Clinical outcome with different doses of low-molecular-weight heparin in patients hospitalized for COVID-19

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000IU) vs. higher (>4000IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400-0.1.792; p=0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Cardiac amyloidosis: do not forget to look for it

Amyloidosis is a systemic disease due to buildup of protein material in the extracellular space, which can affect the heart, mainly in its light chain and transtyretin forms. Historically this condition has been considered very uncommon, and it was certainly under-diagnosed. Today is well known that in certain group of patients its prevalence is, indeed, very high (25% in patients over the age of 80\u2009years; 32% in patients over 75\u2009years with heart failure and preserved systolic function, and 5% in post-mortem series of hypertrophic cardiomyopathy). Some genetically determined form of transthyretin amyloidosis are quite common in certain populations, such as Caribbean origin African-Americans. The wide spectrum of signs, symptoms, and first-level tests often overlapping among various other conditions, represent a diagnostic challenge for the clinical cardiologist. The opportunity to reach the diagnosis with non-invasive testing (first and foremost scintiscan with bone markers), as well as encouraging results of newer classes of drugs, raised the interest in this condition, so far burdened by an ominous prognosis. Early diagnosis of amyloidosis should always be guided by clinical suspicion but should also be supported by a multidisciplinary approach, aimed at optimizing the prognosis of the condition. Despite the newer drugs now available, a late diagnosis affect negatively the prognosis, and the opportunity to implement disease-modifying therapies (e.g. liver transplant in ATTR, or bone marrow transplant in AL) able to cure or at least delay the progression of the disease

Influence of Implant Scanbody Wear on the Accuracy of Digital Impression for Complete-Arch: A Randomized In Vitro Trial

The aim of this study was to evaluate the influence of implant scanbody (ISB) wear on the accuracy of digital impression for complete-arch. A polymethylmethacrylate (PMMA) edentulous mandibular model with four internal hexagonal interlocking conical connections was scanned with an extraoral optical scanner to achieve a reference file. Four cylindrical polyetheretherketone (PEEK) ISBs were scanned 30 times with IOS, and the test files were aligned to the reference file with a best-fit algorithm. For each analog linear (ΔX, ΔY and ΔZ-axis) and angular deviations (ΔANGLE) were assessed. Euclidean distance (ΔEUC) was calculated from the linear deviation, reporting a mean of 82 µm (SD 61) ranging from 8 to 347 µm. ΔANGLE error mean was 0.33° (SD 0.20), ranging from 0.02 to 0.92°. From a multivariate analysis, when ΔEUC was considered as a response variable, a significant influence of ISB wear by scan number in interaction to position for implant 3.6 was identified (p p < 0.0001). The obtained results showed that the ISB wear negatively influenced the accuracy of IOS, suggesting that ISB base wear could be detrimental for the seating of ISBs on angulated implants

Graph Neural Networks for temporal graphs: State of the art, open challenges, and opportunities

Graph Neural Networks (GNNs) have become the leading paradigm for learning on (static) graph-structured data. However, many real-world systems are dynamic in nature, since the graph and node/edge attributes change over time. In recent years, GNN-based models for temporal graphs have emerged as a promising area of research to extend the capabilities of GNNs. In this work, we provide the first comprehensive overview of the current state-of-the-art of temporal GNN, introducing a rigorous formalization of learning settings and tasks and a novel taxonomy categorizing existing approaches in terms of how the temporal aspect is represented and processed. We conclude the survey with a discussion of the most relevant open challenges for the field, from both research and application perspectives

Uncommon case of pericardial effusion

We present the case of a 59-year-old patient with severe aortic stenosis, asymptomatic mild to moderate pericardial effusion and no major risk factors for poor prognosis. He underwent four-week course of non-steroidal anti-inflammatory drugs (ibuprofen 600 mg TID) with no improvement of the effusion. After complete diagnostic work-up and examination, we discovered that he had a prostate cancer with bone metastasis. On the bone scintigraphy, there was particular involvement of ribs and sternum. We decided to treat our patient with an association of docetaxel and hormone therapy, after six months we observed a reduction in the pericardial effusion. Even in the presence of a patient without risk factor of poor prognosis, pericardial effusion can be the first sign of occult neoplasia

