BackgroundVenous thromboembolism (VTE), whether pulmonary embolism (PE) or deep vein thrombosis (DVT), is common in patients with COVID-19. Recommendations on systematic screening in the intensive care unit (ICU) are lacking.Research questionIs there any clinical benefit of systematic screening for DVT in critically ill patients with severe COVID-19?Study design and methodsSingle-center randomized clinical trial (RCT) of COVID-19 cases admitted to the ICU. Patients were randomized into two groups: a study group that underwent ultrasound (US) screening for DVT Mondays and Thursdays, and a control group that was treated according to the unit protocol. The primary outcome was the presence of DVT. Secondary outcomes were ICU total stay, death within 21-day follow-up and bleeding complications (minor or major). A composite outcome of poor prognosis variables was analyzed. We tested a superiority hypothesis with a confidence level of 95% and an equivalence limit of 20%.Results163 patients (84 screening group, 79 control group) were enrolled between April and July 2021. There were 90 men (55.2%) with a mean ± SD age of 49.8 ± 13.58 years. In screening group 16.7% developed DVT versus 3.8% in control group (p = .007), and 3.6% versus 5.1% developed PE, respectively (p = 0.7). Poor outcome variables were male sex, age, COVID-19 vaccination status, Fibrinogen, Urea, Creatinine and Interleukin 6 (IL6) levels; Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scales. The superiority comparison, with a power of 95%, showed no statistically significant differences for a composite endpoint (p = .123). After adjusting by group, the OR for poor outcome is 1.966 (0.761-5.081) p = 0.163InterpretationAmong these patients, a strategy of systematic US screening for DVT was not associated with any significant improvements to clinical outcomes compared with usual care.Clinical Trial RegistrationClinicaltrials.org registration number: NCT05028244.

Coagulation activation and inflammatory derangements are key characteristics of coronavirus disease 2019 (COVID-19). Aspirin therapy in patients with COVID-19 remains uncertain due to conflicting evidence regarding its ability to balance anti-inflammatory and antithrombotic benefits against potential bleeding risks in the context of COVID-19-associated coagulopathy. This study aimed to compare the clinical safety and efficacy of aspirin in patients with COVID-19 in randomized controlled trials (RCTs).

In the present systematic review and meta-analysis, the Medline, Embase, and Cochrane Library databases were searched for RCTs from database inception to January 13, 2023. Data were independently extracted and screened by two authors using structured data collection forms based on published reports. Results were calculated using odds ratios (ORs) and 95% confidence intervals (CIs) with the Mantel-Haenszel method. Quality was assessed using the Cochrane Risk of Bias tool. The main outcomes were short-term all-cause mortality, bleeding events and any thrombosis events. This meta-analysis was registered on PROSPERO.

A total of 922 studies were identified. Finally, six RCTs with low risk of bias were pooled in the analysis. The results showed that aspirin use was not associated with a reduction in all-cause mortality (OR = 0.95, 95% CI [0.88-1.03], I2 = 0%) or the risk of any thrombosis (RR 0.88, 95% CI [0.77-1.01], I2 = 0%), but aspirin use was associated with a higher risk of bleeding (OR 1.72, 95% CI [1.32-2.24], I2 = 0%). No obvious risk of bias was found among the included RCTs for the primary outcome.

Routine low-dose aspirin use does not reduce the risk of short-term mortality and risk of any thrombosis but increases the risk of bleeding. The data does not support the use of low-dose aspirin in patients with COVID-19.

The aim of this study was to analyze whether patients with SARS-CoV-2 who received surgical tracheotomy had a lower incidence of postoperative bleeding if their LMWH was postponed or canceled on the day of surgery.

Patients with SARS-CoV-2 admitted to the intensive care units who underwent surgical tracheotomy were assessed retrospectively through their medical records. Data on comorbidity, LMWH dose, and timing were collected. Bleedings < 72 h post surgery were noted as stomal or airway bleedings.

All 101 patients included were on LMWH. Twenty-two patients had no change of dose of LMWH, 24 patients had their dose of LMWH postponed to post surgery, and 50 patients had their dose reduced to only the evening dose on the day of surgery. Twenty-six patients had a stomal bleeding, one patient had an airway bleeding, and four patients had both stomal and airway bleedings. No significant difference in the incidence of bleeding was identified between various groups of different LMWH doses or timing, reduced dose versus no change of dose, OR 1.29 (95% CI 0.42-3.92). Postponed dose versus no change of dose of LMWH, OR 1.03 (95% CI 0.28-3.75). Increasing age was correlated to a higher risk of bleeding post-surgery by an OR of 1.64 (95% CI 1.06-2.54, p = 0.026 for every 10 years added). No fatal bleeding related to surgical tracheotomy was observed.

Decreased doses of LMWH on the day of surgery were not associated with a risk reduction for post-surgical bleeding in patients with SARS-CoV-2 who received tracheotomy. Increasing age was a risk factor for post-surgical bleeding.

Retrospective, level 3.

The aim of this study was to evaluate the association between SARS-CoV-2 vaccination and the occurrence of thrombotic complications in patients admitted to intensive care for severe COVID-19 pneumonia.

Observational, descriptive, prospective, multicentre study.

Intensive care units of five university hospitals.

A total of 255 patients admitted to the intensive care unit (ICU) with SARS-CoV-2 pneumonia, confirmed by RT-PCR in throat swab or tracheal aspirate, starting the date the first vaccinated patient against SARS-CoV-2 was admitted in one of the participating ICUs, were included in the analysis.

Vaccination status against SARS-CoV-2 and thrombotic events.

18.8% of patients had received some form of vaccination. Thrombotic events occurred in 21.2% of patients. Lack of vaccination was associated with thrombotic events (OR 5.024; 95% CI: 1.104-23.123; p = 0.0037) and death (OR 5.161; 95% CI: 1.075-24.787; p = 0.04). ICU mortality was not associated with the occurrence of thrombotic complications.

In this series of patients, vaccination against SARS-CoV-2 reduced the risk of thrombotic events and mortality in patients with severe COVID-19 admitted to the ICU. Thrombotic complications did not alter ICU mortality.

