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Recurrent pericarditis, an inflammatory syndrome with a pathogenesis not fully elucidated, often presents diagnostic challenges. This study aims to assess the correlation of D-Dimer (D-D) and procalcitonin (PCT) levels with clinical, laboratory and imaging features in recurrent idiopathic pericarditis. We analyzed 412 patients with idiopathic recurrent pericarditis from 2019 to 2023 in our referral center. D-D and PCT values were obtained from emergency room in other Italian facilities. Among the cohort, PCT levels were assessed in 50 of 412 patients (12.1%), with only 4 showing marginal elevation. D-D levels were measured in 48 of 412 patients (11.6%), with 33 of them exhibiting elevated values. None of these patients had venous thromboembolism, and elevated D-D levels were significantly associated with pleural effusion, fever, higher CRP, increased white blood cell counts, higher neutrophil counts, reduced relative lymphocyte counts. Multivariate analysis revealed fever as the sole correlate of elevated D-D. PCT elevation was infrequent and unrelated to any variables. In idiopathic recurrent pericarditis unrelated to specific conditions, we observed a close association between elevated D-D levels and non-specific inflammation markers, including fever, increased CRP, and neutrophil leukocytosis. PCT levels were typically normal or mildly elevated.
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Background: Autonomic function and baroreflex control might influence the survival rate of coronavirus disease 2019 (COVID-19) patients admitted to the intensive care unit (ICU) compared to respiratory failure patients without COVID-19 (non-COVID-19). This study describes physiological control mechanisms in critically ill COVID-19 patients admitted to the ICU in comparison to non-COVID-19 individuals with the aim of improving stratification of mortality risk. Methods: We evaluated autonomic and baroreflex control markers extracted from heart period (HP) and systolic arterial pressure (SAP) variability acquired at rest in the supine position (REST) and during a modified head-up tilt (MHUT) in 17 COVID-19 patients (age: 63 ± 10 years, 14 men) and 33 non-COVID-19 patients (age: 60 ± 12 years, 23 men) during their ICU stays. Patients were categorized as survivors (SURVs) or non-survivors (non-SURVs). Results: We found that COVID-19 and non-COVID-19 populations exhibited similar vagal and sympathetic control markers; however, non-COVID-19 individuals featured a smaller baroreflex sensitivity and an unexpected reduction in the HP-SAP association during the MHUT compared to the COVID-19 group. Nevertheless, none of the markers of the autonomic and baroreflex functions could distinguish SURVs from non-SURVs in either population. Conclusions: We concluded that COVID-19 patients exhibited a more preserved baroreflex control compared to non-COVID-19 individuals, even though this information is ineffective in stratifying mortality risk.
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Background: COVID-19 increases the risk of venous thromboembolism (VTE) through a complex interplay of mechanisms collectively referred to as immunothrombosis. Limited data exist on VTE challenges in the acute setting throughout a dynamic long-term follow-up of COVID-19 patients compared to non-COVID-19 patients. The aim of the study was to investigate acute and long-term management and complications in VTE patients with and without COVID-19. Methods: A prospective, observational, single-center cohort study on VTE patients followed from the acute care stage until 24 months post-diagnosis. Results: 157 patients, 30 with COVID-19-associated VTE and 127 unrelated to COVID-19, were enrolled. The mean follow-up was 10.8 (±8.9) months. COVID-19 patients had fewer comorbidities (1.3 ± 1.29 vs. 2.26 ± 1.68, p < 0.001), a higher proportion of pulmonary embolism at baseline (96.7% vs. 76.4%, p = 0.01), and had a lower probability of remaining on anticoagulant therapy after three months (p < 0.003). The most used initial therapy was low-molecular-weight heparin in 130/157 cases, followed by long-term treatment with direct oral anticoagulants in 123/157. Two (6.7%) COVID-19 vs. three (2.4%) non-COVID-19 patients (p = 0.243) had major hemorrhagic events, all of them within the first three months. Four (3.1%) non-COVID-19 patients had VTE recurrence after six months. Three (2.4%) non-COVID-19 patients developed chronic thromboembolic pulmonary hypertension. There were no fatalities among patients with COVID-19, compared to a mortality of 12/127 (9.4%) in the non-COVID-19 subgroup (p = 0.027). Discussion: Our study offers a comprehensive overview of the evolving nature of VTE management, emphasizing the importance of personalized risk-based approaches, including a limited course of anticoagulation for most COVID-19-associated VTE cases and reduced-dose extended therapy for high-risk subsets.
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Increased vascular permeability is a prevalent feature in a wide spectrum of clinical conditions, but no effective treatments to restore the endothelial barrier are available. Idiopathic systemic capillary leak syndrome (ISCLS) is a life-threatening Paroxysmal Permeability Disorder characterized by abrupt, massive plasma extravasation. This condition serves as a robust model for investigating therapeutic approaches targeting interendothelial junctions. We conducted a single-center, interventional in vitro study at the Referral Center for ISCLS in Italy, involving four diagnosed ISCLS patients, aiming at investigating the effects of FX06, a Bß15-42 fibrin-derived peptide binding to VE-Cadherin, on endothelial barrier exposed to intercritical and acute ISCLS sera. The Transwell Permeability Assay was used to assess the permeability of human umbilical vein endothelial cells (HUVECs) exposed to ISCLS sera with or without FX06 (50 µg/ml). Acute ISCLS serum was also tested in a three-dimensional microfluidic device. Nitric oxide (NO), VE-Cadherin localization, and cytoskeletal organization were also assessed. In two and three-dimensional systems, ISCLS sera increased endothelial permeability, with a more pronounced effect for acute sera. Furthermore, acute sera altered VE-Cadherin localization and cytoskeletal organization. NO levels remained unchanged. FX06 restored the endothelial barrier function by influencing cellular localization rather than VE-Cadherin levels. In conclusion, FX06 prevents and reverts the hyperpermeability induced by ISCLS sera. These preliminary yet promising results provide initial evidence of the in vitro efficacy of a drug targeting the underlying pathophysiological mechanisms of ISCLS. Moreover, this approach may hold potential for addressing hyperpermeability in a spectrum of clinical conditions beyond ISCLS.
