Skull-vibration-induced nystagmus test in patients who are candidates for intratympanic gentamicin injection.

Objective: This study aims to evaluate the utility of the skull-vibration-induced nystagmus test (SVINT) in the selection of patients with Ménière's disease (MD) for intratympanic injection of gentamicin. To date the indications for this treatment have been based only on subjective elements. Methods: A retrospective study was performed in 20 patients diagnosed with unilateral MD. SVINT were performed monthly and the evoked responses were evaluated. After 6 months, the results from patients who were candidates for gentamicin treatment (G group) were compared with those who did not need it (nG group). Correlation with Dizziness Handicap Inventory (DHI) score was evaluated. Results: 120 tests were performed. Positive SVINTs were identified in 52 cases (43.3%) and included excitatory nystagmus in 18 (34.7%), inhibitory nystagmus in 28 (53.8%), and atypical pattern in 6 cases (11.5%). A significant increase excitatory nystagmus was recorded in group G (p = 0.00001). Moreover, there was a significant increase in the DHI score in group G compared with the nG group (p < 0.0001) and in patients with evoked excitatory nystagmus. Conclusions: The finding of excitatory nystagmus during SVINTs performed on several occasions in the follow-up prior to intratympanic injection of gentamicin strengthens this therapeutic choice.

Adaptive perceptual responses to asymmetric rotation for testing otolithic function.

This study aimed to test the role of the otolithic system in self-motion perception by examining adaptive responses to asymmetric off-axis vertical rotation. Self-movement perception was examined after a conditioning procedure consisting of prolonged asymmetric sinusoidal yaw rotation of the head on a stationary body with hemicycle faster than the other hemicycle. This asymmetric velocity rotation results in a cumulative error in spatial self-motion perception in the upright position that persists over time. Head yaw rotation conditioning was performed in different head positions: in the upright position to activate semicircular canals and in the supine and prone positions to activate both semicircular canals and otoliths with the phase of otolithic stimulation reversed with respect to activation of the semicircular canals. The asymmetric conditioning influenced the cumulative error induced by four asymmetric cycles of whole-body vertical axis yaw rotation. The magnitude of this error depended on the orientation of the head during the conditioning. The error increased by 50% after upright position conditioning, by 100% in the supine position, and decreased by 30% in the prone position. The enhancement and reduction of the perceptual error are attributed to otolithic modulation because of gravity influence of the otoliths during the conditioning procedure in supine and prone positions. These findings indicate that asymmetric velocity otolithic activation induces adaptive perceptual errors such as those induced by semicircular canals alone, and this adaptation may be useful in testing dynamic otolithic perceptual responses under different conditions of vestibular dysfunction.

Patterns of Prescription Medicine, Illicit Drugs, and Alcohol Misuse among High-Risk Population: A Factor Analysis to Delineate Profiles of Polydrug Users.

Polydrug use is a serious health and social problem worldwide. Treatment remains a challenge because it requires planning based on estimates of the nature and extent of drug consumption and the characteristics of the population in need. To this end, 103 subjects, who voluntarily asked to begin rehabilitation treatment, were monitored through hair analysis to investigate the nature and extent of their polydrug use. A factor analysis was carried out to delineate polydrug user profiles based on the following variables: age, sex, type of illicit drug use, type of prescription drug misuse, and amount of alcohol consumption. Twenty-three percent of subjects tested positive to more than one illicit drug (mainly cocaine), 44% to unprescribed drugs (mainly benzodiazepines), and 66% were hard drinkers. The profiles of drug users outlined included "single drug cocaine user", and "single drug opiate user". Moreover, a particularly problematic profile of cocaine users, common between genders and age groups, who combine high levels of alcohol and unprescribed benzodiazepines and opiates, emerged ("hard polydrug abusers"). From a treatment policy perspective, these findings support the importance of preventive analysis before rehabilitation treatment begins in order to identify different patterns of drug abusers to implement personalized multidisciplinary measures.

