Drug-Drug Interactions in Vestibular Diseases, Clinical Problems, and Medico-Legal Implications.

Peripheral vestibular disease can be treated with several approaches (e.g., maneuvers, surgery, or medical approach). Comorbidity is common in elderly patients, so polytherapy is used, but it can generate the development of drug-drug interactions (DDIs) that play a role in both adverse drug reactions and reduced adherence. For this reason, they need a complex kind of approach, considering all their individual characteristics. Physicians must be able to prescribe and deprescribe drugs based on a solid knowledge of pharmacokinetics, pharmacodynamics, and clinical indications. Moreover, full information is required to reach a real therapeutic alliance, to improve the safety of care and reduce possible malpractice claims related to drug-drug interactions. In this review, using PubMed, Embase, and Cochrane library, we searched articles published until 30 August 2021, and described both pharmacokinetic and pharmacodynamic DDIs in patients with vestibular disorders, focusing the interest on their clinical implications and on risk management strategies.

Nutraceuticals for Peripheral Vestibular Pathology: Properties, Usefulness, Future Perspectives and Medico-Legal Aspects.

Vestibular disorders may generate complex signs and symptoms, which may alter patients' balance and the quality of life. Dizziness and vertigo can strongly affect daily activities and relations. Despite the presence of conventional drugs, maneuvers, and surgery, another interesting therapeutic opportunity is offered by nutraceuticals. These molecules are often used in the treatment of dizziness and vertigo, but the rationale of their application is not always solidly demonstrated by the scientific evidence. Several substances have shown a variable level of efficacy/usefulness in this field, but there is lack of important evidence for most of them. From a medico-legal point of view, specific information must be provided to the patient regarding the efficacy and possibilities that the use of these preparations can allow. Administering the right nutraceutical to the proper patient is a fundamental clinical skill. Integrating conventional drug treatment with nutraceutical administration seems to be easy, but it may be difficult considering the (in part unexplored) pharmacodynamics and pharmacokinetics of nutraceuticals. The aim of the scientific community should be to elevate nutraceuticals to the same law and technical dignity of conventional drugs.

Data Recorded in Real Life Support the Safety of Nattokinase in Patients with Vascular Diseases.

Nattokinase (NK) is a serine protease enzyme with fibrinolytic activity. Even if it could be used for the treatment of several diseases, no data have been published supporting its use patients who underwent vascular surgery. In this study, we evaluated both the efficacy and the safety of nattokinase (100 mg/day per os) in patients admitted to vascular surgery. Patients were of both sexes, >18 years of age, with vascular diseases (i.e., deep vein thrombosis, superficial vein thrombosis, venous insufficiency), and naïve to specific pharmacological treatments (anticoagulants or anti-platelets). Patients were divided into three groups. Group 1: patients with deep vein thrombosis, treated with fondaparinux plus nattokinase. Group 2: patients with phlebitis, treated with enoxaparin plus nattokinase. Group 3: patients with venous insufficiency after classical surgery, treated with nattokinase one day later. During the study, we enrolled 153 patients (age 22-92 years), 92 females (60.1%) and 61 males (39.9%;), and documented that nattokinase was able to improve the clinical symptoms (p < 0.01) without the development of adverse drug reactions or drug interactions. Among the enrolled patients, during follow-up, we did not record new cases of vascular diseases. Attention to patients' clinical evolution, monitoring of the INR, and timely and frequent adjustment of dosages represent the cornerstones of the safety of care for patients administered fibrinolytic drugs as a single treatment or in pharmacological combination. Therefore, we can conclude that the use of nattokinase represents an efficient and safe treatment able to both prevent and treat patients with vascular diseases.

Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work.

BACKGROUND: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5-7%, and the percentage of positive patients admitted to intensive care units being 9-11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.

Catheter-related Bloodstream Infections: A Root Cause Analysis in a Series of Simultaneous Ochrobactrum anthropi Infections.

OBJECTIVE: Catheter-related bloodstream infections (CRBSIs) pathogenesis is complex and multifactorial mostly due to cutaneous microorganisms migration through the catheter insertion site and catheter tip colonization. Ochrobactrum anthropi is a gram-negative bacterium belonging to the Brucellaceae and related infections are especially observed in immunocompromised patients. METHODS: Therefore, O. anthropi infection prevention and surveillance are relevant issues for healthcare system and risk management, in order to improve healthcare quality and patient safety. Four cases of anthropi-related CRBSIs occurring in immunodepressed patients under chemotherapy treatment are reported and the possible prevention and surveillance strategies are analyzed. RESULTS: In the reported cases, all infections occurred almost simultaneously in the Oncology Unit, leading to hypothesize an identical infection source. Subsequently, a clinical audit was performed in order to investigate infection origin and implement prevention and control strategies. Clinical audit allowed to identify the hand hygiene defects as the primary source of the infections, responsible for catheter flushing solution contamination. CONCLUSION: The aim of this study is to reveal how through correct root cause analysis and clinical audit, several measures could be undertaken in order to promote the prevention of the CRBSIs risk.

Glecaprevir/Pibrentasvir Induced Cholestatic Jaundice in a HCV Patient with Renal Failure. A Case Presentation.

