Incobotulinum booster injections in patients with spasticity and dystonia after stroke

Background.\u2013 Previous results in patients injected with abobotulinum toxin A and onabotulinum toxin A have shown that injection intervals shorter than 2 months may increase the risk for neutralising antibody formation and treatment non-response. As a result, for the last 10 years, we have adopted longer intervals to treat patients with spasticity and/or dystonia secondary to stroke. It has been showed that incobotulinum toxin A does not induce neutralising antibodies. Observations.\u2013 Methods.\u2013 Ten patients with spasticity and/or dystonia due to stroke underwent a booster injection one month after the first injection. The clinical results were compared to those previously obtained in the same 10 patients using a single injection. Secondary dystonia was evaluated using the Unified Dystonia Rating Scale (UDRS), while spasticity was evaluated according to the Modified Ashworth Scale (MAS). Results.\u2013 They showed that the booster injection protocol induced an improvement in 8 subjects. In the remaining 2 subjects, we did not find any difference between the results obtained using the single and the booster injection protocols. Conclusions.\u2013 The use of a booster injection improve the clinical outcome in patients with spasticity and/or dystonia after stroke, allowing an optimal treatment of those muscles that poorly responded to the first injection

A Programmable Neural Interface for Investigating Arbitrary Stimulation Strategies

Accepted versio

Gastrointestinal colonization with multidrug-resistant Gram-negative bacteria during extracorporeal membrane oxygenation: effect on the risk of subsequent infections and impact on patient outcome

Background: In ICU patients, digestive tract colonization by multidrug-resistant (MDR) Gram-negative (G 12) bacteria is a significant risk factor for the development of infections. In patients undergoing extracorporeal membrane oxygenation (ECMO), colonization by MDR bacteria and risk of subsequent nosocomial infections (NIs) have not been studied yet. The aim of this study is to evaluate the incidence, etiology, risk factors, impact on outcome of gastrointestinal colonization by MDR G 12 bacteria, and risk of subsequent infections in patients undergoing ECMO. Methods: This is a retrospective analysis of prospectively collected data: 105 consecutive patients, treated with ECMO, were admitted to the ICU of an Italian tertiary referral center (San Gerardo Hospital, Monza, Italy) from January 2010 to November 2015. Rectal swabs for MDR G 12 bacteria were cultured at admission and twice a week. Only colonization and NIs by MDR G 12 bacteria were analyzed. Results: Ninety-one included patients [48.5 (37\u201356) years old, 63% male, simplified acute physiology score II 37 (32\u201347)] underwent peripheral ECMO (87% veno-venous) for medical indications (79% ARDS). Nineteen (21%) patients were colonized by MDR G 12 bacteria. Male gender (OR 4.03, p = 0.029) and duration of mechanical ventilation (MV) before ECMO > 3 days (OR 3.57, p = 0.014) were associated with increased risk of colonization. Colonized patients had increased odds of infections by the colonizing germs (84% vs. 29%, p < 0.001, OR 12.9), longer ICU length of stay (LOS) (43 vs. 24 days, p = 0.002), MV (50 vs. 22 days, p < 0.001) and ECMO (28 vs. 12 days, p < 0.001), but did not have higher risk of death (survival rate 58% vs. 67%, p = 0.480, OR 0.68). Infected patients had almost halved ICU survival (46% vs. 78%, p < 0.001, OR 4.11). Conclusions: In patients undergoing ECMO for respiratory and/or circulatory failure, colonization by MDR G 12 bacteria is frequent and associated with more the tenfold odds for subsequent infection. Those infections are associated with an increased risk of death

Outcomes following endovascular abdominal aortic aneurysm repair (EVAR): An anatomic and device-specific analysis

ObjectiveWe performed a device-specific comparison of long-term outcomes following endovascular abdominal aortic aneurysm repair (EVAR) to determine the effect(s) of device type on early and late clinical outcomes. In addition, the impact of performing EVAR both within and outside of specific instructions for use (IFU) for each device was examined.MethodsBetween January 8, 1999 and December 31, 2005, 565 patients underwent EVAR utilizing one of three commercially available stent graft devices. Study outcomes included perioperative (≤30 days) mortality, intraoperative technical complications and need for adjunctive procedures, aneurysm rupture, aneurysm-related mortality, conversion to open repair, reintervention, development and/or resolution of endoleak, device related adverse events (migration, thrombosis, or kinking), and a combined endpoint of any graft-related adverse event (GRAE). Study outcomes were correlated by aneurysm morphology that was within or outside of the recommended device IFU. χ2 and Kaplan Meier methods were used for analysis.ResultsGrafts implanted included 177 Cook Zenith (CZ, 31%), 111 Gore Excluder (GE, 20%), and 277 Medtronic AneuRx (MA, 49%); 39.3% of grafts were placed outside of at least one IFU parameter. Mean follow-up was 30 ± 21 months and was shorter for CZ (20 months CZ vs 35 and 31 months for GE and MA, respectively; P < .001). Overall actuarial 5-year freedom from aneurysm-related death, reintervention, and GRAE was similar among devices. CZ had a lower number of graft migration events (0 CZ vs 1 GE and 9 MA); however, there was no difference between devices on actuarial analysis. Combined GRAE was lowest for CZ (29% CZ, 35% GE, and 43% MA; P = .01). Graft placement outside of IFU was associated with similar 5-year freedom from aneurysm-related death, migration, and reintervention (P > .05), but a lower freedom from GRAE (74% outside IFU vs 86% within IFU; P = .021), likely related to a higher incidence of graft thrombosis (2.3% outside IFU vs 0.3% within IFU; P = .026). The differences in outcome for grafts placed within vs outside IFU were not device-specific.ConclusionEVAR performed with three commercially available devices provided similar clinically relevant outcomes at 5 years, although no graft migration occurred with a suprarenal fixation device. As anticipated, application outside of anatomically specific IFU variables had an incremental negative effect on late results, indicating that adherence to such IFU guidelines is appropriate clinical practice

Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells

We identified eukaryotic translation elongation factor 1A (eEF1A) Raf-mediated phosphorylation sites and defined their role in the regulation of eEF1A half-life and of apoptosis of human cancer cells. Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf. Interestingly, S21 belongs to the first eEF1A GTP/GDP-binding consensus sequence. Phosphorylation of S21 was strongly enhanced when both eEF1A isoforms were preincubated prior the assay with C-Raf, suggesting that the eEF1A isoforms can heterodimerize thus increasing the accessibility of S21 to the phosphate. Overexpression of eEF1A1 in COS 7 cells confirmed the phosphorylation of T88 also in vivo. Compared with wt, in COS 7 cells overexpressed phosphodeficient (A) and phospho-mimicking (D) mutants of eEF1A1 (S21A/D and T88A/D) and of eEF1A2 (S21A/D), resulted less stable and more rapidly proteasome degraded. Transfection of S21 A/D eEF1A mutants in H1355 cells increased apoptosis in comparison with the wt isoforms. It indicates that the blockage of S21 interferes with or even supports C-Raf induced apoptosis rather than cell survival. Raf-mediated regulation of this site could be a crucial mechanism involved in the functional switching of eEF1A between its role in protein biosynthesis and its participation in other cellular processes

Prediction of resting energy expenditure in Italian older adults with severe obesity

Background: In the last decade a large number of studies proposed and/or validated equations to estimate the Resting Energy Expenditure (REE) in adults and/or older adults, however, no equation currently available showed good accuracy for older adults with severe obesity. Thus, this study aimed to develop and validate new predictive equations for REE, based on data from the indirect calorimetry, in Italian older adults with severe obesity. Methods: A retrospective study was as conducted with 764 Caucasian older adults with severe obesity (age range: 60-74 years and BMI ≥ 35 kg/m/2). Four models were used to test the accuracy of anthropometry and body composition variables in multivariable prediction of REE. All models were derived by stepwise multiple regression analysis using a calibration group of 382 subjects [295 females and 87 males] and the equations were cross-validated in the remaining 382 subjects [295 females and 87 males] as validation group. The new prediction equations and the other published equations were tested using the Bland-Altman method. Prediction accuracy was defined as the percentage of subjects whose REE was predicted within ± 10% of measured REE. Results: All the equations analyzed predicted higher energy requirements for males than females, and most of them underestimated the energy requirement values of our sample. The highest accuracy values were observed in the new equations, with 62% in the anthropometric model and 63% in the body composition model. Conclusion: Although the accuracy of our equations was slightly higher in comparison with the other taken into consideration, they cannot be considered completely satisfactory for predicting REE in Italians older adults with severe obesity. When predicting equations cannot guarantee precise or acceptable values of REE, the use of indirect calorimetry (if available) should be always recommended, especially in clinical practice

Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells

We identified eukaryotic translation elongation factor 1A (eEF1A) Raf-mediated phosphorylation sites and defined their role in the regulation of eEF1A half-life and of apoptosis of human cancer cells. Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf. Interestingly, S21 belongs to the first eEF1A GTP/GDP-binding consensus sequence. Phosphorylation of S21 was strongly enhanced when both eEF1A isoforms were preincubated prior the assay with C-Raf, suggesting that the eEF1A isoforms can heterodimerize thus increasing the accessibility of S21 to the phosphate. Overexpression of eEF1A1 in COS 7 cells confirmed the phosphorylation of T88 also in vivo. Compared with wt, in COS 7 cells overexpressed phosphodeficient (A) and phospho-mimicking (D) mutants of eEF1A1 (S21A/D and T88A/D) and of eEF1A2 (S21A/D), resulted less stable and more rapidly proteasome degraded. Transfection of S21 A/D eEF1A mutants in H1355 cells increased apoptosis in comparison with the wt isoforms. It indicates that the blockage of S21 interferes with or even supports C-Raf induced apoptosis rather than cell survival. Raf-mediated regulation of this site could be a crucial mechanism involved in the functional switching of eEF1A between its role in protein biosynthesis and its participation in other cellular processes

Adjuvant treatment of severe varicella pneumonia with intravenous varicella zoster virus-specific immunoglobulins

Varicella zoster virus (VZV) pneumonia is associated with significant mortality, especially in the immunocompromised host. VZV-specific immunoglobulins (VZIG) are currently used as post-exposure prophylaxis for at-risk patients, but not as adjunctive therapy. A novel case of VZV pneumonia in an immunocompromised patient, treated successfully with intravenous VZIG in combination with acyclovir, is reported here