Application of a Decision Tree Model to Predict the Outcome of Non-Intensive Inpatients Hospitalized for COVID-19.

Many studies have identified predictors of outcomes for inpatients with coronavirus disease 2019 (COVID-19), especially in intensive care units. However, most retrospective studies applied regression methods to evaluate the risk of death or worsening health. Recently, new studies have based their conclusions on retrospective studies by applying machine learning methods. This study applied a machine learning method based on decision tree methods to define predictors of outcomes in an internal medicine unit with a prospective study design. The main result was that the first variable to evaluate prediction was the international normalized ratio, a measure related to prothrombin time, followed by immunoglobulin M response. The model allowed the threshold determination for each continuous blood or haematological parameter and drew a path toward the outcome. The model's performance (accuracy, 75.93%; sensitivity, 99.61%; and specificity, 23.43%) was validated with a k-fold repeated cross-validation. The results suggest that a machine learning approach could help clinicians to obtain information that could be useful as an alert for disease progression in patients with COVID-19. Further research should explore the acceptability of these results to physicians in current practice and analyze the impact of machine learning-guided decisions on patient outcomes.

Incidental Echocardiographic Finding of a Membranous Ventricular Septal Aneurysm in an 18-Year-Old Asymptomatic Athlete.

Membranous ventricular septal aneurysm (VSA) is an uncommon cardiac abnormality, potentially leading to several cardiac complications such as aortic valve prolapse, arrhythmias, and aneurysm rupture. A young competitive soccer player presented for a post-COVID sports cardiology assessment, denying any previous cardiological evaluations. On transthoracic echocardiography, a membranous VSA was incidentally found with no other cardiac abnormality nor hemodynamic impairment associated. A well-oriented anamnesis guided by echocardiographic findings revealed that a ventricular septal defect was diagnosed at birth with spontaneous closure at 4 years old. From that moment, no further follow-up was performed. Before granting cardiological approval to competitive sport, transesophageal echocardiography and Holter electrocardiogram were performed to confirm the absence of interventricular shunt and any other cardiac abnormality or arrhythmias associated with VSA. This case highlights the value of an accurate and comprehensive clinical and echocardiographic evaluation when performing a cardiological sports assessment, even in a young asymptomatic athlete.

Alcohol-Related Liver Disease in the Covid-19 Era: Position Paper of the Italian Society on Alcohol (SIA).

BACKGROUND: Coronavirus Disease 2019 (COVID-19), firstly reported in China last November 2019, became a global pandemic. It has been shown that periods of isolation may induce a spike in alcohol use disorder (AUD). In addition, alcohol-related liver disease (ALD) is the most common consequence of excessive alcohol consumption worldwide. Moreover, liver impairment has also been reported as a common manifestation of COVID-19. AIMS: The aim of our position paper was to consider some critical issues regarding the management of ALD in patients with AUD in the era of COVID-19. METHODS: A panel of experts of the Italian Society of Alcohology (SIA) met via "conference calls" during the lockdown period to draft the SIA's criteria for the management of ALD in patients with COVID-19 as follows: (a) liver injury in patients with ALD and COVID-19 infection; (b) toxicity to the liver of the drugs currently tested to treat COVID-19 and the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) reorganization of the management of compensated and decompensated ALD and liver transplantation in the COVID-19 era. RESULTS AND CONCLUSIONS: The COVID-19 pandemic has rapidly carried us toward a new governance scenario of AUD and ALD which necessarily requires an in-depth review of the management of these diseases with a new safe approach (management of out-patients and in-patients following new rules of safety, telemedicine, telehealth, call meetings with clinicians, nurses, patients, and caregivers) without losing the therapeutic efficacy of multidisciplinary treatment.

SARS-CoV-2 Infection as a Determining Factor to the Precipitation of Ischemic Priapism in a Young Patient with Asymptomatic COVID-19.

