Search

Enrico Peiretti,1 Chiara Ascardi,2 Francesco Bandello,3 Francesco Boscia,4 Monica Varano,5 Marta Bartezaghi,2 Lorenzo De Santi,2 Giovanni Staurenghi6 1Clinica Oculistica, San Giovanni di Dio Hospital, Azienda Ospedaliera, Universitaria di Cagliari, Cagliari, Italy; 2Novartis Farma S.p.A, Milan, Italy; 3Department of Ophthalmology, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy; 4Department of Medical Science, Neuroscience and Sense Organs, Eye Clinic, University of Bari, Azienda Ospedaliero-Universitaria Policlinico Bari, Bari, Italy; 5IRCCS G.B. Bietti Foundation, Rome, Italy; 6Eye Clinic, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, ItalyCorrespondence: Enrico Peiretti, Head of the Retina Unit, Eye Clinic, University of Cagliari, Via Ospedale 48, Cagliari, 09100, Italy, Email enripei@hotmail.comPurpose: Limited data is available on treatment satisfaction with the management of wet age-related macular degeneration (wAMD) among patients in Italy. In this cross-sectional real-world study, treatment satisfaction with anti-vascular endothelial growth factor (anti-VEGFs) was assessed in patients with wAMD in Italy.Patients and Methods: This was a non-interventional, cross-sectional survey involving patients with wAMD receiving anti-VEGFs. The survey was administered through a virtual assistant via phone. Patients’ treatment satisfaction was assessed using a newly developed Novartis Tailored Treatment Satisfaction Questionnaire (NVS TTSQ) and the validated Macular Disease Treatment Satisfaction Questionnaire (MacTSQ).Results: Overall, 154 evaluable patients were enrolled in 5 centers across Italy. The mean (SD) age of the patients was 76.8 years (7.01). Overall treatment satisfaction score assessed by NVS TTSQ was 40.50 (7.11), with a mean of 9.97 (1.84) on the information domain and 22.98 (4.57) on the unmet need domain. Patients were satisfied with diagnosis communication (4.99 [1.30]), information provided on treatment administration (4.58 [1.49], range 0– 6), the waiting room (4.40 [1.43]), and management of visits and injections at the center (5.14 [1.12]), general management of maculopathy at the center (5.22 [1.01]). Patients were not satisfied with their independence in terms of disease management (2.56 [2.45]); they would like additional information about the disease (5.38 [1.03]) and to discuss the injection procedures (4.02 [1.94]) with already-treated patients. The overall treatment satisfaction score on MacTSQ scale was 55.84 (10.13).Conclusion: Patients with wAMD are satisfied with the overall management of their disease in Italy. However, patients would like to have more information on prognosis and management of the disease.Keywords: anti-VEGF, patient-reported outcomes, real-world study, treatment satisfaction, treatment satisfaction questionnaire, wAMD

The supranuclear paresis of the abducens system, also known as posterior internuclear ophthalmoplegia of abduction, is a very rare disorder clinically characterized by unilateral or bilateral abduction paresis sometimes associated with nystagmus of the contralateral adducting eye, slowing of abduction saccades, and intact horizontal vestibulo-ocular reflex. Here, we report a 35-year-old woman who presented transient left side abduction deficit in conjunction, as the only symptom of self-limited viral encephalitis of the brainstem. Brain MRI including DWI and ADC maps showed an area of abnormal signal intensity in the mid-right ponto-mesencephalic junction. PCR analysis of cerebrospinal fluid showed an enterovirus infection. Spontaneous clinical recovery rapidly occurred 2 days after onset. The brainstem lesion was undetectable at 5-week brain MRI follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Dalbavancin is a semisynthetic lipoglycopeptide long-acting antibiotic approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Its features can be useful in the current healthcare scenario characterized by the shortage of available hospital beds., Materials Methods and Results: We implemented several actions in order to optimize the use of dalbavancin allowing an improvement strategy both from the healthcare system and the patient's perspective in two hospital settings. In the Emergency Department we hospitalized only patients who met the clinical criteria and not the logistic criteria (i.e., the need for antibiotic therapy infusion). During the years 2017-2023, this strategy was applied in 40 cases, thus avoiding 40 hospitalizations for a total saving of 280 days of hospitalization.In the Internal Medicine ward and surgery department when there was no longer any need for hospitalization, we discharged the patient as early as possible. During the years 2017-2023, this strategy was applied in 189 cases, saving at least 1,134 days of hospitalization. The outcome of the treated patients was favorable in 228 out of 229 patients (99.5%)., Conclusions: Our experience using dalbavancin in ABSSSI has been very satisfactory overall. The efficacy was close to 100%. Minor adverse events of slight severity occurred rarely. At the same time, this strategy allowed a more efficient allocation of hospital beds. Dalbavancin presents an ideal pharmacodynamic/pharmacokinetic profile for the management of ABSSSI especially in settings where shortage of hospital beds is critical., (© 2024 The Authors.)

