Comorbidities in Angioedema Due to C1-Inhibitor Deficiency: An Italian Survey.

BACKGROUND: Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency is characterized by unpredictable recurrent episodes of swelling affecting the skin and the mucosa tissues, including gastrointestinal tract and/or oropharyngeal-laryngeal mucosae. Long-term prophylaxis (LTP) is used to prevent attacks. OBJECTIVE: Because C1-INH plays a pivotal role in several biological pathways, we investigated the possible association of comorbidities with C1-INH deficiency and the use of LTP with attenuated androgens (AA) or tranexamic acid (TXA). METHODS: This retrospective cohort study involved adult patients with HAE referred to Milan and Padua angioedema centers in the period 1979-2021. A qualitative comparison was performed to analyze comorbidities versus general population. The incidence of comorbidities was evaluated during LTP with AA or TXA versus patients without LTP. RESULTS: A total of 446 patients were studied. A greater prevalence among patients was found for heart diseases (9.6% vs 4.8%), acute myocardial infarction (5.6% vs 1.4%), hepatitis C virus infection (10.5% vs 2.5%), and appendectomy (15.9% vs 4.3%). In patients taking AA, a greater incidence was found for hypertension (22.8% vs 10.8%; odds ratio [OR]: 2.02), hypercholesterolemia (19.5% vs 5.3%; OR: 3.97), diabetes mellitus (5% vs 1.4%; OR: 3.21), hepatic angioma (4.4% vs 0.7%; OR: 8.35), and focal nodular hyperplasia (2.5% vs 0.4%; OR: 6.9). No association between TXA and comorbidities was found. CONCLUSION: In this large patient population with a rare disease followed for up to a 43-year period, we found a greater prevalence of comorbidities hitherto unreported in the literature and an association between comorbidities and LTP with AA.

Multicentric Observational Study on Safety and Tolerability of COVID-19 Vaccines in Patients with Angioedema with C1 Inhibitor Deficiency: Data from Italian Network on Hereditary and Acquired Angioedema (ITACA).

Angioedema due to C1 inhibitor deficiency (AE-C1-INH) is a rare disease characterized by recurrent and unpredictable attacks of angioedema. Multiple trigger factors, including trauma, emotional stress, infectious diseases, and drugs, could elicit angioedema attacks. The aim of this study was to collect data on the safety and tolerability of COVID-19 vaccines in a population of patients affected by AE-C1-INH. Adult patients with AE-C1-INH, followed by Reference Centers belonging to the Italian Network for Hereditary and Acquired Angioedema (ITACA), were enrolled in this study. Patients received nucleoside-modified mRNA vaccines and vaccines with adenovirus vectors. Data on acute attacks developed in the 72 h following COVID-19 vaccinations were collected. The frequency of attacks in the 6 months after the COVID-19 vaccination was compared with the rate of attacks registered in the 6 months before the first vaccination. Between December 2020 and June 2022, 208 patients (118 females) with AE-C1-INH received COVID-19 vaccines. A total of 529 doses of the COVID-19 vaccine were administered, and the majority of patients received mRNA vaccines. Forty-eight attacks of angioedema (9%) occurred within 72 h following COVID-19 vaccinations. About half of the attacks were abdominal. Attacks were successfully treated with on-demand therapy. No hospitalizations were registered. There was no increase in the monthly attack rate following the vaccination. The most common adverse reactions were pain at the site of injection and fever. Our results show that adult patients with angioedema due to C1 inhibitor deficiency can be safely vaccinated against SARS-CoV-2 in a controlled medical setting and should always have available on-demand therapies.

A decision-making algorithm proposal for PICCs and midlines insertion in patients with advanced kidney disease: A pilot study.