COVID-19 is a disease characterized by respiratory distress, systemic inflammation, multiple organ dysfunction and coagulation disorders, chiefly pulmonary embolism, and deep venous thrombosis. In this case report, we discuss a peculiar case of ischemic priapism in a 36-year-old patient with asymptomatic COVID-19 and no other plausible causes of thrombophilia and/or alternative causes of priapism, as well as discussing possible explanations for such remarkable findings and comparing them to analogous cases recorded in literature. The patient was unsuccessfully treated via cavernous blood aspiration and required several shunting procedures, with no further recurrences and negative testing for pulmonary embolism, deep venous thrombosis, and other causes of thrombophilia.

Lung ultrasonography for long-term follow-up of COVID-19 survivors compared to chest CT scan.

BACKGROUND: While lung ultrasonography (LUS) has utility for the evaluation of the acute phase of COVID-19 related lung disease, its role in long-term follow-up of this condition has not been well described. The objective of this study is to compare LUS and chest computed tomography (CT) results in COVID-19 survivors with the intent of defining the utility of LUS for long-term follow-up of COVID-19 respiratory disease. METHODS: Prospective observational study that enrolled consecutive survivors of COVID-19 with acute hypoxemic respiratory failure (HARF) admitted to the Respiratory Intensive Care Unit. Three months following hospital discharge, patients underwent LUS, chest CT, body plethysmography and laboratory testing, the comparison of which forms the basis of this report. RESULTS: 38 patients were enrolled, with a total of 190 lobes analysed: men 27/38 (71.1%), mean age 60.6 y (SD 10.4). LUS findings and pulmonary function tests outcomes were compared between patients with and without ILD, showing a statistically significant difference in terms of LUS score (p: 0.0002), FEV1 (p: 0.0039) and FVC (p: 0.012). ROC curve both in lobe by lobe and in patient's overall analysis revealed an outstanding ILD discrimination ability of LUS (AUC: 0.94 and 0.95 respectively) with a substantial Cohen's coefficient (K: 0.74 and 0.69). CONCLUSIONS: LUS has an outstanding discrimination ability compared to CT in identifying an ILD of at least mild grade in the post COVID-19 follow-up. LUS should be considered as the first-line tool in follow-up programs, while chest CT could be performed based on LUS findings.

Pulmonary Artery Filling Defects in COVID-19 Patients Revealed Using CT Pulmonary Angiography: A Predictable Complication?

PURPOSE: This study is aimed at assessing the prevalence of pulmonary artery filling defects (PAFDs) consistent with pulmonary artery embolism (PAE) in patients with SARS-CoV-2 infection and at investigating possible radiological or clinical predictors. MATERIALS AND METHODS: Computed Tomography Pulmonary Angiographies (CTPAs) from 43 consecutive patients with a confirmed COVID-19 infection were retrospectively reviewed, taking into consideration the revised Geneva score and the D-dimer value for each patient. Filling defects within the pulmonary arteries were recorded along with pleural and parenchymal findings such as ground glass opacities, consolidation, crazy paving, linear consolidation, and pleural effusion. All these variables were compared between patients with and without PAFD. The predictive performance of statistically different parameters was investigated using the receiver operating characteristics (ROC). RESULTS: Pulmonary embolism was diagnosed in 15/43 patients (35%), whereas CTPA and parenchymal changes related to pulmonary COVID-19 disease were evident in 39/43 patients (91%). The revised Geneva score and the mean D-dimer value obtained using two consecutive measurements were significantly higher in patients with PAFD. The ROC analysis demonstrated that a mean D-dimer value is the parameter with the higher predictivity (AUC 0.831) that is a cut-off value > 1800 µg/l which predicts the probability of PAFD with a sensitivity and specificity of 70% and 78%, respectively. CONCLUSIONS: This single centre retrospective report shows a high prevalence of pulmonary artery filling defects revealed using CTPA in COVID-19 patients and demonstrates that the mean value of multiple D-dimer measurements may represent a predicting factor of this complication.

Gaining Back What Is Lost: Recovering the Sense of Smell in Mild to Moderate Patients After COVID-19.

