The efficacy of standard rehabilitative therapy for improving upper limb functions after stroke is limited; thus, alternative strategies are needed. Vagus nerve stimulation (VNS) paired with ...rehabilitation is a promising approach, but the invasiveness of this technique limits its clinical application. Recently, a noninvasive method to stimulate vagus nerve has been developed. The aim of the present study was to explore whether noninvasive VNS combined with robotic rehabilitation can enhance upper limb functionality in chronic stroke. Safety and efficacy of this combination have been assessed within a proof-of-principle, double-blind, semirandomized, sham-controlled trial. Fourteen patients with either ischemic or haemorrhagic chronic stroke were randomized to robot-assisted therapy associated with real or sham VNS, delivered for 10 working days. Efficacy was evaluated by change in upper extremity Fugl–Meyer score. After intervention, there were no adverse events and Fugl–Meyer scores were significantly better in the real group compared to the sham group. Our pilot study confirms that VNS is feasible in stroke patients and can produce a slight clinical improvement in association to robotic rehabilitation. Compared to traditional stimulation, noninvasive VNS seems to be safer and more tolerable. Further studies are needed to confirm the efficacy of this innovative approach.
Non-invasive brain stimulation (NIBS) has been under investigation as adjunct treatment of various neurological disorders with variable success. One challenge is the limited knowledge on what would ...be effective neuronal targets for an intervention, combined with limited knowledge on the neuronal mechanisms of NIBS. Motivated on the one hand by recent evidence that oscillatory activities in neural systems play a role in orchestrating brain functions and dysfunctions, in particular those of neurological disorders specific of elderly patients, and on the other hand that NIBS techniques may be used to interact with these brain oscillations in a controlled way, we here explore the potential of modulating brain oscillations as an effective strategy for clinical NIBS interventions. We first review the evidence for abnormal oscillatory profiles to be associated with a range of neurological disorders of elderly (e.g., Parkinson's disease (PD), Alzheimer's disease (AD), stroke, epilepsy), and for these signals of abnormal network activity to normalize with treatment, and/or to be predictive of disease progression or recovery. We then ask the question to what extent existing NIBS protocols have been tailored to interact with these oscillations and possibly associated dysfunctions. Our review shows that, despite evidence for both reliable neurophysiological markers of specific oscillatory dis-functionalities in neurological disorders and NIBS protocols potentially able to interact with them, there are few applications of NIBS aiming to explore clinical outcomes of this interaction. Our review article aims to point out oscillatory markers of neurological, which are also suitable targets for modification by NIBS, in order to facilitate in future studies the matching of technical application to clinical targets.
In search for individualized predictors of stroke recovery, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) is attracting great interest, because it has a negative impact on ...neurotrophin function. Since stroke recovery relies on brain plastic processes, on which BDNF is permissive, the dominant thought is in favor of a worse recovery in Met carriers. Conversely, we suggest that Met carriers do not differ in terms of absolute ability to recover from stroke, but they do differ on the way they recover. In particular, Met carriers rely more on subcortical plasticity, while ValVal patients more on intracortical plastic processes. Indeed, the direct evidence of impaired Met carrier recovery is inconsistent, as a high worldwide diffusion of the polymorphism suggests. The plasticity taking place in cortex, which is the one targeted by noninvasive brain stimulation strategies aimed at enhancing recovery, is less pronounced in Met carrier stroke patients, who have instead spared global recovery potential. Enhanced subcortical plasticity sustains better stroke recovery of Met carrier mice: this may also happen in humans, explaining the weaker interhemispheric cortical excitability imbalance recently described in Met carriers. Thus, BDNF haplotype determines mechanisms and structures involved in stroke recovery. The less pronounced cortical plasticity of Met carrier implies that plastic changes induced by interventional neurophysiological protocols would be better predictors of ValVal chronic outcome and those protocols would be more effective to boost their recovery. Other strategies, more focused on subcortical mechanisms, should be used in Met carriers.
