Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331☆.

BACKGROUND: Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC. PATIENTS AND METHODS: CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS). RESULTS: Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%. CONCLUSION: Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.

Clinical value of assessing motor performance in postacute stroke patients.

BACKGROUND: Rehabilitative treatment plans after stroke are based on clinical examinations of functional capacity and patient-reported outcomes. Objective information about daily life performance is usually not available, but it may improve therapy personalization. OBJECTIVE: To show that sensor-derived information about daily life performance is clinically valuable for counseling and the planning of rehabilitation programs for individual stroke patients who live at home. Performance information is clinically valuable if it can be used as a decision aid for the therapeutic management or counseling of individual patients. METHODS: This was an observational, cross-sectional case series including 15 ambulatory stroke patients. Motor performance in daily life was assessed with body-worn inertial sensors attached to the wrists, shanks and trunk that estimated basic physical activity and various measures of walking and arm activity in daily life. Stroke severity, motor function and activity, and degree of independence were quantified clinically by standard assessments and patient-reported outcomes. Motor performance was recorded for an average of 5.03 ± 1.1 h on the same day as the clinical assessment. The clinical value of performance information is explored in a narrative style by considering individual patient performance and capacity information. RESULTS: The patients were aged 59.9 ± 9.8 years (mean ± SD), were 6.5 ± 7.2 years post stroke, and had a National Institutes of Health Stroke Score of 4.0 ± 2.6. Capacity and performance measures showed high variability. There were substantial discrepancies between performance and capacity measures in some patients. CONCLUSIONS: This case series shows that information about motor performance in daily life can be valuable for tailoring rehabilitative therapy plans and counseling according to the needs of individual stroke patients. Although the short recording time (average of 5.03 h) limited the scope of the conclusions, this study highlights the usefulness of objective measures of daily life performance for the planning of rehabilitative therapies. Further research is required to investigate whether information about performance in daily life leads to improved rehabilitative therapy results.

Embolization of tumor cells is rare in patients with systemic cancer and cerebral large vessel occlusion.

BACKGROUND AND PURPOSE: Stroke is a dreaded complication in patients with cancer. Besides paraneoplastic coagulopathy, chemotherapy, radiotherapy and tumor-directed invasive procedures, circulating cancer cells may contribute to thrombus formation and embolic stroke. However, the incidence of tumor cells within the blood clots of cancer patients with stroke is unknown and the role of circulating tumor cells in the formation of cerebrovascular thrombi remains unclear. METHODS: All patients who had undergone cerebrovascular thrombectomy at the University Hospital Zurich between 2014 and 2017 were screened for history of cancer. Clinical information was retrieved from the local stroke registry and the electronic charts and thrombi underwent a thorough histopathological re-review. RESULTS: Thirty-two of 182 patients (18%) with thrombectomy had a history of cancer. The majority of patients had advanced stage cancer. However, even after extensive histopathological re-review, only one specimen revealed tumor cells in the thrombus: a 75-year-old patient with acute occlusion of the middle cerebral artery who had been diagnosed with non-small-cell lung cancer 8.1 months prior to stroke. CONCLUSIONS: The presence of cancer cells in clots from cerebrovascular thrombectomy, indicative of a direct involvement of circulating tumor cells in the causation of stroke, is rare.

Temporal course of gene expression during motor memory formation in primary motor cortex of rats.

Motor learning is associated with plastic reorganization of neural networks in primary motor cortex (M1) that depends on changes in gene expression. Here, we investigate the temporal profile of these changes during motor memory formation in response to a skilled reaching task in rats. mRNA-levels were measured 1h, 7h and 24h after the end of a training session using microarray technique. To assure learning specificity, trained animals were compared to a control group. In response to motor learning, genes are sequentially regulated with high time-point specificity and a shift from initial suppression to later activation. The majority of regulated genes can be linked to learning-related plasticity. In the gene-expression cascade following motor learning, three different steps can be defined: (1) an initial suppression of genes influencing gene transcription. (2) Expression of genes that support translation of mRNA in defined compartments. (3) Expression of genes that immediately mediates plastic changes. Gene expression peaks after 24h - this is a much slower time-course when compared to hippocampus-dependent learning, where peaks of gene-expression can be observed 6-12h after training ended.

Sympathetic activity and early mobilization in patients in intensive and intermediate care with severe brain injuries: a preliminary prospective randomized study.