The purpose of our cohort study was to quantify olfactory deficits in Coronavirus disease 2019 (COVID-19) patients using Sniffin' Sticks and a pre-post design to evaluate olfactory recovery. Thirty adult patients with laboratory-confirmed mild to moderate forms of COVID-19 underwent a quantitative olfactory test performed with the Sniffin' Sticks test (SST; Burghardt, Wedel, Germany), considering olfactory threshold (T), odor discrimination (D), and odor identification (I). Results were presented as a composite TDI score (range 1-48) that used to define functional anosmia (TDI ≤ 16.5), hyposmia (16.5 < TDI < 30.5), or functionally normal ability to smell (TDI ≥ 30.5). Patients also self-evaluated their olfactory function by rating their ability to smell on a visual analogue scale (Visual Analog Scale rating) and answering a validated Italian questionnaire (Hyposmia Rating Scale). Patients were tested during hospitalization and about 2 months after symptoms onset. During the hospitalization, the overall TDI score indicated that our cohort had impairments in their olfactory ability (10% was diagnosed with anosmia and more than 50% were hyposmic). Almost all patients showed a significant improvement at around 1 month following the first test and for all the parts of the SST except for odor identification. None of the subjects at 1 month was still diagnosed with anosmia. We also quantified the improvement in the TDI score based on initial diagnosis. Anosmic subjects showed a greater improvement than hyposmic and normosmic subjects. In conclusion, within a month time window and 2 months after symptoms' onset, in our cohort of patients we observed a substantial improvement in the olfactory abilities.

Long-term management of chronic heart failure patients in internal medicine.

Chronic heart failure (CHF) is one of the main disabilities in elderly patients requiring frequent hospitalizations with high health care costs. We studied the outcome of CHF outpatient management in reducing hospitalization after discharge from a division of Internal Medicine at a large 3rd referral regional Hospital. 147 CHF inpatients (M:F: 63:84; mean age 76 ± 9.6 years) admitted for acute exacerbation of CHF were followed up as outpatients at 1, 6, 12 and 24 months after discharge. At baseline, patients underwent: laboratory tests, ECG, echocardiogram and a dedicated-intensive health care educational program involving also their families. The rate of hospitalization in the same group of patients was compared with data from the previous 24 months, a period when patients had been seen elsewhere without disease management programs. Patients had high prevalence of comorbidities and the majority was in NYHA class III or IV. Hypertension and valvular heart disease were the most common causes for CHF. Systolic function was preserved (LVEF ≥ 50%) in 61.9% of cases. Functional NYHA class improved significantly after 6 months and remained stable at 24 months. There was a significant increase in the use of the renin-angiotensin system blockers, beta-blockers and diuretics compared to admission to the ward. At 24 months, hospital readmissions were decreased by 42% as compared to the previous 24 months. Risk factors for re-hospitalizations were anemia, NYHA class III or IV and previous hospitalizations. Establishing an intensive outpatient management program for CHF patients leads to long-term beneficial effects with improved clinical parameters and decreased hospitalization in the setting of Internal Medicine.

Circulating CRP Levels Are Associated with Epicardial and Visceral Fat Depots in Women with Metabolic Syndrome Criteria.

Sexual dimorphism accounts for significant differences in adipose tissue mass and distribution. However, how the crosstalk between visceral and ectopic fat depots occurs and which are the determinants of ectopic fat expansion and dysfunction remains unknown. Here, we focused on the impact of gender in the crosstalk between visceral and epicardial fat depots and the role of adipocytokines and high-sensitivity C-reactive protein (hs-CRP). A total of 141 outward patients (both men and women) with one or more defining criteria for metabolic syndrome (MetS) were consecutively enrolled. For all patients, demographic and clinical data were collected and ultrasound assessment of visceral adipose tissue (VFth) and epicardial fat (EFth) thickness was performed. Hs-CRP and adipocytokine levels were assessed by enzyme-linked immunosorbent assay (ELISA). Men were characterized by increased VFth and EFth (p-value < 0.001 and 0.014, respectively), whereas women showed higher levels of adiponectin and leptin (p-value < 0.001 for both). However, only in women VFth and EFth significantly correlated between them (p = 0.013) and also with leptin (p < 0.001 for both) and hs-CRP (p = 0.005 and p = 0.028, respectively). Linear regression confirmed an independent association of both leptin and hs-CRP with VFth in women, also after adjustment for age and MetS (p = 0.012 and 0.007, respectively). In conclusion, men and women present differences in epicardial fat deposition and systemic inflammation. An intriguing association between visceral/epicardial fat depots and chronic low-grade inflammation also emerged. In women Although a further validation in larger studies is needed, these findings suggest a critical role of sex in stratification of obese/dysmetabolic patients.

