentinel injuries of rib fractures, intracranial bleeding and abdominal trauma is present.

Analgesia by telemedically supported paramedics compared with physician-administered analgesia: A prospective, interventional, multicentre trial.

BACKGROUND: In German emergency medical services (EMS), the analgesia is restricted to physicians. In this prospective, interventional, multicentre trial, complications with and quality of telemedically delegated analgesia were evaluated. METHODS: If prehospital analgesia was necessary, five telemedically equipped paramedic ambulances from four different districts could consult a telemedicine centre. Analgesics were delegated based on a predefined algorithm. Telemedically assisted cases were compared with local historical regular EMS missions using matched pairs. The primary outcome was the frequency of therapeutic complications (respiratory/circulatory insufficiency, allergic reactions). Secondary outcomes were quality of analgesia (11-point numerical rating scale, NRS) and the frequency of nausea/vomiting. RESULTS: Analgesia was necessary in 106 telemedically assisted missions. In 23 cases, the telemedical procedure was used until an EMS physician arrived. Of the remaining 83 cases, 80 could be matched to comparable controls. Complications did not occur in either the study group or the control group (0 vs. 0; p = N/A). Complete NRS documentation was noted in 65/80 (study group) and 32/80 (control group) cases (p < 0.0001). Adequate initial pain reduction (quality indicator: reduction of NRS ≥ 2 points or NRS < 5 at end of mission) occurred in 61/65 versus 31/32 cases (p = 1.0); NRS reduction during mission was 3.78 ± 2.0 versus 4.38 ± 2.2 points (p = 0.0159). Nausea and vomiting occurred with equal frequency in both groups. CONCLUSIONS: Telemedical delegation of analgesics to paramedics was safe and led to a pain reduction superior to the published minimum standard in both groups. The documentation quality was better in the telemedicine group. WHAT DOES THIS STUDY ADD?: Little is known about the safety and quality of prehospital analgesia carried out by emergency medical services (EMS). Beside potential quality problems, in some countries meaningful pain reduction is limited by legal regulations that allow only physicians to administer analgesics. This first multicentre prospective trial for telemedically delegated analgesia demonstrates that remote analgesia is possible and safe and retains equivalent analgesic quality compared with that administered by onsite EMS physicians.

Striated Nephrogram as an Incidental Finding in MRI Examination of Children.

PURPOSE: A highly striated contrast pattern of the kidneys occasionally appears in abdominal MRI examinations of children following the administration of gadolinium. As this phenomenon is well known but has not yet been explicitly described in literature, we investigated how frequently and in which clinical context this occurred. MATERIAL AND METHODS: 855 abdominal MRI examinations with contrast media of 362 children between 2006 and 2014 were analysed retrospectively. RESULTS: A striated renal parenchyma was found in a total of nine children and eleven examinations (1.3 % of examinations) and did only occur at a field strength of 3 Tesla. Of these children, seven had previously had tumors and chemotherapy. In two children there was no evidence of a previously serious condition with medications or a kidney disease. All of them had a normal renal function. CONCLUSION: A noticeably striated nephrogram in the later phase of an MRI examination following administration of gadolinium may appear as an incidental finding in examinations at 3 Tesla without pathological relevance. KEY POINTS: • striated nephrograms may appear at a field strength of 3 Tesla. • incidental finding without pathological relevance.

[Potential and effectiveness of a telemedical rescue assistance system. Prospective observational study on implementation in emergency medicine]. / Potenzial und Wirksamkeit eines telemedizinischen Rettungsassistenzsystems: Prospektive observationelle Studie zum Einsatz in der Notfallmedizin.

BACKGROUND: The demographic change and an increasing multimorbidity of patients represent increasing challenges for the adequate prehospital treatment of emergency patients. The incorporation of supplementary telemedical concepts and systems can lead to an improved guideline-conform treatment. Beneficial evidence of telemedical procedures is only known for isolated disease patterns; however, no mobile telemedical concept exists which is suitable for use in the wide variety of different clinical situations. AIM: This article presents a newly developed and evaluated total telemedical concept (TemRas) that encompasses organizational, medical and technical components. The use of intelligent and robust communication technology and the implementation of this add-on system allows the telemedical support of the rescue service for all emergencies. METHODS: After development of the telemedical rescue assistance system, which includes organizational, medical and technical components, a telemedical centre and six ambulances in five different districts in North-Rhine Westphalia were equipped with this new tool. During the evaluation phase of 1 year in the routine emergency medical service the rate of complications as well as differences between urban and rural areas were analyzed with respect to different target parameters. RESULTS: Between August 2012 and July 2013 a total of 401 teleconsultations were performed during emergency missions and 24 during secondary interhospital transfers. No complications due to teleconsultation were observed. The mean duration (±SD) of teleconsultations was longer in rural areas than in urban areas with 28.6±12.0 min vs. 25.5±11.1 min (p < 0.0001). In 63.2% of these missions administration of medications was delegated to the ambulance personnel (52.0% urban vs. 73.6% rural, p < 0.0001). The severity of ailments corresponded to scores of III and VI in the National Advisory Committee for Aeronautics (NACA) classification. CONCLUSION: Emergency medical care of patients with support by a telemedical system is technically feasible, safe for the patient and allows medical treatment independent of spatial availability of a physician in different emergency situations.

