Patients with Parkinson's disease and a history of falls have decreased cerebellar grey matter volumes in the cognitive cerebellum.

The objective of this study was to determine if cerebellar gray matter (GM) structure differs between fallers and non-fallers with Parkinson's disease (PD) and their respective association to cognitive function. A total of 48 fallers and 63 non-fallers with PD were identified from the Parkinson's Progression Markers Initiative database. Fallers were categorized as those who self-reported a fall within the past year. Unified Parkinson's Disease Rating Scale-III (UPDRS-III), Montreal Cognitive Assessment (MoCA), Trail Making Test parts A (TMT-A) and B (TMT-B) scores were collected for each patient. Cerebellar GM volumes were derived from magnetic resonance imaging data. Analyses of covariance were used to compare group differences. Partial Pearson's correlations were used to assess the relationship between cerebellar GM volumes to UPDRS-III and cognitive outcomes. Significance was set at P ≤ 0.01. Fallers had significantly decreased GM volumes in lobules V, Crus-1, Crus-2, and VIIb (P<0.01). Cerebellar GM volumes in non-fallers demonstrated little-to-no relationship with UPDRS-III, MoCA, and TMT-B (P>0.01). However, TMT-A performance demonstrated significant, fair association to GM volumes in lobules I-IV, V, VI, Crus-1, and Crus-2 (r=-0.44 - -0.34, P<0.01) in non-fallers. Patients with PD and a history of falls have significantly decreased GM volumes in cerebellar lobules associated with cognitive functions. However, these lobule volumes become disassociated with cognitive function compared to non-fallers.

The management of patients with acute ischemic stroke while on direct oral anticoagulants (DOACs): data from an Italian cohort and a proposed algorithm.

Approximately 1-2% of patients with non-valvular atrial fibrillation have an acute ischemic stroke (AIS) while on direct oral anticoagulant (DOAC) treatment every year. However, current evidence on stroke subtypes, pathophysiology and factors leading to the failure of DOAC preventive therapy in a "real world" setting is still scanty. This study aimed at investigating whether there is any relationship between DOAC plasma levels and the stroke occurrence, on the basis of the phenotypic classification and pathophysiology of the stroke, in a cohort of DOAC-treated patients admitted to our hospital for AIS over 1-year period. A total of 28 patients had DOAC plasma levels determined in emergency and were included in the study, nine patients receiving dabigatran, 11 rivaroxaban and 8 apixaban. The DOAC levels were low in 8/28 patients (28.6% of the sample), intermediate in 4 (14.3%) and high in 16 (57.1%). The most prevalent stroke subtype was the small vessel disease, according to the A-S-C-O phenotypic classification, in 53.6% of our sample. The most common clinical presentation was "minor stroke" in 71.4% of the cases. There was a significantly higher proportion of patients with high DOAC levels in the small vessel group, compared to the cardioembolic group without other phenotypes. The question arises as to the most suitable clinical management of AIS in these patients on DOACs. In the current absence of clear evidence, taking into account the DOAC levels (low/intermediate/high) and the underlying stroke pathophysiology, we present a flowchart of our proposed clinical management of ischemic stroke in patients while on DOAC.

Updating on Italian stroke units: the "CCM study".

The stroke units (SUs) have been demonstrated to be efficient and cost effective for acute stroke care. Nevertheless, the level of stroke unit implementation in Italy does not correspond to expectations yet. This study is a survey, which aims at assessing the current status of in-hospital stroke care in the Italian regions and at updating SUs. The survey was conducted by means of a semi-structured questionnaire, based on 18 stroke care "quality indicators", submitted to all the Italian centres that had taken part in the SITS-MOST study, and to other centres advised by the coordinator of SITS studies and by regional opinion leaders of stroke. SUs were defined as acute wards, with stroke-dedicated beds and dedicated teams that had been formally authorised to administer rt-PA. A statistical analysis was performed by a descriptive statistics and logistic regression model. The study was carried out from November 2009 to September 2010. A total of 168 forms were sent out and 153 replies received. Seven centres, which had not performed any thrombolytic treatment, and 16 which did not fulfil the criteria for the definition of SU were excluded from the study. Most of the centres reported more than 100 stroke patient admissions per year, i.e., 122 (84%) from 100 to 500, 18 (12%) more than 500. The 19% of the centres admitted more than 30% of patients within 3 h from the symptom onset and only 30% admitted more than 30% of patients within 4.5 h. The mean number of thrombolyses performed in the last 6 months was 10 for centres with a doctor on duty 24 h a day, 6 for those that have a doctor on duty from 8 a.m. to 8 p.m. and a doctor on call for night, and 5 for centres with a doctor on call 24 h a day. The territorial distribution of the SUs is remarkably heterogeneous: 87 SUs (67%) are located in the North of Italy, 28 (22%) in the central part of Italy and only 15 (11%) in the South. The last few years have witnessed a rise in both the diffusion of SUs and access to thrombolytic therapy in Italy. Despite this, there are a few large areas, mostly in the south, where the requirements of healthcare legislation are not met, and access to a dedicated SU and thrombolytic treatment is still limited and poor.