Staphylococcus aureus bacteremia presents clinical complexities, with prolonged duration associated with unfavorable outcomes. This research delves into unconventional treatments, such as combinations involving daptomycin, oxacillin, ceftaroline, and fosfomycin, with the aim of swiftly sterilizing bloodstream infection to reduce complications. Our examination of 30 MSSA bacteremia patients with infective endocarditis uncovers differing results between single-agent therapies (oxacillin or daptomycin) and combined treatment plans. Microbiologic clearance at the 72 hour mark demonstrates greater efficacy within the combination cohort (bacteremia persistence 29%) versus monotherapy (bacteremia persistence 78%). This limited case series suggests the potential superiority of combination therapy, prompting further investigations.

To reduce the overburden in the hospital, during the COVID-19 pandemic, some "COVID Committed Home Medical Teams" (CCHTs) were created in Italy. These units consist of a small pool of general practitioners who aim to evaluate all patients with COVID-19 who require a medical examination directly at home. After the first visit (which can end with patient hospitalisation or home management), CCHTs periodically monitor the patients' clinical conditions and vital signs (usually a revaluation every 24-48 hours, except for a sudden worsening). However, this strategy - which reduces the pressure on hospitals - has never been evaluated for patient safety. Our study aims to determine whether a home-based monitoring and treatment strategy for non-severe COVID-19 patients was safe as direct hospital admission by the emergency department. We conducted a retrospective observational study about 1,182 patients admitted to the hospital for COVID-19 between September 2020 and April 2021, confronting in-hospital and 30-day mortality in both CCHT-referred (n=275) and directly admitted by emergency department (n=907). Patients assessed by the CCHT had lower in-hospital and 30-day mortality (18% vs 28%, p=0.001; and 20% vs 30%, p=0.002); but, in the propensity score matching comparison, there was no characteristic between the two groups turned out significantly different. CCHT did not correlate with in-hospital or 30-day mortality. CCHT is a safe strategy to reduce hospital overburden for COVID-19 during pandemic surges., Competing Interests: Competing interests No conflict of interest must be declared for any of the authors., (Copyright © 2016 - 2022 InfezMed.)

A continuous demand for assistance and an overcrowded emergency department (ED) require early and safe discharge of low-risk severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. We developed ( n = 128) and validated ( n = 330) the acute PNeumonia early assessment (aPNea) score in a tertiary hospital and preliminarily tested the score on an external secondary hospital ( n = 97). The score's performance was compared to that of the National Early Warning Score 2 (NEWS2). The composite outcome of either death or oral intubation within 30 days from admission occurred in 101 and 28 patients in the two hospitals, respectively. The area under the receiver operating characteristic (AUROC) curve of the aPNea model was 0.86 (95% confidence interval (CI), 0.78-0.93) and 0.79 (95% CI, 0.73-0.89) for the development and validation cohorts, respectively. The aPNea score discriminated low-risk patients better than NEWS2 at a 10% outcome probability, corresponding to five cut-off points and one cut-off point, respectively. aPNea's cut-off reduced the number of unnecessary hospitalizations without missing outcomes by 27% (95% CI, 9-41) in the validation cohort. NEWS2 was not significant. In the external cohort, aPNea's cut-off had 93% sensitivity (95% CI, 83-102) and a 94% negative predictive value (95% CI, 87-102). In conclusion, the aPNea score appears to be appropriate for discharging low-risk SARS-CoV-2-infected patients from the ED.