Drugs acting on the renin-angiotensin system and SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global Coronavirus 2019 (COVID-19) pandemic, resulting in thousands of deaths worldwide and representing a health challenge with few precedents in human history. Angiotensin-converting enzyme 2 (ACE-2) facilitates the access of SARS-CoV-2 to cells. Therapeutic agents acting on the renin-angiotensin system (RAS) might be able to modulate the concentration of ACE-2 and the various components of the system. Here, we discuss current pharmacological, molecular, and clinical evidence to investigate whether drugs acting on RAS with modulation of the ACE-2 concentration have added value in combating SARS-CoV-2 infection. We also highlight the possible deleterious action of the ACE/Ang-II/AT-1r axis and possible beneficial role of the ACE-2/Ang 1-7/MasR axis in acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2, discussing the possibility of addressing the various RAS components with drug treatments to improve clinical outcomes.

COVID-19 Patients with Pulmonary Fibrotic Tissue: Clinical Pharmacological Rational of Antifibrotic Therapy.

In December 2019, the first data emerged from Wuhan, China, of a serious acute respiratory disease caused by a new coronavirus, SARS-CoV-2 (COVID-19). In a short time, the health emergency became a global pandemic. To date, there are about 18.8 million infected people and about 700,000 deaths. There are currently no effective vaccines, and treatments are mostly experimental. The symptoms associated with COVID-19 are different, ranging from mild upper respiratory tract symptoms to severe acute respiratory distress syndrome (SARS). Data from previous coronavirus outbreaks such as SARS-CoV (2003 outbreak) and emerging epidemiological data from the current global COVID-19 pandemic suggest that there could be substantial tissue fibrotic consequences following SARS-CoV-2 infection, responsible for severe and in some cases fatal lung lesions. Some data show that even patients cured of viral infection have lung fibrotic tissue residues responsible for incorrect respiratory function even after healing. The role of antifibrotic drug therapy in patients with ongoing SARS-CoV-2 infection or in patients cured of residual pulmonary fibrosis is still to be defined and unclear; the scientific rationale for initiating, continuing, or discontinuing therapy is poorly defined. In this article, we describe the advantages of antifibrotic therapy in patients with ongoing SARS-CoV-2 viral infection to prevent the worsening and aggravation of the clinical situation, and the advantages it could have in the role of preventing pulmonary fibrosis after SARS-CoV-2 infection, and in accelerating the complete healing process.

The added value of pirfenidone to fight inflammation and fibrotic state induced by SARS-CoV-2 : Anti-inflammatory and anti-fibrotic therapy could solve the lung complications of the infection?

AIM: SARS-CoV-2 infection has been divided by scientific opinion into three phases: the first as asymptomatic or slightly symptomatic and the second and the third with greater severity, characterized by a hyperinflammatory and fibrotic state, responsible for lung lesions, in some cases fatal. The development of antiviral drugs directed against SARS-CoV-2 and effective vaccines is progressing; meanwhile, the best pharmacological objective is related to the management of all the complications caused by this viral infection, mainly controlling the inflammatory and fibrotic state and preventing the infection from moving into the most serious phases. SUBJECT AND METHOD: Describe the scientific rationale related to the use of an antifibrotic therapy with pirfenidone, as monotherapy and/or in combination with anti-inflammatory drugs to manage and control complications of SARS-CoV-2 infection. RESULTS: Based on the scientific literature and epidemiological results and considering the pathophysiological, biological, and molecular characteristics of SARS-CoV-2, an antifibrotic drug such as pirfenidone as monotherapy or in combination with anti-inflammatory drugs can be (acting early, at the right doses and at the right time) therapeutically effective to avoid serious complications during viral infection. The same approach can also be effective as postinfection therapy in patients with residual pulmonary fibrotic damage. Management of inflammation and fibrotic status with a combination therapy of pirfenidone and IL-6 or IL-1 inhibitors could represent a pharmacological synergy with added value. CONCLUSION: In this article, we consider the role of antifibrotic therapy with pirfenidone in patients with SARS-CoV-2 infection on going or in the stage of postinfection with pulmonary fibrotic consequences. The scientific rationale for its use is also described.