Long-term neurocognitive function and quality of life after multimodal therapy in adult glioma patients: a prospective long-term follow-up.

PURPOSE: Multimodal therapies have significantly improved prognosis in glioma. However, in particular radiotherapy may induce long-term neurotoxicity compromising patients' neurocognition and quality of life. The present prospective multicenter study aimed to evaluate associations of multimodal treatment with neurocognition with a particular focus on hippocampal irradiation. METHODS: Seventy-one glioma patients (WHO grade 1-4) were serially evaluated with neurocognitive testing and quality of life questionnaires. Prior to (baseline) and following further treatment (median 7.1 years [range 4.6-11.0] after baseline) a standardized computerized neurocognitive test battery (NeuroCog FX) was applied to gauge psychomotor speed and inhibition, verbal short-term memory, working memory, verbal and non-verbal memory as well as verbal fluency. Mean ipsilateral hippocampal radiation dose was determined in a subgroup of 27 patients who received radiotherapy according to radiotherapy plans to evaluate its association with neurocognition. RESULTS: Between baseline and follow-up mean performance in none of the cognitive domains significantly declined in any treatment modality (radiotherapy, chemotherapy, combined radio-chemotherapy, watchful-waiting), except for selective attention in patients receiving chemotherapy alone. Apart from one subtest (inhibition), mean ipsilateral hippocampal radiation dose > 50 Gy (Dmean) as compared to < 10 Gy showed no associations with long-term cognitive functioning. However, patients with Dmean < 10 Gy showed stable or improved performance in all cognitive domains, while patients with > 50 Gy numerically deteriorated in 4/8 domains. CONCLUSIONS: Multimodal glioma therapy seems to affect neurocognition less than generally assumed. Even patients with unilateral hippocampal irradiation with > 50 Gy showed no profound cognitive decline in this series.

How are they doing as adults? Psychosocial and socioeconomic outcomes 11-30 years after pediatric epilepsy surgery.

OBJECTIVE: Pediatric epilepsy surgery yields cure from epilepsy or complete seizure control with continued medication in many patients early in life. This study aimed to evaluate the long-term (>10 years) psychosocial and socioeconomic outcomes of pediatric epilepsy surgery and examine the role of comorbid disability, type of surgery, seizure freedom, and age at surgery. METHODS: A novel ad hoc parent/patient questionnaire was used to assess educational and occupational attainment, marital/familial status, mobility, and other outcomes in patients who underwent unilobar or multilobar surgery for drug-refractory epilepsy during their childhood. The questionnaire also captured information on comorbid disability. RESULTS: Of the 353 eligible patients, 203 could still be contacted and 101 of these (50%) returned appropriately filled-in questionnaires (follow-up intervals: 11-30 [mean: 19.6] years). The cure from epilepsy rate was 53%. Type of surgery was strongly confounded by comorbid disability. Patients with comorbid disabilities had significantly lower rates of regular school degrees, gainful employment, marriage, and driving license (N = 29; 12%, 4%, 0%, 3%) compared with non-disabled patients (N = 69; 89%, 80%, 43%, and 67%, respectively). Patients achieved lower school degrees than their siblings and parents. Non-disabled seizure-free patients had better employment and mobility outcomes compared with non-seizure-free patients. Age at surgery (<10 vs. ≥10 years of age) did not have any effect on any outcome in patients with preschool seizure onset. SIGNIFICANCE: Pediatric epilepsy surgery can lead to permanent relief from epilepsy in many patients, but comorbid disability strongly impacts adult life achievement. In non-disabled patients, favorable outcomes in academic, occupational, marital, and mobility domains were achieved, approaching respective rates in the German population. Complete seizure freedom had additional positive effects on employment and mobility in this group. However, in case of chronic comorbid disability the overall life prospects may be limited despite favorable seizure outcomes.

Clinical adult outcome 11-30 years after pediatric epilepsy surgery: Complications and other surgical adverse events, seizure control, and cure of epilepsy.

