Epidemiology, therapy and outcome of hepatocellular carcinoma between 2010 and 2019 in Piedmont, Italy.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide. It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate. HCC patients have increasingly complex and constantly changing characteristics, thus up-to-date and comprehensive data are fundamental. AIM: To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019. METHODS: In this retrospective study, we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at "Santa Croce e Carle" Hospital in Cuneo (Italy) between 1 January 2010 and 31 December 2019. To highlight possible changes in HCC patterns over the 10-year period, we split the population into two 5-year groups, according to the diagnosis period (2010-2014 and 2015-2019). RESULTS: Of the 328 HCC patients who were included (M/F 255/73; mean age 68.9 ± 11.3 years), 154 in the first period, and 174 in the second. Hepatitis C virus infection was the most common HCC risk factor (41%, 135 patients). The alcoholic etiology rate was 18%, the hepatitis B virus infection etiology was 5%, and the non-viral/non-alcoholic etiology rate was 22%. The Child-Pugh score distribution of the patients was: class A 75%, class B 21% and class C 4%. The average Mayo end-stage liver disease score was 10.6 ± 3.7. A total of 55 patients (17%) were affected by portal vein thrombosis and 158 (48%) by portal hypertension. The average nodule size of the HCC was 4.6 ± 3.1 cm. A total of 204 patients (63%) had more than one nodule < 3, and 92% (305 patients) had a non-metastatic stage of the disease. The Barcelona Clinic Liver Cancer (BCLC) staging distribution of all patients was: 4% very early, 32% early, 23% intermediate, 34% advanced, and 7% terminal. Average survival rate was 1.6 ± 0.3 years. Only 20% of the patients underwent treatment. Age, presence of ascites, BCLC stage and therapy were predictors of a better prognosis (P < 0.01). A comparison of the two 5-year groups revealed a statistically significant difference only in global etiology (P < 0.05) and alpha-fetoprotein (AFP) levels (P < 0.01). CONCLUSION: In this study analyzing patients with a new diagnosis of HCC between 2010-2019, hepatitis C virus infection was the most common etiology. Most patients presented with an advanced stage disease and a poor prognosis. When comparing the two 5-year groups, we observed a statistically significant difference only in global etiology (P < 0.05) and AFP levels (P < 0.01).

Diagnosis and Management of Cardiovascular Risk in Patients with Polycythemia Vera.

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by aberrant myeloid lineage hematopoiesis with excessive red blood cell and pro-inflammatory cytokine production. Patients with PV present with a range of thrombotic and hemorrhagic symptoms that affect quality of life and reduce overall survival expectancy. Thrombotic events, transformation into acute myeloid leukemia, and myelofibrosis are largely responsible for the observed mortality. Treatment of PV is thus primarily focused on symptom control and survival extension through the prevention of thrombosis and leukemic transformation. Patients with PV frequently experience thrombotic events and have elevated cardiovascular risk, including hypertension, dyslipidemias, obesity, and smoking, all of which negatively affect survival. To reduce the risk of thrombotic complications, PV therapy should aim to normalize hemoglobin, hematocrit, and leukocytosis and, in addition, identify and modify cardiovascular risk factors. Herein, we review what is currently known about the associated cardiovascular risk and propose strategies for diagnosing and managing patients with PV.

Risk factors that predict mortality in patients with blunt chest wall trauma: an updated systematic review and meta-analysis.

BACKGROUND: Over the last 10 years, research has highlighted emerging potential risk factors for poor outcomes following blunt chest wall trauma. The aim was to update a previous systematic review and meta-analysis of the risk factors for mortality in blunt chest wall trauma patients. METHODS: A systematic review of English and non-English articles using MEDLINE, Embase and Cochrane Library from January 2010 to March 2022 was completed. Broad search terms and inclusion criteria were used. All observational studies were included if they investigated estimates of association between a risk factor and mortality for blunt chest wall trauma patients. Where sufficient data were available, ORs with 95% CIs were calculated using a Mantel-Haenszel method. Heterogeneity was assessed using the I2 statistic. RESULTS: 73 studies were identified which were of variable quality (including 29 from original review). Identified risk factors for mortality following blunt chest wall trauma were: age 65 years or more (OR: 2.11; 95% CI 1.85 to 2.41), three or more rib fractures (OR: 1.96; 95% CI 1.69 to 2.26) and presence of pre-existing disease (OR: 2.86; 95% CI 1.34 to 6.09). Other new risk factors identified were: increasing Injury Severity Score, need for mechanical ventilation, extremes of body mass index and smoking status. Meta-analysis was not possible for these variables due to insufficient studies and high levels of heterogeneity. CONCLUSIONS: The results of this updated review suggest that despite a change in demographics of trauma patients and subsequent emerging evidence over the last 10 years, the main risk factors for mortality in patients sustaining blunt chest wall trauma remained largely unchanged. A number of new risk factors however have been reported that need consideration when updating current risk prediction models used in the ED. PROSPERO REGISTRATION NUMBER: CRD42021242063. Date registered: 29 March 2021. https://www.crd.york.ac.uk/PROSPERO/%23recordDetails.

