Incidence of lower limb deep vein thrombosis in patients with COVID-19 pneumonia through different waves of SARS-CoV-2 pandemic: A multicenter prospective study.

OBJECTIVE: The aim of this study was to evaluate the incidence of deep vein thrombosis (DVT) of the lower limbs in patients hospitalized with COVID-19 pneumonia in a non-ICU setting according to the different waves of the SARS-CoV-2 pandemic. METHODS: Multicenter, prospective study of patients with COVID-19 pneumonia admitted to Internal Medicine units in Italy during the first (March-May 2020) and subsequent waves (November 2020 -April 2021) of the pandemic using a serial compression ultrasound (CUS) surveillance to detect DVT of the lower limbs. RESULTS: Three-hundred-sixty-three consecutive patients were enrolled. The pooled incidence of DVT was 8%: 13.5% in the first wave, and 4.2% in the subsequent waves (p = 0.002). The proportion of patients with early (< 4 days) detection of DVT was higher in patients during the first wave with respect to those of subsequent waves (8.1% vs 1.9%; p = 0.004). Patients enrolled in different waves had similar clinical characteristics, and thrombotic risk profile. Less patients during the first wave received intermediate/high dose anticoagulation with respect to those of the subsequent waves (40.5% vs 54.5%; p = 0.005); there was a significant difference in anticoagulant regimen and initiation of thromboprophylaxis at home (8.1% vs 25.1%; p<0.001). CONCLUSIONS: In acutely ill patients with COVID-19 pneumonia, the incidence of DVT of the lower limbs showed a 3-fold decrease during the first with respect to the subsequent waves of the pandemic. A significant increase in thromboprophylaxis initiation prior to hospitalization, and the increase of the intensity of anticoagulation during hospitalization, likely, played a relevant role to explain this observation.

Role of prognostic scores in predicting in-hospital mortality and failure of non-invasive ventilation in adults with COVID-19.

We tested the prognostic performance of different scores for the identification of subjects with acute respiratory failure by COVID-19, at risk of in-hospital mortality and NIV failure. We conducted a retrospective study, in the Medical High-Dependency Unit of the University-Hospital Careggi. We included all subjects with COVID-19 and ARF requiring non-invasive ventilation (NIV) between March 2020 and January 2021. Clinical parameters, the HACOR score (Heart rate, Acidosis, Consciousness, Oxygenation, Respiratory Rate) and ROX index ((SpO2/FiO2)/respiratory rate) were collected 3 (-3) and 1 day (-1) before the NIV initiation, the first day of treatment (Day0) and after 1 (+1), 2 (+2), 5 (+5), 8 (+8) and 11 (+11) of treatment. The primary outcomes were in-hospital mortality and NIV failure. We included 135 subjects, mean age 69±13 years, 69% male. Patients, who needed mechanical ventilation, showed a higher HACOR score (Day0: 6 [5-7] vs 6 [6-7], p=.057; Day+2: 6 [6-6] vs 6 [4-6], p=.013) and a lower ROX index (Day0: 4.2±2.3 vs 5.1±2.3, p=.055; Day+2: 4.4±1.2.vs 5.5±1.3, p=.001) than those with successful NIV. An HACOR score >5 was more frequent among nonsurvivors (Day0: 82% vs 58%; Day2: 82% vs 48%, all p<0.01) and it was associated with in-hospital mortality (Day0: RR 5.88, 95%CI 2.01-17.22; Day2: RR 4.33, 95%CI 1.64-11.41) independent to age and Charlson index. In conclusion, in subjects treated with NIV for ARF caused by COVID19, respiratory parameters collected after the beginning of NIV allowed to identify those at risk of an adverse outcome. An HACOR score >5 was independently associated with increased mortality rate.

Incidence of deep vein thrombosis through an ultrasound surveillance protocol in patients with COVID-19 pneumonia in non-ICU setting: A multicenter prospective study.