OBJECTIVE: Pediatric epilepsy surgery promises seizure freedom or even cure of epilepsy. We evaluated the long-term (≥10 years) adult clinical outcome including surgery-related adverse events and complications, which are generally underreported. METHODS: A monocentric, single-arm, questionnaire study in now adult patients who underwent epilepsy surgery during childhood. A novel ad hoc parental/patient questionnaire, which addressed diverse outcome domains was applied. RESULTS: From a total of 353 eligible patients, 203 could be contacted (3 patients died of causes unknown) and 101 (50%) returned appropriately filled-in surveys. No evidence for a survey-response bias was found. The rate of surgical complications according to the patient records was 9%. As regards the survey, half of the parents/patients reported surgical adverse events (expected and unexpected issues) and one-third reported permanent aversive sequels. Two-thirds of the patients were seizure-free during the last year before follow-up; 63% were Engel class 1A; favorable seizure outcomes (including auras only) were obtained in 73%; and 54% were seizure-free and off antiseizure medicine (ASM), that is, cured of epilepsy. In non-seizure-free patients, seizure relapse occurred at any time during the follow-up interval but 87% of those with a seizure-free first postoperative year were seizure-free at follow-up. One patient experienced a seizure relapse during the ASM withdrawal trial but became seizure-free again with ASMs. Eleven patients reported an increased number of ASMs as compared to the time before surgery. Earlier focal surgery did not affect the long-term clinical outcome. SIGNIFICANCE: Pediatric epilepsy surgery was capable of curing epilepsy in about one-half of the children and to significantly control seizures in about three-fourths. Long-term success of focal surgery did not depend on age at surgery or duration of epilepsy. Surgical adverse events including complications may be underreported and must be assessed more thoroughly.

Mid-term treatment-related cognitive sequelae in glioma patients.

PURPOSE: Cognitive functioning represents an essential determinant of quality of life. Since significant advances in neuro-oncological treatment have led to prolonged survival it is important to reliably identify possible treatment-related neurocognitive dysfunction in brain tumor patients. Therefore, the present study specifically evaluates the effects of standard treatment modalities on neurocognitive functions in glioma patients within two years after surgery. METHODS: Eighty-six patients with World Health Organization (WHO) grade 1-4 gliomas were treated between 2004 and 2012 and prospectively followed within the German Glioma Network. They received serial neuropsychological assessment of attention, memory and executive functions using the computer-based test battery NeuroCog FX. As the primary outcome the extent of change in cognitive performance over time was compared between patients who received radiotherapy, chemotherapy or combined radio-chemotherapy and patients without any adjuvant therapy. Additionally, the effect of irradiation and chemotherapy was assessed in subgroup analyses. Furthermore, the potential impact of the extent of tumor resection and histopathological characteristics on cognitive functioning were referred to as secondary outcomes. RESULTS: After a median of 16.8 (range 5.9-31.1) months between post-surgery baseline neuropsychological assessment and follow-up assessment, all treatment groups showed numerical and often even statistically significant improvement in all cognitive domains. The extent of change in cognitive functioning showed no difference between treatment groups. Concerning figural memory only, irradiated patients showed less improvement than non-irradiated patients (p = 0.029, η2 = 0.06). Resected patients, yet not patients with biopsy, showed improvement in all cognitive domains. Compared to patients with astrocytomas, patients with oligodendrogliomas revealed a greater potential to improve in attentional and executive functions. However, the heterogeneity of the patient group and the potentially selected cohort may confound results. CONCLUSION: Within a two-year post-surgery interval, radiotherapy, chemotherapy or their combination as standard treatment did not have a detrimental effect on cognitive functions in WHO grade 1-4 glioma patients. Cognitive performance in patients with adjuvant treatment was comparable to that of patients without.

Seizure underreporting in LGI1 and CASPR2 antibody encephalitis.

Patients with anti-leucine-rich glioma-inactivated 1 protein (LGI1) or anti-contactin-associated protein 2 (CASPR2) antibody encephalitis typically present with frequent epileptic seizures. The seizures generally respond well to immunosuppressive therapy, and the long-term seizure outcome seems to be favorable. Consequentially, diagnosing acute symptomatic seizures secondary to autoimmune encephalitis instead of autoimmune epilepsy was proposed. However, published data on long-term seizure outcomes in CASPR2 and LGI1 antibody encephalitis are mostly based on patient reports, and seizure underreporting is a recognized issue. Clinical records from our tertiary epilepsy center were screened retrospectively for patients with LGI1 and CASPR2 antibody encephalitis who reported seizure freedom for at least 3 months and received video-electroencephalography (EEG) for >24 h at follow-up visits. Twenty (LGI1, n = 15; CASPR2, n = 5) of 32 patients with LGI1 (n = 24) and CASPR2 (n = 8) antibody encephalitis fulfilled these criteria. We recorded focal aware and impaired awareness seizures in four of these patients (20%) with reported seizure-free intervals ranging from 3 to 27 months. Our results question the favorable seizure outcome in patients with CASPR2 and LGI1 antibody encephalitis and suggest that the proportion of patients who have persistent seizures may be greater. Our findings underline the importance of prolonged video-EEG telemetry in this population.

