Low-molecular-weight heparin for the prevention of clinical worsening in severe non-critically ill COVID-19 patients: a joint analysis of two randomized controlled trials.

Coronavirus disease 2019 (COVID-19) carries a high risk of vascular thrombosis. However, whether a specific anticoagulation intensity strategy may prevent clinical worsening in severe COVID-19 patients is still debated. We conducted a joint analysis of two randomized controlled trials, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), to assess the efficacy and safety of two anticoagulant regimens in hospitalized severe COVID-19 patients. Subjects with COVID-19-associated respiratory compromise and/or coagulopathy were randomly assigned to low (4000 IU qd) or high (70 IU Kg-1 every 12 h) enoxaparin dose. The primary efficacy endpoint was clinical worsening within 30 days, defined as the occurrence of at least one of the following events, whichever came first: in-hospital death, evidence of arterial or venous thromboembolism, acute myocardial infarction, need for either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) in patients receiving standard oxygen therapy or none at randomization, and need for mechanical ventilation in any patient. The safety endpoint was major bleeding. We estimated the relative risk (RR) and its 95% confidence interval (CI) for the outcomes. Among 283 patients included in the study (144 in the low-dose and 139 in the high-dose group), 118 (41.7%) were on NIV or CPAP at randomization. 23/139 (16.5%) patients in the high-dose group reached the primary endpoint compared to 33/144 (22.9%) in the low-dose group (RR 0.72, 95% CI 0.45-1.17). No major bleeding was observed. No significant differences were found in the clinical worsening of hospitalized COVID-19 patients treated with high versus low doses of enoxaparin.

Clinical-radiological correlations in COVID-19-related venous thromboembolism: Preliminary results from a multidisciplinary study.

INTRODUCTION: Among the multiple complex pathophysiological mechanisms underlying COVID-19 pneumonia, immunothrombosis has been shown to play a key role. One of the most dangerous consequences of the prothrombotic imbalance is the increased incidence of micro- and macrothrombotic phenomena, especially deep vein thrombosis (DVT) and pulmonary embolism (PE). METHODS: We investigated the correlation between radiological and clinical-biochemical characteristics in a cohort of hospitalised COVID-19 patients. RESULTS: PE was confirmed in 14/61 (23%) patients, five (35.7%) had DVT. The radiographic findings, quantified by Qanadli score calculated on CT angiography, correlated with the clinical score and biochemical markers. The ratio between the right and left ventricle diameter measured at CT angiography correlated with the length of hospital stay. CONCLUSION: In our cohort radiological parameters showed a significant correlation with clinical prognostic indices and scores, thus suggesting that a multidisciplinary approach is advisable in the evaluation of PE in COVID-19 patients.

Respiratory dysfunction as first presentation of myasthenia gravis misdiagnosed as COVID-19.

BACKGROUND: The outbreak of the coronavirus disease 2019 (COVID-19) has had profound impact on health care not only for its direct effects, but also because it deeply influenced the whole clinical practice and diagnostic pathways, particularly in the acute setting. CASE REPORT: We present the case of a patient with respiratory dysfunction due to myasthenia gravis (MG) initially misdiagnosed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to ambiguity in the interpretation of radiological and microbiological findings during COVID-19 pandemic. DISCUSSION: Respiratory dysfunction as first clinical manifestation of myasthenia gravis is rare, but potentially very harmful. Emergency physicians should always consider neurological diseases when dyspnea cannot be explained by cardiac or respiratory causes.

Laboratory and clinical risk assessment to treat myelodysplatic syndromes.

Myelodisplastic syndromes (MDS) are heterogeneous myeloid disorders characterized by peripheral cytopenias and increased risk of transformation into acute myelogenous leukemia (AML). MDS are generally suspected in the presence of cytopenia on routine analysis and the evaluation of bone marrow cells morphology and cellularity leads to correct diagnosis of MDS. The incidence of MDS is approximately five cases per 100,000 people per year in the general population, but it increases up to 50 cases per 100,000 people per year after 60 years of age. Typically MDS affect the elderly, with a median age at diagnosis of 65-70 years. Here the current therapeutic approaches for MDS are evaluated by searching the PubMed database. Establishing the prognosis in MDS patients is a key element of therapy. In fact an accurate estimate of prognosis drives decisions about the choice and timing of the therapeutic options. Therapy is selected based on prognostic risk assessment, cytogenetic pattern, transfusion needs and biological characteristics of the disease, comorbidities and clinical condition of the patients. In lower-risk patients the goals of therapy are different from those in higher-risk patients. In lower-risk patients, the aim of therapy is to reduce transfusion needs and transformation to higher risk disease or AML, improving the quality of life and survival. In higher-risk patients, the main goal of therapy is to prolong survival and to reduce the risk of AML transformation. Current therapies include growth factor support, lenalidomide, immunomodulatory and hypomethylating agents, intensive chemotherapy, and allogenic stem cell transplantation. The challenge when dealing with MDS patients is to select the optimal treatment by balancing efficacy and toxicity.

