Early targeted brain COOLing in the cardiac CATHeterisation laboratory following cardiac arrest (COOLCATH)

IntroductionTrials demonstrate significant clinical benefit in patients receiving therapeutic hypothermia (TH) after cardiac arrest. However, incidence of mortality and morbidity remains high in this patient group. Rapid targeted brain hypothermia induction, together with prompt correction of the underlying cause may improve outcomes in these patients. This study investigates the efficacy of Rhinochill^®, an intranasal cooling device over Blanketrol^®, a surface cooling device in inducing TH in cardiac arrest patients within the cardiac catheter laboratory.Methods70 patients were randomized to TH induction with either Rhinochill^® or Blanketrol^®. Primary outcome measures were time to reach tympanic ≤34 °C from randomisation as a surrogate for brain temperature and oesophageal ≤34 °C from randomisation as a measurement of core body temperature. Secondary outcomes included first hour temperature drop, length of stay in intensive care unit, hospital stay, neurological recovery and all-cause mortality at hospital discharge.ResultsThere was no difference in time to reach ≤34 °C between Rhinochill^® and Blanketrol^® (Tympanic ≤34 °C, 75 vs. 107 mins; p = 0.101; Oesophageal ≤34 °C, 85 vs. 115 mins; p = 0.151). Tympanic temperature dropped significantly with Rhinochill^® in the first hour (1.75 vs. 0.94 °C; p < 0.001). No difference was detected in any other secondary outcome measures. Catheter laboratory-based TH induction resulted in a survival to hospital discharge of 67.1%.ConclusionIn this study, Rhinochill^® was not found to be more efficient than Blanketrol^® for TH induction, although there was a non-significant trend in favour of Rhinochill^® that potentially warrants further investigation with a larger trial.     

Stealth lipid coated aquasomes bearing recombinant human interferon-α-2b offered prolonged release and enhanced cytotoxicity in ovarian cancer cells

PurposeIn present investigation, recombinant human interferon-α-2b (rhINF-α-2b) loaded aquasomes were prepared, optimized and overlaid with PEGylated phospholipid to offer prolong release and high therapeutic index against ovarian cancer, SKOV3 cells.Methods and resultsCentral Composite Design (CCD) and Response Surface Methodology (RSM) were employed to calculate the optimized conditions, 1:3 core to coat ratio, sonication power of 12.5 W and time of about 55 min for preparation of aquasomes. Consequently, rhINF-α-2b-Py-5-P-Aq.somes exhibited higher protein loading capacity and retained structural conformations of rhINF-α-2b, as compared to rhINF-α-2b-Cellob-Aq.somes, rhINF-α-2b-Tre-Aq.somes and rhINF-α-2b-Core (CaHPO₄). Further, optimized rhINF-α-2b-Py-5-P-Aq.somes was superimposed with phospholipid-PEG₂₀₀₀ to prolong the release pattern of rhINF-α-2b from aquasomes. The rhINF-α-2b-core (CaHPO₄) released 97.3% of protein in 1 h, while 95.3% of rhINF-α-2b was released by rhINF-α-2b-Tre-Aq.somes in 4 h. Concurrently, rhINF-α-2b-Cellob-Aq.somes and rhINF-α-2b-Py-5-P-Aq.somes released 96.2% and 97.8% of rhINF-α-2b respectively in 6 and 8 h. Ultimately, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG₂₀₀₀ displayed evidence of its prolonged release pattern and released 98.1% of rhINF-α-2b in 336 h. FT–IR and XRD substantiated the involvement of vigorous intermolecular hydrogen bonding and amorphous geometry in rhINF-α-2b-Py-5-P-Aq.somes. In last, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG₂₀₀₀ exhibited the ∼ 4.55, 1.92, 2.3, 2.8, and 3.84 fold reductions in IC₅₀ as compared to free rhINF-α-2b, rhINF-α-2b-Py-5-P-Aq.somes, rhINF-α-2b-Cellob-Aq.somes, rhINF-α-2b-Tre-Aq.somes and rhINF-α-2b-Core (CaHPO₄), respectively.ConclusionTherefore, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG₂₀₀₀ warrant further in depth in vitro and in vivo antitumor study to scale up the technology for clinical intervention.     