Purpose: According to the Surviving Sepsis Campaign, aminoglycosides (AG) can be administered together with a β-lactam in patients with septic shock. Some authors propose administering a single dose of an AG combined with a β-lactam antibiotic in septic patients to extend the spectrum of antibiotic therapy. The aim of this study has been to investigate whether a single shot of AG when septic patients present at the Emergency Department (ED) is associated with acute kidney injury (AKI). Methods: We retrospectively enrolled patients based on a 3-year internal registry of septic patients visited in the Emergency Department (ED) of Pordenone Hospital. We compared the patients treated with a single dose of gentamicin (in addition to the β-lactam) and those who had not been treated to verify AKI incidence. Results: 355 patients were enrolled. The median age was 71 years (IQR 60-78). Less than 1% of the patients had a chronic renal disease. The most frequent infection source was the urinary tract (31%), followed by intra-abdominal and lower respiratory tract infections (15% for both). 131 patients received gentamicin. Unmatched data showed a significant difference between the two groups in AKI (79/131, 60.3% versus 102/224, 45.5%; p=0.010) and in infectious disease specialist's consultation (77/131, 59% versus 93/224, 41.5%; p=0.002). However, after propensity score matching, no significant difference was found. Conclusion: Our experience shows that a single-shot administration of gentamicin upon admission to the ED does not determine an increased incidence of AKI in septic patients., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Multiple sclerosis is characterised by inflammatory neurodegeneration, with axonal injury and neuronal cell death occurring in parallel to demyelination. Regarding the molecular mechanisms responsible for demyelination and axonopathy, energy failure, aberrant expression of ion channels and excitotoxicity have been suggested to lead to Ca 2+ overload and subsequent activation of calcium-dependent damage pathways. Thus, the inhibition of Ca 2+ influx by pharmacological modulation of Ca 2+ channels may represent a novel neuroprotective strategy in the treatment of secondary axonopathy. We therefore investigated the effects of the L-type voltage-gated calcium channel blocker nimodipine in two different models of mouse experimental autoimmune encephalomyelitis (EAE), an established experimental paradigm for multiple sclerosis. We show that preventive application of nimodipine (10 mg/kg per day) starting on the day of induction had ameliorating effects on EAE in SJL/J mice immunised with encephalitic myelin peptide PLP 139-151 , specifically in late-stage disease. Furthermore, supporting these data, administration of nimodipine to MOG 35-55 -immunised C57BL/6 mice starting at the peak of pre-established disease, also led to a significant decrease in disease score, indicating a protective effect on secondary CNS damage. Histological analysis confirmed that nimodipine attenuated demyelination, axonal loss and pathological axonal β-amyloid precursor protein accumulation in the cerebellum and spinal cord in the chronic phase of disease. Of note, we observed no effects of nimodipine on the peripheral immune response in EAE mice with regard to distribution, antigen-specific proliferation or activation patterns of lymphocytes. Taken together, our data suggest a CNS-specific effect of L-type voltage-gated calcium channel blockade to inflammation-induced neurodegeneration., (© 2018 International Society for Neurochemistry.)

Background: Anthropological and genetic data agree in indicating the African continent as the main place of origin for anatomically modern humans. However, it is unclear whether early modern humans left Africa through a single, major process, dispersing simultaneously over Asia and Europe, or in two main waves, first through the Arab Peninsula into southern Asia and Oceania, and later through a northern route crossing the Levant., Results: Here, we show that accurate genomic estimates of the divergence times between European and African populations are more recent than those between Australo-Melanesia and Africa and incompatible with the effects of a single dispersal. This difference cannot possibly be accounted for by the effects of either hybridization with archaic human forms in Australo-Melanesia or back migration from Europe into Africa. Furthermore, in several populations of Asia we found evidence for relatively recent genetic admixture events, which could have obscured the signatures of the earliest processes., Conclusions: We conclude that the hypothesis of a single major human dispersal from Africa appears hardly compatible with the observed historical and geographical patterns of genome diversity and that Australo-Melanesian populations seem still to retain a genomic signature of a more ancient divergence from Africa.

