Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of ...the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.
We report in vivo selection of a severe acute respiratory syndrome coronavirus 2 spike mutation (Q493R) conferring simultaneous resistance to bamlanivimab and etesivimab. This mutation was isolated ...from a patient who had coronavirus disease and was treated with these drugs.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sonography – similar to what happened almost two centuries ago with the introduction of stethoscopes – has completely changed patients’ clinical management in Internal Medicine. The availability of ...performant, sometimes even small-sized and cost-effective machines, has allowed doctors in Internal-Medicine units to perform bedside-ultrasound examinations alongside regular clinical ones. ...
To clarify the major features of the apical ballooning syndrome, we performed a systematic review of the existing literature.
Review of all relevant case series using the MEDLINE and EMBASE databases ...resulted in the identification of 14 studies. These studies suggest that the apical ballooning syndrome accounts for approximately 2.0% of ST-segment elevation infarcts, with most cases described in post-menopausal women. The most common clinical presentations are chest pain and dyspnoea, reported in 67.8 and 17.8% of the patients, respectively. Cardiogenic shock (4.2% of the patients) and ventricular fibrillation (1.5%) were not infrequent. ST-segment elevation was reported in 81.6% of the patients, T wave abnormalities in 64.3%, and Q waves in 31.8%. Cardiac biomarkers were usually mildly elevated, as reported in 86.2% of the patients. Typically, patients had left ventricular (LV) dysfunction on admission, with mean ejection fraction ranging from 20 to 49%. However, over a period of days to weeks, all patients experienced dramatic improvement in LV function. The onset of symptoms was often preceded by emotional (26.8%) or physical stress (37.8%). Norepinephrine concentration was elevated in 74.3% of the patients. Prognosis was generally excellent, with full recovery in most patients. In-hospital mortality was 1.1%. Only 3.5% of the patients experienced a recurrence.
Clinicians should consider this syndrome in the differential diagnosis of patients presenting with chest pain, especially in post-menopausal women with a recent history of emotional or physical stress.
Summary
Little information is available on the incidence of splanchnic vein thrombosis and on mortality rates during the acute phase of the disease. We performed a large epidemiologic study on ...hospital admissions for portal vein thrombosis (PVT) and the Budd-Chiari syndrome (BCS) between 2002 and 2012 in Northwestern Italy. Primary and secondary discharge diagnoses of PVT and BCS were identified using the 9th edition International Classification of Diseases codes 453.0, 572.1 and 452. Hospitalisations for recurrent events were not included. Information was collected on age and gender, vital status at discharge, duration of hospitalisation, and up to five secondary discharge diagnoses. Comorbidity was evaluated using the Charlson comorbidity index (CCI). A total of 3535 patients with PVT and 287 with BCS were hospitalized. The overall gender-specific incidence rates for PVT were 3.78 per 100,000 inhabitants in males and 1.73 per 100,000 inhabitants in females; for BCS 2.0 and 2.2 per million inhabitants, respectively. In-hospital case fatality was 7.3 % in patients with PVT and 4.9 % in patients with BCS. Age, non-abdominal solid cancer, and CCI were independently associated with in-hospital mortality in both PVT and BCS after stepwise regression analysis, male gender and haematologic cancer were associated with mortality in BCS patients only. In this large study we confirmed the low incidence of BCS and we found an incidence of PVT higher than previously reported. This incidence was stable during the period of observation. In-hospital mortality is not negligible, in particular in PVT patients.
Although the BNT162b2 COVID-19 vaccine is known to induce IgG neutralizing antibodies in serum protecting against COVID-19, it has not been studied in detail whether it could generate specific ...immunity at mucosal sites, which represent the primary route of entry of SARS-CoV-2.
Samples of serum and saliva of 60 BNT162b2-vaccinated healthcare workers were collected at baseline, two weeks after the first dose and two weeks after the second dose. Anti-S1-protein IgG and IgA total antibodies titres and the presence of neutralizing antibodies against the Receptor Binding Domain in both serum and saliva were measured by quantitative and by competitive ELISA, respectively.
Complete vaccination cycle generates a high serum IgG antibody titre as a single dose in previously infected seropositive individuals. Serum IgA concentration reaches a plateau after a single dose in seropositive individuals and two vaccine doses in seronegative subjects. After the second dose IgA level was higher in seronegative than in seropositive subjects. In saliva, IgG level is almost two orders of magnitude lower than in serum, reaching the highest values after the second dose. IgA concentration remains low and increases significantly only in seropositive individuals after the second dose. Neutralizing antibody titres were much higher in serum than in saliva.