[Role of Clinical, Sociomedical and Psychological Factors on Return to Work of Patients with Breast Cancer 6 Months after Rehabilitation]. / Einfluss klinischer, sozialmedizinischer und psychologischer Faktoren auf die berufliche Reintegration von Patientinnen mit Brustkrebs 6 Monate nach der Rehabilitation.

AIM OF THE STUDY: The majority of patients with non-metastatic breast cancer return to work after tumor therapy. A rate of up to 80% is given in national and international studies, which can vary considerably depending on the study population and the various social systems. However, it is unclear how many patients are reintegrated into work after medical rehabilitation and which clinical, sociodemographic and psychological factors play a role. METHODS: In a multicentre study, clinical and sociodemographic data were collected from breast cancer patients at the beginning of their medical rehabilitation. Subjectively experienced deficits in attention performance (FEDA), depressive symptoms (PHQ-9) and health-related quality of life (EORTC QLQ-C30) were recorded using standardized questionnaires. The cognitive performance was also examined using a computer-based test battery (NeuroCog FX). A follow-up survey was carried out 6-9 months after medical rehabilitation. The subjective assessment of one's own cognitive performance (FEDA) was recorded again at this time. RESULTS: 396 of the originally 476 patients were included in the study. In the follow-up survey, 323/396 patients (82%) were again employed. In a regression model, sociodemographic factors proved to be particularly predictive with regard to occupational reintegration: employment at the time of the tumor diagnosis, job preserved after medical rehabilitation, employee status and gradual reintegration according to the Hamburg model (Nagelkerke R2=0.685). This model could not be improved by adding psychological variables. The subjective patient information in all questionnaires was highly correlated (r>0.57; p<0.001). CONCLUSION: The vast majority of breast cancer patients return to work after medical rehabilitation. Socio-demographic factors play a crucial role in this. The regression model developed here, including the employment status, professional orientation and gradual reintegration, is of predictive importance and can be used in medical rehabilitation.

Contralesional White Matter Alterations in Patients After Hemispherotomy.

Cerebral lesions may cause degeneration and neuroplastic reorganization in both the ipsi- and the contralesional hemisphere, presumably creating an imbalance of primarily inhibitory interhemispheric influences produced via transcallosal pathways. The two hemispheres are thought to mutually hamper neuroplastic reorganization of the other hemisphere. The results of preceding degeneration and neuroplastic reorganization of white matter may be reflected by Diffusion Tensor Imaging-derived diffusivity parameters such as fractional anisotropy (FA). In this study, we applied Diffusion Tensor Imaging (DTI) to contrast the white matter status of the contralesional hemisphere of young lesioned brains with and without contralateral influences by comparing patients after hemispherotomy to those who had not undergone neurosurgery. DTI was applied to 43 healthy controls (26 females, mean age ± SD: 25.07 ± 11.33 years) and two groups of in total 51 epilepsy patients with comparable juvenile brain lesions (32 females, mean age ± SD: 25.69 ± 12.77 years) either after hemispherotomy (30 of 51 patients) or without neurosurgery (21 of 51 patients), respectively. FA values were compared between these groups using the unbiased tract-based spatial statistics approach. A voxel-wise ANCOVA controlling for age at scan yielded significant group differences in FA. A post hoc t-test between hemispherotomy patients and healthy controls revealed widespread supra-threshold voxels in the contralesional hemisphere of hemispherotomy patients indicating comparatively higher FA values (p < 0.05, FWE-corrected). The non-surgery group, in contrast, showed extensive supra-threshold voxels indicating lower FA values in the contralesional hemisphere as compared to healthy controls (p < 0.05, FWE-corrected). Whereas lower FA values are suggestive of pronounced contralesional degeneration in the non-surgery group, higher FA values in the hemispherotomy group may be interpreted as a result of preceding plastic remodeling. We conclude that, whether juvenile brain lesions are associated with contralesional degeneration or reorganization partly depends on the ipsilesional hemisphere. Contralesional reorganization as observed in hemispherotomy patients was most likely enabled by the complete neurosurgical deafferentation of the ipsilesional hemisphere and, thereby, the disinhibition of the neuroplastic potential of the contralesional hemisphere. The main argument of this study is that hemispherotomy may be seen as a major plastic stimulus and as a prerequisite for contralesional neuroplastic remodeling in patients with juvenile brain lesions.