Pulmonary embolism (PE) is relatively common worldwide. It is a serious condition that can be life-threatening. Studies on the relationship between adverse outcomes of this condition and whether a patient is male or female have yielded inconsistent results. Determining whether there is an association between sex and short-term mortality in patients with acute PE is important as this information may help guide different approaches to PE monitoring and treatment.

To determine whether sex (i.e. being a male or a female patient) is an independent prognostic factor for predicting mortality in adults with acute symptomatic pulmonary embolism.

The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register up to 17 February 2023. We scanned conference abstracts and reference lists of included studies and systematic reviews. We also contacted experts to identify additional studies. There were no restrictions with respect to language or date of publication.

We included phase 2-confirmatory prognostic studies, that is, any longitudinal study (prospective or retrospective) evaluating the independent association between sex (male or female) and mortality in adults with acute PE.

We followed the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) and the Cochrane Prognosis Methods Group template for prognosis reviews. Two review authors independently screened the studies, extracted data, assessed the risk of bias according to the Quality in Prognosis Studies (QUIPS) tool, and assessed the certainty of the evidence (GRADE). Meta-analyses were performed by pooling adjusted estimates. When meta-analysis was not possible, we reported the main results narratively.

We included seven studies (726,293 participants), all of which were retrospective cohort studies with participants recruited and managed in hospitals between 2000 and 2018. Studies took place in the USA, Spain, and Japan. Most studies were multicentre. None were conducted in low- or middle-income countries. The participants' mean age ranged from 62 to 69 years, and the proportion of females was higher in six of the seven studies, ranging from 46% to 60%. Sex and gender terms were used inconsistently. Participants received different PE treatments: reperfusion, inferior vena cava filter, anticoagulation, and haemodynamic/respiratory support. The prognostication time (the point from which the outcome was predicted) was frequently omitted. The included studies provided data for three of our outcomes of interest. We did not consider any of the studies to be at an overall low risk of bias for any of the outcomes analysed. We judged the certainty of the evidence as moderate to low due to imprecision and risk of bias. We found moderate-certainty evidence (due to imprecision) that for female patients there is likely a small but clinically important reduction in all-cause mortality at 30 days (odds ratio (OR) 0.81, 95% confidence interval (CI) 0.72 to 0.92; I2 = 0%; absolute risk difference (ARD) 24 fewer deaths in women per 1000 participants, 95% CI 35 to 10 fewer; 2 studies, 17,627 participants). However, the remaining review outcomes do not indicate lower mortality in female patients. There is low-certainty evidence (due to serious risk of bias and imprecision) indicating that for females with PE, there may be a small but clinically important increase in all-cause hospital mortality (OR 1.11, 95% CI 1.00 to 1.22; I2 = 21.7%; 95% prediction interval (PI) 0.76 to 1.61; ARD 13 more deaths in women per 1000 participants, 95% CI 0 to 26 more; 3 studies, 611,210 participants). There is also low-certainty evidence (due to very serious imprecision) indicating that there may be little to no difference between males and females in PE-related mortality at 30 days (OR 1.08, 95% CI 0.55 to 2.12; I2 = 0%; ARD 4 more deaths in women per 1000 participants, 95% CI 22 fewer to 50 more; 2 studies, 3524 participants). No study data was found for the other outcomes, including sex-specific mortality data at one year. Moreover, due to insufficient studies, many of our planned methods were not implemented. In particular, we were unable to conduct assessments of heterogeneity or publication bias or subgroup and sensitivity analyses.

The evidence is uncertain about sex (being male or female) as an independent prognostic factor for predicting mortality in adults with PE. We found that, for female patients with PE, there is likely a small but clinically important reduction in all-cause mortality at 30 days relative to male patients. However, this result should be interpreted cautiously, as the remaining review outcomes do not point to an association between being female and having a lower risk of death. In fact, the evidence in the review also suggested that, in female patients, there may be a small but clinically important increase in all-cause hospital mortality. It also showed that there may be little to no difference in PE-related mortality at 30 days between male and female patients. There is currently no study evidence from longitudinal studies for our other review outcomes. Although the available evidence is conflicting and therefore cannot support a recommendation for or against routinely considering sex to quantify prognosis or to guide personalised therapeutic approaches for patients with PE, this Cochrane review offers information to guide future primary research and systematic reviews.

Coronavirus disease 2019 (COVID-19) is a strong risk factor for venous thromboembolism (VTE). Few studies have evaluated the effectiveness of COVID-19 vaccination in preventing hospitalization for COVID-19 with VTE.

Adults hospitalized at 21 sites between March 2021 and October 2022 with symptoms of acute respiratory illness were assessed for COVID-19, completion of the original monovalent messenger RNA (mRNA) COVID-19 vaccination series, and VTE. Prevalence of VTE was compared between unvaccinated and vaccinated patients with COVID-19. The vaccine effectiveness (VE) in preventing COVID-19 hospitalization with VTE was calculated using a test-negative design. The VE was also stratified by predominant circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant.

Among 18 811 patients (median age [interquartile range], 63 [50-73] years; 49% women; 59% non-Hispanic white, 20% non-Hispanic black, and 14% Hispanic; and median of 2 comorbid conditions [interquartile range, 1-3]), 9792 were admitted with COVID-19 (44% vaccinated), and 9019 were test-negative controls (73% vaccinated). Among patients with COVID-19, 601 had VTE diagnosed by hospital day 28, of whom 170 were vaccinated. VTE was more common among unvaccinated than vaccinated patients with COVID-19 (7.8% vs 4.0%; P = .001). The VE against COVID-19 hospitalization with VTE was 84% overall (95% confidence interval, 80%-87%), and VE stratified by predominant circulating variant was 88% (73%-95%) for Alpha, 93% (90%-95%) for Delta, and 68% (58%-76%) for Omicron variants.

Vaccination with the original monovalent mRNA series was associated with a decrease in COVID-19 hospitalization with VTE, though data detailing prior history of VTE and use of anticoagulation were not available. These findings will inform risk-benefit considerations for those considering vaccination.