Human herpes virus 8-negative effusion-based lymphoma in a patient with persistent serous effusions.

Diffuse large B-cell lymphoma is the most common histologic diagnosis among the aggressive lymphomas, accounting for 30% of all lymphomas. Human herpes virus 8-negative effusion-based lymphoma (HHV8-negative EBL) is a rare form of lymphoma, under recognized and still not well characterized in the literature. In contrast to primary effusion lymphoma (PEL), HHV8-negative EBL is characterized by malignant effusion in essentially serous body cavity with no detectable contiguous tumor masses and is no associated with human immunodeficiency virus and HHV8 infections. The presence of comorbid medical conditions can hide this type of lymphoma and made diagnosis more challenging. Here, we describe a rare case of an 82-year-old male suffering from peritoneal and pleural effusion and Hepatitis B virus related cirrhosis diagnosed with HHV8-negative EBL.

A retrospective validation study of the STUMBL score for emergency department patients with blunt thoracic trauma.

INTRODUCTION: Blunt thoracic trauma (BTT) is a leading cause of emergency department (ED) trauma-related attendance. Risk prediction tools are commonly to predict patients' outcomes and assign them to the most appropriate care setting. The STUMBL score is a prognostic model for BTT, derived and validated in the United Kingdom; items comprising the score are age, number of rib fractures, use of pre-injury anticoagulants, chronic lung disease and oxygen saturation levels. This study's aim was to validate the STUMBL score in an Italian ED. METHODS: This single-centre retrospective validation study was conducted in the ED of Santa Croce and Carle hub hospital in Cuneo, north-western Italy. All patients with an ED attendance for isolated BTT from 2018 to 2021 were included. Exclusion criteria were an age of under eighteen and the presence of any immediately life-threatening lesion. The primary outcome was the development of trauma-related complications, defined by the occurrence of one or more of the following: in-hospital mortality, pulmonary complications (infection, pleural effusion, haemothorax, pneumothorax, pleural empyema), need for intensive care unit admission, hospital length of stay equal to or greater than seven days. The performance of the STUMBL score was analysed in terms of discrimination with the evaluation of the receiver operating characteristic curve and calibration with the Hosmer-Lemeshow test and with the calibration belt. RESULTS: 745 patients were enroled (median age 64 [25th;75th percentile: 50;78], male/female ratio 1:4, median Charlson comorbidity index 2 [1;4], median STUMBL score 11 [6;17]). 65.2% of patients were discharged home after ED evaluation. 203 patients (27.2%) developed the primary outcome. The STUMBL score was significantly different in patients with complications compared to those without complications (9 [5;13] vs 21 [17;25], p < 0.001). The C index of the score for the primary outcome was 0.90 (95% CI 0.88-0.93), and the result of the Hosmer-Lemeshow test was 9.01 (p = 0.34). STUMBL score = 16 has a sensitivity of 0.80 (95% CI 0.75-0.85), specificity of 0.87 (95% CI 0.84-0.90), a positive predictive value of 0.70 (95% CI 0.64-0.76), and a negative predictive value of 0.92 (95% CI 0.90-0.94). CONCLUSION: In this validation study, the STUMBL score demonstrated excellent discrimination and calibration in predicting the outcome of patients attending the ED with a BTT.

Management of Acute Episodes of Clarkson Disease (Monoclonal Gammopathy-Associated Systemic Capillary Leak Syndrome) With Intravenous Immunoglobulins.

Monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS, Clarkson disease) is a rare disorder defined by transient but recurrent bouts of hypotensive shock and anasarca resulting from plasma extravasation. Although prophylactic treatment with high-dose intravenous immunoglobulins (IVIG, 1-2 g/kg/mo) prevents most disease flares, its utility for acute episodes of ISCLS is unclear. Here, we report the results of a retrospective study of subjects with acute ISCLS treated at or near the onset of symptoms with IVIG. We found that administration of IVIG with minimal additional intravenous fluids was safe and associated with rapid clinical improvement. IVIG given close to the onset of ISCLS-related symptoms is associated with a favorable outcome.

Markers of endothelial glycocalyx dysfunction in Clarkson disease.