OBJECTIVE: The aim of this study was to assess the incidence of deep vein thrombosis (DVT) of the lower limbs, using serial compression ultrasound (CUS) surveillance, in acutely ill patients with COVID-19 pneumonia admitted to a non-ICU setting. METHODS: Multicenter, prospective study of patients with COVID-19 pneumonia admitted to Internal Medicine units. All patients were screened for DVT of the lower limbs with serial CUS. Anticoagulation was defined as: low dose (enoxaparin 20-40 mg/day or fondaparinux 1.5-2.5 mg/day); intermediate dose (enoxaparin 60-80 mg/day); high dose (enoxaparin 120-160 mg or fondaparinux 5-10 mg/day or oral anticoagulation). The primary end-point of the study was the diagnosis of DVT by CUS. RESULTS: Over a two-month period, 227 consecutive patients with moderate-severe COVID-19 pneumonia were enrolled. The incidence of DVT was 13.7% (6.2% proximal, 7.5% distal), mostly asymptomatic. All patients received anticoagulation (enoxaparin 95.6%) at the following doses: low 57.3%, intermediate 22.9%, high 19.8%. Patients with and without DVT had similar characteristics, and no difference in anticoagulant regimen was observed. DVT patients were older (mean 77±9.6 vs 71±13.1 years; p = 0.042) and had higher peak D-dimer levels (5403 vs 1723 ng/mL; p = 0.004). At ROC analysis peak D-dimer level >2000 ng/mL (AUC 0.703; 95% CI 0.572-0.834; p = 0.004) was the most accurate cut-off value able to predict DVT (RR 3.74; 95%CI 1.27-10, p = 0.016). CONCLUSIONS: The incidence of DVT in acutely ill patients with COVID-19 pneumonia is relevant. A surveillance protocol by serial CUS of the lower limbs is useful to timely identify DVT that would go otherwise largely undetected.

The doctor who stared at schistocytes: an intriguing case of suspected thrombotic microangiopathic anemia.

A 33-year-old man with type 1 diabetes mellitus was admitted to the Internal Medicine Unit due to subacute onset of exertional dyspnea, with evidence at initial blood exams of severe macrocytic anemia with thrombocytopenia, biohumoral signs of hemolysis and 5 schistocytes per magnified field on the blood smear. A thrombotic microangiopathy (TMA) was suspected and plasma exchange (PEX) was started soon, since the risk of a life threatening condition. On the second day, after the results of A Disintegrin And Metalloproteinase with ThromboSpondin-1 motif, member 13 (ADAMTS-13) and reticulocytes were available, a critical reappraisal of the clinical scenario was done. B12 vitamin deficiency was evident after completing the diagnostic work-up. Finally, a diagnosis of "pseudo TMA vitamin B12 deficiency-related" was done. This is an intriguing and rare manifestation of cobalamin deficiency, given the very uncommon occurrence of schistocytes in this condition. "Pseudo TMA vitamin B12 deficiency-related" should be kept in mind when facing the differential diagnosis of microangiopathic anemia in the presence of a low proliferative index.

Competence in thoracic ultrasound.

Ultrasound examination is traditionally considered a safe and repeatable exam, but its use is highly operator-dependent. Because of this, lack of sufficient operator skills could lead to diagnostic errors and damage to patient safety related to unnecessary tests or interventional procedures. The indications for lung ultrasound include: diagnosis, quantification, and follow-up of different conditions for which acute respiratory failure or chest pain are the main clinical presentation. Clinicians should have theoretical and practical knowledge on: physics and technology of ultrasound, indications and methodology of ultrasound examination, normal thoracic anatomy identification by echography, and detection of signs of pleuro-pulmonary pathology. Consequently, according to international recommendations, core basic skills and minimum training recommendations for the practice of medical ultrasound and image acquisition are needed to ensure competence of clinicians using ultrasound.

Procalcitonin Kinetics in the First 72 Hours Predicts 30-Day Mortality in Severely Ill Septic Patients Admitted to an Intermediate Care Unit.

BACKGROUND: Severe sepsis and septic shock are leading causes of morbidity and mortality among critically ill patients, thus the identification of prognostic factors is crucial to determine their outcome. In this study, we explored the value of procalcitonin (PCT) variation in predicting 30-day mortality in patients with sepsis admitted to an intermediate care unit. METHODS: This prospective observational study enrolled 789 consecutive patients with severe sepsis and septic shock admitted to a medical intermediate care unit between November 2012 and February 2014. Kinetics of PCT expressed as percentage were defined by the variation between admission and 72 hours, and 24 and 72 hours; they were defined as Δ-PCT0-72h and Δ-PCT24-72h, respectively. RESULTS: The final study group of 144 patients featured a mean age of 73 ± 14 years, with a high prevalence of comorbidities (Charlson index greater than 6 in 39%). Overall, 30-day mortality was 28.5% (41/144 patients). A receiver-operating-characteristic (ROC) analysis identified a decrease of Δ-PCT0-72h less than 15% (area under the curve: 0.75; 95% confidence interval (CI): 0.67 - 0.82) and a decrease of Δ-PCT24-72h less than 20% (area under the curve: 0.83; 95% CI: 0.74 - 0.92) as the most accurate cut-offs in predicting mortality. Decreases of Δ-PCT0-72h less than 15% (HR: 3.9, 95% CI: 1.6 - 9.5; P < 0.0001) and Δ-PCT24-72h less than 20% (HR: 3.1, 95% CI: 1.2 - 7.9; P < 0.001) were independent predictors of 30-day mortality. CONCLUSIONS: Evaluation of PCT kinetics over the first 72 hours is a useful tool for predicting 30-day mortality in patients with severe sepsis and septic shock admitted to an intermediate care unit.