Emerging research underscores the heightened risk of vasculitis and microvascular thrombosis in COVID-19 patients, alongside concerns about prothrombotic events post-severe acute respiratory syndrome coronavirus 2 vaccination. Following the pandemic's end, we sought a comprehensive analysis to elucidate its impact on microsurgical thrombosis rates, informed by empirical and anecdotal evidence.

An institutional review board-approved retrospective review analyzed autologous breast reconstruction cases in women from January 2019 to March 2022. Data on patient history, COVID-19 infection, vaccination status, and postoperative complications were collected. Patients were categorized as prepandemic and pandemic, and based on COVID-19 influence (infection or vaccination) for statistical evaluation.

Among 527 patients, 216 underwent surgery prepandemic and 311 during the pandemic, revealing thrombotic event rates of 3.2% and 5.4%, respectively. Further comparative analysis showed no significant difference in thrombotic events among patients affected by COVID-19 through infection or vaccination during the pandemic.

Contrary to concerns, COVID-19 infection or vaccination status does not significantly increase thrombotic event rates in deep inferior epigastric perforator flap breast reconstructions. This study offers vital insights, affirming the safety and efficacy of microsurgical procedures amid the pandemic, thereby guiding microsurgeons in optimizing patient care in the post-COVID-19 era.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute hypoxic respiratory failure caused by diffuse lung inflammation and edema. ARDS can be precipitated by intrapulmonary factors or extrapulmonary factors, which can lead to severe hypoxemia. Patients suffering from ARDS have high mortality rates, including a 28-day mortality rate of 34.8% and an overall in-hospital mortality rate of 40.0%. The pathophysiology of ARDS is complex and involves the activation and dysregulation of multiple overlapping and interacting pathways of systemic inflammation and coagulation, including the respiratory system, circulatory system, and immune system. In general, the treatment of inflammatory injuries is a coordinated process that involves the downregulation of proinflammatory pathways and the upregulation of anti-inflammatory pathways. Given the complexity of the underlying disease, treatment needs to be tailored to the problem. Hence, we discuss the pathogenesis and treatment methods of affected organs, including 2019 coronavirus disease (COVID-19)-related pneumonia, drowning, trauma, blood transfusion, severe acute pancreatitis, and sepsis. This review is intended to provide a new perspective concerning ARDS and offer novel insight into future therapeutic interventions.

Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase of SARS-CoV-2 infection, affecting approximately 10% to over 30% of those infected. It presents a significant clinical challenge, notably due to pronounced neurocognitive symptoms such as brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing to a central role of cerebromicrovascular dysfunction. This review investigates key pathophysiological mechanisms contributing to cerebrovascular dysfunction in long COVID and their impacts on brain health. We discuss how endothelial tropism of SARS-CoV-2 and direct vascular infection trigger endothelial dysfunction, impaired neurovascular coupling, and blood-brain barrier disruption, resulting in compromised cerebral perfusion. Furthermore, the infection appears to induce mitochondrial dysfunction, enhancing oxidative stress and inflammation within cerebral endothelial cells. Autoantibody formation following infection also potentially exacerbates neurovascular injury, contributing to chronic vascular inflammation and ongoing blood-brain barrier compromise. These factors collectively contribute to the emergence of white matter hyperintensities, promote amyloid pathology, and may accelerate neurodegenerative processes, including Alzheimer's disease. This review also emphasizes the critical role of advanced imaging techniques in assessing cerebromicrovascular health and the need for targeted interventions to address these cerebrovascular complications. A deeper understanding of the cerebrovascular mechanisms of long COVID is essential to advance targeted treatments and mitigate its long-term neurocognitive consequences.

To determine the incidence of VTE and clinical outcomes in a cohort of cancer patients and COVID-19 infection, and to establish possible predictive factors of VTE.

A single-center retrospective cohort study was performed to determine the incidence of VTE and mortality in 118 cancer patients with SARS-CoV-2 infection from March to August 2020. We calculated individual Khorana Risk and CATS-MICA scores in order to evaluate their utility to identify risk of VTE or death. Continuous variables were compared using Wilcoxon or Student's T test, and categorical variables were compared using the Chi-Square or Fisher's exact text among patients with and without VTE. A Log-Rank test was performed to detect mortality differences between the groups.

A total of 118 patients were included. VTE global incidence was 4.2% (n = 5), and mortality 25.4% (n = 30). Obesity (p = 0.05), recent chemotherapy (p = 0.049) and use of steroids (p = 0.006) were related to higher risk of VTE in the univariate analysis, although they were not confirmed in the multivariate analysis as independent risk factors. Statistically significant differences in all-cause, COVID-19-related and cancer-related mortality according to the Khorana risk score (KRS) were observed. CATS-MICA score (CMS) also showed statistically significant differences in mortality between low- and high-risk patients. Prediction of risk of VTE development with these scores showed a tendency towards significance.

In this cohort, VTE incidence was similar to previously reported in the general population with SARS-CoV-2 infection. KRS was associated with overall and specific-cause mortality, and might be a useful prognostic tool in this setting.

During the COVID-19 pandemic, several observational studies proved a certain efficacy of nutraceuticals, herbal products, and other dietary supplements as adjuvant therapies used alongside antiviral drugs. Although their use has not been widespread in Italy, according to preliminary evidence, many supplements with demonstrated immunomodulatory effects, such as vitamins C and D, herbal medicines and essential oils, might relieve the respiratory symptoms of COVID-19, since SARS-CoV-2 can activate inflammasome-mediated inflammatory signaling pathways. Other observational studies have shown that herbal treatments, such as Echinacea purpurea and ginseng, help alleviate respiratory symptoms and reduce serum levels of inflammatory cytokines, which are typically overexpressed in both adult and pediatric SARS-CoV-2 patients. Further, vitamins C and D can attenuate the immune response thanks to their cytokine suppression ability and to their known antimicrobial activity and potential to modulate T helper cell response. The strong immune response triggered by SARS-CoV-2 infection is responsible for the severity of the disease. Preliminary data have also shown that L-arginine, an endothelial-derived relaxing factor, is able to modulate endothelial damage, which appears to be one of the main targets of this systemic disease. Finally, some essential oils and their isolated compounds, such as eucalyptol, may be helpful in reducing many of the respiratory symptoms of COVID-19, although others, such as menthol, are not recommended, since it can lead to an undervaluation of the clinical status of a patient. In this narrative review, despite the lack of strong evidence in this field, we aimed to give an overview of the current available literature (mainly observational and cross-sectional studies) regarding herbal products and dietary supplements and their use in the treatment of mild disease from SARS-CoV-2 infection. Obviously, dietary supplements and herbal products do not constitute a standardized treatment for COVID-19 disease, but they could represent an adjunctive and useful treatment when used together with antivirals.