The influence of post-rewarming temperature management on post-rewarming fever development after cardiac arrest

Aim of the studyWe evaluated the influence of post-rewarming temperature management (PRTM) on post-rewarming fever development and determined the association between the temperature in the immediate post-targeted temperature management (TTM) period and outcomes.MethodsThis retrospective observational study included consecutive adult cardiac arrest survivors treated with TTM from January 2008 to December 2013. Beginning in August 2010, our institution implemented a PRTM protocol involving continued use of temperature management device to maintain normothermia during the first 24 h after rewarming. The outcomes were in-hospital mortality and neurologic outcome at discharge. We evaluated the effect on clinical outcomes of post-rewarming fever defined at a temperature over 38 °C within 48 h after rewarming.ResultsOf 277 included patients, 55.2% underwent PRTM. The incidence of post-rewarming fever did not differ between the PRTM and no-PRTM groups (odds ratio [OR] 0.963, confidence interval [CI] 0.519, 1.787). Post-rewarming fever was associated with decreased in-hospital mortality (OR 0.243, CI 0.110, 0.534) and decreased rate of unfavorable neurologic outcome (OR 0.312, CI 0.182, 0.534). During 48 h following rewarming, mean temperature was 36.5 °C (36.2–36.8 °C), and peak temperature was 37.5 °C (36.8–38.1 °C). On multivariate analyses, lower mean temperature was associated with increased in-hospital mortality (OR 0.099, CI 0.037, 0.262) and unfavorable neurologic outcome (OR 0.071, CI 0.026, 0.193).ConclusionIt appeared that PRTM did not prevent post-rewarming fever development. Post-rewarming fever was associated with favorable outcomes while lower body temperature after rewarming was associated with unfavorable outcomes. Our results require further confirmation by larger prospective studies.     

Assessment of aquo-ethanolic extract of Camellia sinensis against Carbapenem Resistant Escherichia coli: In Vivo Trials in a Murine Model

The prevalence of Carbapenem Resistant Escherichia coli (CRE) has increased considerably during the last decade, which can be ascribed to relative scarcity of effective non toxic antimicrobial agents. The present study was conducted to evaluate the antimicrobial activity of aquo-ethanolic (1:1) extract of leaves of Camellia sinensis (PTRC-31911-A) against Carbapenem Resistant Escherichia coli at preclinical level using peritonitis infection model in Sprague Dawley rats. Efficacy analysis of PTRC-31911-A involved enumeration of CRE colonies in blood and urine samples of test animals for a period of 5 days from infection. A reduction in microbial count of biological fluids was considered as the primary endpoint of the selected murine model. Physical, biochemical, hematological and histological indices of toxicity were employed as secondary relative indicators of the induced disease. Physical manifestations of infected rats included significantly high body temperature (Temp_Infected = 103.18 °F, ∼5% increase) and noteworthy reduction in weight (Weight_Infected = 126.83 g, ∼15% decrease) as compared to control. Significant (P < 0.05) increase in total white blood cells, eosinophil and monocyte counts as well as a significant decrease (P < 0.05) in erythrocytes count, hematocrit volume, red blood cell distribution width and hemoglobin concentration were observed in the infected group as compared to the control group. Furthermore, noteworthy increase in liver and kidney function test parameters were observed in case of infected groups. All the hematological and biochemical parameters were found to be within optimum range in case of treatment group, indicating restoration of homeostasis. Histopathological studies also presented symptoms of hemorrhage and glomerular damage with structural distortion in glomerular capillary loops of infected groups, which were later recovered in treated groups, indicating the nephro-protective potential of PTRC-31911-A. The study clearly points out that Camellia sinensis extract (PTRC-31911-A; single dose of 5 mg/Kg bwt; oral, + 24 h) is highly effective against Carbapenem Resistant Escherichia coli owing mainly to the presence of flavonoids and polyphenolic compounds, identified by LCMS. Ongoing studies are expected to further unravel the mechanism of action and bioactivity determinants of this broad spectrum plant extract.     