Yield of nuclear scan strategy in chest pain unit evaluation of special populations.

BACKGROUND: Patients with chest pain (CP) and nondiagnostic ECG represent heterogeneous population in whom the evaluation of coronary risk factors including metabolic syndrome (MetS) and diabetes mellitus (DM) might improve risk stratification. METHODS: We enrolled 798 consecutive CP patients; 14% presented with MetS and 10% with DM; the remaining 76% presented with other coronary risk profiles (others). All patients underwent maximal exercise tolerance test (ETT) and myocardial perfusion imaging (exercise-MPI). Those with positive testing underwent angiography, whereas the remaining patients were discharged and later followed up. Primary end-point was a composite of coronary stenoses greater than or equal to 50% documented by angiography or coronary events at follow-up. RESULTS: Patients with MetS or DM had significantly lower survival free from end-point than those patients without (P<0.001). Exercise-MPI showed high negative predictive value in MetS, DM, and others (>96%); however, positive predictive value was 69, 74, and 52%, respectively (P<0.05). ETT alone showed negative predictive value (88%) which was significantly lower than exercise-MPI (98%), (MetS vs. others: P<0.001, and DM vs. others: P=0.05). The area under the receiver-operating characteristic curves obtained from the multivariate model includes clinical data alone, clinical data and ETT results, or clinical data and exercise-MPI results increase progressively. CONCLUSION: A nuclear scan strategy in special populations, including CP patients with MetS or DM, is a valuable tool for risk stratification and adds incremental prognostic value over clinical and ETT values.

Myocardial infarction redefined: impact on case-load and outcome of patients with suspected acute coronary syndrome and nondiagnostic ECG at presentation.

Risk stratification of chest pain (CP) is still debated. Objective of this study was to evaluate the performance of a risk stratification model for patients with suspected acute coronary syndrome (ACS) and nondiagnostic ECG at presentation, in whom the occurrence of myocardial infarction was either diagnosed following traditional (t-MI) or the recently redefined (r-MI) criteria. First-line 6-h work-up categorized 3068 patients with suspected ACS and nondiagnostic ECG into low-risk for short-term coronary events, intermediate-risk who entered second-line work-up, and high-risk. Intermediate-risk patients with positive second-line work-up and high-risk patients were considered for urgent coronary angiography. Angina, non-fatal MI, sudden death, and revascularization constituted composite end-point (CE) for in-hospital and 6-month outcome. ACS incidence was 16%; r-MI increased by 62% the diagnosis of MI over t-MI. Among 2024 discharged low-risk patients, 12 (0.6%) had non-fatal CE at 6 months. ACS was diagnosed in 19% of 503 intermediate-risk and 96% of 389 high-risk patients. Among ACS patients, in-hospital CE occurred in 14% of t-MI, 7% of r-MI, and 9% of unstable angina (UA) patients (t-MI vs. r-MI and t-MI vs. UA: p<0.05, for both); 6-month CE occurred in 23%, 16% and 12% of t-MI, r-MI and UA, respectively (t-MI vs. UA: p<005). Sensitivity, specificity and accuracy were high both for diagnostic (97%, 98%, 99%, respectively) and treatment (83%, 98%, 97%, respectively) strategy. Risk stratification, and categorization according to traditional or redefined MI and UA criteria allow safe allocation of resources in CP patients with suspected ACS and nondiagnostic ECG at presentation because outcome is accurately predicted.

[Acquired factor VIII hemophilia in a geriatric patient]. / Emofilia A acquisita: descrizione di un caso clinico in età geriatrica.

Acquired hemophilia is a rare coagulopathy in adults, associated with bleeding complications. Although the etiology of this disorder remains obscure, an autoimmune mechanism produces the development of autoantibodies against factor VIII. About half of cases are associated with other conditions, mainly post-partum, underlying cancer, autoimmune disease. An 81-year-old male was admitted to the hospital with extensive hematomas (neck, chest, arms and lower limbs). There was no family or personal history of congenital bleeding diathesis. He had chronic bronchitis and cerebrovascular disease; no drugs had been used during the month prior to noted symptoms. Laboratory parameters revealed: hemoglobin 10.9 g%, normal platelet count and white blood cells, prolonged activated partial thromboplastin time (98 s), with normal prothrombin time and fibrinogen concentration. An activated partial thromboplastin time mixing study did not show any correction, suggesting a coagulation inhibitor. Lupus anticoagulant and anticardiolipin antibodies were negative. Biochemical, immunological tests and tumor markers were normal. Thoracic and abdominal computed tomographic scan did not reveal pathological images or hematomas. Analysis of clotting factors revealed decreased factor VIII (< 2%) and elevated factor VIII inhibitor (55 Bethesda units). Idiopathic acquired hemophilia diagnosis was made. Red blood cell transfusion and human factor VIII (2000 U/day for 7 days) infusion were initiated, intravenously with methylprednisolone. A progressive improvement in clinical conditions and laboratory parameters was observed. After 18 days the patient was discharged and treated with prednisone. At follow-up control the clinical conditions and laboratory parameters were normal.

