Reperfusion therapies in patients with acute ischaemic stroke and atrial fibrillation: data on safety and effectiveness from a multi-centre cohort study.

BACKGROUND: Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies. METHODS: Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients. RESULTS: Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11-2.31). CONCLUSIONS: Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment.

The Clinical Impact of the Pulmonary Embolism Severity Index on the Length of Hospital Stay of Patients with Pulmonary Embolism: A Randomized Controlled Trial.

BACKGROUND: The Pulmonary Embolism Severity Index (PESI) is an extensively validated prognostic score, but impact analyses of the PESI on management strategies, outcomes and health care costs are lacking. Our aim was to assess whether the adoption of the PESI for patients admitted to an internal medicine ward has the potential to safely reduce the length of hospital stay (LOS). METHODS: We carried out a multicenter randomized controlled trial, enrolling consecutive adult outpatients diagnosed with acute PE and admitted to an internal medicine ward. Within 48 h after diagnosis, the treating physicians were randomized, for every patient, to calculate and report the PESI in the clinical record form on top of the standard of care (experimental arm) or to continue routine clinical practice (standard of care). The ClinicalTrials.gov identifier is NCT03002467. RESULTS: This study was prematurely stopped due to slow recruitment. A total of 118 patients were enrolled at six internal medicine units from 2016 to 2019. The treating physicians were randomized to the use of the PESI for 59 patients or to the standard of care for 59 patients. No difference in the median LOS was found between the experimental arm (8, IQR 6-12) and the standard-of-care arm (8, IQR 6-12) (p = 0.63). A pre-specified secondary analysis showed that the LOS was significantly shorter among the patients who were treated with DOACs (median of 8 days, IQR 5-11) compared to VKAs or heparin (median of 9 days, IQR 7-12) (p = 0.04). CONCLUSIONS: The formal calculation of the PESI in the patients already admitted to internal medicine units did not impact the length of hospital stay.

No contraindication to internal jugular central venous catheter insertion in patients at increased risk of bleeding: Results from a prospective observational study in a internal medicine department.

Implantation of centrally inserted central venous catheter (CICC) may be complicated by bleedings particularly in patients with severe coagulopathy or taking antithrombotic drugs. It has been shown that the application of the Italian Group for Venous Access Devices (GAVeCeLT) bundle reduces the incidence of bleeding in patients admitted to intensive care units (ICU), but its effectiveness has never been demonstrated in different contexts. In this study we evaluated the incidence of bleeding after urgent internal jugular CICC (J-CICC) implantation in patients with increased or no risk of bleeding complications when recommended preventive strategies are applied systematically. We included 185 patients admitted to Internal Medicine Units who underwent urgent J-CICC implantation from April 2016 to December 2018. The incidence of major and minor bleeding immediately after the procedure and in the following 30 days was recorded. None of the enrolled patients showed major bleeding. The incidence of minor bleedings was 2.1% (95% IC: 0.03-4.2) with two patients requiring line removal and repositioning (1.1%; 95% IC: -0.45 to 2.6). Bleeds were not correlated with age or sex, although they all occurred in female subjects. The incidence of bleeds was not increased in patients with increased risk of bleeding compared with those without (5.0% vs 1.3%; p = 0.16). The use of anti-thrombotic medications was significantly associated with increased risk of minor bleedings (p = 0.03). In this study we demonstrated that the application of the GAVeCeLT suggested bundle can minimize the number of bleeding complications even in patients hospitalized in Internal Medicine Units. Further data are needed in patients taking antithrombotic drugs who appear to be more prone to minor bleeding, however the benefit of completing the procedure appears to significantly outweigh the risk of mechanical complications.

The Use of Risk Scores for Thromboprophylaxis in Medically Ill Patients-Rationale and Design of the RICO trial.

