Status epilepticus: impact of therapeutic coma on outcome.

OBJECTIVES: Therapeutic coma is advocated in guidelines for management of refractory status epilepticus; this is, however, based on weak evidence. We here address the specific impact of therapeutic coma on status epilepticus outcome. DESIGN: Retrospective assessment of a prospectively collected cohort. SETTING: Academic hospital. PATIENTS: Consecutive adults with incident status epilepticus lasting greater than or equal to 30 minutes, admitted between 2006 and 2013. MEASUREMENTS AND MAIN RESULTS: We recorded prospectively demographics, clinical status epilepticus features, treatment, and outcome at discharge and retrospectively medical comorbidities, hospital stay, and infectious complications. Associations between potential predictors and clinical outcome were analyzed using multinomial logistic regressions. Of 467 patients with incident status epilepticus, 238 returned to baseline (51.1%), 162 had new disability (34.6%), and 67 died (14.3%); 50 subjects (10.7%) were managed with therapeutic coma. Therapeutic coma was associated with poorer outcome in the whole cohort (relative risk ratio for new disability, 6.86; 95% CI, 2.84-16.56; for mortality, 9.10; 95% CI, 3.17-26.16); the effect was more important in patients with complex partial compared with generalized convulsive or nonconvulsive status epilepticus in coma. Prevalence of infections was higher (odds ratio, 3.81; 95% CI, 1.66-8.75), and median hospital stay in patients discharged alive was longer (16 d [range, 2-240 d] vs 9 d [range, 1-57 d]; p < 0.001) in subjects managed with therapeutic coma. CONCLUSIONS: This study provides class III evidence that therapeutic coma is associated with poorer outcome after status epilepticus; furthermore, it portends higher infection rates and longer hospitalizations. These data suggest caution in the straightforward use of this approach, especially in patients with complex partial status epilepticus

Treatment of multiple adjacent RT 1 gingival recessions with the modified coronally advanced tunnel (MCAT) technique and a collagen matrix or palatal connective tissue graft: 9-year results of a split-mouth randomized clinical trial.

OBJECTIVES To evaluate t he long-term outcomes following treatment of RT 1 multiple adjacent gingival recessions (MAGR) using the modified coronally advanced tunnel (MCAT) with either a collagen matrix CM or a connective tissue graft (CTG). MATERIAL AND METHODS Sixteen of the original 22 subjects included in a randomized, controlled split-mouth clinical trial were available for the 9-year follow-up (114 sites). Recessions were randomly treated by means of MCAT + CM (test) or MCAT + CTG (control). Complete root coverage (CRC), mean root coverage (MRC), gingival recession depth (GRD), probing pocket depth (PD), keratinized tissue width (KTW), and thickness (KGT) were compared with baseline values and with the 12-month results. RESULTS After 9 years, CRC was observed in 2 patients, one in each group. At 9 years, MRC was 23.0 ± 44.5% in the test and 39.7 ± 35.1% in the control group (p = 0.179). The MRC reduction compared to 12 months was - 50.1 ± 47.0% and - 48.3 ± 37.7%, respectively. The upper jaw obtained 31.92 ± 43.0% of MRC for the test and 51.1 ± 27.8% for the control group (p = 0.111) compared to the lower jaw with 8.3 ± 46.9% and 20.7 ± 40.3%. KTW and KGT increased for both CM and CTG together from 2.0 ± 0.7 to 3.1 ± 1.0 mm (< 0.0001). There were no statistically significant changes in PD. CONCLUSION The present results indicate that (a) treatment of MAGR using MCAT in conjunction with either CM or CTG is likely to show a relapse over a period of 9 years, and (b) the outcomes obtained in maxillary areas seem to be more stable compared to the mandibular ones. CLINICAL RELEVANCE The mean root coverage at 12 months could not be fully maintained over 9 years. On a long-term basis, the results seem to be less stable in the mandible as compared to maxillary areas

Intraventricular Thrombus Formation and Embolism in Takotsubo Syndrome: Insights From the International Takotsubo Registry

OBJECTIVE Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×10$^{3}$ cells/μL emerged as independent predictors for thrombus formation or embolism. CONCLUSIONS Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621

Recession coverage using the modified coronally advanced tunnel and connective tissue graft with or without enamel matrix derivative: 5-year results of a randomised clinical trial.