Outcome and risk factors in children after traumatic cardiac arrest and successful resuscitation

IntroductionProspective collected data of the TraumaRegister DGU^® were analyzed to derive survival rates and predictors for non-survival in the children who had suffered traumatic cardiorespiratory arrest. Different time points of resuscitation efforts (only preclinical, in the emergency room (ER) or preclinical + ER) were analyzed in terms of mortality and neurological outcome.MethodsThe database of the TraumaRegister DGU^® comprising 122,742 patients from 1993 to 2013 was analyzed. The main focus of this survey was on the paediatric group defined by an age ≤14 years who could be compared to adults. Different statistical analysis (univariate and multivariate analysis, logistic regression) were performed with mortality as the target variable. Differences between the paedatric group and adults were analysed by Fisher's exact test.ResultsData after preclinical and/or ER resuscitation from 152 children and 1690 adults were analyzed. A good or moderate outcome (GOS 5 + 4) was found in 19.4% of the children's group compared to 12.4% of the adults (p = 0.02).Analysis of the GOS 5 + 4 subgroups after preclinical resuscitation only revealed that these outcomes were achieved by 19.4% of the paediatric group and 13.2% of the adults (p = 0.24), after ER-only resuscitation by 37.0% of the children and 19.6% of the adults (p = 0.046), and after preclinical and ER resuscitation by only 10.9% of the children compared to 2.5% of the adults (p = 0.006). Taking only survivors into account, 84.8% of the children and 62% of the adults had a GOS 4 + 5.The highest risk for mortality in the logistic regression model was associated with preclinical intubation, followed by GCS 3, blood transfusion and severe head injury with AIS ≥3 and ISS.ConclusionsCPR in children after severe trauma seems to yield a better outcome than in adults, and appears to be more justified than the current guidelines would imply. Resuscitation in the ER is associated with better neurological outcomes compared with resuscitation in a preclinical context or in both the preclinical phase and the ER. Our children's outcomes seem to be better than those in most of the earlier studies, and the data presented might support algorithms in the future especially for paediatric resuscitation.     

Qi deficiency is associated with depression in chronic hemodialysis patients

ObjectiveDepression is a common bio-psycho-social problem in hemodialysis (HD) patients. Traditional Chinese medicine has been used for symptom management in patients with depression. Identification of the specific constitution in traditional Chinese medicine is critical for personalized care. However, the association between depression and specific constitution in HD patients is unknown.MethodsWe conducted a cross-sectional study in all chronic HD patients (HD for more than 3 months) at China Medical University Hospital in Taiwan. The depression symptom severity was determined using the Beck Depression Inventory II (BDI-II). Clinical patterns in Chinese medicine were determined using the Constitution in Chinese Medicine Questionnaire. The association between constitution and depression was analyzed using logistic regression.ResultsWe recruited 467 chronic hemodialysis patients, including 219 females and 248 males, with a mean age of 63 ± 12 years. The mean duration of HD was 5.8 years. The mean score for the BDI-II was 11 (interquartile range 8–14). The major constitution was Yang-deficiency (43.7%) among these chronic HD patients. Qi-deficiency was correlated with a duration of HD of more than 5.8 years (p = 0.04). Qi-deficiency [odds ratio (OR): 4.05, 95% confidence interval (CI): 1.69–9.72, p < 0.01] was also associated with depression in logistic regression with adjustments for confounders, including calcium, phosphorus and hemoglobin levels.ConclusionQi-deficiency constitution in Chinese medicine is associated with depression in chronic HD patients. Further studies are needed to determine whether treating Qi-deficiency integrating Chinese medicine treatment can improve patients’ depression symptoms.     

Antidiabetic,antihyperlipidemic and anti-inflammatory effects of tilianin in streptozotocin-nicotinamide diabetic rats