High prevalence of splenic marginal zone lymphoma among patients with acquired C1 inhibitor deficiency.

Marginal zone lymphoma represents about 10% of all non-Hodgkin lymphomas (NHLs). 33% of patients with acquired angioedema (AAE) due to acquired C1-inhibitor (C1-INH) deficiency (C1-INH-AAE) have or will develop NHLs. C1-INH-AAE is a rare condition. We report the follow-up of 72 C1-INH-AAE patients, followed for a median of 15 years (range 1-24). Median age was 71 (range 64-79) years; median age at onset of angioedema symptoms was 57·5 (range 50-66) years and it was 63 [range 45-80) years at diagnosis]. Twenty patients were diagnosed with low-grade non-follicular B-cell lymphomas (75% were splenic MZL), one with follicular and three with high-grade lymphomas (two diffuse large B-cell lymphomas and one mantle cell lymphoma). Fifteen NHLs were diagnosed at onset of AAE or thereafter (3 months to 7 years), eight had already been diagnosed at onset of angioedema. Two of 24 patients remain on watchful wait. Thirthen of 24 received chemotherapy, two received rituximab. Three underwent splenectomy. All 18 patients receiving therapy for NHL experienced post-treatment reduction in AAE symptoms. Our study suggests that clonal B-cell proliferation is the pathology underlying AAE leading to production of C1-INH-neutralizing autoantibodies and to NHLs. The post-germinal centre origin of NHL suggests that immune stimulation may contribute to lymphomagenesis.

Salvage therapy with bortezomib and dexamethasone in elderly patients with relapsed/refractory multiple myeloma.

Bortezomib-dexamethasone (bort-dex) is effective for relapsed/refractory (R/R) multiple myeloma, but few data are available for elderly patients. The aim of this study was to evaluate efficacy and toxicity of bort-dex in elderly R/R MM patients. We evaluated 81 R/R MM patients treated with bort-dex. Eight of them had light-chain disease. The median age of the patients was 73 years (range 65-89 years). All patients were R/R MM patients and had been treated with melphalan and prednisone with or without thalidomide or bortezomib in the first line or with lenalidomide and dexamethasone in the second line. The median number of previous lines was 2. Thirty-nine (48%) patients received bortezomib intravenously and 42 (52%) patients received bortezomib subcutaneously. The median number of bort-dex cycles was 6 (range 1-11). Fifty-three (65.4%) patients achieved at least a partial response, including eight (11%) patients with complete response and nine (12.5%) patients with very good partial responses. The median duration of response, time to next therapy and treatment-free intervals were 8, 11 and 5 months. Duration of response was significantly longer for patients achieving complete response/very good partial response than for those achieving partial response (7.3 vs. 3.8 months, P=0.03). After a median follow-up of 24 months, 78 patients showed disease progression and 70 died. The median time to progression, progression-free survival and overall survival were 8.9, 8.7 and 22 months, respectively. Peripheral neuropathy occurred in 38 (47%) patients. Our data highlight that bort-dex is effective and tolerable in fit elderly patients, thus justifying the efforts for deeper responses. However, awareness of short-lived responses to bort-dex should lead to a thorough evaluation of the need for maintenance.

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.

Long-term fluvastatin reduces the hazardous effect of renal impairment on four-year atherosclerotic outcomes (a LIPS substudy).

Mild renal impairment is an important risk factor for late cardiovascular complications. This substudy of the Lescol Intervention Prevention Study (LIPS) assessed the effect of fluvastatin on outcome of patients who had renal dysfunction and those who did not. Complete data for creatinine clearance calculation (Cockcroft-Gault formula) were available for 1,558 patients (92.9% of the LIPS population). Patients were randomized to fluvastatin or placebo after successful completion of a first percutaneous coronary intervention. Follow-up time was 3 to 4 years. The effect of baseline creatinine clearance on coronary atherosclerotic events (cardiac death, nonfatal myocardial infarction, and coronary reinterventions not related to restenosis) was evaluated. Baseline creatinine clearance (logarithmic transformation) was inversely associated with an incidence of adverse events among patients who received placebo (hazard ratio 0.99, 95% confidence interval 0.982 to 0.998, p = 0.01). However, no association was noted between creatinine clearance and the incidence of adverse events among patients who received fluvastatin (hazard ratio 1.0, 95% confidence interval 0.99 to 1.0, p = 0.63). No further deterioration in creatinine clearance was observed during follow-up, regardless of baseline renal function or allocated treatment. Occurrence of adverse events was not related to changes in renal function during follow-up. Fluvastatin therapy markedly decreased the risk of coronary atherosclerotic events after percutaneous intervention in patients who had lower values of creatinine clearance at baseline. The benefit of fluvastatin was unrelated to any effect on renal function.