OBJECTIVES To evaluate the 5-year results of single and multiple recession type (RT) 1 and 2 (Miller I to III) recessions treated with the modified coronally advanced tunnel (MCAT) and connective tissue graft (CTG) with or without an enamel matrix derivative (EMD). The main outcome variable was the stability of obtained root coverage from 6 months to 5 years. MATERIALS AND METHODS In 24 patients, both complete and mean root coverage (CRC and MRC) and gain of keratinised tissue (KT) were assessed at 6 months and 5 years after recession coverage by means of MCAT and CTG with or without EMD. Aesthetic outcomes after 5 years were evaluated using the root coverage aesthetic score (RES). RESULTS At 5 years, 24 patients with a total of 43 recessions were evaluated. Eight patients (57.14%) of the test and 6 (60.0%) of the control group showed complete root coverage. MRC revealed no statistically significant differences between the two groups, with 73.87 ± 26.83% (test) and 75.04 ± 22.06% (control), respectively. KT increased from 1.14 ± 0.57 mm to 3.07 ± 2.27 mm in the test group and from 1.24 ± 0.92 mm to 3.02 ± 1.55 mm in the control group, respectively. CONCLUSION Treatment of single and multiple RT 1 and 2 recessions by means of MCAT and CTG with or without EMD yielded comparable clinical improvements which could be maintained over a period of 5 years. The additional use of EMD did not influence the clinical outcomes. CLINICAL RELEVANCE The use of MCAT + CTG yielded successful coverage of single and multiple RT 1 and 2 gingival recessions, while the additional application of EMD did not seem to influence the results

Intravenous lacosamide in status epilepticus: Correlation between loading dose, serum levels, and clinical response.

Intravenous lacosamide (LCM) is increasingly used in the treatment of status epilepticus (SE), but optimal loading dose and target serum levels are unclear. We analysed the correlation between LCM serum levels after intravenous loading dose and clinical response. Retrospective study in two centres from December 2014 to May 2016 including consecutive SE patients treated with LCM, in which trough serum levels after intravenous loading dose were available. Trough levels were correlated with the loading dose and the clinical response, defined as LCM introduction terminating SE without the need of further treatment. Correlations were adjusted for other SE characteristics. Among 40 patients, 16 (40%) responded to LCM. LCM serum concentrations within the reference interval (10-20mg/l) were associated with loading doses of &gt;9mg/kg (p=0.003; χ2). However, we observed no difference between LCM serum levels in responders (median 10.4mg/l) versus non-responders (median 9.5mg/l; p=0.36; U test), even after adjusting for other predictors of clinical outcome (SE severity, aetiology, and number of previous treatment). High intravenous LCM loading doses (&gt;9mg/kg) were associated with serum levels within the reference interval, there was however no correlation with the clinical response. Prospective studies are needed to evaluate the benefit of increasing the LCM loading dose in SE

Runoff generation in a pre-alpine catchment: A discussion between a tracer and a shallow groundwater hydrologist

Runoff generation mechanisms vary between catchments and despite decades of research in many catchments, these mechanisms are still not fully understood. In this paper, runoff generation mechanisms in the steep pre-alpine catchments in the Alptal, Switzerland, are discussed. These fast responding catchments are characterized by low permeability soils on top of flysch bedrock. In combination with the high and frequent precipitation, this results in predominantly wet conditions. In many areas, the water table is close to the surface. We review the main results of recent (2009-2016) studies in these catchments that used isotope, stream chemistry and hydrometric data. These field studies focused on the spatial and temporal patterns in groundwater levels, spatial patterns in the isotopic composition and chemistry of streamflow during baseflow conditions, as well as the responses of streamflow and its isotopic composition during rainfall events. The combined results of these studies highlight the establishment of connectivity of areas with a different topographic position and areas with a different land use during rainfall events. They also show the importance of flow in higher conductivity near surface soil layers for runoff generation, as well as the frequent occurrence of surface runoff. Spatial differences in groundwater dynamics are related to topography. Streamflow responses are mainly affected by the rainfall characteristics; differences in streamflow and hydrochemistry between catchments with different portions of forest, meadows and wetlands, were relatively small. However, variations in the chemistry of baseflow along stream reaches within a catchment were considerable. Above all, these studies highlight the value of combining data on spatial patterns of groundwater levels and stream chemistry with long term data on streamflow to derive a more complete picture of the dominant runoff generation mechanisms