BACKGROUND: Patients who experience severe brain injuries are at risk of secondary brain damage, because of delayed vasospasm and edema. Traditionally, many of these patients are kept on prolonged bed rest in order to maintain adequate cerebral blood flow, especially in the case of subarachnoid hemorrhage. On the other hand, prolonged bed rest carries important morbidity. There may be a clinical benefit in early mobilization and our hypothesis is that early gradual mobilization is safe in these patients. The aim of this study was to observe and quantify the changes in sympathetic activity, mainly related to stress, and blood pressure in gradual postural changes by the verticalization robot (Erigo®) and after training by a lower body ergometer (MOTOmed-letto®), after prolonged bed rest of minimum 7 days. METHODS: Thirty patients with severe neurological injuries were randomized into 3 groups with different protocols of mobilization: Standard, MOTOmed-letto® or Erigo® protocol. We measured plasma catecholamines, metanephrines and blood pressure before, during and after mobilization. RESULTS: Blood pressure does not show any significant difference between the 3 groups. The analysis of the catecholamines suggests a significant increase in catecholamine production during Standard mobilization with physiotherapists and with MOTOmed-letto® and no changes with Erigo®. CONCLUSIONS: This preliminary prospective randomized study shows that the mobilization of patients with severe brain injuries by means of Erigo® does not increase the production of catecholamines. It means that Erigo® is a well-tolerated method of mobilization and can be considered a safe system of early mobilization of these patients. Further studies are required to validate our conclusions. TRIAL REGISTRATION: The study was registered in the ISRCTN registry with the trial registration number ISRCTN56402432 . Date of registration: 08.03.2016. Retrospectively registered.

Biphasic plasticity of dendritic fields in layer V motor neurons in response to motor learning.

Motor learning is associated with plastic reorganization of neural networks in primary motor cortex (M1) that advances through stages. An initial increment in spine formation is followed by pruning and maturation one week after training ended. A similar biphasic course was described for the size of the forelimb representation in M1. This study investigates the evolution of the dendritic architecture in response to motor skill training using Golgy-Cox silver impregnation in rat M1. After learning of a unilateral forelimb-reaching task to plateau performance, an increase in dendritic length of layer V pyramidal neurons (i.e. motor neurons) was observed that peaked one month after training ended. This increment in dendritic length reflected an expansion of the distal dendritic compartment. After one month dendritic arborization shrinks even though animals retain task performance. This pattern of evolution was observed for apical and basal dendrites alike - although the increase in dendritic length occurs faster in basal than in apical dendrites. Dendritic plasticity in response to motor training follows a biphasic course with initial expansion and subsequent shrinkage. This evolution takes fourth as long as the biphasic reorganization of spines or motor representations.

[Prevalence of erosive esophagitis and peptic esophageal strictures].

Gastroesophageal reflux disease is a widespread among population in economically developed countries including Russia. It was analyzed the results of 34 903 endoscopic examinations of upper gastrointestinal tract in ethnically and socially homogeneous population of Leningrad region with symptoms of gastric dispepsia. Procedures were performed for the period 2007-2013. Prevalence of erosive esophagitis was 4.9%. Peptic esophageal strictures due to chronic reflux-associated inflammation were revealed in 0.2% of examined patients (3.7% of patients with erosive esophagitis). Obtained data allow to considergastroesophageal reflux disease as a socially significant problem in Russia requiring close attention and further study.

[Prevalence of esophageal syndromes of gastroesophageal reflux disease in population of Leningrad region (according to esophagogastroduodenoscopy findings)].

The article presents an analysis of 34.903 esophagoscopy results performed for population of Leningrad region at the period from 2007 to 2013. A prevalence of erosive esophagitis was 4.9%, peptic strictures--0.18%, columnar-celled metaplasias--1.43% and esophageal adenocarcinoma--0.645%. The data obtained showed a high prevalence of GERD-associated syndromes with injury of mucous coat of esophagus in the local population of Russians.

Upper limb movement quality measures: comparing IMUs and optical motion capture in stroke patients performing a drinking task.