INTRODUCTION: Kidney Disease Outcomes Quality Initiative clinical practice guidelines recommend avoiding placement of peripherally inserted vascular access devices in patients with an estimated glomerular filtration rate (eGFR) <45 ml/min. On the other hand, many patients with severe chronic kidney disease (CKD) have poor prognosis.This study carried out a global assessment of mortality at 2 years through Charlson Comorbidity Index (CCI) and Beclap score in patients with PICCs or Midlines, assuming that in those with an estimated high mortality rate at 2 years, it could be acceptable to implant a peripheral vascular access device (PVAD) despite the presence of CKD. METHODS: We analyzed data on patients with PICCs or Midlines inserted from October 2018 to November 2019. CCI, Beclap score, and eGFR were calculated for each patient at the time of the catheter insertion. We then followed patients for 2 years to assess 2-year mortality for each. RESULTS: One hundred and thirty-one patients were enrolled, 49 (37.4%) had eGFR<45 ml. The 2-year mortality rate was 57.3%. The cut off derived from ROC curve analysis of 15 for Beclap score and 5 for CCI, showed good sensitivity and specificity in predicting mortality of the total population, patients without an oncological disease and patients with eGFR<45 ml/min. CONCLUSION: CCI and Beclap score are good predictors of mortality at 2 years.Physicians and nurses can use these tools in the evaluation of patients at risk for future dialysis, instead of relying exclusively on renal function to decide whether implanting PICCs, Midlines, or other vascular access devices.

Asymptomatic and symptomatic deep venous thrombosis in hospitalized acutely ill medical patients: risk factors and therapeutic implications.

BACKGROUND: Acutely ill medical patients experience deep venous thrombosis (DVT) during the hospitalization, however the time course of DVT is still unclear. OBJECTIVES: To evaluate risk factors in acutely ill hospitalized medical patients for proximal asymptomatic DVT (ADVT) and symptomatic DVT (SDVT) at admission and discharge. PATIENTS/METHODS: In this prospective observational study, consecutive acutely ill medical patients (hospitalized mainly for acute medical disease as infections, neoplasm, anemia, heart failure) underwent compression ultrasonography (CUS) of proximal lower limb veins within 48 h from admission and at discharge to diagnose ADVT and SDVT. Covid-19 patients, anticoagulant therapy, surgical procedures, acute SDVT, and acute pulmonary embolism, were exclusion criteria. Biographical characteristics at hospitalization, D-Dimer (assessed by ELISA)) and DD-improve score. RESULTS: Of 2,100 patients (1002 females, 998 males, age 71 ± 16 years) 58 (2.7%) had proximal ADVT at admission. Logistic regression analysis showed that age, and active cancer were independently associated with ADVT at admission. The median length of hospitalization was 10 days [interquartile range: 6-15]. During the hospital stay, 6 patients (0.3%) with a negative CUS at admission experienced DVT (2 SDVT and 4 ADVT). In the subgroup of patients (n = 1118), in whom D-dimer was measured at admission, D-Dimer and IMPROVE-DD score were associated with ADVT at admission (n = 37) and with all DVT (n = 42) at discharge. ROC curve defined an IMPROVE-DD score of 2.5 as the optimal cut-off for discriminating patients with and without thrombotic events. CONCLUSIONS: We provide evidence of early development of ADVT in unselected acutely ill medical patients suggesting the need of investigating patients by CUS immediately after hospital admission (within 48 h). Advanced age, active cancer, known thrombophilia and increased IMPROVE-DD score may identify patients at risk. The benefit of anticoagulation needs to be investigated in patients with these specific risk factors and negative CUS at admission. TRIAL REGISTRATION: NCT03157843.

Cardiovascular injuries and SARS-COV-2 infection: focus on elderly people.

The novel coronavirus disease (COVID-19) has hit the healthcare system worldwide. The risk of severe infection and mortality increases with advancing age, especially in subjects with comorbidities such as cardiovascular disease, hypertension, diabetes, obesity and cancer. Moreover, cardiovascular complications such as myocardial injury, heart failure and thromboembolism are frequently observed in COVID-19 cases, and several biomarkers (troponin, NTproBNP and D-Dimer) have been identified as prognostic indicators of disease severity and worst outcome. Currently, there is no specific therapy against SARS-CoV-2, although many medications are under investigation. The aim of this review will be to explore the intertwined relationship between COVID-19 disease and the cardiovascular system, focusing on elderly population. The available supportive treatments along with the related concerns in elderly patients, due to their comorbidities and polypharmacotherapy, will be explored.

Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI).

During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managed in Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO2/FiO2 ratio at admission was strongly inversely associated with survival. The use of conventional oxygen supplementation increased with the number of pre-existing comorbidities, but it did not associate with better survival in patients with PaO2/FiO2 ratio < 100. The latter, significantly benefited by the early use of non-invasive mechanical ventilation. Our study identified PaO2/FiO2 ratio at admission and comorbidity as the main alert signs to inform clinical decisions and resource allocation in non-critically ill COVID-19 patients admitted to IMU.

Circulating endothelial progenitors are increased in COVID-19 patients and correlate with SARS-CoV-2 RNA in severe cases.

BACKGROUND: During the course of COVID-19, the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thrombotic phenomena and/or diffuse vascular damage are frequent, and viral elements have been observed within endothelial cells. OBJECTIVES: CD146 + circulating endothelial cells (CD146 + CECs) and their progenitors (CEPs) are increased in cardiovascular, thrombotic, infectious, and cancer diseases. The present study was designed to investigate their kinetics in novel coronavirus (COVID-19) patients. METHODS: We used a validated flow cytometry procedure to enumerate viable and apoptotic CD146 + CECs and CEPs in COVID-19 patients during the course of the disease and in patients who recovered. RESULTS: Viable CEPs per milliliter were significantly increased in COVID-19 patients compared with healthy controls. This increase was observed in patients with mild symptoms and not further augmented in patients with severe symptoms. In patients who recovered, CEPs decreased, but were in a range still significantly higher than normal controls. Regarding mature CD146 + CECs, in COVID-19 patients, their absolute number was similar to those observed in healthy controls, but the viable/apoptotic CD146 + CEC ratio was significantly different. Both mild and severe COVID-19 patients had significantly less apoptotic CD146 + CECs compared with healthy controls. Patients who recovered had significantly less CD146 + CECs per milliliter when compared with controls as well as to mild and severe COVID-19 patients. A positive correlation was found between the copies of SARS-CoV-2 RNA in the cellular fraction and apoptotic CEPs per milliliter in severe COVID-19 patients. CONCLUSIONS: CD146 + CECs and CEPs might be investigated as candidate biomarkers of endothelial damage in COVID-19 patients.

Three-month mortality in permanently bedridden medical non-oncologic patients. The BECLAP study (permanently BEdridden, creatinine CLearance, albumin, previous hospital admissions study).

OBJECTIVE: To predict the 3-months mortality in permanently bedridden medical non-oncologic inpatients. PATIENTS AND METHODS: 2788 consecutive patients admitted in 5 Italian Internal Medicine units from January 2016 through January 2017 were prospectively screened; 644 oncologic patients were excluded; 2144 non-oncologic patients (1021 female) were followed-up for mortality for 6 months. Main outcome was 3-months mortality in permanently bedridden inpatients with at least 2 of: creatinine clearance <35 ml/min; albumin < 2.5 g/dl; at least 2 hospital admissions in the previous 6 months. Advanced dementia and dysphagia were also recorded. RESULTS: Mean age of the 2144 patients was 73.9 (SD, 14.9) years; 374 (17%) were permanently bedridden, 435 (20%) had a creatinine clearance <35 ml/min, 217 (10%) albumin <2,5 g/dl, 112 (5%) at least 2 hospital admissions in the previous 6 months. Seventy-seven (4%) patients were permanently bedridden with at least 2 of the above mentioned items, and 48 of them died within 3 months (62%) (p < 0.001;95% CI 51-73%). Regression coefficients of the variables associated with 3-months mortality in multivariate analysis in 998 patients of unit 1 (training cohort) were used to create a simple score, which was validated in the 1146 patients of the other units (validation cohort) and performed well in predicting the 3-months mortality (https://www.ejcrim.com/beclap/). CONCLUSIONS: Approximately two out of three non-oncologic medical patients permanently bedridden having 2 of the abovementioned items are dead 3 months after index admission; a simple score including bedridden status, creatinine clearance, albumin, dysphagia, age and sex may help discuss management priorities.