To determine if preoperative infection with COVID-19 increased risk for postoperative venous thromboembolism (VTE) in patients undergoing arthroscopic knee surgery.

PearlDiver Mariner 165 database was queried for patients undergoing knee arthroscopy between 2010 and October 2022. Patients were categorized by history of COVID-19 diagnosis and timing in relation to surgery. Multivariate logistic regression was performed to isolate the effect of COVID-19 diagnosis on postoperative VTE rates. Covariates included age, obesity, smoking, oral contraceptive pill use, hypertension, coronary artery disease, congestive heart failure, malignancy, renal disease, and diabetes.

A total of 954,294 patients met inclusion criteria, and 7,637 patients experienced VTE, including deep vein thrombosis (n = 5,830, 0.61%) and pulmonary embolism (n = 2,790, 0.29%). Patients with a COVID-19 diagnosis before surgery (7,858) had an overall higher incidence of VTE (1.72%) compared to patients without a preoperative COVID-19 diagnosis (0.81%) (P < .001). There was no difference in VTE incidence among patients with a preoperative COVID-19 diagnosis undergoing knee arthroscopy in the pre- and post-COVID-19 vaccination eras (odds ratio, 0.82; 95% CI, 0.51-1.31; P = .48). Multivariate regression accounting for covariates showed that patients with a preoperative COVID-19 diagnosis within 6 weeks before arthroscopy had significantly increased odds of experiencing postoperative VTE (odds ratio, 1.68; 95% CI, 1.09-2.45; P = .012). There was no significant difference in VTE risk among patients with a preoperative COVID-19 diagnosis between 6 and 12 weeks before arthroscopy and more than 12 weeks before arthroscopy compared to those with no prior COVID-19 diagnosis.

COVID-19 diagnosis within 6 weeks preceding arthroscopic knee surgery leads to a significantly higher risk for postoperative VTE.

Level III, retrospective case control study.

We aimed to investigate the incidence of new acute myocardial infarction (AMI), in patients with Coronavirus disease (COVID-19) who had old MI. We hypothesized that COVID-19 increases the rate of repeated AMI in this population regardless of age and gender.

A retrospective analysis was conducted for adult patients admitted with COVID-19 and developed thromboembolic event (TEE) in 2020. Patients were categorized based on the history of old MI, new MI, age, and gender.

Among 16,903 patients with COVID-19 who were admitted, 210 (1.2%) developed TEE (89% were males, 55% were <55 years old, and 80.5% had an old MI). COVID-19 was severe in 32% of cases. AMI occurred in 160 patients (42.5% STEMI and 57.5% NSTEMI). In patients with prior MI, 92.5% developed another AMI. NSTEMI was higher in patients with severe COVID-19 than STEMI (33% vs 21%). Patients with severe COVID-19 had higher mortality (39.4% vs 5.6%), fewer rates of prior MI (74% vs 83%), hypertension (40% vs 60%), and STEMI (31.8% vs 46.5%) than mild COVID-19 patients. On multivariable analysis, COVID-19 severity was an independent predictor of mortality (OR10; 95%CI 1.62-67.19) after adjustment for age, gender, diabetes mellitus, C-reactive protein, serum Ferritin, Procalcitonin, and Fibrinogen values, and prior or new MI.

Patients with old MI could develop a new AMI in 80% of COVID-19. However, the mortality was higher in patients without a history of MI due to the severity of COVID-19. Attention should be given to patients who possess thrombotic risk factors in pandemics.

Stroke remains a predominant cause of mortality and accounts for one-third of all stroke-related fatalities worldwide. Increasing expenses associated with stroke are a matter of significant concern; however, this aspect has been insufficiently examined.

The purpose of this study was to analyze in-hospital stroke costs and explore potential factors influencing them across stroke subtypes. The records of stroke patients from 50 hospitals in southeastern China between 2019 and 2022 were reviewed using multistage stratified cluster random sampling. We focused on the cost patterns of four stroke types and used multivariate linear regression to identify cost determinants.

A total of 417 (1.1%) patients had subarachnoid hemorrhage (SAH), 9309 (25.9%) had intracerebral hemorrhage (ICH), 22,248 (61.8%) had ischemic stroke (IS), and 4025 had transient ischemic attack (TIA). The number of stroke patients has sharply increased since the onset of COVID-19, with a majority of them being male (72.2%). Despite the fact that hospitalization costs are highest in tertiary hospitals (Chinese yuan [CNY] 30610.8/United States dollar [USD] 4551.0, interquartile range [IQR] 9944.9, 29668.4/1478.6, 4410.9), the majority of patients are admitted to tertiary hospitals (74.6%) or public hospitals (90.2%). Across all stroke subtypes, patients with SAH had the highest costs (CNY 93,454.9/USD13894.4, IQR 12273.2, 169920.0/1824.7, 25262.8), followed by those with ICH (CNY 48,724.2/USD 7244.0, IQR 16789.6, 57540.7/2496.2, 8554.8), IS (CNY 26,550.3/USD3947.4, IQR 8684.2, 28697.7/1291.1, 4266.6), and TIA (CNY 11,170.1/USD1660.7, IQR 6823.7, 12965.2/1014.5, 1927.6). Therapy fees comprised a significant portion of costs in ICH and IS cases (47.9% and 42.7%, respectively). Materials accounted for the highest proportion of expenses for SAH (56.1%), whereas patients with TIA spent more time on examinations (34.1%). Linear regression analysis revealed that length of stay (LOS), stroke subtype, hospital level, and stroke type were key factors influencing hospitalization costs.