Viridans Group Streptococci (VGS) species-level identification is fundamental for patients management. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has ...been used for VGS identification but discrimination within the Mitis group resulted difficult. In this study, VGS identifications with two MALDI-TOF instruments, the Biotyper (Bruker) and the VITEK MS (bioMérieux) have been compared to those derived from tuf, soda and rpoB genes sequencing. VGS isolates were clustered and a dendrogram constructed using the Biotyper 3.0 software (Bruker). RpoB gene sequencing resulted the most sensitive and specific molecular method for S. pneumonia identification and was used as reference method. The sensitivity and the specificity of the VITEK MS in S. pneumonia identification were 100%, while the Biotyper resulted less specific (92.4%). In non pneumococcal VGS strains, the group-level correlation between rpoB and the Biotyper was 100%, while the species-level correlation was 61% after database upgrading (than 37% before upgrading). The group-level correlation between rpoB and the VITEK MS was 100%, while the species-level correlation was 36% and increases at 69% if isolates identified as S. mitis/S. oralis are included. The less accurate performance of the VITEK MS in VGS identification within the Mitis group was due to the inability to discriminate between S. mitis and S. oralis. Conversely, the Biotyper, after the release of the upgraded database, was able to discriminate between the two species. In the dendrogram, VGS strains from the same group were grouped into the same cluster and had a good correspondence with the gene-based clustering reported by other authors, thus confirming the validity of the upgraded version of the database. Data from this study demonstrated that MALDI-TOF technique can represent a rapid and cost saving method for VGS identification even within the Mitis group but improvements of spectra database are still recommended.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Endothelial dysfunction, coupled with inflammation, induces thrombo-inflammation. In COVID-19, this process is believed to be associated with clinical severity. Von Willebrand factor ...(VWF), and a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS-13), are strong markers of endothelial dysfunction. We evaluated the impact of the VWF/ADAMTS-13 fraction on COVID-19 severity and prognosis. Materials and methods: A cohort study including 74 COVID-19 patients, with 22 admitted to the intensive care unit (ICU) and 52 to the medical ward (MW), was carried out. We also evaluated, in a group of 54 patients who were prospectively observed, whether variations in VWF/ADAMTS-13 correlated with the degree of severity and routine blood parameters. Results: A VWF:RCo/ADAMTS-13 fraction above 6.5 predicted in-hospital mortality in the entire cohort. At admission, a VWF:RCo/ADAMTS-13 fraction above 5.7 predicted admission to the ICU. Furthermore, the VWF:RCo/ADAMTS-13 fraction directly correlated with C-reactive protein (CRP) (Spearman r: 0.51, p < 0.0001) and D-dimer (Spearman r: 0.26, p = 0.03). In the prospective cohort, dynamic changes in VWF:RCo/ADAMTS-13 and the CRP concentration were directly correlated (Spearman r, p = 0.0014). This relationship was significant in both groups (ICU: p = 0.006; MW: p = 0.02).Conclusions: The present findings show that in COVID-19, the VWF/ADAMTS-13 fraction predicts in-hospital mortality. The VWF/ADAMTS-13 fraction may be a helpful tool to monitor COVID-19 patients throughout hospitalization.
Procalcitonin and Mid-regional pro Adrenomedullin have been proposed for sepsis diagnosis, antibiotic therapy guidance and prognosis. A retrospective analysis of PCT and MR-proADM on 571 consecutive ...patients with sepsis diagnosis was performed. Median values were compared using the non-parametric Mann-Whitney's test. Receiver operating characteristic analysis was performed to define cutoff points for sepsis diagnosis. Pretest odds, posttest odds, and posttest probability have been calculated. Data were analyzed using Med-Calc 11.6.1.0 software. PCT resulted excellent in gram-negative, but less performant in gram-positive and fungal etiologies. MR-proADM values resulted homogenously distributed within the different microbial classes and increased significantly in septic shock. PCT highest PPV value was found to distinguish gram-negative from fungal sepsis and septic shock (>3. 57 ng/mL, PPV 0.96 and > 8.77 ng/mL, PPV 0.96, respectively). Good diagnostic accuracy was evidenced to discriminate gram-negative from gram-positive septic shock (>3.88 ng/mL PPV 0.89). Lower diagnostic accuracy was evidenced to discriminate gram-negative and gram-positive sepsis (>0.80 ng/mL, PPV 0.78) and gram-positive from fungal septic shock (>1.74 ng/mL PPV 0.75). The lowest PCT PPV (0.28) was found in gram-positive and fungal sepsis distinction. MR-proADM discriminating cut-offs were homogeneously distributed in Gram-negative and Gram-positive sepsis and were higher in septic shock, but not influenced by pathogen etiologies. MR-proADM cut-off values > 3.39 nmol/L in sepsis and >4.33 nmol/L in septic shock were associated with significant higher risk of 90-days mortality. In conclusion, PCT and MR-proADM combination represents an advantage for sepsis diagnosis and for 90-days mortality risk stratification.