Clustering of blood cell count abnormalities and future risk of death

BACKGROUND: The identification of novel predictors of poor outcome may help stratify cardiovascular risk. Aim was to evaluate the individual contribution of blood cell count parameters, as well as their clustering, on the risk of death and cardiovascular events over the long term in the population-based Malmö Diet and Cancer Study cohort.METHODS: In 30,447 individuals (age 57 ± 8 years), we assessed the incidence of all-cause death (primary endpoint) and major adverse cardiovascular events (MACE, secondary outcome measure) according to absence or presence of one, two and three factors at baseline out of the following: anaemia, leukocytosis and thrombocytosis. Median follow-up was 16 years.RESULTS: The percentages of all-cause death were 19.5% in individuals without factors, 21.3% in those with one factor, 27.4% with two and 46.4% with three (log-rank test P < .001). The crude incidence of MACE was 28.0%, 29.2%, 35.5% and 57.1%, respectively (log-rank test P < .001). At multivariate analysis, we found a stepwise increase in overall mortality with increasing number of prevalent factors (one factor: HR 1.23, 95% CI 1.14-1.31, P < .001; two factors: 1.61, 1.37-1.89, P < .001; three factors: 2.69, 1.44-5.01, P = .002, vs no factor). Similar findings were observed for the incidence of MACE (one factor: adjusted HR 1.18, 95% CI 1.11-1.24, P < .001; two factors: 1.52, 1.33-1.76, P < .001; three factors: 2.03, 1.21-3.67, P < .001, vs no factor).CONCLUSIONS: The easily assessable clustering of anaemia, leukocytosis and thrombocytosis heralds higher incidence of death and adverse cardiovascular events

Interaction between thrombin potential and age on early clinical outcome in patients hospitalized for COVID-19

Patients with Coronavirus Disease-2019 (COVID-19) have haemostatic dysfunction and are at higher risk of thrombotic complications. Although age is a major risk factor for outcome impairment in COVID-19, its impact on coagulative patterns here is still unclear. We investigated the association of Endogenous Thrombin Potential (ETP) with thrombotic and haemorrhagic events according to different ages in patients admitted for COVID-19. A total of 27 patients with COVID-19-related pneumonia, without need for intensive care unit admission or mechanical ventilation at hospital presentation, and 24 controls with non-COVID-19 pneumonia were prospectively included. ETP levels were measured on admission. Patients were evaluated for major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, stroke, transient ischemic attack, venous thromboembolism) and bleeding complications [according to Bleeding Academic Research Consortium (BARC) definition] during in-hospital stay. COVID-19 patients had similar ETP levels compared to controls (AUC 93\u2009\ub1\u200924% vs 99\u2009\ub1\u200921%, p\u2009=\u20090.339). In the COVID-19 cohort, patients with in-hospital MACE showed lower ETP levels on admission vs those without (AUC 86\u2009\ub1\u200914% vs 95\u2009\ub1\u200927%, p\u2009=\u20090.041), whereas ETP values were comparable in patients with or without bleeding (AUC 82\u2009\ub1\u200916% vs 95\u2009\ub1\u200926%, p\u2009=\u20090.337). An interaction between age and ETP levels for both MACE and bleeding complications was observed, where a younger age was associated with an inverse relationship between ETP values and adverse event risk (pint 0.018 for MACE and 0.050 for bleeding). Patients with COVID-19 have similar thrombin potential on admission compared to those with non-COVID-19 pneumonia. In younger COVID-19 patients, lower ETP levels were associated with a higher risk of both MACE and bleeding