The visiting rate and charges were highest in tertiary public hospitals, and hospitalization costs were higher in hemorrhagic types of stroke than in ischemic types of stroke; the proportion of hospitalization cost categories varied among different types of stroke, with LOS, hospital type, and level substantially affecting hospitalization costs. Enhancing medical insurance reimbursement rates for hemorrhagic strokes, implementing a hierarchical medical system, tailoring cost categories to accommodate varying stroke subtypes, and shortening LOS may help alleviate the economic burden of stroke.

The Spanish Society of Medical Oncology (SEOM) last published clinical guidelines on venous thromboembolism (VTE) and cancer in 2019, with a partial update in 2020. In this new update to the guidelines, SEOM seeks to incorporate recent evidence, based on a critical review of the literature, to provide practical current recommendations for the prophylactic and therapeutic management of VTE in patients with cancer. Special clinical situations whose management and/or choice of currently recommended therapeutic options (low-molecular-weight heparins [LMWHs] or direct-acting oral anticoagulants [DOACs]) is controversial are included.

Pulmonary embolism is a complication of COVID-19 infection. The aim of this study is to assess prognosis and treatment response, including incidences of chronicity, relapse, and mortality among outpatients diagnosed with COVID-19-related pulmonary embolism between 2020 and 2022. A total of 101 patients with pulmonary embolism, started on anticoagulation during or within a month of COVID-19 infection, were included after testing positive by PCR. Data about comorbidities, Pulmonary Embolism Severity Index scores, PE diagnostic modalities, biochemical parameters, and transthoracic echocardiographic findings at diagnosis and at 24-month follow-up were collected. Cardiac catheterization parameters were recorded and compared between groups at diagnosis and at the 24-month follow-up. Groups were comparable with respect to gender, age, body mass index, and comorbidity score. Use of Q-SPECT for diagnosis was found significantly higher in patients with COVID-19-related pulmonary embolism (P < .001). The incidence of deep vein thrombosis was similar. In the study group, 43.6% of patients received anticoagulants for 3 months, with 49.1% using low molecular weight heparin and 50.9% using direct oral anticoagulants. At 24 months, rate of patients continuing treatment was comparable between groups. Specific pulmonary artery blockage value was found to be higher in patients with chronic thromboembolic pulmonary hypertension compared to those who demonstrated a response to pulmonary embolism treatment (P = .009). No adverse effects of anticoagulant therapy were observed during course of treatment. Over 24-month follow-up period, mortality, relapse, chronic thromboembolic hypertension and thromboembolic disease was observed in 2%, 2.2%, 4.9%, and 9.9% of patients, respectively.

Coronavirus disease 2019 (COVID-19) is known to increase the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE). However, the incidence, predictors, and outcomes of clinical thrombosis for inpatients with COVID-19 are not well known. This study aimed to enhance our understanding of clinical thrombosis in COVID-19, its associated factors, and mortality outcomes.

Hospitalised adult (≥18 years of age) patients with COVID-19 in 2020 were retrospectively identified from the US National Inpatient Sample database. Clinical characteristics, incident VTE, ATE, and in-hospital mortality outcomes were recorded. Multivariable logistic regression was performed to identify clinical factors associated with thrombosis and in-hospital mortality in COVID-19 inpatients.

A total of 1,583,135 adult patients with COVID-19 in the year 2020 were identified from the National Inpatient Sample database; patients with thrombosis were 41% females with a mean age of 65.4 (65.1-65.6) years. The incidence of thrombosis was 6.1% (97,185), including VTE at 4.8% (76,125), ATE at 3.0% (47,790), and the in-hospital mortality rate was 13.4% (212,785). Patients with thrombosis were more likely to have respiratory symptoms of COVID-19 (76.7% vs 75%, p<0.001) compared with patients without thrombosis. The main factors associated with overall thrombosis, VTE, and ATE were paralysis, ventilation, solid tumours without metastasis, metastatic cancer, and acute liver failure. Although all thrombosis categories were associated with higher in-hospital mortality for COVID-19 inpatients in univariable analyses (p<0.001), they were not in multivariable analyses-thrombosis (odds ratio [OR] 1.24; 95% confidence interval [CI] 0.90-1.70; p=0.19), VTE (OR 0.70; 95% CI 0.52-1.00; p=0.05), and ATE (OR 1.07; 95% CI 0.92-1.25; p=0.36).

The association of COVID-19 with thrombosis and VTE increases with increasing severity of the COVID-19 disease. Risk stratification of thrombosis is crucial in COVID-19 patients to determine the necessity of thromboprophylaxis.

Despite medical interventions, COVID-19 continues to persist at pandemic proportions. A hypercoagulation state was rapidly observed in the severely ill, and the incidence of thromboembolic events remains elevated. Interleukin inhibitors have demonstrated positive effects on the hyperactivation of the immune system in COVID-19, with the interleukin-6 inhibitor tocilizumab showing promising results in reducing mortality. Nevertheless, the impact of interleukin inhibitors on the coagulation system remains incompletely understood.

In this clinical trial conducted in Stockholm, Sweden, interleukin inhibitors, namely anakinra (ANA) or tocilizumab (TOCI), were randomly administered in addition to standard care (SC) to hospitalized patients with COVID-19. A control group received only SC. The primary outcome sought to measure effects on global hemostasis, as indicated by changes in functional coagulation tests, specifically Rotational Thromboelastometry (ROTEM) or Overall Hemostatic Potential (OHP), visualized through scanning electron microscopy images. Secondary outcomes included effects on conventional coagulation laboratory tests.