Ramsay Hunt syndrome (RHS) is a frequent cause of facial palsy. It is a consequence of the infection of geniculate ganglion by herpes zoster or herpes simplex virus. In the lack of randomized controlled trials, RHS is empirically treated by a combination therapy of antiviral agents and steroids given orally. However, RHS has, per se, a poorer prognosis than idiopathic facial palsy (Bell's palsy). We describe a case series of two patients with RHS unsuccessfully treated with antiviral drugs and oral corticosteroids, showing an almost complete recovery after late administration of intravenous (i.v.) high dose methylprednisolone. Both patients had all recognized negative prognostic factors including age of onset, a high grade facial weakness, absence of R1 and R2 response at blink reflex test, and in the first case, the involvement of greater superficial petrosal nerve. We propose that i.v. high dose methylprednisolone should be considered, even as a late treatment option, in patients with RHS non recovering after standard antiviral and oral steroid therapy as well as presenting clinical features suggestive of a poor prognosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In multiple sclerosis, neuropathic pain is a frequent condition, negatively influencing the overall quality of life. Cranial neuralgias, including trigeminal, glossopharyngeal neuralgias, as well as occipital neuralgia, are typical expression of neuropathic pain. Neuralgias are characterised by paroxysmal painful attacks of electric shock-like sensation, occurring spontaneously or evoked by innocuous stimuli in specific trigger areas. In multiple sclerosis, demyelination in the centrally myelinated part of the cranial nerve roots plays an important role in the origin of neuralgic pain. These painful syndromes arising in multiple sclerosis are therefore considered "symptomatic", in contrast to classic cranial neuralgias, in which no cause other than a neurovascular contact is identified. At this time, the evidence on the management of symptomatic cranial neuralgias in multiple sclerosis is fragmentary and a comprehensive review addressing this topic is still lacking. For that reason, treatment is often based on personal clinical experience as well as on anecdotal reports. The aim of this review is to critically summarise the latest findings regarding the pathogenesis, the diagnosis, the instrumental evaluation and the medical as well as neurosurgical treatment of symptomatic trigeminal, glossopharyngeal and occipital neuralgia in multiple sclerosis, providing useful insights for neurologists and neurosurgeons and a broad range of specialists potentially involved in the treatment of these painful syndromes., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) patients frequently develop some form of ocular motor dysfunction during the disease. In previous studies, ocular motor abnormalities were found to correlate with clinical disability and with impaired cognitive performance. The objective of this study was to assess the pursuit ocular movement (POM) frequency in relapsing-remitting (RR) and secondary progressive (SP) MS patients by using a vision-based non-intrusive eye tracker. POM frequency was significantly lower (p < 0.001) in MS patients compared to normal controls. No differences between RR and SP-MS patients and no correlation between POM and expanded disability status scale (EDSS) score were found. This exploratory study suggests that our vision-based system is a new simple non-intrusive method showing impairment of POM values in MS patients, even in the absence of association with clinical disability (EDSS). Future works on larger cohorts of MS patients might validate this eye tracking in MS clinical practice.

Purpose: We performed a retrospective study to investigate seizure, EEG, social and cognitive outcome in adult LGS subjects., Methods: We retrospectively evaluated 27 LGS patients aged 40-59 years. We assessed in particular the evolution of different seizure types and EEG findings, as well as cognitive and social outcome., Results: During the early stages of the disease, all patients presented tonic seizures (TS) during wakefulness and sleep, 20/27 had atypical absences (AA), more rarely other seizure types. EEG showed slow background activity in 21/27 patients, diffuse slow spike-wave discharges (DSSW) during wakefulness in 22/27, and bursts of diffuse fast rhythms (DFR) in sleep in all patients. At last observation, 11 patients only had TS during wakefulness, but all still presented TS during sleep; AA persisted in 6 patients. EEG showed normal BA in 12/27 patients; only 7/27 still presented DSSW. On the contrary, sleep EEG showed the persistence of DFR in all. A moderate to severe cognitive impairment was observed in 26/27 patients., Conclusions: In adult LGS patients TS during sleep remain the major seizure type; moreover, a standard waking EEG may be normal. Thus, polysomnography represents the most important mean of investigation also in adult LGS patients., (Copyright 2010 Elsevier B.V. All rights reserved.)

The interaction between the immune and nervous systems can be both detrimental and beneficial. Experimental autoimmune encephalomyelitis (EAE) is an animal model of autoimmune demyelination that histologically and clinically mimics multiple sclerosis (MS). Myelin-reactive T cells produce and release brain-derived neurotrophic factor (BDNF) directly in the central nervous system, which stimulates tissue repair after traumatic injury. In EAE and MS, T cells in the vicinity of actively demyelinating lesions express BDNF, suggesting a neuroinflammatory reaction that is designed to limit brain damage and contribute to the repair process. Despite some evidence supporting MS therapies that enhance BDNF production by immune cells, no published reports have actually demonstrated that increased BDNF production can substantially ameliorate the clinical symptoms of MS. BDNF binds to a small subset of peripheral T cells that express TrkB, which is the BDNF receptor. This binding confers a partial resistance to apoptosis upon T cell activation, which could underlie the chronic nature of the inflammatory process. Here we will review the main aspects of BDNF and TrkB receptor involvement in neuroprotective autoimmunity in both EAE and MS. We will also discuss the latest findings with respect to the role of the BDNF/TrkB axis in regulating the survival of autoreactive T cells, with a focus on potential selectively immunomodulating strategies that may favor neuroprotection in MS.