Background Venous thromboembolism (VTE) in hospitalized medically ill patients is a significant cause of morbidity and mortality. Guidelines suggest that VTE and bleeding risk assessment models (RAMs) should be integrated into the clinical decision-making process on thromboprophylaxis. However, poor evidence is available comparing the use of a RAM versus clinical judgement in evaluating VTE and bleeding occurrence. Methods Reducing Important Clinical Outcomes in hospitalized medical ill patients (RICO) is a multicenter, cluster-randomized, controlled clinical trial (ClinicalTrials.gov Identifier: NCT04267718). Acutely ill patients hospitalized in Internal Medicine wards are randomized to the use of RAMs-namely the Padua Prediction Score and the International Medical Prevention Registry on Venous Thromboembolism Bleeding Score-or to clinical judgement. The primary study outcome is a composite of symptomatic objectively confirmed VTE and major bleeding at 90-day follow-up. Secondary endpoints include the evaluation of clinical outcomes at hospital discharge and the assessment of VTE prophylaxis prescription during the study period. In order to demonstrate a 50% reduction in the primary outcome in the experimental group and assuming an incidence of the primary outcome of 3.5% in the control group at 90-day; 2,844 patients across 32 centers will be included in the study. Discussion The RICO trial is a randomized study of clinical management assessing the role of RAMs in hospitalized medical ill patients with the aim of reducing VTE and bleeding occurrence. The study has the potential to improve clinical practice since VTE still represents an important cause of morbidity and mortality in this setting.

A new score to predict Clostridioides difficile infection in medical patients: a sub-analysis of the FADOI-PRACTICE study.

Medical divisions are at high risk of Clostridioides difficile infection (CDI) due to patients' frailty and complexity. This sub-analysis of the FADOI-PRACTICE study included patients presenting with diarrhea either at admission or during hospitalization. CDI diagnosis was confirmed when both enzyme immunoassay and A and B toxin detection were found positive. The aim of this sub-analysis was the identification of a new score to predict CDI in hospitalized, medical patients. Five hundred and seventy-two patients with diarrhea were considered. More than half of patients was female, 40% on antibiotics in the previous 4 weeks and 60% on proton pump inhibitors (PPIs). CDI diagnosis occurred in 103 patients (18%). Patients diagnosed with CDI were older, more frequently of female sex, recently hospitalized and bed-ridden, and treated with antibiotics and PPIs. Through a backward stepwise logistic regression model, age > 65 years, female sex, recent hospitalization, recent antibiotic therapy, active cancer, prolonged hospital stay (> 12 days), hypoalbuminemia (albumin < 3 g/dL), and leukocytosis (white blood cells > 9 × 10^9/L) were found to independently predict CDI occurrence. These variables contributed to building a clinical prognostic score with a good sensitivity and a modest specificity for a value > 3 (79% and 58%, respectively; AUC 0.75, 95% CI 0.71-0.79, p < 0.001), that identified low-risk (score ≤ 3; 42.5%) and high-risk (score > 3; 57.5%) patients. Although some classical risk factors were confirmed to increase CDI occurrence, the changing landscape of CDI epidemiology suggests a reappraisal of common risk factors and the development of novel risk scores based on local epidemiology.

Effectiveness, Safety, and Acceptance of an Interim Orthosis in Patients with Diabetes in the Immediate Postoperative Chopart Surgery.

Chopart amputation is the consequence of severe diabetes-related foot complications. A new interim orthosis allowing the patient a greater degree of mobility after Chopart surgery than currently used systems is now available. The aim of this study was to evaluate the effectiveness of the new orthosis compared with traditional treatment. Safety and level of patient acceptance of the device were also investigated. We performed a retrospective case-control observational study involving people with diabetes who underwent Chopart amputation between January 2016 and January 2018. The sample of subjects treated with the innovative orthosis was compared with consecutive patients, who were treated with traditional management. The main study outcomes include major amputation occurrence, ulcer recurrence, healing time, and patient acceptance of the orthosis. Patient satisfaction was evaluated using the Italian validated version of the Orthotic Prosthetic User's Survey (OPUS) questionnaire. Overall, 27 subjects were enrolled using the new device (mean age 68.7 ± 8.4 years, 70.4% males, mean diabetes duration 22.7 ± 15 years). Clinical baseline characteristics were comparable between the cases and the controls. There was no difference between the groups in the healed wound rate (81.5% vs 80.0% for cases and the control group, respectively, P = .53). The ulcer recurrence rate was higher in the control group compared with subjects using the new orthosis (62.5% vs 24.0%, respectively, P = .04). The use of the innovative orthosis was associated with an 81% lower probability to have ulcer recurrence (odds ratio 0.19, 95% confidence interval 0.04-1.04). No between groups difference was detected for a major amputation rate. The wound healing time was faster for cases compared with controls (160.4 ± 114.1 vs 256.5 ± 112.9 days, P = .05). No adverse events related to the use of the new orthosis were recorded. Patient acceptance of the new orthosis was high. This orthosis can be recommended as an efficient, safe, and well-accepted device after Chopart amputation.