BACKGROUND: Clarkson disease (monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome, ISCLS) is a rare idiopathic condition marked by transient, relapsing-remitting episodes of systemic microvascular hyper-permeability, which liberates plasma fluid and macromolecules into the peripheral tissues. This pathology manifests clinically as the abrupt onset of hypotensive shock, hemoconcentration, and hypoalbuminemia. METHODS: We analysed endothelial glycocalyx (eGCX)-related markers in plasma from patients with ISCLS during acute disease flares and convalescence by ELISA and comprehensive proteomic profiling. We evaluated eGCX-related components and gene expression in cultured endothelial cells using RNA-sequencing, real-time PCR, and fluorescence staining. RESULTS: Serum levels of eGCX-related core components including hyaluronic acid (HA) and the core proteoglycan soluble syndecan-1 (sCD138) were elevated at baseline and during acute ISCLS flares. Serial measurements demonstrated that sCD138 levels peaked during the recovery (post-leak) phase of the illness. Proteomic analysis of matched acute and convalescent ISCLS plasma revealed increased abundance of eGCX-related proteins, including glypicans, thrombospondin-1 (TSP-1), and eGCX-degrading enzymes in acute compared to remission plasma. Abundance of endothelial cell damage markers did not differ in acute and baseline plasma. Expression of several eGCX-related genes and surface carbohydrate content in endothelial cells from patients with ISCLS did not differ significantly from that observed in healthy control cells. CONCLUSIONS: eGCX dysfunction, but not endothelial injury, may contribute to clinical symptoms of acute ISCLS. Serum levels of of eGCX components including sCD138 may be measured during acute episodes of ISCLS to monitor clinical status and therapeutic responses.

RDW-based clinical score to predict long-term survival in community-acquired pneumonia: a European derivation and validation study.

An excess long-term mortality has been observed in patients who were discharged after a community-acquired pneumonia (CAP), even after adjusting for age and comorbidities. We aimed to derive and validate a clinical score to predict long-term mortality in patients with CAP discharged from a general ward. In this retrospective observational study, we derived a clinical risk score from 315 CAP patients discharged from the Internal Medicine ward of Cuneo Hospital, Italy, in 2015-2016 (derivation cohort), which was validated in a cohort of 276 patients discharged from the pneumology service of the Barakaldo Hospital, Spain, from 2015 to 2017, and from two internal medicine wards at the Turin University and Cuneo Hospital, Italy, in 2017. The main outcome was the 18-month follow-up all-cause death. Cox multivariate analysis was used to identify the predictive variables and develop the clinical risk score in the derivation cohort, which we applied in the validation cohort. In the derivation cohort (median age: 79 years, 54% males, median CURB-65 = 2), 18-month mortality was 32%, and 18% in the validation cohort (median age 76 years, 55% males, median CURB-65 = 2). Cox multivariate analysis identified the red blood cell distribution width (RDW), temperature, altered mental status, and Charlson Comorbidity Index as independent predictors. The derived score showed good discrimination (c-index 0.76, 95% CI 0.70-0.81; and 0.83, 95% CI 0.78-0.87, in the derivation and validation cohort, respectively), and calibration. We derived and validated a simple clinical score including RDW, to predict long-term mortality in patients discharged for CAP from a general ward.

Fever During Anti-integrin Therapy: New Immunodeficiency.

BACKGROUND: The causes of inflammatory bowel disease (IBD) have not yet been clearly elucidated, but it is known that genetic susceptibility, altered gut microbiota and environmental factors are all involved, and that a combination of these factors causes an inappropriate immune response, resulting in impaired intestinal barrier function. With regard to the treatment of IBD, the use of conventional immunosuppressive drugs has been complemented by more specific therapeutic agents, including biological drugs. Systemic immune suppression is a risk factor for cytomegalovirus (CMV) infection, which is associated with considerable morbidity and mortality in immunocompromised hosts. CASE REPORT: A 33-year-old male patient was admitted to our medical unit complaining of a 10-day history of fever, fatigue and headache. He had been suffering from ulcerative colitis and primary sclerosing cholangitis for five years and was currently being treated with azathioprine and vedolizumab. In the past he had already taken infliximab, adalimumab and golimumab without any clinical response. After the exclusion of systemic infectious diseases, his serology was consistent with a primary CMV infection. This was successfully treated with intravenous ganciclovir therapy. CONCLUSION: Vedolizumab is an anti-integrin biological agent approved for IBD treatment. Its gut-selective mechanism of action would appear to increase its safety profile, however data on this are still limited. Moreover, it should always be remembered that IBD patients have an increased risk of CMV infection, both primary and reactivation, because of their concurrent immunosuppression. LEARNING POINTS: It is important to consider CMV infection (primary and reactivation) in patients affected by IBD.

Red cell distribution width predicts mid-term prognosis in patients hospitalized with acute heart failure: the RDW in Acute Heart Failure (RE-AHF) study.

