Pure autonomic failure versus prodromal dysautonomia in Parkinson’s disease: Insights from the bedside

Autonomic failure may include orthostatic hypotension, supine hypertension, bowel and bladder disturbances, impaired thermal regulation, and sexual dysfunction, all of which can be features of Parkinson's disease (PD) and other a‐synucleinopathies. All patients with pure autonomic failure, most patients with multiple system atrophy, and 18% of patients with PD will develop symptomatic orthostatic hypotension. However, the extent of central and peripheral norepinephrine deficiency, parasympathetic nuclei degeneration, and arterial baroreflex failure may be differentially impaired in these disorders. Consequently, clinical features and prognostic implications of autonomic dysfunction in a‐synucleinopathies may be more complex than previously envisioned. The case described in this report highlights the clinical similarities between PD and pure autonomic failure, raising the question of whether pure autonomic failure represents a restricted Lewy body synucleinopathy or an early manifestation of PD

West Nile Virus infection in Northern Italy: Case-crossover study on the short-term effect of climatic parameters.

BACKGROUND: Changes in climatic conditions are hypothesized to play a role in the increasing number of West Nile Virus (WNV) outbreaks observed in Europe in recent years. OBJECTIVES: We aimed to investigate the association between WNV infection and climatic parameters recorded in the 8 weeks before the diagnosis in Northern Italy. METHODS: We collected epidemiological data about new infected cases for the period 2010-2015 from the European Center for Disease Control and Prevention (ECDC) and meteorological data from 25 stations throughout the study area. Analyses were performed using a conditional Poisson regression with a time-stratified case-crossover design, specifically modified to account for seasonal variations. Exposures included weekly average of maximum temperatures, weekly average of mean temperatures, weekly average of minimum temperatures and weekly total precipitation. RESULTS: We found an association between incidence of WNV infection and temperatures recorded 5-6 weeks before diagnosis (Incidence Rate Ratio (IRR) for 1 °C increase in maximum temperatures at lag 6: 1.11; 95% CI 1.01-1.20). Increased weekly total precipitation, recorded 1-4 weeks before diagnosis, were associated with higher incidence of WNV infection, particularly for precipitation recorded 2 weeks before diagnosis (IRR for 5 mm increase of cumulative precipitation at lag 2: 1.16; 95% CI 1.08-1.25). CONCLUSIONS: Increased precipitation and temperatures might have a lagged direct effect on the incidence of WNV infection. Climatic parameters may be useful for detecting areas and periods of the year potentially characterized by a higher incidence of WNV infection

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

ABSTRACT Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach

Mortality and prognosis in patients with neurogenic orthostatic hypotension

The prognosis of neurogenic orthostatic hypotension (NOH) has been poorly studied. The aim of this study was to evaluate retrospectively comorbidities and causes of death in patients with NOH. Clinical information and causes of death were obtained for 104 patients (45 with multiple system atrophy, 9 with pure autonomic failure, 43 with Parkinson’s disease, and 7 with other types of autonomic neuropathy) referred to the Autonomic Unit from 1996 to 2009. Cardiovascular diseases (hypertension, cardiac comorbidities, atrial fibrillation and heart failure) were present in 53 (51%) NOH patients. At the end of follow-up, 44 patients were deceased. Type of NOH was the main factor associated with mortality. The main causes of death were infectious/respiratory (54%) and cardiac (16%). In NOH patients, cardiovascular diseases are frequent, although mortality is mainly due to infectious and respiratory causes. Detection of cardiovascular diseases may be useful in the choice of anti-hypotensive treatments

Cardiovascular Response to Posture Changes: Multiscale Modeling and in vivo Validation During Head-Up Tilt

In spite of cardiovascular system (CVS) response to posture changes have been widely studied, a number of mechanisms and their interplay in regulating central blood pressure and organs perfusion upon orthostatic stress are not yet clear. We propose a novel multiscale 1D-0D mathematical model of the human CVS to investigate the effects of passive (i.e., through head-up tilt without muscular intervention) posture changes. The model includes the main short-term regulation mechanisms and is carefully validated against literature data and in vivo measures here carried out. The model is used to study the transient and steady-state response of the CVS to tilting, the effects of the tilting rate, and the differences between tilt-up and tilt-down. Passive upright tilt led to an increase of mean arterial pressure and heart rate, and a decrease of stroke volume and cardiac output, in agreement with literature data and present in vivo experiments. Pressure and flow rate waveform analysis along the arterial tree together with mechano-energetic and oxygen consumption parameters highlighted that the whole system approaches a less stressed condition at passive upright posture than supine, with a slight unbalance of the energy supply-demand ratio. The transient dynamics is not symmetric in tilt-up and tilt-down testing, and is non-linearly affected by the tilting rate, with stronger under- and overshoots of the hemodynamic parameters as the duration of tilt is reduced. By enriching the CVS response to posture changes, the present modeling approach shows promise in a number of applications, ranging from autonomic system disorders to spaceflight deconditioning