Efficacy of ivermectin to control Strongyloides stercoralis infection in sheltered dogs.

In dogs, information on treatments against S. stercoralis infection is rare and anecdotal. The aim of the present work was to evaluate the treatment outcome of S. stercoralis natural infection in sheltered dogs. Furthermore, based on the potential risk of infection, people working in the infected shelter were also tested. Seventeen sheltered dogs positive to S. stercoralis using the Baermann test were treated with ivermectin 200 µg/kg/sid/os for two consecutive days. Only two dogs showed clinical signs suggestive of strongyloidiasis (diarrhea, weigh loss) at diagnosis. All dogs showed consistently negative results for S. stercoralis at weekly monitoring after treatment using both the direct microscopy and Baermann test. Real-time PCR confirmed negative results at the last follow up 2 months after treatment. Serology performed at the first diagnosis showed that 82% and 41% of dogs were positive for S. stercoralis using an IFAT (titres ranging from 1:40 to 1:320) and ELISA, respectively. Two months after treatment, IFAT titres were strongly reduced in all animals. The results of clinical pathological laboratory tests at diagnosis in the positive dogs were within normal ranges, except for the two symptomatic dogs. Serum collected from two out of 14 shelter workers tested positive with titres 1:20 and 1:40 for S. stercoralis using an IFAT. Results of the study confirm that ivermectin was an effective treatment option to control S. stercoralis infection in dogs. Shelter workers are at risk of infection with S. stercoralis, thus the application of correct deworming protocols to reduce the environmental infective larval burden is essential to protect dogs and probably also shelter workers from the risk of infection.

Diagnosis and treatment of acute alcohol intoxication and alcohol withdrawal syndrome: position paper of the Italian Society on Alcohol.

The chronic use of alcohol can lead to the onset of an alcohol use disorder (AUD). About 50% of subjects with an AUD may develop alcohol withdrawal syndrome (AWS) when they reduce or discontinue their alcohol consumption and, in 3-5% of them, convulsions and delirium tremens (DTs), representing life-threatening complications, may occur. Unfortunately, few physicians are adequately trained in identifying and treating AWS. The Italian Society on Alcohol has, therefore, implemented a task force of specialists to draw up recommendations for the treatment of AWS with the following main results: (1) while mild AWS may not require treatment, moderate and severe AWS need to be pharmacologically treated; (2) out-patient treatment is appropriate in patients with mild or moderate AWS, while patients with severe AWS need to be treated as in-patients; (3) benzodiazepines, BDZs are the "gold standard" for the treatment of AWS and DTs; (4) alpha-2-agonists, beta-blockers, and neuroleptics may be used in association when BDZs do not completely resolve specific persisting symptoms of AWS; (5) in the case of a refractory form of DTs, the use of anaesthetic drugs (propofol and phenobarbital) in an intensive care unit is appropriate; (6) alternatively to BDZs, sodium oxybate, clomethiazole, and tiapride approved in some European Countries for the treatment of AWS may be employed for the treatment of moderate AWS; (7) anti-convulsants are not sufficient to suppress AWS, and they may be used only in association with BDZs for the treatment of refractory forms of convulsions in the course of AWS.

[New frontiers of therapy: bibliotherapy.] / Le nuove frontiere della terapia: la biblioterapia.