Prognostic impact of fractional flow reserve measurements in patients with acute coronary syndromes: a subanalysis of the FLORIDA study

Randomized trials suggest benefits for fractional flow reserve (FFR)-guided vs. angiography-guided treatment strategies in well-defined and selected patient cohorts with acute coronary syndromes (ACS). The long-term prognostic value of FFR measurement in unselected all-comer ACS patients, however, remains unknown. This subanalysis of the Fractional FLOw Reserve In cardiovascular DiseAses (FLORIDA) study sought to investigate the long-term effects of FFR in the management of lesions in patients with acute coronary syndrome (ACS). FLORIDA was an observational all-comer cohort study performed in Germany, that was population-based and unselected. Patients enrolled into the anonymized InGef Research Database presenting with ACS and undergoing coronary angiography between January 2014 and December 2015 were included in the analysis. Patients were stratified into either the FFR-guided or the angiography-guided treatment arm, based on the treatment received. A matched cohort study design was used. The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiovascular events (MACE), a composite of death, non-fatal myocardial infarction (MI), and repeat revascularization. Follow-up time was 3 years. Rates of 3-year mortality were 10.2 and 14.0% in the FFR-guided and the angiography-guided treatment arms (p = 0.04), corresponding to a 27% relative risk reduction for FFR in ACS patients. Rates of MACE were similar in both arms (47.7 vs. 51.5%, p = 0.14), including similar rates of non-fatal MI (27.7 vs. 25.4%, p = 0.47) and revascularization (9.9 vs. 12.1%, p = 0.17). In this large, all-comer observational study of ACS patients, FFR-guided revascularization was associated with a lower mortality at 3 years. This finding encourages the routine use of FFR to guide lesion revascularization in patients presenting with ACS

Adiponectin, free fatty acids, and cardiovascular outcomes in patients with type 2 diabetes and acute coronary syndrome

OBJECTIVE: In observational cohorts, adiponectin is inversely associated and free fatty acids (FFAs) are directly associated with incident coronary heart disease (CHD). Adiponectin tends to be reduced and FFAs elevated in type 2 diabetes. We investigated relationships of adiponectin and FFA and major adverse cardiovascular events (MACEs) and death in patients with acute coronary syndrome (ACS) and type 2 diabetes using data from the AleCardio trial, which compared the PPAR-α/γ agonist aleglitazar with placebo. RESEARCH DESIGN AND METHODS: Using Cox regression adjusted for demographic, laboratory, and treatment variables, we determined associations of baseline adiponectin and FFAs, or the change in adiponectin and FFAs from baseline, with MACEs (cardiovascular death, myocardial infarction, or stroke) and death. RESULTS: A twofold higher baseline adiponectin (n = 6,998) was directly associated with risk of MACEs (hazard ratio [HR] 1.17 [95% CI 1.08-1.27]) and death (HR 1.53 [95% CI 1.35-1.73]). A doubling of adiponectin from baseline to month 3 (n = 6,325) was also associated with risk of death (HR 1.20 [95% CI 1.03-1.41]). Baseline FFAs (n = 7,038), but not change in FFAs from baseline (n = 6,365), were directly associated with greater risk of MACEs and death. There were no interactions with study treatment. CONCLUSIONS: In contrast to prior observational data for incident CHD, adiponectin is prospectively associated with MACEs and death in patients with type 2 diabetes and ACS, and an increase in adiponectin from baseline is directly related to death. These findings raise the possibility that adiponectin has different effects in patients with type 2 diabetes and ACS than in populations without prevalent cardiovascular disease. Consistent with prior data, FFAs are directly associated with adverse outcomes