The 3Ks (kava, kratom and khat) are herbals that can potentially induce liver injuries. On the one hand, growing controversial data have been reported about the hepatotoxicity of kratom, while, on the other hand, even though kava and khat hepatotoxicity has been investigated, the hepatotoxic effects are still not clear. Chronic recreational use of kratom has been associated with rare instances of acute liver injury. Several studies and case reports have suggested that khat is hepatotoxic, leading to deranged liver enzymes and also histopathological evidence of acute hepatocellular degeneration. Numerous reports of severe hepatotoxicity potentially induced by kava have also been highlighted, both in the USA and Europe. The aim of this review is to focus on the different patterns and the mechanisms of hepatotoxicity induced by “the 3Ks”, while trying to clarify the numerous aspects that still need to be addressed.

Work-related noise exposure is one of the major factors contributing to the development of adult-onset hearing loss and tinnitus. The aim of this study was to analyze, in patients with chronic tinnitus and long-term occupational noise exposure, (A) characteristics of hearing loss, tinnitus, comorbidities, demographic characteristics and a history of work-related noise exposure and (B) differences among individuals employed in occupations with high and low risk of developing work-related noise-induced hearing loss (NIHL). One hundred thirty six patients with chronic tinnitus and at least a 10 year-long working history were divided into two groups based on the risk of their profession to induce NIHL. Individuals employed in jobs at high risk for NIHL were mostly males and exhibited a poorer hearing threshold, more evident in the left ear. Tinnitus was mostly bilateral; the next largest presentation was left-sided; patients described their tinnitus as buzzing or high-pitched. Correlation between age, length of tinnitus and worse hearing was found. Patients with a higher degree of hearing impairment were mostly males and were more likely to have a family history of hearing loss and at least one cardiovascular comorbidity. Our study shows some differences in individuals with tinnitus and a history of a profession associated with increased exposure to NIHL compared to those without such a history.

Autism spectrum disorder (ASD) is a neurodevelopmental disease which affects 1 in 88 children. Its etiology remains basically unknown, but it is apparent that neuroinflammation is involved in disease development. Great attention has been focused on pro-inflammatory cytokines, and several studies have reported their dysfunction unbalance in serum as well as in the brain. The present work aimed at evaluating putative dysregulation of interleukin-18 (IL-18), a pro-inflammatory cytokine of the IL-1 family in the sera of patients with ASD of different grades, compared to healthy controls, as well as in postmortem brain samples obtained from patients with tuberous sclerosis as well as acute inflammatory diseases. Moreover, quantitative analysis of IL-18 was performed in the sera and brain obtained from Reeler mice, an experimental model of autism. Serum IL-18 levels were measured by ELISA. IL-18 was localized by immunohistochemical analysis in brain sections obtained from tuberous sclerosis and encephalitis patients, as well as from gender- and age-matched controls, and in the brain sections of both Reeler and wild-type mice. IL-18 was also quantified by Western blots in homogenates of Reeler and wild-type mice brains. IL-18 binding protein (IL-18BP) was evaluated in Reeler and wild-type mice plasma as well as in their brains (sections and homogenates). IL-18 content decreased in the sera of patients with autism compared to healthy subjects and in Reeler sera compared to wild-type controls. IL-18 was detected within glial cells and neurons in the brain of subjects affected by tuberous sclerosis and encephalitis whereas in healthy subjects, only a weak IL-18 positivity was detected at the level of glial cells. Western blot identified higher amounts of IL-18 in Reeler brain homogenates compared to wild-type littermates. IL-18BP was expressed in higher amounts in Reeler brain compared to the brain of wild-type mice, whereas no significant difference was detected comparing IL-18BP plasma levels. IL-18 is dysregulated in ASD patients. Further studies seemed necessary to clarify the molecular details behind IL-18 increase in the brain and IL-18 decrease in the sera of patients. An increase in the size of the patient cohort seems necessary to ascertain whether decreased IL-18 content in the sera can become a predictive biomarker of ASD and whether its measure, in combination with other markers (e.g., increased levels of brain-derived neurotrophic factor (BDNF)), may be included in a diagnostic panel.

Background: COVID-19 causes major changes in day-to-day hospital activity due to its epidemiological characteristics and the clinical challenges it poses, especially in internal medicine wards. Therefore, it is necessary to understand and manage all of the implicated factors in order to maintain a high standard of care, even in sub-par circumstances. Methods: This was a three-phase, mixed-design study. Initially, the Delphi method allowed us to analyze the causes of poor outcomes in a cohort of an aggregate of Italian COVID-19 wards via an Ishikawa diagram. Then, for each retrieved item, a score was assigned according to a pros/cons, opportunities/threats system. Scores were also assigned according to potential value/perceived risk. Finally, the performances of MCs (Medicine-COVID-19 wards) and MCFs (Medicine-COVID-19-free: Internal Medicine wards) units were represented via a Barber’s nomogram. Results: MCFs hospitalized 790 patients (−23.90% compared to 2019 Internal Medicine admissions). The main risk factors for mortality were patients admitted from local facilities (+7%) and the presence of comorbidities (>3: 100%, ≥5: 24.7%). A total of 197 (25%) patients were treated with non-invasive ventilation (NIV). The most deaths (57.14%) occurred in patients admitted from local facilities. Conclusions: Medicine-COVID-19 wards show higher complexity and demand compared to non-COVID-19 ones and they are comparable to sub-intensive therapy wards. It is necessary to promote the use of NIV in such settings.