Association between inherited thrombophilia and venous thromboembolism in patients with non-O blood type: a meta-analysis.

INTRODUCTION: Hereditary conditions, including non­O blood group or thrombophilic alterations such as factor V Leiden (FVL) and G20210A prothrombin mutation (G20210A PTM), are usually considered risk factors for venous thromboembolism (VTE). OBJECTIVE: This meta­analysis was carried out to find out if simultaneous occurrence of FVL or PTM and the non­O blood group may increase the risk of developing VTE. PATIENTS AND METHODS: MEDLINE and EMBASE databases were explored until March 2021. Eleven publications, comprising 82 465 patients, and 6 studies, including 70 004 patients, were analyzed to evaluate the association between FVL/non­O group and PTM/non­O group, respectively. Pooled odds ratios (OR) and 95% CIs were obtained by a random­effects model. RESULTS: Nearly 6% of the enrolled patients manifested both FVL and the non­O group, whereas only 1.4% had PTM and the non­O group. The VTE risk was considerably amplified in FVL and the non­O group (OR, 5.94; 95% CI, 5.33-6.61; P <0.01), more than if just 1 of these 2 risk factors was present. The equivalent population attributable risk (PAR) of VTE was around 21%. The patients with PTM and the non­O group manifested a significantly augmented risk of VTE (OR, 4.01; 95% CI, 3.00-5.36; P = 0.01), although PAR was considerably lower (3.7%). CONCLUSIONS: The co­occurrence of FVL and the non­O group enhances the risk of VTE that could have clinical influence and drive therapeutic corrections. The coexistence of PTM and the non­O blood group seems to play a less important role in the incidence of VTE.

COVID-19-Associated Pneumonia in a B-Cell-Depleted Patient With Non-Hodgkin Lymphoma: Recovery With Hyperimmune Plasma.

Coronavirus disease 2019 (COVID-19) can have a severe course in immunocompromised hosts and patients with hematological malignancies. In some cases, the bad prognosis is associated with the lack of B lymphocytes, with impaired antibody production and inefficient viral clearance. We report a case of a 67-year-old woman with a story of non-Hodgkin lymphoma treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), who got a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while being totally depleted of B cells. This condition has determined a severe and prolonged course of COVID-19, with persistently positive nasopharyngeal molecular swabs and lack of anti-SARS-CoV-2 specific antibodies. The clinical recovery was favored by the administration of convalescent hyperimmune plasma.

Correlation of SpO2/FiO2 and PaO2/FiO2 in patients with symptomatic COVID-19: An observational, retrospective study.

Some patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience acute hypoxemic respiratory failure progressing toward atypical acute respiratory distress syndrome (ARDS). The aim of the study is to evaluate whether a correlation between ratio of peripheral saturation of oxygen (SpO2) and fraction of inspired oxygen (S/F) and ratio of arterial partial pressure of oxygen and fraction of inspired oxygen (P/F) exists in COVID-19-related ARDS as already known in classical ARDS. In this multicenter, retrospective, observational study, consecutive, adult (≥ 18 years) patients with symptomatic coronavirus disease 2019 (COVID-19) admitted to different COVID-19 divisions in Italy between March and December 2020 were included. Patients with SpO2 > 97% or missing information were excluded. We included 1,028 patients (median age 72 years, prevalence of males [62.2%]). A positive correlation was found between P/F and S/F (r = 0.938, p < 0.0001). A receiver operating characteristic (ROC) curve analysis showed that S/F accurately recognizes the presence of ARDS (P/F ≤ 300 mmHg) in COVID-19 patients, with a cut-off of ≤ 433% showing good sensitivity and specificity. S/F was also tested against P/F values ≤ 200 and ≤ 100 mmHg (suggestive for moderate and severe ARDS, respectively), the latter showing great accuracy for S/F ≤ 178%. S/F was accurate in predicting ARDS for SpO2 ≥ 92%. In conclusion, our findings support the routine use of S/F as a reliable surrogate of P/F in patients with COVID-19-related ARDS.

Immunotherapy of COVID-19: Inside and Beyond IL-6 Signalling.

