Atezolizumab With Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial.

Purpose: Combining standard of care (pertuzumab-trastuzumab [PH], chemotherapy) with cancer immunotherapy may potentiate antitumor immunity, cytotoxic activity, and patient outcomes in high-risk, human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We report the phase III IMpassion050 primary analysis of neoadjuvant atezolizumab, PH, and chemotherapy in these patients.

Methods: Patients with a primary tumor of > 2 cm and histologically confirmed, positive lymph node status (T2-4, N1-3, M0) were randomly assigned 1:1 to atezolizumab/placebo with dose-dense doxorubicin/cyclophosphamide, followed by paclitaxel, and PH.

Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Immunotherapy in combination with chemotherapy has shown promising efficacy across many different tumour types. We report the prespecified second interim overall survival analysis of the phase 3 IMpassion130 study assessing the efficacy and safety of atezolizumab plus nab-paclitaxel in patients with unresectable, locally advanced or metastatic triple-negative breast cancer.

Methods: In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 246 academic centres and community oncology practices in 41 countries, patients aged 18 years or older, with previously untreated, histologically documented, locally advanced or metastatic triple-negative breast cancer, and Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible.

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer.

Background: Unresectable locally advanced or metastatic triple-negative (hormone-receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)-paclitaxel may enhance the anticancer activity of atezolizumab.

Methods: In this phase 3 trial, we randomly assigned (in a 1:1 ratio) patients with untreated metastatic triple-negative breast cancer to receive atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel; patients continued the intervention until disease progression or an unacceptable level of toxic effects occurred.

Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial.

Background: Alectinib--a highly selective, CNS-active, ALK inhibitor-showed promising clinical activity in crizotinib-naive and crizotinib-resistant patients with ALK-rearranged (ALK-positive) non-small-cell lung cancer (NSCLC). We aimed to assess the safety and efficacy of alectinib in patients with ALK-positive NSCLC who progressed on previous crizotinib.

Methods: We did a phase 2 study at 27 centres in the USA and Canada.

Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial.

Background: The addition of bevacizumab to chemotherapy improves progression-free survival in metastatic breast cancer and pathological complete response rates in the neoadjuvant setting. Micrometastases are dependent on angiogenesis, suggesting that patients might benefit from anti-angiogenic strategies in the adjuvant setting. We therefore assessed the addition of bevacizumab to chemotherapy in the adjuvant setting for women with triple-negative breast cancer.

Diagnostic performance of the universal visual scoring system (UniViSS) on occlusal surfaces.

Aim of this investigation was to evaluate the validity and reproducibility of the universal visual scoring systems (UniViSS) on occlusal surfaces in vitro. The validity study included 65 third molars. Following to reach a UniViSS consensus diagnosis for each surface, all teeth were histologically prepared and evaluated according to the newly developed caries-extension-index (CE-index).

Safety and efficacy of SITAgliptin plus GRanulocyte-colony-stimulating factor in patients suffering from Acute Myocardial Infarction (SITAGRAMI-Trial)--rationale, design and first interim analysis.

Aims: Our pre-clinical studies demonstrated that G-CSF based stem cell mobilization in combination with genetic or pharmaceutical CD26/DPP-IV inhibition after acute myocardial infarction leads to improved cardiac homing of stem cells, enhanced heart function and increased survival. Thereupon, we initiated a phase III, multi-centre, randomised, placebo-controlled efficacy and safety study (n=100) analyzing the effect of combined application of G-CSF and Sitagliptin, which is a clinically admitted, anti-diabetic DPP-IV-inhibitor, after acute myocardial infarction ("SITAGRAMI-Trial"; EudraCT Number: 2007-003941-34).

Methods: The primary objective of the study is to assess myocardial regeneration by improved myocardial homing of mobilized stem cells, as measured by cardiac function using MRI analysis.

Epidemiology and quality control of 245 000 outpatient colonoscopies.

Introduction: Screening colonoscopy is an effective means for early detection of colorectal carcinoma. Any exhaustive evaluation of the method must take further factors into account: epidemiology of colorectal adenomas and carcinomas in the target population, acceptance by the patients, structure, process, and outcome quality, and health economics.

Methods: The internet-based colonoscopy database of the Bavarian Association of Statutory Health Insurance Physicians (ASHIP) for the year 2006 includes data on 86.

G-CSF in patients suffering from late revascularised ST elevation myocardial infarction: final 1-year-results of the G-CSF-STEMI Trial.

Aims: The aims of this trial were to investigate the effect of granulocyte colony-stimulating factor (G-CSF) on left-ventricular ejection fraction and event-free survival in patients suffering from sub-acute myocardial infarction (STEMI).

Methods: We enrolled 44 patients suffering from sub-acute STEMI with late revascularization achieved by percutaneous coronary intervention (PCI). Patients were randomized to receive either G-CSF (Filgrastim) at a dose of 10 μg/kg body weight/day subcutaneously or placebo.

Myofascial trigger points in children with tension-type headache: a new diagnostic and therapeutic option.

The goal of this pilot study was to evaluate the effect of a trigger point-specific physiotherapy on headache frequency, intensity, and duration in children with episodic or chronic tension-type headache. Patients were recruited from the special headache outpatient clinic. A total of 9 girls (mean age 13.

