Real-Life Experience of Molnupiravir in Hospitalized Patients Who Developed SARS-CoV2-Infection: Preliminary Results from CORACLE Registry

Real-life experience of molnupiravir treatment is lacking, especially in people hospitalized for underlying diseases not related to COVID-19. We conducted a retrospective analysis regarding molnupiravir therapy in patients with SARS-CoV-2 infection admitted for underlying diseases not associated with COVID-19. Forty-four patients were included. The median age was 79 years (interquartile range [IQR]: 51-93 years), and most males were 57,4%. The median Charlson Comorbidity Index and 4C score were, respectively, 5 (IQR: 3-10) and 9.9 (IQR: 4-12). Moreover, 77.5% of the patients had at least two doses of the anti-SARS-CoV-2 vaccine, although 10.6% had not received any SARS-CoV-2 vaccine. Frequent comorbidities were cardiovascular diseases (68.1%), and diabetes (31.9%), and most admissions were for the acute chronic heart (20.4%) or liver (8.5%) failure. After molnupiravir started, 8 (18.1%) patients developed acute respiratory failure, and five (11.4%) patients died during hospitalisation. Moreover, molnupiravir treatment does not result in a statistically significant change in laboratory markers except for an increase in the monocyte count (p = 0.048, Z = 1.978). Molnupiravir treatment in our analysis was safe and well tolerated. In addition, no patients' characteristics were found significantly related to hospital mortality or an increase in oxygen support. The efficacy of the molecule remains controversial in large clinical studies, and further studies, including larger populations, are required to fill the gap in this issue

Visceral Leishmaniasis after Anti-Interleukin 17A (IL-17A) Therapy in a Patient Affected by Psoriatic Arthritis

The reactivation of latent Leishmania infection in chronic diseases and immunocompromised hosts is a broad and heterogeneous field in medicine and infectious diseases. We reported one of the first cases of Visceral Leishmaniasis occurring in a Caucasian middle-aged man living in an endemic country (Italy) for Leishmania infantum infection following secukinumab treatment for psoriatic arthritis. The patient was cured with a Liposomal Amphotericin B (L-AmB, 3 mg/Kg on days 1–5, followed by a dose on days 10, 17, 24, 31 and 38) regimen, after which his anti-interleukin 17 treatment was restarted—without recurrence in the follow-up

Phylogeny of Polycladida (Platyhelminthes) based on mtDNA data

A phylogenetic analysis of Polycladida based on two partial mitochondrial genes (cox1 and 16S) is provided. The analysis includes 30 polyclad terminals that represent species from the two taxa which traditionally divide the groups Cotylea and Acotylea. Our phylogenetic analyses produced a well-supported hypothesis that confirms the monophyly of Polycladida, as well as Acotylea and Cotylea. Within Acotylea, there are two lineages not highly supported: on one hand, Leptoplanoidea (excluding Hoploplana elisabelloi) and one Stylochoidea member (Pseudostylochus intermedius) (classification sensu Faubel, 1983, 1984), and on the other hand, Stylochoidea members together with Discocelis tigrina and H. elisabelloi. The genera Stylochus and Imogine are not monophyletic. Within Cotylea, Pseudocerotidae and Euryleptidae are monophyletic, though not highly supported, while Prosthiostomidae is not. Euryleptoidea is paraphyletic. The genera Pseudobiceros and Pseudoceros are monophyletic and highly supported. Our results suggest that, within Acotylea, the prostatoid organs of Discocelis may have been derived from a prostatic vesicle. The genus Hoploplana could be included in Stylochoidea. Within Cotylea, the common ancestor of Euryleptidae and Pseudocerotidae might have been an aposematic animal with tentacles.Fil: Aguado Molina, María Teresa. Universidad Autónoma de Madrid. Facultad de Ciencias; EspañaFil: Noreña Janssen, Carolina. Consejo Superior de Investigaciones Cientificas. Museo Nacional de Ciencias Naturales; EspañaFil: Alcaraz, L.. Consejo Superior de Investigaciones Cientificas. Museo Nacional de Ciencias Naturales; EspañaFil: Marquina, D.. Consejo Superior de Investigaciones Cientificas. Museo Nacional de Ciencias Naturales; España. Naturhistoriska riksmuseet; SueciaFil: Brusa, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División de Zoología Invertebrados; ArgentinaFil: Damborenea, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División de Zoología Invertebrados; ArgentinaFil: Almon, B.. Grupo de Estudo do Medio Mariño; EspañaFil: Bleidorn, C.. Consejo Superior de Investigaciones Cientificas. Museo Nacional de Ciencias Naturales; EspañaFil: Grande, C.. Universidad Autónoma de Madrid. Facultad de Ciencias; Españ

Effects of two weeks of cerebellar theta burst stimulation in cervical dystonia patients

Dystonia is generally regarded as a disorder of the basal ganglia and their efferent connections to the thalamus and brainstem, but an important role of cerebellar-thalamo-cortical (CTC) circuits in the pathophysiology of dystonia has been invoked. Here in a sham controlled trial, we tested the effects of two-weeks of cerebellar continuous theta burst stimulation (cTBS) in a sample of cervical dystonia (CD) patients. Clinical evaluations were performed by administering the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). We used TMS to measure the inhibitory connectivity between the cerebellum and the contralateral motor cortex (cerebellar brain inhibition [CBI]), and the excitability of the contralateral primary motor cortex assessing intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Paired associative stimulation (PAS) was tested to evaluate the level and the topographical specificity of cortical plasticity, which is abnormally enhanced and non-focal in CD patients. Two weeks of cerebellar stimulation resulted in a small but significant clinical improvement as measured by the TWSTRS of approximately 15%. Cerebellar stimulation modified the CBI circuits and reduced the heterotopic PAS potentiation, leading to a normal pattern of topographic specific induced plasticity. These data provide novel evidence CTC circuits could be a potential target to partially control some dystonic symptoms in patients with cervical dystonia