Acting on the cytokine cascade is key to preventing disease progression and death in hospitalised patients with COVID-19. Among anti-cytokine therapies, interleukin (IL)-6 inhibitors have been the most used and studied since the beginning of the pandemic. Going through previous observational studies, subsequent randomised controlled trials, and meta-analyses, we focused on the baseline characteristics of the patients recruited, identifying the most favourable features in the light of positive or negative study outcomes; taking into account the biological significance and predictivity of IL-6 and other biomarkers according to specific thresholds, we ultimately attempted to delineate precise windows for therapeutic intervention. By stimulating scavenger macrophages and T-cell responsivity, IL-6 seems protective against viral replication during asymptomatic infection; still protective on early tissue damage by modulating the release of granzymes and lymphokines in mild-moderate disease; importantly pathogenic in severe disease by inducing the proinflammatory activation of immune and endothelial cells (through trans-signalling and trans-presentation); and again protective in critical disease by exerting homeostatic roles for tissue repair (through cis-signalling), while IL-1 still drives hyperinflammation. IL-6 inhibitors, particularly anti-IL-6R monoclonal antibodies (e.g., tocilizumab, sarilumab), are effective in severe disease, characterised by baseline IL-6 concentrations ranging from 35 to 90 ng/mL (reached in the circulation within 6 days of hospital admission), a ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2) between 100 and 200 mmHg, requirement of high-flow oxygen or non-invasive ventilation, C-reactive protein levels between 120 and 160 mg/L, ferritin levels between 800 and 1600 ng/mL, D-dimer levels between 750 and 3000 ng/mL, and lactate dehydrogenase levels between 350 and 500 U/L. Granulocyte-macrophage colony-stimulating factor inhibitors might have similar windows of opportunity but different age preferences compared to IL-6 inhibitors (over or under 70 years old, respectively). Janus kinase inhibitors (e.g., baricitinib) may also be effective in moderate disease, whereas IL-1 inhibitors (e.g., anakinra) may also be effective in critical disease. Correct use of biologics based on therapeutic windows is essential for successful outcomes and could inform future new trials with more appropriate recruiting criteria.

Transient perivascular inflammation of the carotid artery (TIPIC) syndrome.

Background: The Transient Perivascular Inflammation of the Carotid artery (TIPIC) syndrome is presumably a very rare disease characterized by a local transient inflammation of the tissue around the carotid artery. Its pathophysiology remains unknown. We performed an updated study of TIPIC syndrome cases in the setting of a multinational collaborative study. Methods: This study was conducted as an observational multinational retrospective individual patient level cohort study. Information from all known cases diagnosed with TIPIC syndrome in the literature (2005-2020) was collected after a semi-structured literature search of PubMed and Web of Science. We also collected unpublished information of patients from French, Swiss, and Italian vascular medicine or radiology departments. Results: A total of 72 patients were included and served for data analysis: 42 (58.3%) were women; the mean age was 47.9 (SD=11.4) years. Symptoms were unilateral in 92% of patients and 81.4% required pain killers. At baseline, irrespective of the imaging method used, the median thickness of the carotid lesions was 5 (Q1-Q3: 4-7; range: 2-11) mm and the median length of the lesion was 20 (Q1-Q3: 10-30; range: 3-50) mm. We found a positive linear correlation between thickness and length. At follow-up, the thickness of the carotid lesions decreased to a median of 2 (Q1-Q3: 1-3; range: 0-6) mm; the length decreased to a median 10 (Q1-Q3: 5-15; range: 0-41) mm. A linear correlation between baseline and follow-up values was observed for both thickness and length measurements. Symptoms disappeared after a median of 14 (Q1-Q3: 10-15) days. Thirteen patients experienced a recurrence after a median follow-up of 6 (Q1-Q3: 2-12) months. Conclusions: The present analysis elucidates clinical and sonographic characteristics of TIPIC syndrome, indicating the benign nature of this condition. A future international registry will study the long-term course of the disease.

Upper extremity deep vein thrombosis in COVID-19: Incidence and correlated risk factors in a cohort of non-ICU patients.