•Sepsis is a severe systemic syndrome characterized by high mortality rate.•PCT and MR-proADM can provide useful information at diagnostic and prognostic purposes.•PCT highest PPV value was evidenced to distinguish gram-negative from fungal sepsis and septic shock.•MR-proADM values was homogenously distributed within the different microbial classes increasing significantly in case of septic shock.•PCT and MR-proADM combination represents an advantage for sepsis diagnosis and for 90-days mortality risk stratification.
Zoonotically transmitted coronaviruses were responsible for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), causing the dramatic Coronavirus Disease-2019 (CoViD-19) pandemic, which ...affected public health, the economy, and society on a global scale. The impact of the SARS-CoV-2 pandemic permeated into our environment and wildlife as well; in particular, concern has been raised about the viral occurrence and persistence in aquatic and marine ecosystems. The discharge of untreated wastewaters carrying infectious SARS-CoV-2 into natural water systems that are home to sea mammals may have dramatic consequences on vulnerable species. The efficient transmission of coronaviruses raises questions regarding the contributions of virus-receptor interactions. The main receptor of SARS-CoV-2 is Angiotensin Converting Enzyme-2 (ACE-2), serving as a functional receptor for the viral spike (S) protein. This study aimed, through the comparative analysis of the ACE-2 receptor with the human one, at assessing susceptibility to SARS-CoV-2 for different species of marine mammals living in Italian waters. We also determined, by means of immunohistochemistry, ACE-2 receptor localization in the lung tissue from different cetacean species, in order to provide a preliminary characterization of ACE-2 expression in the marine mammal respiratory tracts. Furthermore, to evaluate if and how Italian wastewater management and coastal exposition to extreme weather events may led to susceptible marine mammal populations being exposed to SARS-CoV-2, geomapping data were carried out and overlapped. The results showed the potential SARS-CoV-2 exposure for marine mammals inhabiting Italian coastal waters, putting them at risk when swimming and feeding in specific risk areas. Thus, we highlighted the potential hazard of the reverse zoonotic transmission of SARS-CoV-2 infection, along with its impact on marine mammals regularly inhabiting the Mediterranean Sea, while also stressing the need for appropriate action in order to prevent further damage to specific vulnerable populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background: The clinical course of COVID-19 is more severe in elderly patients with cardio-metabolic co-morbidities. Chronic kidney disease is considered an independent cardiovascular risk factor. We ...aimed to evaluate the impact of reduced eGFR on the composite outcome of admission to ICU and death in a sample of consecutive COVID-19 hospitalized patients. Methods: We retrospectively evaluated clinical records of a consecutive sample of hospitalized COVID-19 patients. A total of 231 patients were considered for statistical analysis. The whole sample was divided in two groups on the basis of eGFR value, e.g., ≥ or <60 mL/min/1.73 m2. Patients with low eGFR were further divided among those with a history of chronic kidney disease (CKD) and those without (AKI, acute kidney injury). The primary outcome was a composite of admission to ICU or death, whichever occurred first. The single components were secondary outcomes. Results: Seventy-nine (34.2%) patients reached the composite outcome. A total of 64 patients (27.7%) died during hospitalization, and 41 (17.7%) were admitted to the ICU. A significantly higher number of events was present among patients with low eGFR (p < 0.0001). Age (p < 0.001), SpO2 (p < 0.001), previous anti-platelet treatment (p = 0.006), Charlson’s Comorbidities Index (p < 0.001), serum creatinine (p < 0.001), eGFR (p = 0.003), low eGFR (p < 0.001), blood glucose levels (p < 0.001), and LDH (p = 0.003) were significantly associated with the main outcome in univariate analysis. Low eGFR (HR 1.64, 95% CI 1.02–2.63, p = 0.040) and age (HR per 5 years 1.22, 95% CI 1.10–1.36, p < 0.001) were significantly and independently associated with the main outcome in the multivariate model. Patients with AKI showed an increased hazard ratio to reach the combined outcome (p = 0.059), while those patients with both CKD had a significantly higher probability of developing the combined outcome (p < 0.001). Conclusions: Patients with reduced eGFR at admission should be considered at high risk for clinical deterioration and death, requiring the best supportive treatment in order to prevent the worst outcome.