<i>Legionella pneumophila</i> Infections during a 7-Year Retrospective Analysis (2016–2022): Epidemiological, Clinical Features and Outcomes in Patients with Legionnaires’ Disease

Legionella pneumophila (LP) is one of the main causative agents of community-acquired pneumonia in Europe and its fifth bacterial cause in Italy (4.9%). We conducted a seven year retrospective analysis of LP infection serogroup 1 in Asti, Piedmont, between 2016 and 2022. Patients were included if they tested positive for the Legionella urinary antigen. Clinical, laboratory, and radiologic data were analyzed to describe the risk factors for mortality. Fifty patients with LD were collected, mainly male, with a median age of 69 years. The main comorbidities were cardiovascular diseases (50%), pulmonary diseases (26%), and neurological diseases (12%). The most common clinical presentations were fever, respiratory, gastrointestinal, and neurologic symptoms. Older age (p = 0.004), underlying cardiovascular diseases (p = 0.009), late diagnosis at admission (p = 0.035), and neurological symptoms at diagnosis (p = 0.046) were more common in the non-survivor group. Moreover, a septic-shock presentation or the need for non-invasive ventilation at admission were associated with a higher mortality. No considerable differences in the biochemical data were found between the two groups except for the median neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio, and PCT value. We did not find any differences in mortality related to the choice of antibiotic regimen. Differences in outcome were associated with the median duration of treatment (p =< 0.001) but not to the choice of antibiotic regimen (mainly levofloxacin or azithromycin). In conclusion, early individuation of the wide spectrum of clinical characteristics of LP infection such as respiratory, cardiac, and neurological manifestations of the patient’s comorbidities, and significant biochemical data should help clinicians flag high risk patients and potentially improve their outcome

Autochthonous West Nile Virus Infection Outbreak in Humans (Asti, Piedmont, Italy, August&ndash;October 2018) and Long-Term Sequelae Follow-Up

West Nile virus (WNV) infection is a reemerging zoonosis recently provoking significant outbreaks throughout Europe. During the summer of 2018, the number of WNV infections rose with a peak of new diagnoses of West Nile neuro-invasive disease (WNND). Most of the Italian cases were clustered in the Po River Valley. We present a case series of nine patients with WNV infection admitted to the Cardinal Massaia Hospital from 30 August 2018 to 1 October 2018. Demographic, immunovirological, clinical and therapeutic data are shown, and a report on clinical sequelae from the subsequent follow-up in patients with WNV and WNND. We showed the clinical, radiological and biochemical characteristics of WNV-infected patients. The risk factors and the clinical presentation of WNV in most patients in our case series were typical of that described in the literature, although, despite the high morbidity and mortality of WNND, we showed survival of 100% and long-term sequelae in only three patients. Environmental conditions may be essential in WNV outbreaks, and WNND can be clinically neurological multiform. Our long-lasting follow-up with clinical or radiological monitoring confirmed the morbidity of long-term neurological sequelae after WNND. Further studies are needed to investigate the epidemiology and physiopathology of bacterial superinfections after WNV infection

Frequency and phenotypes of LRRK2 G2019S mutation in Italian patients with Parkinson's disease

To evaluate the frequency of the LRRK2 G2019S mutation in Italy, we tested 1,072 probands with Parkinson's disease (PD; 822 sporadic and 250 familial): 20 patients (1.9%) carried the G2019S mutation, 11 patients (1.3%) were sporadic, and 9 (4.3%) had a positive family history. Considering only probands with autosomal dominant inheritance, the G2019S frequency raises to 5.2%. All presented a typical phenotype with variable onset and shared the common ancestral haplotype. Mutation frequency raised from 1.2% in early onset PD to 4.0% in late onset PD

GBA ‐Related Parkinson's Disease: Dissection of Genotype–Phenotype Correlates in a Large Italian Cohort

Background Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. Objectives We determined the frequency of GBA ‐related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. Methods Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. β‐glucocerebrosidase activity was measured. The Kaplan‐Meier method and Cox proportional hazard regression models were performed. Results Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA‐PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA‐PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA‐PD had the lowest β‐glucocerebrosidase activity. Conclusions GBA‐PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles

PINK1 heterozygous rare variants: Prevalence, significance and phenotypic spectrum

Heterozygous rare variants in the PINK1 gene, as well as in other genes Causing autosomal recessive parkinsonism, have been reported both in patients and healthy controls. Their pathogenic significance is uncertain, but they have been suggested to represent risk factors to develop Parkinson disease (PD). The few large Studies that assessed the frequency of PINK1 heterozygotes in cases and controls yielded controversial results, and the phenotypic spectrum is largely unknown. We retrospectively analyzed the occurrence of PINK1 heterozygous rare variants in over 1100 sporadic and familial patients of all onset ages and in 400 controls. Twenty patients and 6 controls were heterozygous, with frequencies (1.8% vs. 1.5%) not significantly different in the two groups. Clinical features of heterozygotes were indistinguishable to those of wild-type patients, with mean disease onset 10 years later than in carriers of two imitations but Worse disease progression. A meta-analysis indicated that, in PINK1 heterozygotes, the PD risk is only slightly increased with a non significant odds ratio of 1.62. These findings Suggest that PINK1 heterozygous rare variants play only a minor susceptibility role in the context of a multifactorial model of PD. Hence, their significance Should be kept distinct from that Of homozygous/compound heterozygous Initiations, that cause parkinsonism inherited in a mendelian fashion. (c) 2008 Wiley-Liss, Inc