Introduction: Clinical assessment of upper limb sensorimotor function post-stroke is often constrained by low sensitivity and limited information on movement quality. To address this gap, recent studies proposed a standardized instrumented drinking task, as a representative daily activity combining different components of functional arm use. Although kinematic movement quality measures for this task are well-established, and optical motion capture (OMC) has proven effective in their measurement, its clinical application remains limited. Inertial Measurement Units (IMUs) emerge as a promising low-cost and user-friendly alternative, yet their validity and clinical relevance compared to the gold standard OMC need investigation. Method: In this study, we conducted a measurement system comparison between IMUs and OMC, analyzing 15 established movement quality measures in 15 mild and moderate stroke patients performing the drinking task, using five IMUs placed on each wrist, upper arm, and trunk. Results: Our findings revealed strong agreement between the systems, with 12 out of 15 measures demonstrating clinical applicability, evidenced by Limits of Agreement (LoA) below the Minimum Clinically Important Differences (MCID) for each measure. Discussion: These results are promising, suggesting the clinical applicability of IMUs in quantifying movement quality for mildly and moderately impaired stroke patients performing the drinking task.

Real-time fMRI neurofeedback: progress and challenges.

In February of 2012, the first international conference on real time functional magnetic resonance imaging (rtfMRI) neurofeedback was held at the Swiss Federal Institute of Technology Zurich (ETHZ), Switzerland. This review summarizes progress in the field, introduces current debates, elucidates open questions, and offers viewpoints derived from the conference. The review offers perspectives on study design, scientific and clinical applications, rtfMRI learning mechanisms and future outlook.

Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial.

BACKGROUND: Ipilimumab, an anti-CTLA4 monoclonal antibody, demonstrated survival benefit in melanoma with immune-related (ir) adverse events (irAEs) managed by the protocol-defined guidelines. This phase 2 study evaluated ipilimumab+paclitaxel (Taxol)/carboplatin in extensive-disease-small-cell lung cancer (ED-SCLC). DESIGN: Patients (n=130) with chemotherapy-naïve ED-SCLC were randomized 1: 1: 1 to receive paclitaxel (175 mg/m2)/carboplatin (area under the curve=6) with either placebo (control) or ipilimumab 10 mg/kg in two alternative regimens, concurrent ipilimumab (ipilimumab+paclitaxel/carboplatin followed by placebo+paclitaxel/carboplatin) or phased ipilimumab (placebo+paclitaxel/carboplatin followed by ipilimumab+paclitaxel/carboplatin). Treatment was administered every 3 weeks for a maximum of 18 weeks (induction), followed by maintenance ipilimumab or placebo every 12 weeks. End points included progression-free survival (PFS), irPFS, best overall response rate (BORR); irBORR, overall survival (OS), and safety. RESULTS: Phased ipilimumab, but not concurrent ipilimumab, improved irPFS versus control [HR (hazard ratio)=0.64; P=0.03]. No improvement in PFS (HR=0.93; P=0.37) or OS (HR=0.75; P=0.13) occurred. Phased ipilimumab, concurrent ipilimumab and control, respectively, were associated with median irPFS of 6.4, 5.7 and 5.3 months; median PFS of 5.2, 3.9 and 5.2 months; median OS of 12.9, 9.1 and 9.9 months. Overall rates of grade 3/4 irAEs were 17, 21 and 9% for phased ipilimumab, concurrent ipilimumab and control, respectively. CONCLUSION: These results suggest further investigation of ipilimumab in ED-SCLC.

Anorectal malformations and pregnancy-related disorders: a registry-based case-control study in 17 European regions.

OBJECTIVE: To identify pregnancy-related risk factors for different manifestations of congenital anorectal malformations (ARMs). DESIGN: A population-based case-control study. SETTING: Seventeen EUROCAT (European Surveillance of Congenital Anomalies) registries, 1980-2008. POPULATION: The study population consisted of 1417 cases with ARM, including 648 cases of isolated ARM, 601 cases of ARM with additional congenital anomalies, and 168 cases of ARM-VACTERL (vertebral, anal, cardiac, tracheo-esophageal, renal, and limb defects), along with 13 371 controls with recognised syndromes or chromosomal abnormalities. METHODS: Multiple logistic regression analyses were used to calculate adjusted odds ratios (ORs) for potential risk factors for ARM, such as fertility treatment, multiple pregnancy, primiparity, maternal illnesses during pregnancy, and pregnancy-related complications. MAIN OUTCOME MEASURES: Adjusted ORs for pregnancy-related risk factors for ARM. RESULTS: The ARM cases were more likely to be firstborn than the controls (OR 1.6, 95% CI 1.4-1.8). Fertility treatment and being one of twins or triplets seemed to increase the risk of ARM in cases with additional congenital anomalies or VACTERL (ORs ranging from 1.6 to 2.5). Maternal fever during pregnancy and pre-eclampsia were only associated with ARM when additional congenital anomalies were present (OR 3.9, 95% CI 1.3-11.6; OR 3.4, 95% CI 1.6-7.1, respectively), whereas maternal epilepsy during pregnancy resulted in a five-fold elevated risk of all manifestations of ARM (OR 5.1, 95% CI 1.7-15.6). CONCLUSIONS: This large European study identified maternal epilepsy, fertility treatment, multiple pregnancy, primiparity, pre-eclampsia, and maternal fever during pregnancy as potential risk factors primarily for complex manifestations of ARM with additional congenital anomalies and VACTERL.