Authors discuss therapeutic potential of reading activity, partially still unknown. Starting from Menninger's work in the early 30's until most recent studies from Frude, Berns, Comer who confirmed its efficacy in both the so-called non-organic diseases and chronic pathological conditions. Their studies strongly suggested psychobiological mechanisms through which reading activity exerts its therapeutic effects. The Authors of this paper hope that bibliotherapy in the next future may become a suitable tool in the therapeutical management of the these diseases.

Validation of a Simple Scoring System to Predict Sorafenib Effectiveness in Patients with Hepatocellular Carcinoma.

BACKGROUND: Sorafenib is recommended for the treatment of advanced-stage hepatocellular carcinoma (HCC). Nonetheless, it is expensive, effective in few patients, and may cause significant adverse effects. Therefore, accurate selection of patients is needed. In a previous study, we constructed a simple scoring system to predict patients' outcomes based on the occurrence of sorafenib adverse effects. OBJECTIVE: The present study aimed to validate this scoring system in a real-life cohort of HCC patients. PATIENTS AND METHODS: Clinical records of 279 outpatients treated with sorafenib in eight Italian centers were retrospectively analyzed. Adverse effects considered to calculate the score were skin toxicity, diarrhea, and arterial hypertension, occurring during the first month of therapy. For each adverse effect, 1 point was assigned if present; and 0 points if absent (resulting in a total score between 0 and 3). RESULTS: Median overall survival (OS) was 10.8 months and median time to progression (TTP) was 5.1 months. At multivariate analysis, performance status, α-fetoprotein (AFP), and Child-Pugh score were independently associated with TTP and OS. A progressive increase of OS and TTP was observed in patients with scores from 0 to 3 (p < 0.001). Six-, 12-, and 24-month survival probabilities were 55.1, 24.5, and 7.9% in score 0 patients, and 100, 80.9, and 46.2% in score 3 patients, respectively. Complete response was observed in one patient (0.4%), partial responses in 41 (15.2%), and stable disease in 117 (43.5%). The disease control rate in patients with scores of 0, 1, 2, and 3 was 34.3, 51.6, 80.9, and 96.3%, respectively (p < 0.001). Complete or partial responses were not observed in score 0 patients. CONCLUSIONS: We have validated a useful scoring system to predict outcomes in sorafenib-treated HCC patients. This score is easy to calculate and suitable for implementation in daily clinical practice.

Immunotherapeutic approaches for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a cancer with a high mortality rate due to the fact that the diagnosis usually occurs at anadvanced stage. Even in case of curative surgical treatment, recurrence is common. Sorafenib and regorafenib are the only therapeutic agents that have been demonstrated to be effective in advanced HCC, thus novel curative approaches are urgently needed. Recent studies focus on the role of immune system in HCC. In fact, the unique immune response in the liver favors tolerance, which can represent a real challenge for conventional immunotherapy in these patients. Spontaneous immune responses against tumor antigens have been detected, and new immune therapies are under investigation: dendritic cell vaccination, immune-modulator strategy, and immune checkpoint inhibition. In recent years different clinical trials examining the use of immunotherapy to treat HCC have been conducted with initial promising results. This review article will summarize the literature data concerning the potential immunotherapeutic approaches in HCC patients.

Risperidone and Cardiometabolic Risk in Children and Adolescents: Clinical and Instrumental Issues.

PURPOSE/BACKGROUND: Although second-generation antipsychotics are used to treat and manage symptoms for several psychiatric disorders, data about their adverse effects in developmental age are limited. The aim of this prospective observational study was to verify the cardiovascular and metabolic risk in a sample of antipsychotic-naive children/adolescent patients starting risperidone therapy. METHODS: Twenty-two patients, younger than 18 years, were recruited. The assessment included anthropometric data, cardiovascular parameters, blood tests, and ultrasonographic abdominal study. RESULTS: After an average follow-up period of 7.6 months, statistically significant increases in mean values of waist circumference, body mass index (BMI), BMI percentile, BMI z score, total cholesterol, and prolactin were found. Other cardiometabolic parameters showed an upward trend in time. Subjects in pubertal/postpubertal stage and female patients were more susceptible to developing cardiometabolic changes. Moreover, significant correlations between changes in anthropometric and several metabolic parameters were found. A tendency to change in constitution of the liver parenchyma and distribution of the abdominal fat mass with ultrasonographic abdominal study was also evident. CONCLUSIONS: In our sample, several metabolic parameters showed a sensitivity to risperidone treatment. Because most of these parameters are age dependent, metabolic syndrome criteria used for adults were inappropriate in children and adolescents. Periodic clinical and instrumental evaluations and guidelines for monitoring of any metabolic, laboratory, and instrumental complications are necessary in the perspective of even long-time second-generation antipsychotics treatment in children and adolescents.

