Posterior Globe Depth for Optic Nerve Sheath Diameter Measurement in Ocular Ultrasound in Healthy Volunteers.

BACKGROUND: Point-of-care ultrasound (POCUS) is a readily available imaging modality in many emergency departments and health care facilities globally. Optic nerve sheath diameter (ONSD) measurement via ocular ultrasound has been shown to accurately predict increased intracranial pressure. Classically, the preferred technique for sonographic measurement of ONSD has specified measurement at an optimal position of 3 mm posterior to the globe. This study aims to validate an alternative approach of depth measurement (between 3 and 8 mm), with the hypothesis that ONSD should not change in size as the distance posterior to the globe increases. METHODS: Healthy volunteers aged > 18 years were studied. A point 3 mm posterior to the optic disc was located. This was repeated at a point 5 mm as well as 8 mm posterior to the globe. RESULTS: We enrolled 10 healthy participants. When evaluating variability in ONSD measurements at each of the three distances, we found that the difference in the measurements at each distance was statistically significant. In investigating pairwise comparisons, there was no difference between 3 and 5 mm, but there were differences in ONSD measurements at 3 and 8 mm, as well as at 5 and 8 mm. CONCLUSION: POCUS is readily available in many emergency departments and health care facilities across the world. The classically preferred technique for sonographic measurement of ONSD has specified measurement at an optimal position of 3 mm posterior to the globe. Our results identified that ONSD can be measured between 3 and 5 mm with no significant changes.

Management of hepatorenal syndrome and treatment-related adverse events.

Hepatorenal Syndrome is a critical complication of liver failure, mainly in cirrhotic patients and rarely in patients with acute liver disease. It is a complex spectrum of conditions that leads to renal dysfunction in the liver cirrhosis population; the pathophysiology is characterized by a specific triad: circulatory dysfunction, nitric oxide (NO) dysfunction and systemic inflammation but a specific kidney damage has never been demonstrated, in a clinicopathological study, kidney biopsies of patients with cirrhosis showed a wide spectrum of kidney damage. In addition, the absence of significant hematuria or proteinuria does not exclude renal damage. It is estimated that 40% of cirrhotic patients will develop hepatorenal syndrome with in-hospital mortality of about one-third of these patients. The burden of the problem is dramatic considering the worldwide prevalence of more than 10 million decompensated cirrhotic patients, and the age-standardized prevalence rate of decompensated cirrhosis has gone through a significant rise between 1990 and 2017. Given the syndrome's poor prognosis, the clinician must know how to manage early treatment and any complications. The widespread adoption of albumin and vasopressors has increased Hepatorenal syndrome-acute kidney injury reversal and may increase overall survival, as previously shown. Further research is needed to define whether the subclassification of patients may allow to find a personalized strategy to treat Hepatorenal Syndrome and to define the role of new molecules and extracorporeal treatment may allow better outcomes with a reduction in treatment-related adverse effects. This review aims to examine both pharmacological and non-pharmacological treatment of hepatorenal syndrome, with a particular focus on managing adverse events caused by treatment.

Medicinal cannabis products for the treatment of acute pain.

For thousands of years, medicinal cannabis has been used for pain treatment, but its use for pain management is still controversial. Meta-analysis of the literature has shown contrasting results on the addition of cannabinoids to opioids compared with placebo/other active agents to reduce pain. Clinical studies are mainly focused on medicinal cannabis use in chronic pain management, for which the analgesic effect has been proven in many studies. This review focuses on the potential use of medical cannabis for acute pain management in preclinical studies, studies on healthy subjects and the few pioneering studies in the clinical setting.

Burden of severe infections due to carbapenem-resistant pathogens in intensive care unit.

Intensive care units (ICU) for various reasons, including the increasing age of admitted patients, comorbidities, and increasingly complex surgical procedures (e.g., transplants), have become "the epicenter" of nosocomial infections, these are characterized by the presence of multidrug-resistant organisms (MDROs) as the cause of infection. Therefore, the perfect match of fragile patients and MDROs, as the cause of infection, makes ICU mortality very high. Furthermore, carbapenems were considered for years as last-resort antibiotics for the treatment of infections caused by MDROs; unfortunately, nowadays carbapenem resistance, mainly among Gram-negative pathogens, is a matter of the highest concern for worldwide public health. This comprehensive review aims to outline the problem from the intensivist's perspective, focusing on the new definition and epidemiology of the most common carbapenem-resistant MDROs (Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales) to emphasize the importance of the problem that must be permeating clinicians dealing with these diseases.

Antimicrobial approach of abdominal post-surgical infections.