[Mesh hiatal closure in antirelux surgery].

The article analyzes the experience of application of polymeric (mesh) implants for hiatal closure in patients with gastroesophageal reflux disease (GERD). The authors showed the main principles of the choice of mesh implants and recommendations to their usage. Principal technical stages of surgery are described. It is noted, that the application of prostheses had the high efficiency and safety in antireflux surgery.

[The detection rate of the esophageaL GERD complications among residents of the Leningrad Region (according to the data of esophagogastroduodenoscopy tests)].

This article presents the analysis of 24384 endoscopic investigations of the upper gastrointestinal tract in population of Leningrad region with symptoms of dyspepsia during the period 2007-2011.The results revealed erosive esophagitis in 5.4%, peptic strictures of the esophagus--0.2%, the columnar-lining esophagus (Barrett's esophagus)--1.1%, and esophageal adenocarcinoma--0.045%. This data shows a high prevalence of esophageal complications of GERD in a local population of Russians.

Endovascular therapy outcome in isolated posterior cerebral artery occlusion strokes: A multicenter analysis of the Swiss Stroke Registry.

PURPOSE: There is little data on the safety and efficacy of endovascular treatment (EVT) in comparison with intravenous thrombolysis (IVT) in acute ischemic stroke due to isolated posterior cerebral artery occlusion (IPCAO). We aimed to investigate the functional and safety outcomes of stroke patients with acute IPCAO treated with EVT (with or without prior bridging IVT) compared to IVT alone. METHODS: We did a multicenter retrospective analysis of data from the Swiss Stroke Registry. The primary endpoint was overall functional outcome at 3 months in patients undergoing EVT alone or as part of bridging, compared with IVT alone (shift analysis). Safety endpoints were mortality and symptomatic intracranial hemorrhage. EVT and IVT patients were matched 1:1 using propensity scores. Differences in outcomes were examined using ordinal and logistic regression models. FINDINGS: Out of 17,968 patients, 268 met the inclusion criteria and 136 were matched by propensity scores. The overall functional outcome at 3 months was comparable between the two groups (EVT vs IVT as reference category: OR = 1.42 for higher mRS, 95% CI = 0.78-2.57, p = 0.254). The proportion of patients independent at 3 months was 63.2% in EVT and 72.1% in IVT (OR = 0.67, 95% CI = 0.32-1.37, p = 0.272). Symptomatic intracranial hemorrhages were overall rare and present only in the IVT group (IVT = 5.9% vs EVT = 0%). Mortality at 3 months was also similar between the two groups (IVT = 0% vs EVT = 1.5%). CONCLUSION: In this multicenter nested analysis, EVT and IVT in patients with acute ischemic stroke due to IPCAO were associated with similar overall good functional outcome and safety. Randomized studies are warranted.

[The combined treatment of peptic esophagus strictures in patients with gastro-esophageal reflux].

The clinical picture of peptic esophagus strictures in 16 patients with gastro-esophageal reflux was analyzed. The strategy of the combined treatment, including surgery, has been thoroughly substantiated. The method of endoscopic dysphagia elimination has been described. The possibilities and technical features of antireflux gastroesophageal reconstructions were analyzed. Early and long-term follow-up results were obtained and used in practical recommendations.

[Columnar-celled metaplasia and adenocarcinoma of the esophagus in inhabitants of the Leningrad oblast (by the data of esophagogastroduodenoscopy)].