Laser interstitial thermotherapy (LiTT) in pediatric epilepsy surgery.

Laser interstitial thermotherapy (LiTT) is a novel stereotactic approach to the surgical treatment of severe drug-resistant focal epilepsies. This review extends our recent general review on this topic (Hoppe et al. Laser interstitial thermotherapy [LiTT] in epilepsy surgery. Seizure 2017; 48:45-52) with a focus on children (age <18 years). A PubMed search retrieved 25 uncontrolled case series reports that included a total of 179 pediatric patients as well as 7 review papers that specifically referred to using LiTT in pediatric epilepsy surgery (due August 31, 2018). Hypothalamic hamartomas (HH) represented the most frequent indication (64.2%) while therapeutic evidence for other more frequent etiologies underlying severe focal childhood epilepsies (e.g. focal cortical dysplasia, mesiotemporal sclerosis) is still scarce (n<20). For the published cases, the rate of severe complications was 3.4% and the overall complication rate was 23.5%. The seizure freedom rate (Engel class 1) was 57.5% (including patients with early follow-up and repeat thermoablations). None of the studies included the systematic evaluation of the cognitive outcome. Overall, the published evidence does not yet allow a scientific or clinical judgement on the utility of LiTT for pediatric epilepsy surgery. LiTT is likely to extend the neurosurgical toolbox with regard to deep brain lesions (e.g. HH). However, in cases that are equally accessible for both approaches therapeutic superiority of LiTT over open resective surgery still remains to be demonstrated. Recommendations for controlled though non-randomized outcome studies are provided.

Parents' view of the cognitive outcome one year after pediatric epilepsy surgery.

OBJECTIVES: The cognitive outcome of pediatric epilepsy surgery has mainly been examined on the basis of standardized tests. Here, we analyzed the outcome in six cognitive domains from the parents' view. METHODS: Included were consecutive surgical pediatric patients whose parents filled-in a comprehensive questionnaire on cognitive problems in children and adolescents (Kognitive Probleme bei Kindern und Jugendlichen (KOPKIJ); Gleissner et al. 2006) at the preoperative baseline (T1) as well as twelve months thereafter (T2). All children also underwent standard neuropsychological assessments at T1 and T2. RESULTS: Parents of 96 patients provided pre- and postoperative KOPKIJ data. Overall, 80% of the children became seizure-free at the follow-up. Group means indicated a strong positive effect of time on KOPKIJ and neuropsychological performance. We found postoperative improvements in five out of six cognitive domains (language, memory, executive functions, attention, school; unchanged: visuospatial abilities). Individually, improvements were twice as likely as declines. However, 33 patients (35%) experienced significant decline in at least one cognitive domain. Later onset of epilepsy resulted in better performance but had no effect on change scores. Seizure-free status, lower antiseizure drug load, and stronger drug reduction after surgery contributed to postoperative cognitive improvements as perceived by the parents; no other effects of clinical factors were obtained (e.g., localization/lateralization). Despite their similar outcome patterns, change scores as derived from parental ratings and neuropsychological assessment were not correlated. CONCLUSIONS: Parents acknowledged the overall positive neurocognitive development after pediatric epilepsy surgery as previously shown by standardized tests. Seizure freedom and lower antiseizure drug load contributed to the beneficial cognitive outcome. Even if cognitive improvements outweighed declines, a risk for cognitive decline with impact on everyday functioning does exist.

Pediatric Temporal Lobe Epilepsy Surgery in Bonn and Review of the Literature.