Flavonoids from medicinal plants have been used in traditional medicine to treat a variety of prevalent diseases. Flavones activate the signaling pathways promoting fuel metabolism and insulin sensitizing in hepatocytes and adipocytes, which suggests that flavones may have the potential to exert in vivo antidiabetic and antihyperlipidemic effects. Thus, the aim of the current study was to determine the antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in diabetic rats. Also, to understand the mechanism involved using in vitro 3T3-L1 cells and tissues from experimental animals treated with test samples through molecular profile studies.Non insulin-dependent diabetic mellitus (NIDDM) rats were treated over a short period (for 10 days) with 60 mg/Kg/day of tilianin. After treatment, a biochemical blood profile was determined. Also, adipose and thoracic aortic tissues were used to determine pro-inflammatory profile, adiponectin and adhesion molecules by real-time PCR. In 3T3-L1 cells pretreated with tilianin (10 μM), PPARα, PPARγ, GLUT4, FATP-1 and ACSL-1 mRNA expression were measured. In order to explain the potential PPARα interaction with tilianin, a docking study with PPARα was carried out. Thus, intragastric administration of tilianin and metformin induced a decrease in plasma glucose (GLU) in diabetic rats on day 6, and remained significantly lower until the end of the treatment; also blood triacylglycerides (TAG) and cholesterol (CHOL) (p < 0.05) were diminished. Moreover, IL-1β and IL-18 expression was significantly decreased in adipose tissue (p < 0.05); meanwhile adiponectin was significantly overexpressed (p < 0.05). Besides, ICAM-1 expression was significantly reduced in aortic tissue (p < 0.05). In 3T3-L1 cells it was found that tilianin increased PPARα and ACSL1 mRNA levels (p < 0.05). Finally, tilianin docking studies with PPARα showed polar interactions with Glu269, Tyr314, His 440 and Tyr464 residues. In conclusion, short-term tilianin treatment might exert its antidiabetic and antihyperlipidemic effect by modulating a pro-inflammatory profile, and increasing adiponectin expression. In addition, our results suggest the possible interaction of tilianin with PPARα.     

Changes in treatments and outcomes among elderly patients with out-of-hospital cardiac arrest between 2002 and 2012: A post hoc analysis of the SOS-KANTO 2002 and 2012

BackgroundLittle is known about recent changes in pre- and in-hospital treatments and outcomes for elderly patients with out-of-hospital cardiac arrest (OHCA).MethodsWe compared data collected for the SOS-KANTO study in 2002 and 2012. We included patients aged ≥65 years who experienced OHCA of cardiac aetiology. The primary endpoint was favourable neurological outcomes 1 month after cardiac arrest.ResultsA total of 8,964 (2002 vs. 2012: 3,544 vs. 5,420) patients were eligible for the current analysis. The proportion of pre-hospital return of spontaneous circulation (ROSC) increased significantly (3.8 vs. 5.6%, p < 0.001). Among patients achieving ROSC, the proportion of advanced in-hospital treatments (i.e. extracorporeal membrane oxygenation, therapeutic hypothermia, and/or percutaneous coronary angiogram/intervention) provided increased significantly in 2012 (1.2 vs. 5.5%, p < 0.001; 2.6 vs. 15.1%, p < 0.001; 4.9 vs. 16.5%, p < 0.001; respectively). The proportion of favourable neurological outcomes at 1 month increased significantly in 2012 (1.6 vs. 2.7%, p = 0.001). A logistic regression analysis that did not consider advanced in-hospital treatments showed a significantly higher rate of favourable neurological outcomes in the 2012 group than that in the 2002 group (OR, 2.2; 95% CI, 1.4–3.5). However, this difference was no longer observed in the second regression model that accounted for advanced in-hospital treatments (OR, 1.6; 95% CI, 0.9–2.9).ConclusionThere was an increased proportion of aggressive treatment, both pre- and in-hospital, for elderly patients with cardiogenic OHCA in the Kanto area, Japan. Favourable neurological outcomes improved significantly over 10 years.     

Smoothened activates breast cancer stem-like cell and promotes tumorigenesis and metastasis of breast cancer