The study enrolled 74 patients who were randomized to receive either ANA or TOCI in addition to SC, or SC alone. In the TOCI group, ROTEM variables exhibited less hypercoagulation after 29 days compared with ANA or SC treatment groups, characterized by prolonged clot formation time and decreased clot firmness. OHP decreased, but there were no significant differences among the three treatment groups. Plasma fibrinogen levels, initially elevated, decreased significantly in TOCI recipients over time.

Tocilizumab treatment demonstrated a significant reduction of hypercoagulation in hospitalized COVID-19 patients, by improvements in both global coagulation tests and conventional laboratory tests, in comparison with anakinra or SC alone. This finding underscores the significance of tocilizumab as a viable treatment option in severe COVID-19 cases, with the potential to decrease thrombosis incidence.

SARS-CoV-2 (COVID-19) infection and multisystem inflammatory syndrome in children (MIS-C) are risk factors for venous thromboembolism (VTE). Guidelines for VTE prophylaxis were established at our institution at the beginning of the pandemic. Patients who had any VTE risk factors in addition to COVID-19 met criteria for anticoagulation prophylaxis. Patients who were diagnosed with MIS-C met criteria regardless of additional risk factors.

We conducted a retrospective review of patients admitted with COVID-19 or MIS-C to determine compliance with VTE prophylaxis guidelines and to evaluate the incidence of VTE and bleeding events in our population.

Among a total of 678 patients admitted with COVID-19 or MIS-C, 519 (76 %) patients met criteria for VTE prophylaxis and 348 (65.6 %) started prophylaxis. Logistic regression analysis identified a personal or family history of thrombosis or thrombophilia, diagnosis of MIS-C, admission to the intensive care unit, and presence of a central venous catheter as significantly associated with starting VTE prophylaxis. There were 18 patients who developed VTE. Minor bleeding events occurred in 19 patients (5 %), patient important bleeding, no intervention occurred in 8 patients (2 %), clinically relevant nonmajor bleeding in 8 patients (2 %), and major bleeding in 10 patients (3 %). The incidence of VTE in our patients with COVID-19 and MIS-C is similar to VTE rates at other institutions. We found that universally recognized VTE risk factors were appropriate to include as risk factors for thrombosis in hospitalized children with COVID-19 and MIS-C.

Blood coagulation dysfunction is a risk factor for adverse outcomes in patients with coronavirus disease 2019 (COVID-19), especially in severe cases. The evidence for the effects of anticoagulation therapy on prognosis of COVID-19 patients and its risk of causing bleeding events is accumulating. Here we conducted a meta-analysis to assess the efficacy and safety of anticoagulants in COVID-19 patients of different severity.

We searched PubMed, Embase databases, Cochrane Trials, OVID MEDLINE from December 2019 to April 2023. We included randomized controlled trials (RCTs) involving COVID-19 patients over 18 years of age, which explored the effect of anticoagulant and its dose on outcomes including all-cause mortality, bleeding events or thrombotic events. We calculated the risk ratio (RR) and its 95% confidence interval (CI) for each outcome. We also performed subgroup analyses to assess the impact of disease severity, using a fixed-effect model to test for heterogeneity. The risk of bias, publication bias, and the quality of evidence were also evaluated.

A total of 20 RCTs were included for final analysis. When compared with standard care, anticoagulation treatment reduced all-cause mortality (RR 0.47, 95% CI: 0.29-0.76) and thrombotic events (RR 0.35, 95% CI: 0.15-0.83) in the whole population with COVID-19 (n=2,365), without increase in bleeding events (total: RR 1.47, 95% CI: 0.54-4.00). Most of the studies only enrolled non-severe patients (n=2,329), while the number of severe patients (n=36) was scarce. In RCTs compared therapeutical and prophylactic doses of anticoagulants, no significant difference in on all-cause mortality was found in the whole population and non-severe and severe subgroups (total: RR 1.01, 95% CI: 0.92-1.10; non-severe: RR 1.03, 95% CI: 0.81-1.32; severe: RR 1.00, 95% CI: 0.91-1.11). Therapeutical dose reduced risk of thrombotic events (total: RR 0.59, 95% CI: 0.48-0.73; subtotal of non-severe: RR 0.57, 95% CI: 0.39-0.84; Subtotal of severe: RR 0.61, 95% CI: 0.47-0.78), while risk of bleeding was increased (total: RR 1.98, 95% CI: 1.47-2.66; non-severe: RR 2.38, 95% CI: 1.56-3.62; severe: RR 1.63, 95% CI: 1.07-2.47). Study heterogeneity was found only in the analysis of effects of anticoagulants on risk of thrombotic events.

Anticoagulant therapy reduces all-cause mortality and risk of thrombosis in non-severe COVID-19 patients. Therapeutic dose of anticoagulant therapy can be considered in both non-severe and severe COVID-19 patients to reduce thrombosis, but may be associated with increased bleeding events.

The high prevalence of deep vein thrombosis (DVT) in patients admitted to intensive care unit (ICU) for COVID-19-related acute respiratory distress syndrome (ARDS) would justify systematic screening of these patients or higher therapeutic dose of heparin for thromboprophylaxis.

We performed a systematic echo-Doppler of the lower limb proximal veins during the first 48 h (visit 1) and from 7 to 9 days after visit 1 (visit 2) in consecutive patients admitted to the ICU of a university-affiliated tertiary hospital for severe proven COVID-19 during the second wave. All patients received intermediate-dose heparin (IDH). The primary objective was to determine DVT incidence on venous Doppler ultrasound. Secondary objectives were to determine whether the presence of DVT modifies the anticoagulation regimen, the incidence of major bleeding according to International Society on Thrombosis and Haemostasis (ISTH) criteria, and the mortality rate of patients with and without DVT.

We included 48 patients (30 [62.5%] men) with a median age of 63 years [IQR, 54-70]. The prevalence of proximal deep vein thrombosis was 4.2% (2/48). In these two patients, after DVT diagnosis, anticoagulation was changed from intermediate to curative dose. Two patients (4.2%) had a major bleeding complication according to ISTH criteria. Among the 48 patients, 9 (18.8%) died before hospital discharge. No DVT or pulmonary embolism was diagnosed in these deceased patients during their hospital stay.