The aim of the study was to evaluate the prognostic role of red cell distribution width (RDW) in a broad population of patients hospitalized for acute heart failure (AHF). In a retrospective cohort observational study, 451 consecutive patients discharged for AHF were categorized in patients with low RDW (≤ 14.8%) and high RDW (> 14.8%). The rates of death from all causes or of hospital readmission for worsening heart failure and death were determined after a median follow-up of 18 months. The overall population has a median age of 80 years (IQR 72-85), 235 patients (52%) were males. Patients with a higher RDW have more comorbidities and a higher Charlson Index. At follow-up, 200 patients (44%) had died and 247 (54%) had died or were readmitted for HF: in the cohort with low RDW, 70 patients (36.4%) had died, whereas in the cohort with high RDW, 165 patients (63.7%) had died: the unadjusted risk ratio of patients with high RDW was 2.03 (log-rank test: p < 0.0001). In a multivariate Cox regression model, the hazard ratio for death from any cause in the 'high RDW' cohort is 1.73 (95% confidence interval 1.2-2.48; p = 0.003); the RDW adds prognostic information beyond that provided by conventional predictors, including age; etiology of HF; anemia; hyponatremia; estimated glomerular filtration rate; NT-proBNP levels; Charlson comorbidity score, atrial fibrillation, functional status, therapy with renin-angiotensin-aldosterone system inhibitors, beta-blockers. RDW is a powerful marker of worse long-term outcomes in patients with AHF, and its prognostic value is maintained beyond that provided by other well-established risk factors or biomarkers.

Characteristics and management of pyogenic liver abscess: A European experience.

Pyogenic liver abscess (PLA) are space-occupying lesions in the liver associated with high morbidity and mortality. The aim of this study is to review an Italian hospital experience in epidemiological, clinical patterns, and management of PLA.We performed a retrospective, descriptive case series at a single center assessing demographic characteristics, presentation patterns, etiological factors, microbiological etiology, and management for patients treated for PLA between 2000 and 2016.Around 109 patients were identified. The majority of patients presented with fever (73%); right upper abdominal pain in 63.3%, vomiting and nausea in 28.4%. The most common laboratory abnormality among included items was increased C-reactive protein and fibrinogen blood levels, respectively, in 98% and 93.9% of cases. Abdominal ultrasound was the diagnostic investigation in 42.4% of cases; CT scan and MR imaging were performed in 51.1% and 3.3% of cases respectively. We observed blood or pus culture study in 99 cases of which only 53.5% came with positive microbial reports. The most common organism identified was Escherichia coli (26.5%), followed by Streptococcus spp (13.2%). Early antibiotic treatment started on all patients and 66.7% of cases required different approaches, Ultrasound or CT-guided needle aspiration of PLA was performed in 13 patients (11%) and percutaneous abscess drainage was performed on 72 patients (67%).PLA is a diagnostically challenging problem due to nonspecific presenting characteristics. The microbiological yield identified was a typical European spectrum with a preponderance of Escherichia coli infections. Once recognized, percutaneous drainage and antibiotic treatment are the mainstay of management for PLA.

Hepatitis C-associated osteosclerosis: a new case with long-term follow-up and a review of the literature.

Hepatitis C-associated osteosclerosis (HCAO) is an uncommon condition characterized by increased bone density, skeletal pain and elevated bone formation markers. Since 1992, only 17 cases have been reported. We herein describe the case of a 61-year-old woman affected by severe pain involving the lower limbs. The laboratory data showed an elevated serum alkaline phosphatase level, and the patient was found to be seropositive for hepatitis C virus infection. In addition, an X-ray skeleton survey showed marked cortical thickening of both femurs and tibias, and a whole-body bone scan revealed an increased cortical radionuclide uptake in the involved bones. These findings were consistent with a diagnosis of HCAO. In this report, we discuss the patient's clinical course over 16 years and, for the first time, show a normalized radioisotope uptake on bone scanning 10 years after the diagnosis.

Hepatic brucelloma.

We present a case of hepatic abscess caused by Brucella melitensis (or hepatic brucelloma) diagnosed in a 59-year-old man 33 years after an episode of acute brucellosis that had completely resolved. Recovery from symptoms and a decrease in lesion size seen on radiological assessment were achieved through prolonged combined antibiotic therapy, without the need for surgery. Hepatic brucelloma is a rare complication of brucellosis, which is the most common zoonosis globally, mainly occurring in specific endemic areas and causing a range of clinical manifestations. In this Grand Round, we review the clinical manifestations, diagnostic approach (through laboratory, radiology, and histology findings), differential diagnosis, treatment, and prognosis of hepatic brucelloma.