Abdominal surgical site infections (SSIs) are infections that occur after abdominal surgery. They can be superficial, involving the skin tissue only, or more profound, involving deeper skin tissues including organs and implanted materials. Currently, SSIs are large global health problem with an incidence that varies significantly depending on the United Nations' Human Development Index. The purpose of this review is to provide a practical update on the latest available literature on SSIs, focusing on causative pathogens and treatment with an overview of the ongoing studies of new therapeutic strategies.

Current status of COVID-19 treatment: An opinion review.

The pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has garnered the attention of scientists worldwide in the search for an effective treatment while also focusing on vaccine development. Several drugs have been used for the management of coronavirus disease 2019 (COVID-19), which has affected many hospitals and health centers worldwide. Statistically significant results are lacking on the effectiveness of the experimented drugs in reducing COVID-19 morbidity or mortality, as there are very few published randomized clinical trials. Despite this, the literature offers some material for study and reflection. This opinion review attempts to address three burning questions on COVID-19 treatment options. (1) What kind of studies are currently published or ongoing in the treatment of patients with COVID-19? (2) What drugs are currently described in the literature as options of treatment for patients affected by the infection? And (3) Are there specific clinical manifestations related to COVID-19 that can be treated with a customized and targeted therapy? By answering these questions, we wish to create a summary of current COVID-19 treatments and the anti-COVID-19 treatments proposed in the recent clinical trials developed in the last 3 mo, and to describe examples of clinical manifestations of the SARS-CoV-2 infection with a cause-related treatment.

Spontaneous bacterial peritonitis due to carbapenemase-producing Enterobacteriaceae: Etiology and antibiotic treatment.

Carbapenem antibiotics were first introduced in the 1980s and have long been considered the most active agents for the treatment of multidrug-resistant gram-negative bacteria. Over the last decade, carbapenem-resistant Enterobacteriaceae (CRE) have emerged as organisms causing spontaneous bacterial peritonitis. Infections caused by CRE have shown a higher mortality rate than those caused by bacteria sensitive to carbapenem antibiotics. Current antibiotic guidelines for the treatment of spontaneous bacterial peritonitis are insufficient, and rapid de-escalation of empiric antibiotic treatment is not widely recognized. This review summarizes the molecular characteristics, epidemiology and possible treatment of spontaneous bacterial peritonitis caused by CRE.

Neutrophilic Dermatoses and Their Implication in Pathophysiology of Asthma and Other Respiratory Comorbidities: A Narrative Review.

Neutrophilic dermatoses (ND) are a polymorphous group of noncontagious dermatological disorders that share the common histological feature of a sterile cutaneous infiltration of mature neutrophils. Clinical manifestations can vary from nodules, pustules, and bulla to erosions and ulcerations. The etiopathogenesis of neutrophilic dermatoses has continuously evolved. Accumulating genetic, clinical, and histological evidence point to NDs being classified in the spectrum of autoinflammatory conditions. However, unlike the monogenic autoinflammatory syndromes where a clear multiple change in the inflammasome structure/function is demonstrated, NDs display several proinflammatory abnormalities, mainly driven by IL-1, IL-17, and tumor necrosis factor-alpha (TNF-a). Additionally, because of the frequent association with extracutaneous manifestations where neutrophils seem to play a crucial role, it was plausible also to consider NDs as a cutaneous presentation of a systemic neutrophilic condition. Neutrophilic dermatoses are more frequently recognized in association with respiratory disorders than by chance alone. The combination of the two, particularly in the context of their overlapping immune responses mediated primarily by neutrophils, raises the likelihood of a common neutrophilic systemic disease or an aberrant innate immunity disorder. Associated respiratory conditions can serve as a trigger or may develop or be exacerbated secondary to the uncontrolled skin disorder. Physicians should be aware of the possible pulmonary comorbidities and apply this knowledge in the three steps of patients' management, work-up, diagnosis, and treatment. In this review, we attempt to unravel the pathophysiological mechanisms of this association and also present some evidence for the role of targeted therapy in the treatment of both conditions.