The article presents an analysis of results of 24 384 endoscopic examinations of the upper gastrointestinal tract in population of the Leningrad oblast with symptoms of gastric dyspepsia during the period from 2007 to 2011. The detection of the columnar-celled metaplasia was 1.1%, adenocarcinoma of the esophagus--0.045%. Esophageal adenocarcinoma occurred in 3.95% of cases of the column-celled esophagus. Barrett's esophagus was revealed in males more often than in women (56.5% and 54.5% respectively). The peak incidence of esophageal adenocarcinoma in males was at the age from 46 to 60 years (36.4% of patients), in females--from 61 to 75 years (27.3% of patients). Intestinal metaplasia was detected in 72.7% of cases with esophageal adenocarcinoma: The diagnosis of long and short segment of column-celled esophagus revealed no significant difference in the development of esophageal adenocarcinoma.

Outcomes after reperfusion therapies in patients with ACA stroke: A multicenter cohort study from the EVATRISP collaboration.

BACKGROUND: Patients with stroke secondary to occlusions of the anterior cerebral artery (ACA) often have poor outcomes. The optimal acute therapeutic intervention for these patients remains unknown. METHODS: Patients with isolated ACA-stroke were identified from 10 centers participating in the EndoVascular treatment And ThRombolysis in Ischemic Stroke Patients (EVATRISP) prospective registry. Patients treated with endovascular thrombectomy (EVT) were compared to those treated with intravenous thrombolysis (IVT). Odds ratios with 95% confidence intervals (OR; 95%CI) were calculated using multivariate regression analysis. RESULTS: Included were 92 patients with ACA-stroke. Of the 92 ACA patients, 55 (60%) were treated with IVT only and 37 (40%) with EVT (±bridging IVT). ACA patients treated with EVT had more often wake-up stroke (24% vs. 6%, p = 0.044) and proximal ACA occlusions (43% vs. 24%, p = 0.047) and tended to have higher stroke severity on admission [NIHSS: 10.0 vs 7.0, p = 0.054). However, odds for favorable outcome, mortality or symptomatic intracranial hemorrhage did not differ significantly between both groups. Exploration of the effect of clot location inside the ACA showed that in patients with A1 or A2/A3 ACA occlusions the chances of favorable outcome were not influenced by treatment allocation to IVT or EVT. DISCUSSION: Treatment with either IVT or EVT could be safe with similar effect in patients with ACA-strokes and these effects may be independent of clot location within the occluded ACA.

[Signs of upper airways digestive tract cancers and the general practitionner. Study of the practices by a Script Test Concordance]. / Les signes d'appels des cancers des voies aéro-digestives et le Médecin généraliste. Etude de pratique par un Test de Concordance de Script.

INTRODUCTION: Upper Airways digestive tract cancers are the 4th more frequent cancer. They are responsible for non specific symptoms. The examination of this antomical region is very difficult for a general practitioner. The precoce diagnosis of these cancers is based on the good recognition of the clinical situations by the general practitioner. The aim of this study was to test the practice of the general practitioner in front of clinical situations typical of head and neck cancers by a Script test concordance. METHOD: The study was performed on 107 parisian general practitioners who answered a questionnaire based on a Script Concordance Test (SCT). The SCT is a questionnaire that test the clinical way of thinking comparing the use of an information of experts versus non experts. RESULTS: The answers of the practitioners tested were quite in accordance with the panel of experts' anwers. They were particularly good concerning the risk factors and the buccal and oropharyngeal cancers. The scores were lower concerning the nasopharyngeal, laryngeal and paranasal sinuses cancers. The scores were significantly better for the most experimented practitioners. DISCUSSION: The fact that the rhinopharygeal, the laryngeal and the paranasal sinuses cancers are less frequent and the fact that these cancers can not be seen directly during a standard physical examination of general practitioner can explain the lower scores for these types of head and neck cancers. That is why practitioners have to be particularly aware of the symptoms and have to ask a specialized advice in case of doubt.

[Characteristics of tumor growth in patients with locally-advanced gastric cancer].

Locally-advanced gastric cancer features predominance of prognostically unfavorable histological patterns (infiltrative growth--in 87.9%, tumor grades II-IV--69.5%). Tumor invasion into two adjacent organs or more frequently occurs in totally-involved stomach (65.2+/-9.7%), poorly-differentiated (grade Ill) tumors (44.9+/-4.5%) under-differentiated ones (grade IV) (45.9+/-8.2%). Invasion into one adjacent organ is significantly predominant (p