Smoothened (Smo) is a G protein-coupled receptor protein encoded by the Smo gene of the hedgehog signalling pathway, which is thought to play an important role in maintaining organ patterning, cell differentiation and self-renewal. The possible role of Smo in the process of tumorigenesis and metastasis of breast cancer still remains unclear. The present experiments were to investigate the effect of Smo on activating breast cancer stem-like CD44⁺CD24⁻ cells and the tumorigenesis and metastasis of breast cancer. By injected CD44⁺CD24⁻ cells (1 × 10⁴) into the cleared fat pad of NOD/SCID mice, it was observed that CD44⁺CD24⁻ cells possess higher tumor-initiating capacity and metastasis properties than equal numbers of non-CD44⁺CD24⁻ cells. The mRNA and protein expressions of Smo in CD44⁺CD24⁻ cells were higher than those in non-CD44⁺CD24⁻ cells, indicating that Smo may play a role in maintaining breast cancer stem cell features. qRT–PCR results revealed that expressions of STAT3, Bcl-2 and cyclinD1 mRNA in MCF-7 cells were decreased after transfected by Smo siRNA. In addition, the expressions of MMP-2 and MMP-9 were downregulated in MCF-7 cells after Smo expression was inhibited. Smo inhibition may be a possible therapeutic target that potentially suppresses breast tumor formation and development.     

Prognostic values of gray matter to white matter ratios on early brain computed tomography in adult comatose patients after out-of-hospital cardiac arrest of cardiac etiology

Aim of the studyPrevious studies found that the gray matter to white matter ratio (GWR) on brain computed tomography (CT) could be used to predict poor outcomes in cardiac arrest survivors. However, these studies have included cardiac arrests of both cardiac and non-cardiac etiologies. We sought to evaluate if the GWR on brain CT can help to predict poor outcomes after out-of-hospital cardiac arrest (OHCA) of cardiac etiology.MethodsUsing a multicenter retrospective registry of adult cardiac arrest survivors treated with therapeutic hypothermia, we identified survivors of OHCA of cardiac etiology who underwent brain CT within 24 h after successful resuscitation. Gray and white matter attenuations were measured, and the GWRs were calculated as in previous studies. The prognostic values of the GWRs were analyzed, and a logistic regression analysis was performed to determine the contribution of the GWR in predicting poor outcomes (Cerebral Performance Category 3–5).Resultsof 283 included patients, 140 had good outcomes and 143 had poor outcomes. Although the GWRs could predict poor outcomes with statistical significance, the sensitivities were remarkably low (3.5% to 5.6%) at cutoff values with 100% specificity. No significant difference in predictive performance was found between the primary predictive model, containing independent poor outcome predictors, and the primary predictive model combined with the GWR.ConclusionIn a cohort of comatose adults after OHCA of cardiac etiology, the GWR demonstrated poor predictive performance and was not helpful in predicting poor outcomes.     

Moderate Cardiorespiratory Fitness Is Positively Associated With Resting Metabolic Rate in Young Adults

ObjectiveTo determine whether moderate cardiorespiratory fitness (CRF) or moderate to vigorous physical activity (MVPA) is associated with elevations in resting metabolic rate (RMR) similar to findings previously observed in endurance athletes.Participants and MethodsUsing a cross-sectional design, we measured CRF, RMR, body composition, energy expenditure, and time in MVPA via an arm-based activity monitor in 423 young adults (mean age, 27.6 years). Based on the results of a fitness test, participants were classified into CRF tertiles (low, moderate, or high) by sex.ResultsThere were significant differences among the low-, moderate-, and high-CRF groups for mean ± SD body mass index (calculated as the weight in kilograms divided by the height in meters squared) (28.1±4.1, 25.1±3.4, and 23.6±2.5, respectively; P<.001) and fat mass (28.8±9.7, 20.5±8.2, and 14.8±6.5 kg, respectively; P<.001) but not fat-free mass (53.1±11.5, 53.5±12.4, and 54.7±12.1 kg, respectively; P=.49). There were no differences in mean ± SD unadjusted RMR among the groups (1533.2±266.2, 1519.7±267.6, and 1521.9±253.9 kcal/d, respectively). However, after statistical adjustment for differences in body composition, the moderate- and high-CRF groups had a higher RMR compared with low-CRF individuals by 39.7 and 59.9 kcal/d, respectively (P<.05). After further adjustment for MVPA, RMR was higher in the high-CRF group compared with the low-CRF group by 51.2 kcal/d (P<.05).ConclusionIn this large sample of young adults representing a range of CRF, there was a positive stepwise gradient in RMR across tertiles of CRF independent of body composition. Also, MVPA was independently associated with RMR, although this relationship was modest. These findings underscore the multidimensional role of CRF and MVPA on health.Trial Registrationclinicaltrials.gov Identifier: NCT01746186     