In critically ill patients with COVID-19, management with IDH results in a low incidence of DVT. Although our study is not designed to demonstrate any difference in outcome, our results do not suggest any signal of harm when using intermediate-dose heparin (IDH) COVID-19 with a frequency of major bleeding complications less than 5%.

Coagulopathy and thromboembolic events are associated with poor outcomes in coronavirus disease 2019 (COVID-19) patients. There is conflicting evidence on the effects of chronic anticoagulation on mortality and severity of COVID-19 disease.

To summarize the body of evidence on the effects of pre-hospital anticoagulation on outcomes in COVID-19 patients.

A Literature search was performed on LitCovid PubMed, WHO, and Scopus databases from inception (December 2019) till June 2023 for original studies reporting an association between prior use of anticoagulants and patient outcomes in adults with COVID-19. The primary outcome was the risk of thromboembolic events in COVID-19 patients taking anticoagulants. Secondary outcomes included COVID-19 disease severity, in terms of intensive care unit admission or invasive mechanical ventilation/intubation requirement in patients hospitalized with COVID-19 infection, and mortality. The random effects models were used to calculate crude and adjusted odds ratios (aORs) with 95% confidence intervals (95%CIs).

Forty-six observational studies met our inclusion criteria. The unadjusted analysis found no association between prior anticoagulation and thromboembolic event risk [n = 43851, 9 studies, odds ratio (OR)= 0.67 (0.22, 2.07); P = 0.49; I 2 = 95%]. The association between prior anticoagulation and disease severity was non-significant [n = 186782; 22 studies, OR = 1.08 (0.78, 1.49); P = 0.64; I 2 = 89%]. However, pre-hospital anticoagulation significantly increased all-cause mortality risk [n = 207292; 35 studies, OR = 1.72 (1.37, 2.17); P < 0.00001; I 2 = 93%]. Pooling adjusted estimates revealed a statistically non-significant association between pre-hospital anticoagulation and thromboembolic event risk [aOR = 0.87 (0.42, 1.80); P = 0.71], mortality [aOR = 0.94 (0.84, 1.05); P = 0.31], and disease severity [aOR = 0.96 (0.72, 1.26); P = 0.76].

Prehospital anticoagulation was not significantly associated with reduced risk of thromboembolic events, improved survival, and lower disease severity in COVID-19 patients.

Angiotensin-converting enzyme 2 receptors (ACE2R) are requisite to enter the host cells for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). ACE2R is constitutive and functions as a type I transmembrane metallo-carboxypeptidase in the renin-angiotensin system (RAS). On thyroid follicular cells, ACE2R allows SARS-CoV-2 to invade the thyroid gland, impose cytopathic effects and produce endocrine abnormalities, including stiff back, neck pain, muscle ache, lethargy, and enlarged, inflamed thyroid gland in COVID-19 patients. Further damage is perpetuated by the sudden bursts of pro-inflammatory cytokines, which is suggestive of a life-threatening syndrome known as a "cytokine storm". IL-1β, IL-6, IFN-γ, and TNF-α are identified as the key orchestrators of the cytokine storm. These inflammatory mediators upregulate transcriptional turnover of nuclear factor-kappa B (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and mitogen-activated protein kinase (MAPK), paving the pathway for cytokine storm-induced thyroid dysfunctions including euthyroid sick syndrome, autoimmune thyroid diseases, and thyrotoxicosis in COVID-19 patients. Targeted therapies with corticosteroids (dexamethasone), JAK inhibitor (baricitinib), nucleotide analogue (remdesivir) and N-acetyl-cysteine have demonstrated effectiveness in terms of attenuating the severity and frequency of cytokine storm-induced thyroid dysfunctions, morbidity and mortality in severe COVID-19 patients. Here, we review the pathogenesis of cytokine storms and the mechanisms and pathways that establish the connection between thyroid disorder and COVID-19. Moreover, cross-talk interactions of signalling pathways and therapeutic strategies to address COVID-19-associated thyroid diseases are also discussed herein.

We compared the risks and benefits of COVID-19 vaccines using a causal pathway analysis to weigh up possible risk factors of thromboembolic events post-vaccination. The self-controlled case series (SCCS) method examined the association between thromboembolic events and vaccination while a case-control study assessed the association between thromboembolic events and COVID-19, addressing under-reported infection data issues. The net vaccine effect was estimated using results from SCCS and case-control studies. We used electronic health record data from Corewell Health (16,640 subjects in SCCS and 106,143 in case-control). We found increased risks of thromboembolic events post-vaccination (incidence rate ratio: 1.19, 95% CI: [1.08, 1.31] after the first dose; 1.22, 95% CI: [1.11, 1.34] after the second dose). Vaccination attenuated infection-associated thromboembolic risks (odds ratio: 4.65, 95% CI: [4.18, 5.17] in unvaccinated vs 2.77, 95% CI: [2.40, 3.24] in vaccinated). After accounting for vaccine efficacy and protection against infection-associated thromboembolic events, vaccination decreases thromboembolic event risk, especially during high infection rate periods.

Venous thromboembolism (VTE) is a common, deadly disease with an increasing incidence despite preventive efforts. Clinical observations have associated elevated antibody concentrations or antibody-based therapies with thrombotic events. However, how antibodies contribute to thrombosis is unknown. Here, we show that reduced blood flow enabled immunoglobulin M (IgM) to bind to FcμR and the polymeric immunoglobulin receptor (pIgR), initiating endothelial activation and platelet recruitment. Subsequently, the procoagulant surface of activated platelets accommodated antigen- and FcγR-independent IgG deposition. This leads to classical complement activation, setting in motion a prothrombotic vicious circle. Key elements of this mechanism were present in humans in the setting of venous stasis as well as in the dysregulated immunothrombosis of COVID-19. This antibody-driven thrombosis can be prevented by pharmacologically targeting complement. Hence, our results uncover antibodies as previously unrecognized central regulators of thrombosis. These findings carry relevance for therapeutic application of antibodies and open innovative avenues to target thrombosis without compromising hemostasis.