Malar rash is a predictor of subclinical airway inflammation in patients with systemic lupus erythematosus: a pilot study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, auto-immune, multi-organ disease that can affect both the skin and the lungs. Malar rash is a common skin manifestation of SLE and is linked to SLE disease activity, whereas lung involvement is a generally negative prognostic factor for these patients. However, a sensitive and non-invasive screening tool for potential lung involvement in SLE patients is still not available. METHODS: This study aimed to investigate the relationship between malar rash and airway inflammation in adult SLE patients who were not known to have any lung involvement (clinical or radiologic). The study comprised of the measurement of the concentration of NO in exhaled breath or fraction of exhaled nitric oxide (FeNO) and levels were compared between those with and without malar rash. This tool is considered as a sensitive and non-invasive method that is routinely used in patients with asthma or other respiratory diseases to identify airway inflammation. RESULTS: A total of 125 patients (100 females, 25 males) were enrolled during the study period from January 2011 to December 2014. Patients with malar rash (N = 35) had a significant decrease in serum levels of C4 (p < 0.05) compared to patients without malar rash (N = 90). The mean levels of FeNO in overall patients were 36.44 ± 8.87 ppb. A statistically significant difference in FeNO50 values between patients with malar rash (43.46 ± 6.72 ppb) and without (29.43 ± 3.64 ppb) was found (p < 0.001). FeNO50 values were inversely correlated only with serum C4 (p < 0.01). However, no correlation between FeNO50 values and SLE clinical disease activity scores was found. CONCLUSIONS: The presence of a malar rash may predict sub-clinical airway inflammation in SLE patients. Further prospective studies are needed to confirm the usefulness of FeNO measurements in monitoring SLE-associated airway inflammation.

Outcomes assessment of hepatitis C virus-positive psoriatic patients treated using pegylated interferon in combination with ribavirin compared to new Direct-Acting Antiviral agents.

AIM: To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C (CHC) treated with new Direct-Acting Antiviral agents (DAAs) compared to pegylated interferon-2α plus ribavirin (P/R) therapy. METHODS: This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus (HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017. The patients were divided into two groups: patients that underwent therapy with DAAs and patients that underwent HCV treatment with P/R. Patients were assessed by a dermatologist for psoriasis symptoms, collecting Psoriasis Area Severity Index (PASI) scores and the Dermatology Quality of Life Index (DLQI). PASI and DLQI scores were evaluated 24 wk after the end of HCV treatment and were assumed as an outcome of the progression of psoriasis. Switching to a different bDMARD was considered as an inadequate response to biological therapy. The dropout of HCV therapy and sustained virological response (SVR) were considered as outcomes of HCV therapy. RESULTS: Fifty-nine psoriatic patients in biological therapy underwent antiviral therapy for CHC. Of this, 27 patients were treated with DAAs and 32 with P/R. After 24 wk post treatment, the DLQI and the PASI scores were significantly lower (P < 0.001 and P < 0.005, respectively) in the DAAs group compared with P/R group. None of the patients in the DAAs group (0/27) compared to 8 patients of the P/R group (8/32) needed a shift in biological treatment. CONCLUSION: DAAs seem to be more effective and safe than P/R in HCV-positive psoriatic patients on biological treatment. Fewer dermatological adverse events may be due to interferon-free therapy.

Psoriasis and Respiratory Comorbidities: The Added Value of Fraction of Exhaled Nitric Oxide as a New Method to Detect, Evaluate, and Monitor Psoriatic Systemic Involvement and Therapeutic Efficacy.

Psoriasis is a chronic inflammatory systemic disease characterized by a wide range of comorbidities. Respiratory comorbidities are currently poorly characterized and with discordant results. The systemic state of inflammation caused by psoriasis acts de novo on respiratory tissues and amplifies preexisting inflammation from asthma or chronic obstructive pulmonary disease. Because the lungs act as a gas exchanger between the internal and external environment, the impact of chronic psoriasis inflammation may be easily assessed through the analysis of exhaled breath. The fraction of exhaled nitric oxide test (FeNO) is a potential noninvasive solution that can provide quantitative and qualitative indices of respiratory airway inflammation. FeNO is routinely used to screen and manage asthmatic patients. Recent pilot studies contain encouraging data that underscore its possible use with systemic inflammatory nonpulmonary diseases, such as psoriasis. FeNO may therefore be a useful tool to evaluate underestimated airway inflammation and at the same time globally evaluate the impact of systemically antipsoriatic therapies.

NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network.

Congenital heart defects can be caused by mutations in genes that guide cardiac lineage formation. Here, we show deletion of NKX2-5, a critical component of the cardiac gene regulatory network, in human embryonic stem cells (hESCs), results in impaired cardiomyogenesis, failure to activate VCAM1 and to downregulate the progenitor marker PDGFRα. Furthermore, NKX2-5 null cardiomyocytes have abnormal physiology, with asynchronous contractions and altered action potentials. Molecular profiling and genetic rescue experiments demonstrate that the bHLH protein HEY2 is a key mediator of NKX2-5 function during human cardiomyogenesis. These findings identify HEY2 as a novel component of the NKX2-5 cardiac transcriptional network, providing tangible evidence that hESC models can decipher the complex pathways that regulate early stage human heart development. These data provide a human context for the evaluation of pathogenic mutations in congenital heart disease.