The Journey Through the Pathogenesis and Treatment of Venous Thromboembolism in Inflammatory Bowel Diseases: A Narrative Review.

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract including Crohn's disease and ulcerative colitis, which may result in several extraintestinal complications (∼20-30% of cases), such as increased risk of venous thromboembolism (VTE). The main pathophysiological mechanism of VTE is an inflammation-induced hypercoagulable state, and recent data have shown that endothelial dysregulation due to gut and systemic inflammation may also lead to a prothrombotic state. Several prothrombotic alterations have been described, such as the activation of the coagulation system, platelet abnormalities, and dysregulation of fibrinolysis. Furthermore, the dysregulation of the gut microbiome seems to play a vital role in increasing systemic inflammation and thus inducing a procoagulant state. Our review aims to examine the main correlations between IBD and VTE, the underlying pathophysiology, and current therapeutic options.

The Diagnostic Role of Lung Ultrasound and Contrast-Enhanced Ultrasound in Pulmonary Embolism.

The diagnosis of pulmonary embolism (PE) relies essentially on a probabilistic approach that requires careful clinical assessments, targeted laboratory tests, and the use of appropriate imaging tools. Nowadays, the diagnostic gold standard is computed tomographic pulmonary angiography. Lung ultrasound (LUS) can play a role in the diagnosis of PE mainly by allowing the visualization of peripheral lung infarctions. Hypoechoic, pleural-based parenchymal consolidation is the most typical and common finding of pulmonary infarction. More than 85% of infarct lesions are wedge-shaped, extending to the pleural surface and are localized to where the patient complains of pleuritic chest pain. Contrast-enhanced ultrasound can be performed in addition to basic ultrasound examination to ascertain nonvascularization of the consolidation, thus confirming that the lesion is an infarct. The aim of this narrative review is to summarize the latest evidence on the application of LUS to the diagnosis of PE, focusing purely on thoracic/lung signs.

Real-world use of remdesivir for the treatment of patients admitted to Italian hospitals with COVID-19: the nationwide retrospective FADOI-RECOVER study.

BACKGROUND: Remdesivir is widely used for treatment of SARS-CoV-2 pneumonia. The aim of this study was to evaluate the characteristics of patients with moderate-to-severe COVID-19 treated with remdesivir, and their outcomes during hospitalization. METHODS: This retrospective observational multicenter study included consecutive patients, hospitalized for moderate-to-severe COVID-19 (September 2020-September 2021), who were treated with remdesivir. RESULTS: One thousand four patients were enrolled, all with onset of symptoms occurring less than 10 days before starting remdesivir; 17% of patients had 4 or more concomitant diseases. Remdesivir was well tolerated, adverse drug reactions (ADRs) being reported in 2.3% of patients. In-hospital death occurred in 80 patients (8.0%). The median timing of the first remdesivir dose was 5 days after symptom onset. The following endpoints did not differ according to the time span from the onset of symptoms to the first dose: length of hospitalization, in-hospital death, composite outcome (in-hospital death and/or endotracheal intubation). Advanced age, number of comorbidities ≥ 4, and severity of respiratory failure at admission were associated with poor in-hospital outcomes. CONCLUSION: In a real-world setting, remdesivir proved to be a safe and well-tolerated treatment for moderate-to-severe COVID-19. In patients receiving remdesivir less than 3 or 5 days from the onset of SARS-CoV-2 symptoms, mortality and the need for mechanical ventilation did not differ from the rest of the sample.

External validation of the ITA.LI.CA prognostic system for patients with hepatocellular carcinoma: A multicenter cohort study.