Inter-critical and critical excessive daily sleepiness in episodic migraine patients.

The objective of this study was to determine the relationship between sleepiness and migraine in the intercritical period and to evaluate the time course of critical drowsiness during the attacks. One hundred patients fulfilling IHCD 2nd (2004) criteria for migraine without aura were compared to 100 healthy subjects. Habitual excessive daily sleepiness, evaluated by means of Epworth Sleepiness Scale, was not more frequent in patients with episodic migraine than in controls (12% migraineurs vs. 8% controls, NS). The analysis of critical sleepiness by means of Stanford Sleepiness Scale (SSS) revealed a beginning of sleepiness increase before the attack onset, starting 12 h before, a peak of SSS values at the migraine attack onset and then a gradual decrease to reach baseline values only 12-24 h later. Moreover, patients responding to symptomatic drugs showed a greater and faster decrease of critical sleepiness in comparison with non-responder migraineurs; this finding allows excluding the role of medications in promoting critical somnolence and together with critical drowsiness time-course supports the hypothesis that vigilance impairment could be related to migraine pathogenesis.

Sclerotium oryzae biocontrol in flooded rice fields with floating microcarrier technology: The effect of chitosan molecular weight.

BACKGROUND: Biocontrol strategies are of significant concern for their application in crops. Various green practices have been designed, but almost all of them had delivery constraints. In particular, to design biocontrol strategies against Sclerotium oryzae in flooded rice fields, the active agent should be retained on the plant leaves by spreading application, nevertheless the direct application onto the water produces the biocontrol agent dilution. An effective delivery model was needed. This work aimed to evaluate the effects of chitosan molecular weight on the formation of positively charged Pseudomonas fluorescens-chitosan complex as a floating microcarrier against Sclerotium oryzae. To this end, three different sizes of chitosan [molecular weights (MWs) 20 000, 250 000, and 1 250 000 g mol-1 ] at different pH values (4, 6, and 7) were tested. The electrostatic interaction was analyzed through ζ-potential measurement. An adjustment of the experimental values was carried out for making predictions. The bacteria antifungal activity into the carrier with different chitosan MWs was analyzed. RESULTS: Our results suggest that it is possible to form a bacteria-chitosan complex with a net positive charge under condition that improve bacteria incorporation to the microcarrier technology without harming bacteria viability and antifungal activity. Thus, high chitosan MW (1 250 000 g mol-1 ) at pH 6 is preferable for microcarrier technology. CONCLUSION: Our findings provide relevant information about bacteria-chitosan interaction and may be useful in biocontrol programs that involved these two components as well as situations in which bacteria adsorption to an anionic carrier or anionic surface is desirable.

Does sphenopalatine endoscopic ganglion block have an effect in paroxysmal hemicrania? A case report.

The authors report the case of a 69-year-old woman suffering from paroxysmal hemicrania (PH), intolerant to indomethacin and resistant to multiple therapies, in which sphenopalatine endoscopic ganglion block (SPG) dramatically modified the clinical outcome. SPG blockade could be considered a reasonable alternative in drug-resistant PH cases where indomethacin is contraindicated.

Is oxidative stress associated with disease severity, pulmonary function and metabolic syndrome in chronic obstructive pulmonary disease? / ¿Está el estrés oxidativo asociado a la gravedad de la enfermedad, a la función pulmonar y al síndrome metabólico en la enfermedad pulmonar obstructiva crónica?