Basal and bevacizumab-based therapy-induced changes of lactate dehydrogenases and fibrinogen levels and clinical outcome of previously untreated metastatic colorectal cancer patients: a multicentric retrospective analysis.

BACKGROUND: To assess the predictive role of lactate dehydrogenases (LDH) and fibrinogen (FBG) serum levels in metastatic colorectal cancer (mCRC) patients receiving a first-line bevacizumab-based therapy. OBJECTIVES: The aim of the present analysis was to retrospectively evaluate the role of basal and post-treatment LDH and FBG serum levels in predicting the clinical outcome of 139 mCRC patients receiving first-line chemotherapy in combination with bevacizumab. RESULTS: A statistically significant association between high pre-treatment LDH and FBG levels and progressive disease was observed with respect to low basal LDH and FBG patients. Furthermore, median progression-free survival was 7.3 versus 10.8 months and 7.3 versus 9.4 months for high and low LDH and FBG levels, respectively. Within the high LDH group, we observed a statistically significant reduction of LDH mean value compared with pre-treatment values in patients with objective response rate and stable disease. CONCLUSIONS: High LDH and FBG levels correlated with prognosis. A significant correlation between bevacizumab-based chemotherapy-induced reduction in LDH serum levels and response to treatment was observed within the high LDH group. These results, if confirmed in larger prospective studies, could be helpful for early identification of patients responsive to bevacizumab-based chemotherapy or candidate to more aggressive treatments.

Natural history of malignant bone disease in hepatocellular carcinoma: final results of a multicenter bone metastasis survey.

BACKGROUND: Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC). Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC. PATIENTS AND METHODS: Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed. RESULTS: The median age was 70 years; 172 patients were male (81.5%). The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis); 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%). Most of these lesions were osteolytic (82.4%); 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819). The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005), ECOG performance status (p = 0.002) and treatment with bisphosphonate (p = 0.024) were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE) (p = 0.021) and OS (p = 0.001). CONCLUSIONS: This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life.

T16189C mitochondrial DNA variant is associated with metabolic syndrome in Caucasian subjects.

OBJECTIVES: Different nuclear genes are thought to be involved in the regulation of the complex phenotype of metabolic syndrome (MS) and their number is increasing. A mutation in mitochondrial DNA (mtDNA), T4291C in transfer RNA isoleucine (tRNAile), has been associated with MS in a large American family. In addition, a mtDNA T16189C variant, already known to be associated with insulin resistance and type 2 diabetes mellitus in Caucasians, seems to underlie susceptibility to MS in the Chinese population. Our aim was to verify the T4291C and T16189C variants in subjects affected by different phenotypes of MS. METHODS: Seventy patients with MS and 35 healthy individuals were investigated for the presence of the mtDNA variants by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The T4291C variant was absent in patients and in controls. The T16189C variant was more frequent in patients with MS than in control subjects (21.4% versus 5.7%, P<0.04) and was associated with hypertension (P=0.01), waist circumference (P=0.02), body mass index (P=0.009), visceral fat thickness (P=0.04), homeostasis model assessment (P=0.03), and the number of MS diagnostic criteria (P=0.01). CONCLUSION: The mtDNA T16189C variant is associated with MS and its different clinical expressions. Prospective studies are warranted to establish the clinical relevance of this association.