Several staging systems for hepatocellular carcinoma (HCC) have been developed. The Barcelona Clinic Liver Cancer staging system is considered the best in predicting survival, although limitations have emerged. Recently, the Italian Liver Cancer (ITA.LI.CA) prognostic system, integrating ITA.LI.CA tumor staging (stages 0, A, B1-3, C) with the Child-Turcotte-Pugh score, Eastern Cooperative Oncology Group performance status, and alpha-fetoprotein with a strong ability to predict survival, was proposed. The aim of our study was to provide an external validation of the ITA.LI.CA system in an independent real-life occidental cohort of HCCs. From September 2008 to April 2016, 1,508 patients with cirrhosis and incident HCC were consecutively enrolled in 27 Italian institutions. Clinical, tumor, and treatment-related variables were collected, and patients were stratified according to scores of the Barcelona Clinic Liver Cancer system, ITA.LI.CA prognostic system, Hong Kong Liver Cancer system, Cancer of the Liver Italian Program, Japanese Integrated System, and model to estimate survival in ambulatory patients with hepatocellular carcinoma. Harrell's C-index, Akaike information criterion, and likelihood-ratio test were used to compare the predictive ability of the different systems. A subgroup analysis for treatment category (curative versus palliative) was performed. Median follow-up was 44 months (interquartile range, 23-63 months), and median overall survival was 34 months (interquartile range, 13-82 months). Median age was 71 years, and patients were mainly male individuals and hepatitis C virus carriers. According to ITA.LI.CA tumor staging, 246 patients were in stage 0, 472 were in stage A, 657 were in stages B1/3, and 133 were in stage C. The ITA.LI.CA prognostic system showed the best discriminatory ability (C-index = 0.77) and monotonicity of gradients compared to other systems, and its superiority was also confirmed after stratification for treatment strategy. CONCLUSION: This is the first study that independently validated the ITA.LI.CA prognostic system in a large cohort of Western patients with incident HCCs. The ITA.LI.CA system performed better than other multidimensional prognostic systems, even after stratification by curative or palliative treatment. This new system appears to be particularly useful for predicting individual HCC prognosis in clinical practice. (Hepatology 2018;67:2215-2225).

Restaging Patients With Hepatocellular Carcinoma Before Additional Treatment Decisions: A Multicenter Cohort Study.

Prognostic assessment of patients with hepatocellular carcinoma (HCC) at the time of diagnosis remains controversial and becomes even more complex at the time of restaging when new variables need to be considered. The aim of the current study was to evaluate the prognostic utility of restaging patients before proceeding with additional therapies for HCC. Two independent Italian prospective databases were used to identify 1,196 (training cohort) and 648 (validation cohort) consecutive patients with HCC treated over the same study period (2008-2015) who had complete restaging before decisions about additional therapies. The performance of the Italian Liver Cancer (ITA.LI.CA) prognostic score at restaging was compared with that of the Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, and Cancer of the Liver Italian Program systems. A multivariable Cox survival analysis was performed to identify baseline, restaging, or dynamic variables that were able to improve the predictive performance of the prognostic systems. At restaging, 35.3% of patients maintained stable disease; most patients were either down-staged by treatment (27.2%) or had disease progression (37.5%). The ITA.LI.CA scoring system at restaging demonstrated the best prognostic performance in both the training and validation cohorts (c-index 0.707 and 0.722, respectively) among all systems examined. On multivariable analysis, several variables improved the prognostic ability of the ITA.LI.CA score at restaging, including progressive disease after the first treatment, Model for End-Stage Liver Disease at restaging, and choice of nonsurgical treatment as additional therapy. A new ITA.LI.CA restaging model was created that demonstrated high discriminative power in both the training and validation cohorts (c-index 0.753 and 0.745, respectively). CONCLUSION: Although the ITA.LI.CA score demonstrated the best prognostic performance at restaging, other variables should be considered to improve the prognostic assessment of patients at the time of deciding additional therapies for HCC.

Management and prognosis of hepatocellular carcinoma in the elderly: Results of an in-field multicenter cohort study.

AIMS: This multicentre cohort study evaluated the role of ageing on clinical characteristics, treatment allocation and outcome of new hepatocellular carcinomas (HCCs), in clinical practice. MATERIAL & METHODS: From September 2008, 541 patients >70 years old (elderly group), and 527 ≤70 years old (non-elderly group) with newly diagnosed HCC were consecutively enrolled in 30 Italian centres. Differences in clinical characteristics and treatment allocation between groups were described by a multivariable logistic regression model measuring the inverse probability weight to meet the elderly group. Survival differences were measured by unadjusted and adjusted (by inverse probability weight) survival analysis. RESULTS: Elderly patients were mainly females, hepatitis C virus infected and with better conserved liver function (P<.001). At presentation, HCC median size was similar in both groups while, in youngers, HCC was more frequently multinodular (P=.001), and associated with neoplastic thrombosis (P=.009). Adjusted survival analysis showed that age did not predict short-mid-term survival (within 24 months), while it was a significant independent predictor of long-term survival. Moreover, age had a significant long-term survival impact mainly on early HCC stages (Barcelona Clinic for Liver Cancer [BCLC] 0-A), its impact on BCLC B stage was lower, while it was negligible for advanced-terminal stages. CONCLUSIONS: Age per se does not impact on short-mid-term prognosis (≤24 months) of HCC patients, and should not represent a limitation to its management.

Trend of improving prognosis of hepatocellular carcinoma in clinical practice: an Italian in-field experience.