COVID-19 can cause profound inflammation and coagulopathy, and while many mechanisms have been proposed, there is no known common pathway leading to a prothrombotic state.

From the beginning of the COVID-19 pandemic, elevated levels of extracellular histones have been found in plasma of patients infected with SARS-CoV-2. We hypothesized that platelet activation triggered by extracellular histones might represent a unifying mechanism leading to increased thrombin generation and thrombosis.

We utilized blood samples collected from an early clinical trial of hospitalized COVID-19 patients (NCT04360824) and recruited healthy subjects as controls. Using plasma samples, we measured the procoagulant and prothrombotic potential of circulating extracellular histones and extracellular vesicles (EVs). Platelet prothrombotic activity was assessed via thrombin generation potential and platelet thrombus growth. Circulating EVs were assessed for thrombin generation potential in vitro in plasma and enhancement of thrombotic susceptibility in vivo in mice.

Compared with controls, COVID-19 patients had elevated plasma levels of citrullinated histone H3, cell-free DNA, nucleosomes, and EVs. Plasma from COVID-19 patients promoted platelet activation, platelet-dependent thrombin generation, thrombus growth under venous shear stress, and release of platelet-derived EVs. These prothrombotic effects of COVID-19 plasma were inhibited by an RNA aptamer that neutralizes both free and DNA-bound histones. EVs isolated from COVID-19 plasma enhanced thrombin generation in vitro and potentiated venous thrombosis in mice in vivo.

We conclude that extracellular histones and procoagulant EVs drive the prothrombotic state in COVID-19 and that histone-targeted therapy may prove beneficial.

To investigate the prevalence of cerebrovascular MRI markers in unselected patients hospitalized for COVID-19 (Coronavirus disease 2019), we compared these with healthy controls without previous SARS-CoV-2 infection or hospitalization and subsequently, investigated longitudinal (incidental) lesions in patients after three months.

CORONIS (CORONavirus and Ischemic Stroke) was an observational cohort study in adult hospitalized patients for COVID-19 and controls without COVID-19, conducted between April 2021 and September 2022. Brain MRI was performed shortly after discharge and after 3 months. Outcomes included recent ischemic (DWI-positive) lesions, previous infarction, microbleeds, white matter hyperintensities (WMH) and intracerebral hemorrhage and were analysed with logistic regression to adjust for confounders.

125 patients with COVID-19 and 47 controls underwent brain MRI a median of 41.5 days after symptom onset. DWI-positive lesions were found in one patient (1%) and in one (2%) control, both clinically silent. WMH were more prevalent in patients (78%) than in controls (62%) (adjusted OR: 2.95 [95% CI: 1.07-8.57]), other cerebrovascular MRI markers did not differ. Prevalence of markers in ICU vs. non-ICU patients was similar. After three months, five patients (5%) had new cerebrovascular lesions, including DWI-positive lesions (1 patient, 1.0%), cerebral infarction (2 patients, 2.0%) and microbleeds (3 patients, 3.1%).

Overall, we found no higher prevalence of cerebrovascular markers in unselected hospitalized COVID-19 patients compared to controls. The few incident DWI-lesions were most likely to be explained by risk-factors of small vessel disease. In the general hospitalized COVID-19 population, COVID-19 shows limited impact on cerebrovascular MRI markers shortly after hospitalization.

We investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic.

This retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records.

The overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41-6.54, p = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63-6.63, p < 0.001) emerged as independent risk factors for early MG exacerbation.

Generally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended.

In patients with severe acute respiratory syndrome coronavirus 2 (which causes coronavirus disease 2019 [COVID-19]), oxidative stress (OS) is associated with disease severity and death. OS is also involved in the pathogenesis of atherosclerosis (AS). Previous studies have shown that geniposide has anti-inflammatory and anti-viral properties, and can protect cells against OS. However, the potential target(s) of geniposide in patients with COVID-19 and AS, as well as the mechanism it uses, are unclear. We combined pharmacology and bioinformatics analysis to obtain geniposide against COVID-19/AS targets, and build protein-protein interaction network to filter hub genes. The hub genes were performed an enrichment analysis by ClueGO, including Gene Ontology and KEGG. The Enrichr database and the target microRNAs (miRNAs) of hub genes were predicted through the MiRTarBase via Enrichr. The common miRNAs were used to construct the miRNAs-mRNAs regulated network, and the miRNAs' function was evaluated by mirPath v3.0 software. Two hundred forty-seven targets of geniposide were identified in patients with COVID-19/AS comorbidity by observing the overlap between the genes modulated by geniposide, COVID-19, and AS. A protein-protein interaction network of geniposide in patients with COVID-19/AS was constructed, and 27 hub genes were identified. The results of enrichment analysis suggested that geniposide may be involved in regulating the OS via the FoxO signaling pathway. MiRNA-mRNA network revealed that hsa-miR-34a-5p may play an important role in the therapeutic mechanism of geniposide in COVID-19/AS patients. Our study found that geniposide represents a promising therapy for patients with COVID-19 and AS comorbidity. Furthermore, the target genes and miRNAs that we identified may aid the development of new treatment strategies against COVID-19/AS.

We present a case of an unvaccinated, 43-year-old African American female patient with COVID-19 infection and clinical evidence of a left hemispheric stroke. A non-occlusive thrombus with a radiographic target lesion was identified on computed tomography angiography (CTA). A multi-disciplinary discussion regarding concern for embolization was provided due to its unstable nature, as well as evidence of recent stroke. Given her acute COVID-19 infection, symptomatology, and radiographic findings, it was concluded that the etiology of her stroke appeared most consistent with a hypercoagulable-related embolism rather than an atheroembolic event. The patient underwent left carotid artery thrombectomy with bovine patch angioplasty. Operative findings included: left carotid thrombus, minimal plaque after evacuation of the thrombus, and a small proximal internal carotid artery diameter. Given concern for stenosis with primary repair a bovine pericardial patch angioplasty was performed. We present a paradigm for extracranial carotid thrombectomy with therapeutic anticoagulation for COVID-related spontaneous arterial thrombosis.