OBJECTIVE: To investigate associations between oxidant/antioxidant biomarkers with the disease severity, pulmonary function and diagnosis of metabolic syndrome (MetS) in patients with COPD. METHODS: Seventy-four subjects were included, 39 with COPD (age 69±7 years; female 41%) and 35 for control group (age 69±7 years; female 43%). They were diagnosed with MetS and allocated in one of 4 subgroups: COPD and control, with and without MetS, respectively. Advanced oxidation protein products (AOPP), paraoxonase-1, catalase activity, sulfhydryl group and total lipid hydroperoxide were assayed. Pulmonary function was performed with a plethysmograph. RESULTS: COPD severity (GOLD≥3) and pulmonary function were associated with sulfhydryl group and AOPP (P≤.03 for all). The prevalence of MetS was associated with AOPP in COPD (P=.04). Individuals with COPD and MetS showed higher AOPP compared to COPD without MetS (P<.0001). CONCLUSION: COPD severity, worse pulmonary function and presence of metabolic syndrome are associated with oxidative stress in individuals with COPD.

Model for End-Stage Liver Disease (MELD) score and organ allocation from cadaveric donors for 198 liver transplantation procedures performed in a single center.

Since February 2002, the United Network for Organ Sharing (UNOS) proposed to adopt a modified version of the Model for End-Stage Liver Disease (MELD) to assign priority on the waiting list for orthotopic liver transplantation (OLT). In this study, we evaluated the impact of MELD score on liver allocation in a single center series of 198 liver recipients (mean age of patients, 52.21+/-8.92 years), considering the relationship between clinical urgency derived from MELD score (overall MELD, 18.7+/-6.83; MELD <15 in 69 patients, MELD >or=15 in 129 patients) and geographical distribution of cadaveric donors (inside/outside Liguria Region, 125/73). The waiting time for OLT was 230+/-248 days, whereas the 3-month and 1-year patient survivals were 87.37% and 79.79%, respectively. No difference was observed for MELD score retrospectively calculated for patients who underwent OLT before February 2002 (n=71) compared with MELD score calculated for patients who received a liver thereafter (18.26+/-6.68 vs 18.94+/-6.92; P= .504). No significant difference was found in waiting time before and after adoption of MELD score (213+/-183 vs 238+/-278 days; P= .500), or by stratifying patients for MELD <15/>or=15 (225+/-234 vs 232+/-256 days; P= .851). Using the geographical distribution of donors as a grouping variable (outside vs inside Liguria Region), no significance occurred for MELD score (19.68+/-7.42 vs 18.17+/-6.42; P= .135) or waiting time (211+/-226 vs 242+/-261 days; P= .394). In our series, more OLTs were performed among sicker patients and no differences were found in the management of livers procured from cadaveric donors outside or inside Liguria Region. However, further efforts are needed to reduce the waiting time among patients with higher MELD scores.

Sirolimus therapy in liver transplant patients: an initial experience at a single center.

Sirolimus (SRL) is an mTOR inhibitor that has been shown, in contrast to calcineurin inhibitors (CNI), to inhibit cancers in experimental models. Since February 2005, we introduced SRL in liver transplant patients in group a, in whom the primary disease was hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic or autoimmune liver cirrhosis, and group b, HCC-negative patients who developed posttransplantation cancers de novo. Of 18 patients in group a, 11 received SRL ab initio (subgroup a1), starting for 10 patients at 66.1+/-29.2 days after surgical healing and after 10 days in 1 case; the remaining 7 patients (subgroup a2) received SRL at 31.2+/-24.2 months. Three patients in group b, included 1 with Kaposi's sarcoma, 1 with bladder cancer, and 1 with thyroid cancer. In this group, SRL was introduced at 80.8+/-40.4 months. In all patients but one, who received a single 5 mg loading dose, SRL was started at 2 mg/d and adjusted to 6 to 8 ng/mL blood levels. CNI drugs, present as primary therapy, were gradually tapered to low levels and eventually stopped. The following observations were drawn from this initial experience: (1) 4/21 (19.0%) patients had to discontinue SRL because of early and late side effects: thrombocytopenia (n=2) and headache with leukopenia and leg edema associated with knee joint arthralgia (n=2); (2) 14 patients (11 in group a and 3 in group b) are still on SRL monotherapy; (3) 1 HCC recurrence and 1 de novo pancreatic adenocarcinoma were observed at 14 and 16 months, respectively (at the time of transplantation, both patients were beyond the MIlan HCC criteria), and (4) 1 patient, from subgroup a1, died after 99 days due to pneumonitis and possible relation to SRL lung toxicity. In conclusion, SRL appeared to be an effective immunosuppressant that could be used as monotherapy in liver transplant patients. Any conclusion on SRL anticancer effects can only come from randomized large studies after long follow-up.