BACKGROUND: Epilepsy surgery is well established as safe and successful for children with temporal lobe epilepsy (TLE). Despite evidence from available data, there remains some reluctance to refer children with medically refractory epilepsy for preoperative evaluation and workup for possible surgery. OBJECTIVE: To present the largest case series of pediatric (TLE) patients thus far, in order to better understand the predictability of preoperative evaluation on seizure outcome, and to better understand longitudinal outcomes in a large pediatric cohort. METHODS: One hundred eighty-three pediatric patients with TLE who underwent surgical treatment between 1988 and 2012 were retrospectively reviewed. Preoperative seizure history, noninvasive and invasive preoperative evaluation, surgical results, pathological results, long-term seizure outcomes, and complications were evaluated. A review of pediatric TLE in the literature was also undertaken to better understand reported complications and long-term outcomes. RESULTS: Mean follow-up was 42 mo (range 12-152 mo); 155 patients had good seizure outcomes (Engel I/II; 84.8%) and 28 patients had poor seizure outcomes (Engel III/IV; 15.2%); 145 patients were Engel I (78.8%). Only 10 patients did not have worthwhile improvement (Engel class IV; 5.4%). A review of the literature identified 2089 unique cases of pediatric TLE. Satisfactory seizure outcomes occurred in 1629 patients (79%) with unsatisfactory outcomes in 433 patients (21%). CONCLUSION: Pediatric patients benefit from surgery for medically refractory TLE with an acceptable safety profile regardless of histopathological diagnosis, seizure frequency, or seizure type. Seizure freedom appears to have extensive durability in a significant proportion of surgically treated patients.

NeuroCog FX study: A multicenter cohort study on cognitive dysfunction in patients with early breast cancer.

OBJECTIVE: Complaints about cognitive dysfunction (CD) reportedly persist in approximately one third of breast cancer patients, but the nature of CD and possible risk factors are unknown. METHODS: A cross-sectional, multicenter study was set up at 9 German oncological rehabilitation centers. Objective cognitive performance was assessed by the NeuroCog FX test, a short computerized screening (duration <30 minutes) which assesses working memory, alertness, verbal/figural memory, and language/executive. Patients' test performance was correlated with treatment factors (chemo-, radiotherapy), subjective performance (FEDA), depression (PHQ-9), quality of life (EORTC QLQ-30), and clinical characteristics. RESULTS: From February 2013 to December 2014, a clinically homogenous sample of 476 patients was recruited (early tumor stage [T0-T2]: 93%; node-negative: 67%; chemotherapy: 61%; radiotherapy: 84%). NeuroCog FX could be administered in 439 patients (92%; median age: 50 [24-62] years). Patients showed decreased performance in attentional-executive functions (but not verbal/figural memory) and a 3-fold rate of CD in terms of below average performance in at least 1 cognitive domain (42%). Approximately 40% of the patients also reported subjective cognitive impairment (FEDA). No therapy-specific effect on test performance was obtained in the NeuroCog FX test. CONCLUSIONS: Breast cancer survivors showed objective attentional-executive and subjective cognitive impairments. No therapy-specific adverse side effect on objective cognitive performance was found. Depression strongly contributed to objective and subjective cognitive complaints and reduced quality of life.

PEALD of SiO2 and Al2O3 Thin Films on Polypropylene: Investigations of the Film Growth at the Interface, Stress, and Gas Barrier Properties of Dyads.

A study on the plasma-enhanced atomic layer deposition of amorphous inorganic oxides SiO2 and Al2O3 on polypropylene (PP) was carried out with respect to growth taking place at the interface of the polymer substrate and the thin film employing in situ quartz-crystal microbalance (QCM) experiments. A model layer of spin-coated PP (scPP) was deposited on QCM crystals prior to depositions to allow a transfer of findings from QCM studies to industrially applied PP foil. The influence of precursor choice (trimethylaluminum (TMA) vs [3-(dimethylamino)propyl]-dimethyl aluminum (DMAD)) and of plasma pretreatment on the monitored QCM response was investigated. Furthermore, dyads of SiO2/Al2O3, using different Al precursors for the Al2O3 thin-film deposition, were investigated regarding their barrier performance. Although the growth of SiO2 and Al2O3 from TMA on scPP is significantly hindered if no oxygen plasma pretreatment is applied to the scPP prior to depositions, the DMAD process was found to yield comparable Al2O3 growth directly on scPP similar to that found on a bare QCM crystal. From this, the interface formed between the Al2O3 and the PP substrate is suggested to be different for the two precursors TMA and DMAD due to different growth modes. Furthermore, the residual stress of the thin films influences the barrier properties of SiO2/Al2O3 dyads. Dyads composed of 5 nm Al2O3 (DMAD) + 5 nm SiO2 exhibit an oxygen transmission rate (OTR) of 57.4 cm3 m-2 day-1, which correlates with a barrier improvement factor of 24 against 5 when Al2O3 from TMA is applied.

Neuropsychologist's (re-)view: Resective versus ablative amygdalohippocampectomies.

