PURPOSE OF REVIEWProtein requirement in healthy young and old individuals is traditionally defined as the lowest protein intake sufficient to achieve neutral body protein balance. This concept, ...however, cannot be applied to those conditions characterized by unavoidable protein catabolism despite optimal nutrition, such as inactivity and diseases associated with systemic inflammation.
RECENT FINDINGSThe ability of dietary proteins to promote protein anabolism is reduced by inactivity and inflammatory mediators, whereas physical exercise ameliorates the efficiency in using dietary proteins. Consequently, the protein intake level associated with the lowest rate of catabolism in inactivity and/or inflammation is greater than the minimum protein intake required to achieve neutral protein balance in healthy, physically active individuals. A protein intake of 1.2 g·kg·day is currently recommended for inactive healthy individuals, whereas guidelines recommend up to 1.5 g·kg·day in patients with severe systemic inflammation, such as those affected by critical illness or cancer. High protein intake accelerates progression of renal insufficiency but does not affect renal function in healthy individuals.
SUMMARYIn inflammation and/or inactivity a relatively high protein intake may be required to promote synthesis of specific proteins, prevent depletion of selected amino acids (e.g., glutamine or arginine), modulate immune functions, counteract insulin resistance and redox unbalance. Thus, an optimal protein/amino acid intake may be greater than that required to decrease whole body protein wasting.
PURPOSE OF REVIEWCachexia is a disease-related multifactorial syndrome characterized by inflammation, massive muscle protein catabolism and carbohydrate and lipid metabolism disorder.Several studies ...tried to define the impact of either nutrition or physical exercise (single approach strategy) or their combination (multimodal approach strategy) on prevention and/or treatment of muscle wasting in cachectic patients.
RECENT FINDINGSSingle approach strategies (i.e. nutrition or physical exercise) have the potential of preventing and improving features of the cachexia syndrome possibly with a differential impact according to the underlying disease. Limited information is available on the beneficial effect of multimodal approach strategies.
SUMMARYMultimodal approaches appear to be more effective than those based on single interventions in physiological condition and in cachectic patients with COPD or chronic kidney disease. Further studies, however, are required in cachexia induced by heart failure, cancer and critical illness.
The study assessed the clinical response to add‐on brivaracetam (BRV) in real‐world practice by means of time‐to‐baseline seizure count methodology. Patients with focal epilepsy who were prescribed ...add‐on BRV were identified. Primary endpoint was the time‐to‐baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three‐hundred eighty‐seven patients were included. The overall median time‐to‐baseline seizure count was 150 (95% confidence interval CI = 130‐175) days. The median time‐to‐baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV‐naive patients, 126 (95% CI = 105‐150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128‐291) days for patients who discontinued LEV due to adverse events (P = .002). The number of prior antiseizure medications (adjusted hazard ratio adjHR = 1.07, 95% CI = 1.02‐1.13, P = .009) and baseline monthly seizure frequency (adjHR = 1.004, 95% CI = 1.001‐1.008, P = .028) were independently associated with the primary endpoint. Add‐on BRV improved seizure control in LEV‐naive and LEV‐prior patients. The time‐to‐baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs.
Purpose
To establish whether a slow or a rapid withdrawal of antiepileptic monotherapy influences relapse rate in seizure-free adults with epilepsy and calculates compliance and differences in the ...severity of relapses, based on the occurrence of status epilepticus, seizure-related injuries, and death.
Methods
This is a multicentre, prospective, randomized, open label, non-inferiority trial in people aged 16 + years who were seizure-free for more than 2 years. Patients were randomized to slow withdrawal (160 days) or rapid withdrawal (60 days) and were followed for 12 months. The primary outcome was the probability of a first seizure relapse within the 12-months follow-up. The secondary outcomes included the cumulative probability of relapse at 3, 6, 9, and 12 months. A non-inferiority analysis was performed with non-inferiority margin of − 0.15 for the difference between the probabilities of seizure recurrence in slow versus rapid withdrawal.
Results
The sample comprised 48 patients, 25 randomized to slow withdrawal and 23 to rapid withdrawal. Median follow-up was 11.9 months. In the intention-to-treat population, 3 patients in the slow-withdrawal group and 1 in the rapid withdrawal group experienced seizure relapses. The corresponding probabilities of seizure recurrence were 0.12 for slow withdrawal and 0.04 for rapid withdrawal, giving a difference of 0.08 (95% CI − 0.12; 0.27), which is entirely above the non-inferiority margin. No patients developed status epilepticus and seizure-related injuries or died. Risks were similar in the Per-Protocol population.
Conclusions
Seizure-relapse rate after drug discontinuation is lower than in other reports, without complications and unrelated to the duration of tapering.
•BRV proved to be useful and safe for the treatment of status epilepticus.•Time to seizures resolution appears shorter when it is administered in the early phases of status epilepticus.•The use of ...the BRV within 6 h from SE onset was independently associated to an early seizures’ resolution.•No severe treatment emergent adverse events were observed.
to evaluate the use, effectiveness, and adverse events of intravenous brivaracetam (BRV) in status epilepticus (SE).
a retrospective multicentric study involving 24 Italian neurology units was performed from March 2018 to June 2020. A shared case report form was used across participating centres to limit biases of retrospective data collection. Diagnosis and classification of SE followed the 2015 ILAE proposal. We considered a trial with BRV a success when it was the last administered drug prior the clinical and/or EEG resolution of seizures, and the SE did not recur during hospital observation. In addition, we considered cases with early response, defined as SE resolved within 6 h after BRV administration.