Low Rate of Intrahospital Deep Venous Thrombosis in Acutely Ill Medical Patients: Results From the AURELIO Study.

OBJECTIVE: To evaluate the effect of hospitalization on deep venous thrombosis (DVT) rate by the cumulative incidence of DVT in the proximal venous tract of the lower limbs at admission and discharge. METHODS: The AURELIO (rAte of venoUs thRombosis in acutEly iLl patIents hOspitalized in internal medicine wards) multicenter observational study was carried out in hospital-university internal medicine wards including consecutive acutely ill medical patients. Patients underwent compression ultrasonography (CUS) of proximal lower limb veins at admission and discharge. The occurrence of DVT was the primary end point of the study. RESULTS: Among 1340 patients, 26 (1.9%; 95% CI, 1.3%-2.8%) had asymptomatic DVT at admission and were excluded. During the follow-up, 144 patients were excluded because of hospitalization less than 5 days. The remaining 1170 patients underwent a CUS at discharge. Two hundred fifty (21%) underwent prophylaxis with parenteral anticoagulants; the remaining 920 (79%) were not treated with anticoagulants. The mean length of hospitalization was 13±8 days. Compared with patients without prophylaxis, those treated with parenteral anticoagulants had a higher incidence of active cancer, heart and respiratory failure, pneumonia, renal failure, previous venous thromboembolism, reduced mobility, and elderly age. During the hospital stay, 3 patients with a negative CUS at admission experienced DVT in the proximal tract (0.025%, rate of 1 per 5017 patient-days); 2 of them were in prophylaxis with parenteral anticoagulants. CONCLUSION: We provide evidence that in the real world acutely ill medical patients display more than 90% (1.9%) asymptomatic DVT at admission, whereas the intrahospital DVT occurrence is very low. This suggests a novel diagnostic workup and a careful reanalysis of anticoagulant prophylaxis.

Target organ damage in a population at intermediate cardiovascular risk, with adjunctive major risk factors: CArdiovascular PREvention Sacco Study (CAPRESS).

The objective of the study is to assess the prevalence of target organ damage (TOD) at carotid, cardiac, renal and peripheral vascular levels in a population at intermediate cardiovascular risk, with adjunctive major risk factors (AMRF). From March 2007 to July 2009 we examined 979 subjects at intermediate cardiovascular risk, as indicated by the Italian algorithm "Progetto Cuore"; the patients were aged 40-69 years, sensitized by one or more AMRF such as family history for cardiovascular disease (CVD), being overweight or obese, and smoking habit (more than 10 cigarettes/day). We measured common carotid intima-media thickness (cc-IMT) and plaque at any level, left ventricular mass index (LVMI), urine albumin/creatinine ratio (UACR), and ankle-brachial index (ABI). The prevalence of at least one TOD was 63% (617 subjects), cc-IMT was high in 48.2% (472), UACR abnormal in 14.1% (138), LVMI high in 12.6% (117) and ABI pathological in 9.1% (89). In those with carotid damage 423 had a plaque, amounting to 43.2% of the total population. Of note, carotid damage was present in all subjects with 3 TODs, and in 92% of subjects with 2 TODs. A multivariate logistic regression model including conventional factors and AMRF indicated that age 50-69 years, systolic blood pressure, relevant smoking and CV risk score ≥15 were independently and significantly associated with at least one TOD, and at least, with carotid damage. Among the AMRF, peripheral arterial disease was associated with relevant smoking, with an odds ratio (OR) of 3 [confidence interval (CI) 1.80-4.97, p < 0.0001]; overweight and obesity both had selective associations with cardiac damage with OR 2.75 (CI 1.2-6.3, p < 0.01) and OR 3.89 (CI 1.61-9.73, p < 0.01). A substantial proportion of people at intermediate risk, with at least one AMRF have at least one TOD, a major predictor of cardiovascular outcomes.