Pharmacoresistant mesial temporal lobe epilepsy (mTLE) represents the major indication for epilepsy surgery. Since epilepsy surgery is an elective treatment option, preserving cognition is a high priority. Given the essential role of temporomesial structures in declarative long-term memory formation, surgical treatment for mTLE is primarily associated with a risk of material-specific memory decline, but other cognitive domains may be affected as well. The major determinants for the neuropsychological outcome are the functional integrity of surgically affected tissues, the functional reserve capacities of the remnant brain, the postoperative seizure outcome, as well as the quantitative and qualitative changes of antiepileptic drugs. Anterior temporal lobectomy has long been the standard procedure for treating mTLE. However, if an exclusive mesial pathology is present, then functional non-pathological tissues of the temporal pole and neocortex are sacrificed. As a result, more selective or tailored surgical approaches have been developed which strive towards minimizing iatrogenic effects. However, whether or not these approaches are equipotential with regard to seizure control is still a matter of debate. The quality of the presurgical diagnostics could also be decisive. Selective surgery should indeed be selective in terms of preventing evitable collateral cortical damage along the approach. Invasivity and risks of collateral damage associated with "open" selective resective surgery are further minimized by stereotactic ablative surgery via thermocoagulation, or eventually even eliminated by gamma knife surgery. From a neuropsychological point of view, this development is consequent and desirable, but no clear scientific evidence of a superior cognitive outcome after radiosurgery or thermocoagulation currently exists. The studies that are available contain significant methodological limitations. Thus, randomized head-to-head cognitive outcome studies of competing selective procedures are needed, which should meet the minimum requirements for study design and neuropsychological evaluations. Finally, none of the surgical treatment variants can systematically prevent memory decline when the hippocampus is targeted.

Laser interstitial thermotherapy (LiTT) in epilepsy surgery.

Besides other innovative stereotactic procedures (radiofrequency thermocoagulation, focused ultrasound, gamma knife) laser interstitial thermotherapy (LiTT) provides minimally invasive destruction of pathological soft tissues which could be especially relevant for epilepsy surgeries involving adult and pediatric patients. Unlike standard resections, no craniotomy is required; just a tiny borehole trepanation is sufficient. Damage to cortical areas when accessing deep lesions can be minimized or completely avoided, and treating epileptogenic foci near eloquent or even vital brain areas becomes possible. Here, we briefly describe the history and rationale of laser neurosurgery as well as the technical key features of the two currently available systems for magnetic resonance-guided LiTT (Visualase®, NeuroBlate®; CE marks pending for both). We also discuss the published clinical experience with LiTT in the field of epilepsy surgery (approximately 200 cases) with regard to complications, LiTT-induced, long-term brain structural alterations, seizure outcome, preliminary neuropsychological findings and first estimates of treatment costs. Overall, the seizure outcome appears to be slightly worse than for resective surgery. Due to insufficient research methods (e.g. non-established measures, lack of a control condition), the expected neuropsychological superiority over resective surgery has not been unambiguously demonstrated thus far. Also, the cost-benefit ratio requires further critical evaluation. Clinical, multi-center and adequately controlled outcome studies of high quality should also accompany the imminent introduction of LiTT into the field of epilepsy surgery and therewith permit critical scientific evaluation and rational, individual, clinical decisions.

Influenza and other respiratory viruses: standardizing disease severity in surveillance and clinical trials.

INTRODUCTION: Influenza-Like Illness is a leading cause of hospitalization in children. Disease burden due to influenza and other respiratory viral infections is reported on a population level, but clinical scores measuring individual changes in disease severity are urgently needed. Areas covered: We present a composite clinical score allowing individual patient data analyses of disease severity based on systematic literature review and WHO-criteria for uncomplicated and complicated disease. The 22-item ViVI Disease Severity Score showed a normal distribution in a pediatric cohort of 6073 children aged 0-18 years (mean age 3.13; S.D. 3.89; range: 0 to 18.79). Expert commentary: The ViVI Score was correlated with risk of antibiotic use as well as need for hospitalization and intensive care. The ViVI Score was used to track children with influenza, respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus infections and is fully compliant with regulatory data standards. The ViVI Disease Severity Score mobile application allows physicians to measure disease severity at the point-of care thereby taking clinical trials to the next level.

Cryoballoon ablation for pulmonary vein isolation in patients with atrial fibrillation: preliminary results using novel short-tip cryoballoon.