BACKGROUND: Recent data suggest that outcome of hepatocarcinoma is improving. AIMS: In order to explore whether survival is also increasing in clinical practice, we compared two multicenter independent in-field cohorts of cirrhotics with newly diagnosed HCCs. METHODS: Cohort 1 (C1) consisted of 327 patients enrolled between January and December 1998, and cohort 2 (C2) included 826 patients enrolled between September 2008 and November 2012. Patients were stratified according to Child-Pugh score, MELD score, and HCC staged according to TNM, BCLC systems. RESULTS: At baseline, C2 patients were significantly older, with more frequent comorbidities and better liver function. In C2, HCC was more frequently detected under regular ultrasound surveillance (P < 0.001), BCLC early stages were more frequent, and rates of smaller and uni/paucinodular tumors were significantly higher. Treatment of any type was more frequently offered to C2 patients (P < 0.001). Proportion of patients treated by TACE increased, and radiofrequency ablation was the most used ablative treatment. Survival rate was significantly higher in C2 being C1 and C2 survival at 1-3 years 72-25 and 75-44 %, respectively. Child-Pugh score A, BCLC stage A, single nodule, size ≤ 3 cm, belonging to cohort C2 and treatment per se independently predicted survival. CONCLUSIONS: This in-field study showed a trend on improved HCC outcomes over time, which seems to be mainly due to a better presentation thanks to the wider application of surveillance and increased propensity to treat patients. These encouraging data should support further efforts to implement such approach to HCC in everyday clinical practice.

The importance of ultrasound-guided biopsy: lesson from a case of liver metastasis from uveal melanoma.

Melanoma is an extremely aggressive malignant neoplasm. Uveal melanoma is the most common primary intraocular malignancy in adults, representing 3-5% of all melanomas. Liver metastases can be clinically detected in 10-20% of patients with metastatic disease from cutaneous melanoma. However, while liver is typically not the first site of disease spread in cutaneous melanoma, ocular melanoma has been showed to primarily metastasize from the eye to the liver; indeed, liver metastases are detected in approximately 87% of patients with metastatic uveal melanoma. Therefore, liver metastasis can be challenging to identify in early stages, thus being essentially asymptomatic until the disease has advanced. Here we report the case of a patient who came to our ultrasound unit reporting a large liver mass. Both contrast-enhanced abdominal computed tomography and magnetic resonance imaging did not establish a definitive diagnosis. The final diagnosis was made only through an ultrasound-guided biopsy of the mass, thus revealing a uveal melanoma metastasis. This is followed by a review of the literature on imaging follow-up of patients with melanoma.

Ultrasound-guided diagnosis on a parapharyngeal mass.

Masses in the parapharyngeal area are rare and often due to infectious phenomena arising from the oral cavity or pharynx which lead to abscess formation. Less frequently, the lesion can be neoplastic. Tumours of the parapharyngeal space are rare, accounting for less than 1% of all head and neck neoplasms. We report the case of a patient who came to our observation for mandibular pain. Multiparametric diagnostic imaging was done thus showing a parapharyngeal mass. An ultrasound guided biopsy was performed by a transcutaneous route with a high median approach at neck level, to characterize the mass in the right tonsillar region. The histological examination reported the final histological diagnosis of sarcomatoid carcinoma.

Ultrasound diagnosis of a pseudoaneurysm of the internal right mammary artery.

One of the principles of managing trauma patients is that of their continuous re-evaluation over the hours and days. Even if the execution of the computed tomography method is classically recommended, especially in the most serious cases and in polytraumas with major dynamics, the clinician can use or request an ultrasound examination, especially in subsequent re-evaluations. Here we report a clinical case demonstrating how an ultrasound re-evaluation after the acute event can lead to a correct diagnosis of a rare complication of thoracic trauma. The findings were suggestive for a pseudoaneurysm of the internal right mammary artery. Subsequently, an ultrasound-guided injection of thrombin was carried out until complete interruption of the flow within the formation. At subsequent follow-up, no arterial or venous blush was highlighted.

All B-lines are equal, but some B-lines are more equal than others.

In this pictorial essay the theme of the differential diagnosis between the different causes of lung interstitial disease will be discussed, which can be detected on lung ultrasound as B lines. In particular, from the experience obtained during the covid-19 pandemic, the term B line may appear too simplified, and new data in the literature show that it is necessary to update the terminology and the differential diagnosis of this ultrasound sign.

The case of a liver adenoma that looked like a hemangioma.