A semiparametric Bayesian proportional hazards model for interval censored data with frailty effects.

Background: Multivariate analysis of interval censored event data based on classical likelihood methods is notoriously cumbersome. Likelihood inference for models which additionally include random effects are not available at all. Developed algorithms bear problems for practical users like: matrix inversion, slow convergence, no assessment of statistical uncertainty.

Serum concentrations of cortisol, interleukin 6, leptin and adiponectin predict stress induced insulin resistance in acute inflammatory reactions.

Introduction: Inflammatory stimuli are causative for insulin resistance in obesity as well as in acute inflammatory reactions. Ongoing research has identified a variety of secreted proteins that are released from immune cells and adipocytes as mediators of insulin resistance; however, knowledge about their relevance for acute inflammatory insulin resistance remains limited. In this study we aimed for a clarification of the relevance of different insulin resistance mediating factors in an acute inflammatory situation.

Short-term effects of treatment-induced hormonal changes on cognitive function in breast cancer patients: results of a multicenter, prospective, longitudinal study.

Background: It is suspected that estrogen depletion resulting from treatment may contribute to cognitive compromise in patients with breast cancer. However, the evidence for estrogen effects on cognition is inconclusive, and the consequences of hormonal changes for cognitive function in patients with cancer rarely have been investigated. In this study, the authors investigated the effects of treatment-induced menopause and antiestrogen therapy with tamoxifen and aromatase inhibitors (AIs) on cognitive function.

Validity of temporomandibular disorder examination procedures for assessment of temporomandibular joint status.

Introduction: This hypothesis-generating study was performed to determine which items in the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and additional diagnostic tests have the best predictive accuracy for joint-related diagnoses.

Methods: One hundred forty-nine TMD patients and 43 symptom-free subjects were examined in clinical examinations and with magnetic resonance imaging (MRI). The importance of each variable of the clinical examination for correct joint-related diagnosis was assessed by using MRI diagnoses.

Abnormal motor cortex excitability in congenital stroke.

The aim of the present study was to investigate corticospinal and intracortical excitability in patients with congenital stroke. In adults, stroke sequelae reduce corticospinal excitability, as indicated by an elevated threshold for motor evoked potentials (MEP), and increase intracortical excitability, as indicated by reduced intracortical inhibition. Ten patients with pre- or perinatally acquired, unilateral cortico-subcortical infarctions in the middle cerebral artery territory were studied with single pulse transcranial magnetic stimulation (TMS) to measure motor threshold (MT) and with paired pulse TMS to study short interval intracortical inhibition (SICI) and intracortical facilitation (ICF).

Reproducibility of DIAGNOdent 2095 and DIAGNOdent Pen measurements: results from an in vitro study on occlusal sites.

The aim of this in vitro study was to investigate the intra- and interdevice reproducibility of the DIAGNOdent 2095 (DD2095) and the new DIAGNOdent Pen (DDPen) on non-cavitated occlusal caries sites. Altogether, 241 sites on 90 molars were inspected twice with both devices and by four examiners. The intra/interdevice reproducibilities were assessed by means of the intraclass correlation coefficient (ICC) as well as by the range of the 95% limits of agreement of Bland & Altman.

In vitro leakage associated with three root-filling techniques in large and extremely large root canals.

This study assessed the apical leakage of ultrasonically condensed root fillings in extremely large canals, compared to cold lateral condensation and thermoplastic compaction. Ninety single-rooted teeth were used. In 45 teeth canals were enlarged to size 70 (large).

Prediction of TMJ arthralgia according to clinical diagnosis and MRI findings.

Purpose: The aim of this study was to investigate the ability of clinical and magnetic resonance imaging (MRI) diagnoses to predict pain in the temporomandibular joint (TMJ).

Materials And Methods: One hundred forty-nine patients were examined by 2 calibrated examiners in strict accordance with the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). All patients who presented with a defined clinical RDC/TMD diagnosis were included and underwent bilateral coronal and sagittal MRI of the TMJ.

The vital threat of an upper gastrointestinal bleeding: Risk factor analysis of 121 consecutive patients.

Aim: To analyze the importance in predicting patients risk of mortality due to upper gastrointestinal (UGI) bleeding under today's therapeutic regimen.

Methods: From 1998 to 2001, 121 patients with the diagnosis of UGI bleeding were treated in our hospital. Based on the patients' data, a retrospective multivariate data analysis with initially more than 270 single factors was performed.

Conservative therapy in patients with anterior disc displacement without reduction using 2 common splints: a randomized clinical trial.

Purpose: We performed a comparative evaluation of different types of splint therapy for anterior disc displacement without reduction (ADDWR) of the temporomandibular joint.

Patients And Methods: Seventy-four patients agreed to participate (65 females and 9 males). All patients were examined using a clinical temporomandibular joint disorder examination protocol, including muscle palpation, mandibular range-of-motion measurement, and joint sound detection.

Impact of serum creatinine measurement error on dose adjustment in renal failure.

Background: Doses of renally eliminated drugs should be adjusted according to kidney function to prevent adverse drug events and cost. Dose adjustment can be based on serum creatinine level, subsequent creatinine clearance estimation, and dosage calculation with consideration of the renal elimination properties of the respective compound.

Objective: Our objective was to quantify the impact and relevance of serum creatinine measurement error on dose adjustment in renal failure.