PURPOSE: In this study, we aimed to report our preliminary experience regarding the impact of the novel short-tip (ST) cryoballoon (CB) on procedural efficacy and signal quality during pulmonary vein (PV) isolation for both paroxysmal and persistent atrial fibrillation. METHODS: Between March, 2015, and August, 2015, we enrolled a total of 64 patients (47 patients male, 73 %) with a mean age of 60 ± 11 years. In the study population, 31 patients (48 %) underwent PVI using Advance (ADV) CB and 33 (52 %) patients with ST CB. In all patients, a 28-mm balloon was used. RESULTS: Acute procedural success rates were 100 % for the entire study population. A statistically insignificant increase in the percentage of PV signal recordings was observed with ST CB in all PVs compared to ADV CB [88 vs. 81 % for left superior PV (LSPV), 82 vs. 78 % for left inferior PV (LIPV), 85 vs. 84 % for right superior PV (RSPV), 82 vs. 71 % for right inferior PV (RIPV), p < 0.05]. Additionally, the difference in minimum temperature reached during the procedure per PV was not statistically significant between ST CB and ADV CB except the LIPV (LSPV -44.2 ± 5.9 vs. -45.6 ± 5.3 °C, p = 0.970; LIPV -38.7 ± 4.6 °C vs -44.6 ± 6.8 °C, p < 0.001; RSPV -45.6 ± 7.4 °C vs.-47.2 ± 6.1 °C, p = 0.168; RIPV -41.4 ± 5.1 °C vs.-43.7 ± 6.3 °C, p = 0.360). Time to isolation for each PV was similar between ST and ADV CB (p > 0.05). CONCLUSION: Our preliminary findings indicated similar acute procedural success for the novel ST CB compared with second generation ADV CB. The increase in the ratio of PV signal recordings obtained during the PVI using the novel ST CB was not significant.

Characterization of Electrical Reconnection Following Pulmonary Vein Isolation Using First- and Second-Generation Cryoballoon.

BACKGROUND: Second-generation cryoballoon (CB-2) is associated with improved outcomes for pulmonary vein isolation (PVI) compared to first generation (CB-1). However, data regarding the predictors of pulmonary vein (PV) electrical reconnection are limited. In this study, we aimed to characterize the predilection sites and predictors of reconnection in patients with recurrent atrial tachyarrhythmia (ATa) after PVI using CB-1 and CB-2. METHODS: A total of 59 patients (mean age: 62 ± 11 years and 66% male) with recurrent ATa after previous CB-PVI, using either a 28-mm CB-1 or CB-2, underwent repeat ablation. PV reisolation was performed by irrigated radiofrequency ablation using three-dimensional electroanatomical mapping systems. RESULTS: Electrical PV reconnection was detected in 10 of 11 (91%) of CB-1 patients compared to 41 of 48 (85%) of CB-2 patients. Time to redo procedure after index CB-1 was 8.9 ± 10.2 months and 11.2 ± 7.0 months in CB-2. Bonus freeze was applied in all patients with CB-1 and 41% of the patients with CB-2. Superior quadrants of both superior PVs and inferior quadrants of the both inferior PVs exhibited higher predilection for conduction compared to other quadrants (P < 0.001). Multivariate binary logistic analysis revealed that right inferior PV (RIPV; odds ratio [OR]: 1.52, 95% confidence interval [CI]: 1.09-2.13, P = 0.014) and minimum temperature (OR: 1.09, 95% CI: 1.03-1.15, P = 0.004) were the independent predictors of electrical reconnection after CB-2 ablation. CONCLUSION: Conduction gaps after CB-1 and CB-2 were higher in inferior PVs compared to superior PVs. The RIPV and minimum CB temperature were independent predictors of PV electrical reconnection after CB-2.

The Total Incidence of Complications and the Impact of an Anticoagulation Regime on Adverse Events After Cryoballoon Ablation of Atrial Fibrillation: A Single-Center Study of 409 Patients.