Conflicting data exist on expression of gp145trkB, the high affinity receptor for brain-derived neurotrophic factor (BDNF), on peripheral blood immunocompetent cells in multiple sclerosis (MS). We analyzed expression of gp145trkB by western blotting and flow cytometry in myelin basic protein (MBP)- and ovalbumin (OVA)-T cell lines prepared from 12 patients with relapsing-remitting MS and 12 normal healthy subjects (NHS) and correlated it with activation-induced apoptosis. We found a higher percentage of gp145trkB-expressing MBP-T cells in MS patients than in NHS (p=0.011). gp145trkB was mainly expressed by CD8(+) T cells to a higher extent in MS patients than in NHS (p=0.04). MBP-T cell lines from MS patients showed significantly lower apoptosis intensity than those from NHS (p=0.011). We found also a significant negative correlation between gp145trkB expression and apoptosis intensity in MS patients only (p=0.02). OVA-T cell lines showed a gp145trkB expression similar to that of MBP-T cell lines, with a higher expression in MS patients than NHS, and similar correlations with apoptosis intensity in MS. These findings suggest that gp145trkB is mainly expressed on T cell lines from MS patients and that the BDNF/gp145trkB axis is involved in the regulation of peripheral T cell apoptosis in MS.

Occipital neuralgia may be related to traumatic, compressive, or inflammatory injury to the occipital nerve or C2 radicular level and cervical spinal cord lesions. We report a series of 3 patients with definite relapsing-remitting multiple sclerosis (MS) who experienced sudden occipital neuralgiform pain with or without diminished sensation in the cervical region and associated with magnetic resonance imaging (MRI) evidence of a new active or new T2-weighted demyelinating C2 cervical lesion. We suggest that sudden paroxysmal occipital pain may signal relapse of MS and cervical MRI with gadolinium should be considered; these patients show good clinical response to high-dose intravenous corticosteroids.

A 62-year-old woman with relapsing-remitting multiple sclerosis suddenly complained of diplopia associated with bilateral adduction impairment, nystagmus of the abducting eye bilaterally, and sparing of abduction, convergence, and vertical eye movements, consistent with bilateral internuclear ophthalmoplegia. Within 1 week, she had developed a complete horizontal gaze paralysis even with the oculocephalic maneuver. Vertical saccades were slow and convergence was preserved. There was a right lower motor neuron seventh cranial nerve palsy. Brain MRI showed a new enhancing lesion involving the pontine tegmentum. Clinical and MRI follow-up showed recovery after 6 months. The slowing of vertical saccades may have been due to spread of the demyelinating lesion to the adjacent paramedian pontine reticular formation, which contains omnipause neurons lying in the raphe interpositus nucleus thought to inhibit excitatory burst neurons for horizontal and vertical saccades. Our patient verifies the fact that vertical saccadic abnormalities may occur from a lesion apparently confined to the pons.

To assess the role of CSF oligoclonal bands (OB) in determining the clinical outcome in patients with relapsing-remitting multiple sclerosis (RRMS) treated with IFN-beta, we carried out a retrospective, multicentre, observational study recruiting 209 RRMS patients from six MS centres from northern, central and southern areas of Italy under treatment with IFN-beta-1a i.m., IFN-beta-1a s.c. and IFN-beta-1b s.c. Twenty-two of 209 patients (10.6%) showed no OB in CSF. The patients without had, at disease onset, significantly higher frequency of visual disturbances (p=0.02) and less sensory involvement (p=0.04) than those with OB. A statistical trend (p=0.056) towards a longer time to reach sustained disability progression during treatment was found in patients without compared to those with OB. Thirty-six of 187 (19%) patients with OB worsened by at least 1 EDSS point compared to none of 22 (0%) OB-negative patients (p=0.017). The delaying of disability progression in OB-negative patients during treatment was significantly dependent only on the number of baseline MRI T2-weighted lesions (p=0.012) that was found to be significantly lower in OB-negative than in OB-positive patients (p=0.04). The absence of OB and low number of baseline T2-weighted lesions in this cohort of MS patients are favourable prognostic factors influencing the clinical response to IFN-beta treatment in RRMS patients.

We studied the relationship between restoration of weight loss and healing of the "non-healing wound." Eight consecutive patients with large "non-healing wounds" of an average of 12 months duration, despite good local wound care, were studied. All had a weight loss of 10 percent or more of body weight, mainly lean body mass. Optimizing nutrition (4 weeks) did not significantly increase weight or healing. The addition of the oral anabolic agent oxandrolone increased restoration of weight (4 lbs/week) over a 12-week period. Five wounds completely closed and three closed by 75 percent during this period. We noted a significant correlation (r = 0.67) between restoration of weight loss and closure of the previously "non-healing wound." The rate of wound healing was most prominent after 50 percent of weight loss had been restored. This finding reflects the key relationship between restoring body weight, body protein stores, and wound healing.