Assessment of patients with low-risk chest pain in the emergency department: Head-to-head comparison of exercise stress echocardiography and exercise myocardial SPECT.

OBJECTIVES: The aim of the study was to compare head-to-head the performance of exercise tolerance test-stress echocardiography (ex-Echo) and exercise stress-perfusion nuclear imaging (exercise-single-photon emission computed tomography [ex-SPECT]) for the diagnosis of coronary artery disease (CAD) in patients evaluated at the chest pain unit with delay from chest pain (CP) onset. BACKGROUND: As an early triage strategy for CAD in emergency medicine, ex-Echo could have the advantage of widespread availability and low costs. METHODS: In the years 2000-2002, 503 consecutive patients (mean age 60 years) with recent (<24 hours) CP and nonischemic electrocardiogram (ECG), in whom CAD remained undiagnosed after first line 6-hour work-up including serum markers of myocardial injury and resting echocardiogram, underwent ex-Echo and ex-SPECT within 24 hours. Patients with (+)ex-Echo or (+)ex-SPECT or (+)ex-ECG or abnormal troponin I were referred to coronary angiography; otherwise, they were discharged and followed up. End points were coronary stenosis > or =50% and cardiovascular events at 6-month follow-up. RESULTS: Ninety-nine patients (20%) had (+)ex-Echo and 121 (24%) (+)ex-SPECT; CAD was diagnosed in 81% and 67%, respectively; positive tests were concordant in 69%. In negative ex-Echo and ex-SPECT, final evidence of CAD emerged in 14 and 13, respectively. Ex-Echo demonstrated higher accuracy than ex-SPECT (93% +/- 1% vs 89% +/- 1%), optimal specificity (95% +/- 5% vs 90% +/- 5%), and positive predictive value (81% +/- 4% vs 67% +/- 4%); moreover, in the case of (-)ex-ECG, observed effective likelihood ratio indicates a (+)synergy between ex-ECG and ex-Echo. CONCLUSIONS: Ex-Echo can be an effective diagnostic strategy in the early triage of CP patients, improving diagnosis in case of (-)ex-ECG and reducing unnecessary angiography number. Its drawback is represented by the 5% of missed diagnosis.

Updated management of non-st-segment elevation acute coronary syndromes: selection of patients for low-cost care: an analysis of outcome and cost effectiveness.

BACKGROUND: The management of patients with acute coronary syndromes without ST-segment elevation (NSTEACS) in a chest pain unit (CPU) should represent a cost-effective advantage over conventional management in a coronary care unit (CCU). However, the safety and advantages of this approach are still unresolved. MATERIAL/METHODS: Outcomes and management costs were evaluated in patients with NSTEACS with intermediate-high TIMI risk scores (> or =3) randomized to receive management in a CPU or a CCU. Coronary events (CEs: angina, myocardial infarction, and death), revascularization, and resource utilization were compared between the two groups during hospital stay and at 6 months. RESULTS: Two hundred and ten patients were enrolled, 104 in the CPU and 106 in the CCU group. CEs were similar in both groups both during hospitalization (28% vs. 26%, respectively) and at 6 months (17% vs. 16%). Angiography was performed in 67% vs. 75%; CPU patients less frequently underwent revascularization (53% vs. 76%; p=0.002). In-hospital duration was similar in both groups (7.5 days vs. 5.7 days). CPU patients had a 22% reduction in overall hospitalization costs compared with conventional management (9,913 vs. 12,056 euros/patient; p=0.01). This gain was particularly relevant (29%) when patients with TIMI risk score < or =4 were considered (10,599 vs. 13,699 euros/patient; p=0.004). CONCLUSIONS: CPU care of NSTEACS is a safe and cost-effective alternative to conventional CCU management, particularly appealing with regard to patients presenting with intermediate TIMI risk score (< or =4) in whom CPU management could optimize the use of cath-lab facilities and dedicated cardiologists.