Abstract
Objective
We investigated the genetic diversity, molecular epidemiology and evolutionary dynamics of Staphylococcus aureus (SA) isolated from SLE patients by means of phylogenetic analysis.
...Methods
Consecutive SLE patients (ACR 1997 criteria) were enrolled: clinical/laboratory data were collected and nasal swab for SA identification was performed. On the basis of the translation elongation factor (tuf) gene, a phylogenetic analysis was performed to investigate relationships and to assess significant clades. Selective pressure analysis was used to investigate the evolution of the SA tuf gene. The gene sequences from non-SLE individuals, downloaded from the GenBank database, were compared through phylogenetic analysis with the tuf gene from SLE patients.
Results
We enrolled 118 patients M/F 10/108; median (interquartile range (IQR)) age 45.5 (13.2) years; median (IQR) disease duration 120 (144) months. Twenty-four patients (20.3%) were SA carriers (SA+), three of them MRSA. SA+ SLE showed significantly higher SLEDAI-2k values SA+: median (IQR) 2 (3.75); SA−: 0 (2); P = 0.04. The phylogenetic analysis, restricted to 21 non-MRSA SA+, revealed a statistically supported larger clade (A, n = 17) and a smaller one (B, n = 4). Patients located in clade A showed a significantly higher prevalence of joint involvement (88.2%) in comparison with clade B (50.0%, P < 0.0001) and SA− (62.7%, P < 0.0001). Haematological manifestations were significantly more frequent in clade A (64.7%) compared with B (50.0%, P = 0.004).
Conclusion
We suggest a possible role of SA nasal carriage status in SLE disease activity. Moreover, our findings support the hypothesis that bacterial genetic variants may be associated with specific disease features.
microorganisms cause important bacterial infections in humans. Recently, carbapenem resistant isolates carrying the
KPC gene were described and their clonal transmission in different nosocomial ...outbreaks reported. In this study, the relative numbers of
species, their antimicrobial susceptibility along 3 years of observation and the identification ability of the two most common MALDI-TOF platforms were evaluated. A clustering analysis was performed to identify changes in the microbial population within the nosocomial environment.
were identified using two platforms (MALDI-TOF Biotyper and VITEK MS). Antimicrobial susceptibility was tested by Vitek2 Compact and MIC
and MIC
was evaluated using GraphPad software. Clustering analysis was performed by MALDI-TOF and a dendrogram was built with both platforms and compared. The most frequent species isolated were
and
with a gradual increase of
in 2017. MALDI-TOF platforms showed a very good sensitivity and specificity except for
identification that was reliable only by MALDI-TOF MS Biotyper. An increase of resistance for
, confirmed by the isolation of extended spectrum beta-lactamase (ESBL) strains and the emergence of
multidrug-resistant (MDR) and carbapenem resistant strains, was observed. A clonal route of transmission involving general surgery and geriatric wards was evidenced as previously described for
MDR strains in the same nosocomial setting. These data represent an important source of information about the spreading of
in the nosocomial environment.
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