Preliminary results of liver transplantation for hepatocellular carcinoma among allocation organ policy strategies, neoadjuvant treatments, and intention-to-treat analysis.

We retrospectively evaluated the impact of our strategy for patients with hepatocellular carcinoma (HCC) according to an intention-to-treat analysis and drop-out probability. We evaluated only patients within the Milan criteria. We analyzed the outcomes of neoadjuvant strategies for HCC, organ allocation policy, and systematic application of strategies to increase the deceased donor pool as the current tendency to expand transplantability criteria for those patients. Kaplan-Meier survival probability rates at 1, 3, and 5 years according to an intention-to-treat analysis were 87.02%, 74.53%, and 65.93% for transplanted patients (n=108), and 50%, 14.29%, and 14.29% for the excluded or waiting list group (n=13), respectively (P< .0001). Drop-out risk at 3, 6, and 12 months was 2.40%, 8.59%, and 16.54%, respectively. During the same period, the mortality probability rates at 3, 6, and 12 months among patients without HCC awaiting orthotopic liver transplantation (OLT) were 3.60%, 9.50%, and 18.34%, respectively. Drop-out rate was lower among patients treated before OLT (P< .0001). On the basis of the neoadjuvant treatment results to reduce drop-out risk, we suggest avoiding the high priority for the HCC cohort, particularly within the first 6 months from entrance on the waiting list, because this approach can reduce the chances of patients with end-stage liver disease (ESLD) alone.

Medical report type in liver transplantation as a quality system document: new prospects for computerization.

The usage of a computerized system to organize data and ease the activity procedures of liver transplantation is useful in clinical transplantation. Preliminary cognitive research on systems of clinical transplantation database concerning medical reports was performed to verify their development level. The survey highlighted that, so far, there has been no experimentation that can be applied to a medical report type devoted to liver transplantation. Regulations in force substantially point out that the medical report ought to contain all items that have to be taken into account in handling the patient from pretransplantation to follow-up. The Department of Transplantation of Genoa chose its medical report model for liver transplantation. The medical report model included the following items: personal data; case history; diagnosis; initial examination for prelisting; fitness for transplantation; assistance context; clinical data including subjective, objective, and instrumental parameters; pharmacological therapies; informed consent, evaluation of fitness; nursing data; counseling and clinical evaluations according to protocols and guidelines of the national transplantation centers. If the computing is well trained, it is supposed to help maintain a whole data view provided it is supplied information in an adequate way. Immediate clinical procedural advantages and useful scientific observations may be obtained from a high-quality database. In fact, all functions have to be applied to specific clinical, administrative needs to be remotely shared and conveniently integrated with each other to make the liver transplantation medical report an easy and handy instrument for inputting and handling data. It must be a precise, complete instrument that may be accessible in real time from any site connected with the intranet network, be unchangeable, and be protected to ensure certification and forensic medicine value.

Split liver transplantation for acute Wilson's disease: new option for urgent recipient?

Wilson's disease is a rare metabolic disorder that may lead to fulminant hepatitis and subsequent liver failure. Herein, we present a case of split liver transplantation performed on a patient with acute Wilson's disease. A 27-year-old female with acute presentation of Wilson's disease and advanced neurological impairment, received a Right Split liver Graft (Segments: IV, V, VI, VII and VIII) transplant. The graft was obtained by an in situ splitting technique. The graft implantation was performed in a standard fashion. No acute rejection episodes of the organ occurred. The postoperative course was uneventful. The graft function, ceruloplasmine level and copper levels progressively normalized. The patient totally recovered from neurological symptoms and the Kayser-Fleischer rings disappeared within one month. At 13 months of follow-up, the patient presented with no symptoms and in good condition. The current literature reports high preoperative mortality rate in patients that underwent partial liver graft for acute hepatic failure. However, our experience indicates that in situ split technique of liver may be a feasible and effective alternative to whole graft transplantation in urgent cases. Moreover, to our knowledge, this is the first successfully case of in situ split liver transplantation for acute Wilson's disease described in literature.

A pharmacoeconomic evaluation of oral triptans in the treatment of migraine in Italy.