Relationship Between Exercise Heart Rate and Age in Men vs Women

ObjectiveTo analyze a large cohort of patients who underwent exercise testing and also report sex differences in other exercise heart rate (HR) parameters to determine whether separate sex-based equations to predict peak HR are indicated.Patients and MethodsPatients aged 40 to 89 years who performed treadmill exercise tests (Bruce protocol) from September 21, 1993, to December 20, 2010, were included. Patients with cardiovascular disease or taking HR-attenuating drugs were excluded. After analyses on preliminary cohort, peak HR–modifying factors were eliminated to obtain a pure data set. Analysis of variance was used to test difference in HR responses by sex with age adjustment.ResultsA total of 37,010 patients (67.3% men) were included in the preliminary cohort. Men had higher peak HR (166±17 vs 163±16 beats/min [bpm]; P<.001), HR reserve (90±19 vs 84±17 bpm; P<.001), and HR recovery (19±8 vs 18±9 bpm; P<.03). Poor exercise capacity, current smoking, diabetes, and obesity had significant peak HR–lowering effects (all P<.001). In a pure cohort of 19,013 patients (51.3% of full cohort) without these factors, regression lines approximated more closely the traditional line of 220 – age. For men, the regression line in our final cohort was peak HR = 220 – 0.95 × age. For women, both slope (0.79 bpm/y) and intercept (210 bpm) were still substantially different from those obtained with the traditional formula.ConclusionThe HR responses to exercise are different in men and women. The HR response of men was close to that obtained with the traditional formula, but peak HR in women had a lower intercept and decreased more slowly with age. A separate formula for peak HR in women appears to be appropriate.     

Safety and Efficacy of Extracorporeal Shock Wave Myocardial Revascularization Therapy for Refractory Angina Pectoris

ObjectiveTo assess the safety and efficacy of extracorporeal shockwave myocardial revascularization (ESMR) therapy in treating patients with refractory angina pectoris.Patients and MethodsA single-arm multicenter prospective trial to assess safety and efficacy of the ESMR therapy in patients with refractory angina (class III/IV angina) was performed. Screening exercise treadmill tests and pharmacological single-photon emission computed tomography (SPECT) were performed for all patients to assess exercise capacity and ischemic burden. Patients were treated with 9 sessions of ESMR to ischemic areas over 9 weeks. Efficacy end points were exercise capacity by using treadmill test as well as ischemic burden on pharmacological SPECT at 4 months after the last ESMR treatment. Safety measures included electrocardiography, echocardiography, troponin, creatine kinase, and brain natriuretic peptide testing, and pain questionnaires.ResultsFifteen patients with medically refractory angina and no revascularization options were enrolled. There was a statistically significant mean increase of 122.3±156.9 seconds (38% increase compared with baseline; P=.01) in exercise treadmill time from baseline (319.8±157.2 seconds) to last follow-up after the ESMR treatment (422.1±183.3 seconds). There was no improvement in the summed stress perfusion scores after pharmacologically induced stress SPECT at 4 months after the last ESMR treatment in comparison to that at screening; however, SPECT summed stress score revealed that untreated areas had greater progression in ischemic burden vs treated areas (3.69±6.2 vs 0.31±4.5; P=.03). There was no significant change in the mean summed echo score from baseline to posttreatment (0.4±5.1; P=.70). The ESMR therapy was performed safely without any adverse events in electrocardiography, echocardiography, troponins, creatine kinase, or brain natriuretic peptide. Pain during the ESMR treatment was minimal (a score of 0.5±1.2 to 1.1±1.2 out of 10).ConclusionIn this multicenter feasibility study, ESMR seems to be a safe and efficacious treatment for patients with refractory angina pectoris. However, larger sham-controlled trials will be required to confirm these findings.     