BACKGROUND: Direct-acting Antivirals (DAA) are currently used in the treatment of chronic HCV infection. In patients with renal failure Glecaprevir/Pibrentasvir (genotype 1-6) is recommended for its safety and efficacy. CASE PRESENTATION: Although these pharmacological characteristics, an adverse drug reaction (ADR) has been reported during Glecaprevir/Pibrentasvir treatment, such as the development of cholestatic jaundice in an elderly patient with chronic HCV (genotype 2) infection. At examination, patient was jaundiced associated with intense pruritus. RESULTS: Ultrasound and laboratory biochemical tests excluded a liver failure (e.g. liver cancer, and liver lithiasis) or pancreatic cancer while Naranjo probability scale (score 6) suggested an association between cholestatic jaundice and Glecaprevir/Pibrentasvir administration. About 1 month after drug discontinuation, an improvement has been documented in both jaundice and pruritus, with a normalization in bilirubin levels (total bilirubin: 0.96 mg/dL), HCV-RNA was undetected also. It is worth mentioning that although we reported the development of cholestatic jaundice upon treatment with Glecaprevir/Pibrentasvir we recorded a clinical efficacy (HCV-RNA <15 IU/L) after 4 weeks from the beginning of the treatment, with a complete remission of clinical symptoms until 7 months after drug discontinuation. CONCLUSION: These data support the clinical efficacy of Glecaprevir/Pibrentasvir association in elderly patients, despite the sub-optimal period of treatment.

New evidence for a critical role of elastin in calcification of native heart valves: immunohistochemical and ultrastructural study with literature review.

AIMS: Calcific aortic stenosis is a progressive disease characterized by massive fibrosis andmineralization of the valve leaflets. The aim of this study was to determine whether the onset of native calcific aortic stenosis is associated primarily with matrix remodelling events, and particularly with elastin degradation. METHODS AND RESULTS: The immunohistochemical expression profile of matrix degradating enzymes and tenascin-C was investigated in both healthy and native calcified aortic valves. Collagen and elastic tissue were studied by light microscopy and electron microscopy. Immunophenotypic analysis of inflammatory cells was carried out by using monoclonal antibodies to macrophages, T and B lymphocytes. Immunoreactivity for tenascin-C and matrix metalloproteinase-12 (MMP-12) was associated with areas of dense mineralization, which were characterized by fibrosis, fragmentation and calcification of elastic fibres a positive reaction was also found around small islands of calcification. MMP-11 was not detected in the diseased valves. Osteopontin and osteonectin were also found at sites of mineralization. All calcified valves examined showed inflammatory cell infiltration. CONCLUSIONS: Our results demonstrate the direct involvement of MMP-12 in native aortic valve stenosis. MMP-mediated degradation of elastic fibres might contribute actively to valve mineralization by inducing calcium deposition onto fragmented elastin.

Histopathological, clinical, and electrophysiological features influencing postoperative outcomes in carpal tunnel syndrome.

Data on the outcome predictors of surgical result of carpal tunnel syndrome (CTS) is sparse and often conflicting. The purpose of this prospective comparative study was to evaluate the neurophysiologic findings and histological characteristics of the flexor tenosynovium in patients with CTS, assessing possible associations between these findings and preoperative patient status or surgical outcome. We evaluated 30 consecutive patients with a diagnosis of idiopathic CTS who were referred for surgery. Demographic data, subjective and objective data, and responses on an expanded assessment set, were collected before and 6 months after surgery. All patients underwent diagnostic neurophysiological testing prior to surgery, and histological analysis of tenosynovium specimens that were removed during surgery. Ten fresh-frozen cadavers served as controls. There was significant improvement in most of the disease specific (Boston questionnaire and Hi-Ob scale) and health generic (SF-36 questionnaire) evaluation tools used in the study at the 6-month follow-up. Vascular changes were noted in the tenosynovium of the flexor tendon of patients with CTS when compared with controls. Greater synovial vascularization was negative predictor of the SF-36's physical summary score before surgery. Bilateral presentation of symptoms and low nerve conduction velocity were negative predictors of the quality of life of patients after surgery for CTS. These findings have to be considered when discussing with patients as for the expected and desired outcomes of CTS surgery. The increased vascularization of flexor tenosynovium is associated with patients' functional status.

Hepatonecrosis and cholangitis related to long-term phenobarbital therapy: an autopsy report of two patients.

Phenobarbital (PB) has a reputation for safety, and it is commonly believed that PB-related increases in serum aminotransferase levels do not indicate or predict the development of significant chronic liver disease. Here we report of two adult patients with a long history of epilepsy treated with PB who died suddenly: one as consequence of cardiac arrest, the other of acute bronchopneumonia. At autopsy, analysis of liver parenchyma revealed rich portal inflammatory infiltrate, which consisted of mixed eosinophil and monocyte cells, associated with several foci of necrosis surrounded by a hard ring of non-specific granulomatous tissue. Inflammatory reactions of internal and external hepatic biliary ducts were also seen. Our findings illustrate that PB may be associated with chronic liver damage, which may lead to more serious and deleterious consequences. For this reason, each clinician should recognize this entity in the differential diagnosis of PB-related asymptomatic chronic hepatic enzyme dysfunction.