AIM: The goal of this economic evaluation was to compare the cost-efficacy of oral triptans currently used in the treatment of migraine in Italy. METHODS: The cost analysis of drugs was conducted through a structured decision tree, built up taking into account the National Healthcare System perspective. Data on the clinical efficacy and tolerability of oral triptans were derived from a published meta-analysis of 53 randomized, controlled trials. Drug cost-allocation included either the oral triptans price and costs related to management of treatment-associated chest and central nervous system (CNS) adverse events. Necessary resources for management of the unwanted events were identified by asking an experienced panel of experts how they would treat patients with triptan-related chest and CNS adverse events. To further improve the economic scenario and to allow a broader inference of pharmacoeconomic analysis, the number needed to treat (NNT) to attain 100 sustained pain free (SPF) patients, and 100 patients with SPF and no adverse events (SNAE) were also calculated. RESULTS: Study results show cost-effective differences among oral triptans. The best cost-efficacy ratios were attained by almotriptan 12.5 mg and rizatriptan 5 mg, with 18.47 Euro and 26.37 Euro respectively per patient successfully treated (SPF). Similarly, the NNT analysis favoured almotriptan, which requires 386 patients to attain 100 SPF patients, and 393 patients to attain 100 SNAE patients. Rizatriptan 10 mg resulted the closest competitor, requiring 395 and 457 patients, respectively. CONCLUSIONS: On the basis of published data and within the limitations of this model analysis that included several assumptions, results suggest the economical advantage of almotriptan 12.5 mg among the oral triptans approved for the treatment of migraine in Italy. This evidence could drive selection of the most appropriate oral treatment for acute migraine attacks based on both individual patient's needs and cost-effective drugs.

COVID-19 mortality and health-care resources: Organization / Mortalidad de COVID-19 y recursos sanitarios: organización

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Rizatriptan does not change cerebral blood flow velocity during migraine attacks.

Rizatriptan represents a major advance in the treatment of migraine attack: inhibition of peripheral trigeminal nerve and constriction of intracranial extracerebral blood vessels have been proposed as its main antimigraine mechanisms of action. Although many studies may suggest that rizatriptan causes highly selective vasoconstriction within intracranial extracerebral vessels (i.e., meningeal arteries), no literature data are available to date on possible cerebral hemodynamic changes in humans after treatment with rizatriptan. The aim of this study was to evaluate the effect of rizatriptan on cerebral blood flow velocity performing transcranial Doppler during spontaneous attacks of migraine without aura. Fourteen patients suffering from migraine without aura were monitored to evaluate mean flow velocity changes on both middle cerebral arteries during migraine attack 30 min before and 120 min after oral administration of rizatriptan 10mg. Monitoring was repeated for 30 min during the pain-free period. All patients turned out to be drug responders and no significant mean flow velocity changes were observed between the pain-free period and pre-treatment phase; besides no significant difference in mean flow velocity value have been detected between the periods after the drug administration during the attack versus both pre-treatment period and pain-free phase. These findings indicate that the antimigraine action of rizatriptan is not associated with clear intracranial cerebral hemodynamic changes and may support its cerebrovascular safety.

Impact of different cadaveric donor age cut-offs on adult recipient survival after liver transplantation: a single-center analysis.

The increase in the number of patients awaiting liver transplantation (OLT) has forced the use of cadaveric donors (CD) with suboptimal characteristics. Of these, donor age is perhaps the most investigated parameter. Although excellent outcomes were observed for OLT using CD aged over 60 years, the European Liver Transplant Registry (ELTR) Group found an increased risk by using CD of more than 55 years. The Italian National Transplant Center has recently assumed that CD age more than 60 years is a potential risk factor for OLT. In this study, a single-center analysis was performed by stratifying CD by three age cut-offs (< or =55 or >55, < or =60 or >60, and < or =65 or >65 years) to evaluate effects on OLT outcome. Although no significant difference in 6-month and 1-year patient or graft survival occurred after stratification for each donor age cut-off, a better survival was observed with OLT performed using livers procured from CD >55 years. A significant increase in cold ischemia time (CIT) was observed among OLT performed with grafts procured from CD < or =55 and < or =65 years (P = .007), and there was an inverse correlation between overall CIT and donor age (R = -0.300; P = .0022). However, no impact on 1-year patient survival was observed by introducing CIT in univariate logistic regression models as well as donor age, recipient age, donor/recipient age ratio, donor/recipient sex mismatch, ELTR diagnostic categories, and UNOS status. The results of this study suggest the suitability of CD of more than 55 years for OLT and the need to further investigate the cut-off value for CIT-related risk.