[Sensitivity and Specificity of the Nerve Fibre Imaging Using Scanning Laser Ophthalmoscopy and of Optic Nerve Analysis Using Heidelberg Retina Tomography in Glaucoma]. / Sensitivität und Spezifität der Nervenfaserdarstellung mittels Scanning-Laser-Ophthalmoskop und der quantitativen Sehnervenanalyse bei Glaukom.

PURPOSE: Imaging of the optic nerve head and the nerve fibre layer are used in the diagnosis of glaucoma. We have investigated the diagnostic precision of nerve fibre layer imaging using a manually operated scanning laser ophthalmoscope and analysis of the optic nerve head using the Heidelberg Retina Tomograph II (HRT). PATIENTS AND METHODS: 42 patients with glaucoma, 16 patients with ocular hypertension (OHT) and 24 healthy control subjects were included in a clinical study. Nerve fibre layer imaging was performed using a scanning laser ophthalmoscope (SLO, Rodenstock Instr. argon laser 488 nm). Nerve fibre layer defects were analysed peripapillarily for every single degree (defect or no defect) at 1.7 mm (near) and at 3.4 mm (far) distance to the optic nerve head. Specificity and sensitivity of the HRT II were calculated using the Moorfields regression analysis (MRA). RESULTS: Patients with glaucoma were found to have 109 ± 92° (near) and 109 ± 92° (far) defects of the nerve fibre layer. Patients with OHT (8 ± 14° [far] and 6 ± 11° [near]) and control subjects (0 ± 0° [far] and 0 ± 1° [near]) showed significantly smaller defects (p < 0.0001). Sensitivity at > 90 % specificity for POAG and controls was 85.7 % (far) and 82.9 % (near). Sensitivity at > 90 % specifity for OHT and POAG was 85.7 % (far) und 82.9 % (near). Specificity of controls for the MRA was 83.3 % (borderline classified as normal). Specificity of OHT patients was 93.8 % (borderline classified normal). Sensitivity of the MRA for POAG was 80.9 % (borderline classified normal) and 90.5 % (borderline classified glaucoma). CONCLUSIONS: Nerve fiber layer imaging using a manually operated scanning laser ophthalmoscope was found to achieve a higher diagnostic precision as compared to optic disc evaluation using the HRT II.

Innovative Clinical Trials: The LUNG-MAP Study.

Although the proportion of patients with squamous cell carcinoma of the lung has declined over the last two decades, the disease is still fatal for tens of thousands of patients each year. The treatment of non-small cell lung cancer has advanced rapidly over the past decade, providing novel, targeted therapeutic options to patients, but has mostly been limited to the adenocarcinoma histology. Efforts are currently underway to bring squamous cell carcinoma of the lung into this new era of targeted therapy. This article reviews the rationale and trial design for the "LUNG-MAP: S1400 Phase II/III Biomarker-Driven Master Protocol for Second Line Therapy of Squamous Cell Lung Cancer" study. This multi-institutional, multi-cooperative group trial aims to individualize treatment for patients with metastatic squamous cell carcinoma to one of five arms based on the genomic profile of the tumor. The goal of this clinical trial is to rapidly identify new active drugs and bring them as soon as possible through a registration process for patients with squamous cell lung cancer by utilizing a novel trial design and involving all key stakeholders in drug development in a national effort. This could serve as a paradigm for drug development for malignancies with wide molecular heterogeneity.

Significance of MR angiography in the diagnosis of aberrant renal arteries as the cause of ureteropelvic junction obstruction in children.

PURPOSE: To determine the importance of MRI with contrast-enhanced MRA for the detection or exclusion of aberrant or obstructing renal arteries in ureteropelvic junction obstruction in children. MATERIALS AND METHODS: Key word-based search in RIS database (ureteropelvic junction obstruction/ MRI) and retrospective comparison of arterial findings from preoperative contrast -enhanced MRA and intra-operative inspection. From 2007 to 2013, 19 children with ureteropelvic junction obstruction underwent contrast-enhanced MRA. Based on the results of the MRI scan and MAG3 scintigraphy, the children were referred to surgery (Anderson-Hynes-pyeloplasty). RESULTS: An aberrant renal artery was diagnosed with MRI in 14 of 19 children, and intra-operative inspection confirmed 13 of those 14. In the remaining 5 children, no aberrant vessel could be observed in MRI and this was confirmed intra-operatively in 3 of the 5 cases, while in the remaining 2, an aberrant vessel was found. Of the 14 children with aberrant vessels, 12 underwent surgery due to assumed ureteral obstruction, which was confirmed by surgery in 11 cases. In one case, an aberrant artery was found intra-operatively, but obstruction could not be confirmed. In one of the 14 children, the vessel was found in MRI, but its obstructing character was negated via MRA, which was confirmed intra-operatively. In the diagnosis of aberrant and obstructing renal arteries, contrast-enhanced MRA presents 85% sensitivity and 80% specificity, with a positive predictive value of 0.8. CONCLUSION: MRI with contrast-enhanced MRA is suitable to detect aberrant and obstructing renal arteries. An obstructive effect of the aberrant vessel is to be assumed if the vessel has a close relationship to the ureteropelvic junction and if it is linearly stretched. KEY POINTS: • MRI with contrast-enhanced MRA is a sure method for the detection of aberrant renal arteries in children with ureteropelvic junction obstruction. • The obstructive effect of the aberrant vessel can be derived from the close proximity of the vessel to the ureteropelvic junction and from the streched course of the vessel.