The mRNA BNT162b2 vaccination elicits a strong systemic immune response by drastically boosting neutralizing antibodies development in serum, but not in saliva, indicating that at least oral mucosal immunity is poorly activated by this vaccination protocol, thus failing in limiting virus acquisition upon its entry through this route.
This work was funded by the Department of Medicine and Surgery, University of Insubria, and partially supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020).
It is well known that the ABO blood group exerts a major influence on hemostasis, as O blood group individuals have lower von Willebrand factor and factor VIII levels than non-O blood group subjects. ...To evaluate the possible clinical implication of the different ABO blood groups on the risk of developing venous thromboembolism (VTE), we conducted a meta-analysis of the existing literature. After an electronic search strategy using Medline and Embase and a manual review of abstract books of the International Society on Thrombosis and Haemostasis and of reference lists of all retrieved articles, we included in the systematic review 38 studies with 10,305 VTE cases. The prevalence of non-O blood group was significantly higher in VTE patients compared with controls with a resulting pooled odds ratio (OR) of 2.09 (95% confidence interval CI, 1.83, 2.38; p < 0.00001). Similar findings were obtained when the genotypes A1O/BO/A2B (OR 1.73, 95% CI, 1.47, 2.05; p < 0.00001) and A1B/A1A1/BB (OR 1.87, 95% CI, 1.84, 2.44; p < 0.00001) were analyzed. The maximum VTE risk was observed in non-O-factor V Leiden patients (OR 7.60, 95% CI, 3.21, 17.99), while for G20210A prothrombin mutation it was not possible to perform a pooled analysis due to a paucity of published studies. Finally, the association between non-O blood group and VTE was weaker when provoked VTE cases were considered (OR 1.33, 95% CI, 1.18, 1.50), while it was substantially unchanged when unprovoked VTE cases were analyzed (OR 1.88, 95% CI, 1.42, 2.50). In conclusion, considering its prevalence, non-O blood group is a candidate to be one of the most important genetic risk factors for venous thrombosis.
Initially described as a factor involved in liver regeneration and neuronal differentiation, proprotein convertase subtilisin/kexin type 9 (PCSK9) has become one of the key regulators of low-density ...lipoprotein cholesterol. Beside that, a number of studies have suggested PCSK9 may play a role in cancer biology. This is particularly true for gastroenteric (gastric and liver cancers) and lung cancers, where higher PCSK9 levels were associated with the increased ability of the tumor to develop and give metastasis as well as with reduced overall survival. Accordingly, monoclonal antibodies blocking PCSK9 were recently shown to synergize with immunotherapy in different types of cancers to achieve tumor growth suppression through an increased intratumoral infiltration of cytotoxic T cells. Anti-PCSK9 vaccines have been tested in animal models with encouraging results only in colon carcinoma. As most of this evidence is based on pre-clinical studies, this has led to some controversies and inconsistencies, thus suggesting that additional research is needed to clarify the topic. Finally, modulation of intracellular PCSK9 levels by silencing RNA (siRNA) may help understand the physiological and pathological mechanisms of PCSK9.
Background: Venous thromboembolism (VTE) is the third most common vascular disease. Medical inpatients, long-term care residents, persons with minor injuries, and long-distance travelers are at ...increased risk.
Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support patients, clinicians, and others in decisions about preventing VTE in these groups.
Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and adult patients. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess evidence and make recommendations, which were subject to public comment.
Results: The panel agreed on 19 recommendations for acutely ill and critically ill medical inpatients, people in long-term care facilities, outpatients with minor injuries, and long-distance travelers.
Conclusions: Strong recommendations included provision of pharmacological VTE prophylaxis in acutely or critically ill inpatients at acceptable bleeding risk, use of mechanical prophylaxis when bleeding risk is unacceptable, against the use of direct oral anticoagulants during hospitalization, and against extending pharmacological prophylaxis after hospital discharge. Conditional recommendations included not to use VTE prophylaxis routinely in long-term care patients or outpatients with minor VTE risk factors. The panel conditionally recommended use of graduated compression stockings or low-molecular-weight heparin in long-distance travelers only if they are at high risk for VTE.
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