Imaging Pandora's Box: Incidental Findings in Elderly Patients Evaluated for Transcatheter Aortic Valve Replacement

ObjectiveTo determine the frequency and clinical impact of noncardiovascular incidental findings (IFs) detected on preoperative computed tomographic angiography (CTA) of the chest/abdomen/pelvis performed in elderly patients with severe aortic stenosis being considered for transcatheter aortic valve replacement (TAVR).Patients and MethodsThe CTA studies for 424 consecutive patients being evaluated for TAVR between January 1, 2009, through January 24, 2012, were reviewed for noncardiovascular IFs (62.0% male; median ± SD age, 82±8.3 years). The electronic medical record was reviewed to assess for subsequent clinical management and survival.ResultsPotentially pathologic IFs (PPIFs) were present in 285 patients (67.2%). The mean ± SD number of PPIFs per patient was 1.1±1.0 (range, 0-4). Factors associated with higher numbers of PPIFs were reduced ejection fraction (P=.02) and history of smoking (P=.06). Potentially pathologic incidental findings prompted clinical work-up in 39 patients (9.2%) and delayed or canceled treatment plans for aortic stenosis in 7 patients (1.7%). The number needed to image to diagnose a new malignancy or medical condition was 19. The number of PPIFs was predictive of poor overall survival before (hazard ratio, 1.58; 95% CI, 1.31-1.88) and after (hazard ratio, 1.45; 95% CI, 1.19-1.76) adjustment for baseline clinical variables (P<.001 for both).ConclusionThis investigation found that PPIFs are common in elderly patients undergoing TAVR-CTA scans and, once discovered, commonly generate further clinical evaluation. Higher numbers of PPIFs may be predictive of poorer survival, but further study is required to guide the appropriateness of pursuing diagnostic evaluations for asymptomatic PPIFs in this elderly population.     

A new choice of stent for transjugular intrahepatic portosystemic shunt creation: Viabahn ePTFE covered stent/bare metal stent combination

ObjectivesTo compare the clinical outcomes in terms of structure and function between the insertion of a transjugular intrahepatic portosystemic shunt (TIPS) created with the Viabahn ePTFE covered stent/bare metal stent (BMS) combination and the Fluency ePTFE covered stent/BMS combination.MethodsA total of 101 consecutive patients who received a TIPS from February 2016 to August 2018 in our center were retrospectively analyzed. Sixty-four subjects were enrolled in the Viabahn group and 37 were enrolled in the Fluency group. The geometry characteristics of the TIPS were calculated, and the associated occurrence of shunt dysfunction, survival, overt hepatic encephalopathy, and variceal rebleeding were evaluated.ResultsThe technical success rate was 100%. After the insertion of the TIPS, the rate of shunt dysfunction during the first 3 months was significantly different between the Viabahn and Fluency groups (1.6% and 13.5%, respectively; p ​= ​0.024). Multivariate analysis indicated that the angle of portal venous inflow (α) was the only independent risk factor for shunt dysfunction (hazard ratio ​= ​1.060, 95% confidence interval ​= ​1.009–1.112, p ​= ​0.020). In addition, 3 months after the TIPS insertion, the α angle distinctly increased from 20.9° ​± ​14.3°–26.9° ​± ​20.1° (p ​= ​0.005) in the Fluency group but did not change significantly in the Viabahn group (from 21.9° ​± ​15.1°–22.9° ​± ​17.6°, p ​= ​0.798).ConclusionsShunt dysfunction was related to the α angle owing to the slight effect on the α angle after the implantation of the TIPS. The Viabahn ePTFE covered stent/BMS combination was more stable in structure and promised higher short-term stent patency compared with the Fluency ePTFE covered stent/BMS combination.     

Influence of Early Surgical Treatment on the Prognosis of Left-Sided Infective Endocarditis: A Multicenter Cohort Study