Benign focal liver lesions are among the most frequent findings on ultrasound. Liver hemangiomas are often easily recognizable on ultrasound examination and are characterized by a clear benign prognosis. In some cases, hemangiomas display an atypical appearance both on B-mode and on contrast-enhanced ultrasound, thus raising concerns for differential diagnosis both with adenomas and with lesions of malignant nature. We report here the case of a patient who presented with a liver lesion with all signs suggestive for hemangioma on B-mode, but it showed atypical features on contrast-enhanced ultrasound examination and final diagnosis of liver adenoma.

Contrast-Enhanced Ultrasound Follow-Up for Acute Pyelonephritis Patients.

Contrast-enhanced ultrasound (CEUS) is increasingly used in clinical practice as the first diagnostic method in patients with suspected pyelonephritis rather than abdominal CT with contrast medium, especially in young subjects. We performed a retrospective analysis on patients in for whom a CEUS examination was utilized as a follow-up method after acute pyelonephritis as normal clinical practice. Through evaluating all patients, in terms duration between CEUS examination and normalization (healing) of the renal disease, we found that the mean duration is 25.9 days. Our ultrasound findings did not induce any therapeutic modifications, not even in the cases in which the examination was repeated several times. Therefore, setting up a CEUS follow-up examination after 25 days from the first diagnosis can reduce the number of repeated tests, benefitting patients and the healthcare system in terms of reducing costs.

Gastrointestinal Ultrasound in Emergency Setting.

Acute bowel diseases are responsible for more than one third of subjects who were referred to the emergency department for acute abdominal pain and gastrointestinal evaluation. Gastrointestinal ultrasound (GIUS) is often employed as the first imaging method, with a good diagnostic accuracy in the setting of acute abdomen, and it can be an optimal diagnostic strategy in young females due to the radiation exposure related to X-ray and computed tomography methods. The physician can examine the gastrointestinal system in the area with the greatest tenderness by ultrasound, thus obtaining more information and data on the pathology than the standard physical examination. In this comprehensive review, we have reported the most relevant indications and advantages to using ultrasound in the investigation of abdominal acute pain.

From NAFLD to MAFLD: Definition, Pathophysiological Basis and Cardiovascular Implications.

Non-alcoholic fatty liver disease (NAFLD) is defined as a chronic liver disease characterized by excessive fat accumulation in the liver without another obvious cause (no excessive alcohol consumption, hepatotoxic medications, toxins, viral infections, genetic hepatic diseases), therefore it is an exclusion diagnosis. The term NAFLD literally refers to non-alcohol related hepatopathy and does not adequately correlate with metabolic dysfunction and related cardiovascular risks. Therefore, researchers and scientific societies have moved towards changing the terminology. The novel nomenclature for a metabolic-associated fatty liver disease (MAFLD) has been proposed in 2020 by a group of experts to overcome the issues related to the old terminology. The diagnosis of MAFLD is based on the presence of hepatic steatosis and at least one between these three conditions: type 2 diabetes mellitus (T2DM), obesity or metabolic dysregulation. MAFLD has been shown to be an independent risk factor for cardiovascular diseases and atherosclerosis. It is better related to the main risk factors for atherosclerosis and cardiovascular diseases than NAFLD, such as dyslipidemia, T2DM and hypertension. The aim of this review is to highlight the reasons why the term NAFLD is moving to the term MAFLD, what are the conceptual basis of this choice and its clinical implications, particularly in the cardiovascular field.

Infectious Pneumonia and Lung Ultrasound: A Review.

The application of thoracic ultrasound examination has not long been developed because ultrasound's interaction with the lung does not generate an anatomical image but an artifactual one. Subsequently, the evaluation of pulmonary artifacts and their correlation to specific diseases allowed the development of ultrasound semantics. Currently, pneumonia still represents one of the main causes of hospitalization and mortality. Several studies in the literature have demonstrated the ultrasound features of pneumonia. Although ultrasound cannot be considered the diagnostic gold standard for the study of all lung diseases, it has experienced an extraordinary development and growth of interest due to the SARS-CoV-2 pandemic. This review aims to provide essential information on the application of lung ultrasound to the study of infectious pneumonia and to discuss the differential diagnosis.

Hepatobiliary cystoadenoma: a wolf in sheep's clothing.

Hepatobiliary cystoadenoma is a rare cystic tumor of the liver that can undergo malignant change and become lethal. Accurate diagnosis of such lesions, even though not always possible, is of importance as the management is totally different from that of other nonneoplastic cysts. We report a case of a 60-year-old woman with aspecific symptoms, which was diagnosed using ultrasound scan and CT scan and treated with hepatic resection, and review the main features of this tumor.