56 patients were included (mean age 62 years; 57 % male). A previous diagnosis of epilepsy was present in 21 (38 %). Regarding SE etiology classification 46 % were acute symptomatic, 18 % remote and 16 % progressive symptomatic. SE episodes with prominent motor features were the majority (80 %). BRV was administered as first drug after benzodiazepine failure in 21 % episodes, while it was used as the second or the third (or more) drug in the 38 % and 38 % of episodes respectively. The median loading dose was 100 mg (range 50−300 mg). BRV was effective in 32 cases (57 %). An early response was documented in 22 patients (39 % of the whole sample). The use of the BRV within 6 h from SE onset was independently associated to an early SE resolution (OR 32; 95 % CI 3.39–202; p = 0.002). No severe treatment emergent adverse events were observed.
BRV proved to be useful and safe for the treatment of SE. Time to seizures resolution appears shorter when it is administered in the early phases of SE.
Bickerstaff brainstem encephalitis (BBE) is a rare neurological disease that generally has a good prognosis. We describe an atypical case of a patient with severe BBE; the presentation was uncommon ...because of the lack of ophthalmoplegia and because of evidence of both peripheral neuropathy and brainstem encephalitis. The article reports clinical and biochemical evaluation and focuses on magnetic resonance imaging (MRI) findings in diagnosis and management of the patient. Notably, we found a previously unreported dramatic spinal cord involvement on MRI. We believe these findings could add to diagnostic tools, and that this case may represent a new variant of BBE with more aggressive behavior.
ABSTRACTHallmark of retinitis pigmentosa (RP) is the primary, genetic degeneration of rods followed by secondary loss of cones, caused by still elusive biologic mechanisms. We previously shown that ...exposure of rd10 mutant mice, modeling autosomal recessive RP, to environmental enrichment (EE), with enhanced motor, sensorial and social stimuli, results into a sensible delay of retinal degeneration and vision loss. Searching for effectors of EE‐mediated retinal protection, we performed transcriptome analysis of the retina of rd10 enriched and control mice and found that gene expression at the peaks of rod and cone degeneration is characterized by a strong inflammatory/immune response, which is however measurably lower in enrichment conditions. Treating rd10 mice with dexamethasone during the period of maximum photoreceptors death lowered retinal inflammation and caused a preservation of cones and cone‐mediated vision. Our findings indicate a link between retinal inflammation and bystander cone degeneration, reinforcing the notion that cone vision in RP can be preserved using anti‐inflammatory approaches.—Guadagni, V., Biagioni, M., Novelli, E., Aretini, P., Mazzanti, C. M., Strettoi, E. Rescuing cones and daylight vision in retinitis pigmentosa mice. FASEB J. 33, 10177–10192 (2019). www.fasebj.org
Glaucoma and other optic neuropathies are characterized by a loss of retinal ganglion cells (RGCs), a cell layer located in the posterior eye segment. Several preclinical studies demonstrate that ...neurotrophins (NTs) prevent RGC loss. However, NTs are rarely investigated in the clinic due to various issues, such as difficulties in reaching the retina, the very short half-life of NTs, and the need for multiple injections. We demonstrate that NTs can be conjugated to magnetic nanoparticles (MNPs), which act as smart drug carriers. This combines the advantages of the self-localization of the drug in the retina and drug protection from fast degradation. We tested the nerve growth factor and brain-derived neurotrophic factor by comparing the neuroprotection of free versus conjugated proteins in a model of RGC loss induced by oxidative stress. Histological data demonstrated that the conjugated proteins totally prevented RGC loss, in sharp contrast to the equivalent dose of free proteins, which had no effect. The overall data suggest that the nanoscale MNP-protein hybrid is an excellent tool in implementing ocular drug delivery strategies for neuroprotection and therapy.
Hepatic resection is the only chance of cure for a subgroup of patients with colorectal cancer liver metastasis. As the oncologic outcomes of intra-operative microwaves ablation combined with hepatic ...resection still remain uncertain in this setting, we aimed to compare this approach with surgery alone in patient's candidate to metastases resection with radical intent.
Using a case-matched methodology based on age, gender, American Society of Anesthesiology score, Body Mass Index, and burden that take in consideration the number and maximum size of lesions, 20 patients undergoing hepatic resection plus intra-operative microwaves (SURG + IMW group) and 20 patients undergoing hepatic resection alone (SURG group), were included. Relapse-free Survival and post-resection Overall Survival were compared between patients of two groups.
At the median follow up of 22.4 ± 17.8, 12/20 patients (60%) in SURG +IMW group and 13/20 patients (65%) in the SURG group experienced liver metastasis recurrence (p=0.774). None of them had recurrence at the same surgical or ablation site of the first hepatic treatment. 7/12 patients in the SURG+IMW group and 7/13 patients in the SURG group underwent at least one further surgical treatment after relapse (p = 1.000). No difference was reported between the two groups in terms of Relapse-free Survival (p = 0.685) and post-resection Overall Survival (p = 0.151). The use of intra-operative microwaves was not an independent factor affecting Relapse-free Survival and post-resection Overall Survival at univariate and multivariate analysis.
Patients with colorectal cancer liver metastasis undergoing surgery plus intra-operative microwaves have similar post-operative results compared with surgery alone group. The choice between the two approaches could be only technical, depending on the site, number, and volume of the metastases. This approach could also be used in patients with liver metastasis relapse who have already undergone hepatic surgery.
PDF