AIM: Data evaluating the complications of pulmonary vein isolation (PVI) using second-generation cryoballoons (CB) related to different anticoagulation regimes are limited. This study evaluates the total complications and the impact of novel oral anticoagulants (NOACs) compared to phenprocoumon on adverse events in the setting of PVI using CB. METHODS AND RESULTS: PVI was performed using second-generation CB by two experienced investigators. A total of 409 patients (58.9% male; mean age = 61 ± 10 years) with atrial fibrillation were included in this study. In group I, 150/409 (36.7%) patients received phenprocoumon therapy, and in group II, 259/409 (63.3%) patients were treated with NOACs (rivaroxaban: n = 193; dabigatran: n = 48; and apixaban: n = 18). In both groups, the rates of major complications were similar (group I [phenprocoumon]: four pts (2.7%) vs. Group II [NOACs]: seven pts (2.7%); P = 0.999). In this cohort, 275 patients were ablated with the bonus freeze protocol, and 134 patients were ablated without bonus freezes. The procedure duration significantly decreased with the bonus freeze protocol from 102.3 ± 24.6 min to 68.5 ± 16.2 min (P < 0.001). The impact of the bonus freeze on the postprocedural increase of C-reactive protein (CRP) levels was significant compared to the postprocedural CRP levels after procedures without the bonus freeze protocol (postprocedural CRP level+ bonus protocol: 1.6 ± 1.2 mg/L vs. postprocedural CRP level+ nonbonus protocol: 1.3 ± 1.3 mg/L; P = 0.04). CONCLUSION: The incidence of adverse events in PVI using the second-generation CB with the periprocedural administration of NAOCs was not significantly different compared to phenprocoumon. Further, large-scale randomized studies are needed to evaluate the safety of two anticoagulation regimes comparing vitamin K antagonists and NOACs, as well as different NOAC regimes, in patients undergoing PVI using cryoballoon ablation.

Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta-analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common pathogen identified in young children with acute lower respiratory infection (ALRI) as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV-associated ALRI. We aimed to identify risk factors for RSV-associated ALRI in young children. METHODS: We carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN) collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta-analyses to estimate odds ratios with 95% confidence intervals (CI) for individual risk factors. RESULTS: We identified 20 studies (3 were unpublished data) with "good quality" that investigated 18 risk factors for RSV-associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV-associated ALRI. The meta-estimates of their odds ratio (ORs) with corresponding 95% confidence intervals (CI) are prematurity 1.96 (95% CI 1.44-2.67), low birth weight 1.91 (95% CI 1.45-2.53), being male 1.23 (95% CI 1.13-1.33), having siblings 1.60 (95% CI 1.32-1.95), maternal smoking 1.36 (95% CI 1.24-1.50), history of atopy 1.47 (95% CI 1.16-1.87), no breastfeeding 2.24 (95% CI 1.56-3.20) and crowding 1.94 (95% CI 1.29-2.93). Although there were insufficient studies available to generate a meta-estimate for HIV, all articles (irrespective of quality scores) reported significant associations between HIV and RSV-associated ALRI. CONCLUSIONS: This study presents a comprehensive report of the strength of association between various socio-demographic risk factors and RSV-associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause) ALRI and thus, in addition to the future impact of novel RSV vaccines, national action against ALRI risk factors as part of national control programmes can be expected to reduce burden of disease from RSV. Further research which identifies, accesses and analyses additional unpublished RSV data sets could further improve the precision of these estimates.

Cryoballoon Ablation for Pulmonary Vein Isolation in Patients With Persistent Atrial Fibrillation: One-Year Outcome Using Second Generation Cryoballoon.

BACKGROUND: Data regarding the freedom from atrial fibrillation (AF) in the follow-up of persistent AF patients is limited. The second-generation cryoballoon has better cooling properties compared with first-generation cryoballon. In this study, we aimed to assess the medium-term efficacy of second-generation cryoballoon in patients with persistent AF. METHODS AND RESULTS: A total of 100 patients (63±10 years, 80% male) with symptomatic persistent AF, despite ≥1 antiarrhythmic drug(s), who were scheduled for pulmonary vein isolation using second-generation cryoballoon were enrolled in this study. Follow-up was based on outpatient clinic visits, including Holter ECGs. Recurrence was defined as a symptomatic or documented arrhythmia episode of >30 seconds excluding a 3-month blanking period. As a result, 393 pulmonary veins (7 patients with common ostium) were successfully isolated. Mean procedural and fluoroscopy times were 96.2±21.3 and 19.7±6.7 minutes, respectively. Phrenic nerve palsy occurred in 3% (3/100) of the patients. At a mean follow-up duration of 10.6±6.3 months, 67% of the patients were in sinus rhythm. Stepwise multivariable Cox proportional hazard regression analysis showed that early AF recurrence (hazard ratio 3.83, 95% confidence interval 1.91-7.68, P<0.001) was the only independent predictor for late AF recurrence apart from other clinical and echocardiographic variables. CONCLUSIONS: Our findings indicated that second-generation cryoballoon use is associated with favorable outcomes in patients with persistent AF. Recurrence at blanking period was the only predictor of long-term AF recurrence.