BACKGROUND: Venous thromboembolism is a frequent complication of COVID-19 infection. Less than 50% of pulmonary embolism (PE) is associated with the evidence of deep venous thrombosis (DVT) of the lower extremities. DVT may also occur in the venous system of the upper limbs especially if provoking conditions are present such as continuous positive airway pressure (CPAP). The aim of this study was to evaluate the incidence of UEDVT in patients affected by moderate-severe COVID-19 infection and to identify potential associated risk factors for its occurrence. METHODS: We performed a retrospective analysis of all patients affected by moderate-severe COVID-19 infection admitted to our unit. In accordance with the local protocol, all patients had undergone a systematic screening for the diagnosis of UEDVT, by vein compression ultrasonography (CUS). All the patients were receiving pharmacological thromboprophylaxis according to international guidelines recommendations. Univariate and multivariate analyses were used to identify risk factors associated with UEDVT. RESULTS: 257 patients were included in the study, 28 patients were affected by UEDVT with an incidence of 10.9% (95% CI, 7.1-14.7). At univariate analysis UEDVT appeared to be significantly associated (p< 0.05) with pneumonia, ARDS, PaO2/FiO2, D-dimer value higher than the age adjusted cut off value and need for CPAP ventilation. Multivariate analysis showed a significant association between UEDVT and the need for CPAP ventilation (OR 5.95; 95% IC 1.33-26.58). Increased mortality was found in patients affected by UEDVT compared to those who were not (OR 3.71; 95% CI, 1.41-9.78). CONCLUSIONS: UEDVT can occur in COVID-19 patients despite adequate prophylaxis especially in patients undergoing helmet CPAP ventilation. Further studies are needed to identify the correct strategy to prevent DVT in these patients.

Superior vena cava syndrome after pacemaker implantation treated with direct oral anticoagulation.

BACKGROUND: Superior Vena Cava (SVC) syndrome, is a quite rare but serious complication after pacemaker lead implantation; most patients are asymptomatic due to the development of adequate venous collateral circulation. CASE PRESENTATION: We report a case of a 75-year-old woman who developed SVC syndrome after transvenous pacemaker implantation with complete resolution of the thrombosis after 3 months of oral anticoagulation. CONCLUSIONS: Generally other causes as malignancy are considered to be the most common etiology of SVC syndrome, but benign iatrogenic causes, mainly intravascular devices (central vein catheters, cardiac defibrillators and pacemaker wires), are becoming increasingly common. Procedures performed on venous vasculature, causing a possible intimal injury or vein stenosis, provoked by transvenous leads, seem to be the most reasonable explanation for the observed complication.

Lung Function and Symptoms in Post-COVID-19 Patients: A Single-Center Experience.

OBJECTIVE: To address the lack of information about clinical sequelae of coronavirus disease 2019 (COVID-19). PATIENTS AND METHODS: Previously hospitalized COVID-19 patients who were attending the outpatient clinic for post-COVID-19 patients (ASST Ovest Milanese, Magenta, Italy) were included in this retrospective study. They underwent blood draw for complete blood count, C-reactive protein, ferritin, D-dimer, and arterial blood gas analysis and chest high-resolution computed tomography (HRCT) scan. The primary endpoint was the assessment of blood gas exchanges after 3 months. Other endpoints included the assessment of symptoms and chest HRCT scan abnormalities and changes in inflammatory biomarkers after 3 months from hospital admission. RESULTS: Eighty-eight patients (n = 65 men; 73.9%) were included. Admission arterial blood gas analysis showed hypoxia and hypocapnia and an arterial partial pressure of oxygen/fractional inspired oxygen ratio of 271.4 (interquartile range [IQR]: 238-304.7) mm Hg that greatly improved after 3 months (426.19 [IQR: 395.2-461.9] mm Hg, P<.001). Forty percent of patients were still hypocapnic after 3 months. Inflammatory biomarkers dramatically improved after 3 months from hospitalization. Fever, resting dyspnea, and cough were common at hospital admission and improved after 3 months, when dyspnea on exertion and arthralgias arose. On chest HRCT scan, more than half of individuals still presented with interstitial involvement after 3 months. Positive correlations between the interstitial pattern at 3 months and dyspnea on admission were found. C-reactive protein at admission was positively associated with the presence of interstitial involvement at follow-up. The persistence of cough was associated with presence of bronchiectasis and consolidation on follow-up chest HRCT scan. CONCLUSION: Whereas inflammatory biomarker levels normalized after 3 months, signs of lung damage persisted for a longer period. These findings support the need for implementing post-COVID-19 outpatient clinics to closely follow-up COVID-19 patients after hospitalization.