ObjectiveTo analyze the influence of early valve operation on mortality in patients with left-sided infective endocarditis (IE).Patients and MethodsA multicenter cohort study was carried out between 1990 and 2010. Data from consecutive patients with definite IE and possible left-sided IE were collected. Propensity score matching and adjustment for survivor bias were used to control for confounders. The primary outcome was in-hospital mortality.ResultsA total of 1019 patients with a mean age of 61 years (interquartile range, 47-71 years) were included. Early surgical treatment was performed in 417 episodes (40.9%). By propensity score, we matched 316 episodes: 158 who underwent early surgical treatment and 158 who did not (medical treatment group). In-hospital mortality and late mortality were lower in the surgically treated group (26.6% vs 41.8%; absolute risk reduction [ARR], −15.2%; P=.004 and 29.7% vs 46.2%; ARR, −16.5%; P=.002, respectively). Operation was independently associated with a lower risk of in-hospital mortality (odds ratio, 0.42; 95% CI, 0.22-0.79; P=.007). Operation was associated with reduced mortality in patients with paravalvular complications (ARR, −40.5%), severe heart failure (ARR, −32%), and native valve endocarditis (ARR, −17.8%).ConclusionThis study supports the benefit of surgical treatment in patients with left-sided IE carried out during the initial phase of hospitalization, especially in patients with moderate or severe heart failure and paravalvular extension of infection.     

Examining the Function In Sitting Test for Validity,Responsiveness, and Minimal Clinically Important Difference in Inpatient Rehabilitation

ObjectivesTo determine the responsiveness of the Function In Sitting Test (FIST), compare scores at admission and discharge from inpatient rehabilitation (IPR) with other balance and function measures, and determine the minimal clinically important difference (MCID).DesignProspective, nonblinded, reference-standard comparison study.SettingFour accredited inpatient rehabilitation units.ParticipantsPopulation-based sample of adults (N=125) with sitting balance dysfunction, excluding persons with spinal cord injury, significant bracing/orthotics, and inability to perform testing safely.InterventionsNot applicable.Main Outcome MeasuresFIST, FIM, and Berg Balance Scale (BBS) at admission and discharge, and Global Rating of Change for function and balance at discharge.ResultsThe FIST demonstrated good to excellent concurrent validity with the BBS and FIM at admission and discharge (Spearman ρ=.71–.85). Significant improvement (P<.000; 95% confidence interval [CI], 10.73–15.41) occurred in the FIST from admission (mean ± SD: 36.81±15.53) to discharge (mean ± SD: 49.88±6.90). The standard error of measurement for the FIST was 1.40, resulting in a minimal detectable change of 5.5 points. The receiver operator characteristic curve differentiated participants with meaningful balance changes (area under the curve, .78; P>.000; 95% CI, .66–.91), with a change in FIST score of ≥6.5 points designating the MCID. Findings support the strong responsiveness of the FIST during IPR as evidenced by the large effect size (.83), standardized response mean (1.04), and index of responsiveness (1.07).ConclusionsIn this study, the FIST correlated well with balance and function measures (concurrent validity) and was responsive to change during IPR. A clinically meaningful change was indicated by an increase in score of ≥6.5 points.     

Maternal Vitamin D Supplementation to Improve the Vitamin D Status of Breast-fed Infants: A Randomized Controlled Trial

ObjectiveTo determine whether a single monthly supplement is as effective as a daily maternal supplement in increasing breast milk vitamin D to achieve vitamin D sufficiency in their infants.Patients and MethodsForty mothers with exclusively breast-fed infants were randomized to receive oral cholecalciferol (vitamin D₃) 5000 IU/d for 28 days or 150,000 IU once. Maternal serum, breast milk, and urine were collected on days 0, 1, 3, 7, 14, and 28; infant serum was obtained on days 0 and 28. Enrollment occurred between January 7, 2011, and July 29, 2011.ResultsIn mothers given daily cholecalciferol, concentrations of serum and breast milk cholecalciferol attained steady levels of 18 and 8 ng/mL, respectively, from day 3 through 28. In mothers given the single dose, serum and breast milk cholecalciferol peaked at 160 and 40 ng/mL, respectively, at day 1 before rapidly declining. Maternal milk and serum cholecalciferol concentrations were related (r=0.87). Infant mean serum 25-hydroxyvitamin D concentration increased from 17±13 to 39±6 ng/mL in the single-dose group and from 16±12 to 39±12 ng/mL in the daily-dose group (P=.88). All infants achieved serum 25-hydroxyvitamin D concentrations of more than 20 ng/mL.ConclusionEither single-dose or daily-dose cholecalciferol supplementation of mothers provided breast milk concentrations that result in vitamin D sufficiency in breast-fed infants.Clinical Trial Registrationclinicaltrials.gov NCT01240265