Subject(s)
Capillary Leak Syndrome , Humans , Capillary Leak Syndrome/metabolism , Endothelial Cells , Capillary Permeability , Endothelium, Vascular , Cadherins/metabolism , ItalyABSTRACT
Coronavirus disease 2019 (COVID-19) carries a high risk of vascular thrombosis. However, whether a specific anticoagulation intensity strategy may prevent clinical worsening in severe COVID-19 patients is still debated. We conducted a joint analysis of two randomized controlled trials, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), to assess the efficacy and safety of two anticoagulant regimens in hospitalized severe COVID-19 patients. Subjects with COVID-19-associated respiratory compromise and/or coagulopathy were randomly assigned to low (4000 IU qd) or high (70 IU Kg-1 every 12 h) enoxaparin dose. The primary efficacy endpoint was clinical worsening within 30 days, defined as the occurrence of at least one of the following events, whichever came first: in-hospital death, evidence of arterial or venous thromboembolism, acute myocardial infarction, need for either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) in patients receiving standard oxygen therapy or none at randomization, and need for mechanical ventilation in any patient. The safety endpoint was major bleeding. We estimated the relative risk (RR) and its 95% confidence interval (CI) for the outcomes. Among 283 patients included in the study (144 in the low-dose and 139 in the high-dose group), 118 (41.7%) were on NIV or CPAP at randomization. 23/139 (16.5%) patients in the high-dose group reached the primary endpoint compared to 33/144 (22.9%) in the low-dose group (RR 0.72, 95% CI 0.45-1.17). No major bleeding was observed. No significant differences were found in the clinical worsening of hospitalized COVID-19 patients treated with high versus low doses of enoxaparin.
Subject(s)
COVID-19 , Heparin, Low-Molecular-Weight , Humans , Anticoagulants/adverse effects , COVID-19/complications , Enoxaparin/adverse effects , Hemorrhage/chemically induced , Heparin, Low-Molecular-Weight/adverse effects , Hospital Mortality , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Categorization of severe COVID-19 related acute respiratory distress syndrome (CARDS) into subphenotypes does not consider the trajectories of respiratory mechanoelastic features and histopathologic patterns. This study aimed to assess the correlation between mechanoelastic ventilatory features and lung histopathologic findings in critically ill patients who died because of CARDS. METHODS: Mechanically ventilated patients with severe CARDS who had daily ventilatory data were considered. The histopathologic assessment was performed through full autopsy of deceased patients. Patients were categorized into two groups according to the median worst respiratory system compliance during ICU stay (CrsICU). RESULTS: Eighty-seven patients admitted to ICU had daily ventilatory data. Fifty-one (58.6%) died in ICU, 41 (80.4%) underwent full autopsy and were considered for the clinical-histopathological correlation analysis. Respiratory system compliance at ICU admission and its trajectory were not different in survivors and non-survivors. Median CrsICU in the deceased patients was 22.9 ml/cmH2O. An inverse correlation was found between the CrsICU and late-proliferative diffuse alveolar damage (DAD) (r = -0.381, p = 0.026). Late proliferative DAD was more extensive (p = 0.042), and the probability of stay in ICU was higher (p = 0.004) in the "low" compared to the "high" CrsICU group. Cluster analysis further endorsed these findings. CONCLUSIONS: In critically ill mechanically ventilated patients, worsening of the respiratory system compliance correlated pathologically with the transition from early damage to late fibroproliferative patterns in non-survivors of CARDS. Categorization of CARDS into ventilatory subphenotypes by mechanoelastic properties at ICU admission does not account for the complexity of the histopathologic features.
Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , COVID-19/complications , Critical Illness , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/etiology , Respiration, Artificial/adverse effectsABSTRACT
Angioedema without Urticaria: Medical History and Findings Abstract. Abstracts: We present the case of a woman with repeated attacks of angioedema without wheals. Given that there was no benefit from systemic steroid and antihistamines therapy, we interpretated the clinical picture as bradykinin- (and not histamine-) induced. Owing to the late onset and a negative family history, we suspected a case of angioedema due to acquired C1-INH deficiency. This hypothesis was later confirmed by specific hematological tests. We therefore started a specific prophylaxis and therapy in case of acute attacks.
Subject(s)
Angioedema , Urticaria , Female , Humans , Angioedema/diagnosis , Angioedema/drug therapy , Angioedema/etiology , Urticaria/diagnosis , Urticaria/drug therapy , Urticaria/etiology , Bradykinin/therapeutic useABSTRACT
Background: Systemic capillary leak syndrome (SCLS) is a potentially fatal disorder characterized by relapses of hypovolemic shock episodes. Case Summary: We present a case of a 58-year-old man who presented to the Emergency Department with a history of recurrent episodes of syncope in the last hours. A few days before medical contact the patient complained of sore throat, fever, and flu-like symptoms. He was initially admitted with a diagnosis of suspected myopericarditis. Forty-eight hours later, the haemodynamic status suddenly deteriorated to a mixed cardiogenic and shock; an endomyocardial biopsy showed localized inflammatory infiltrates and areas of necrosis of cardiomyocytes with positive viral search for parvovirus B19 (PVB19), therefore the patient was treated with methylprednisolone pulses. Based on the concurrent presence of the typical triad of hypotension, hypoalbuminaemia, and haemoconcentration we suspected systemic leak capillary syndrome potentially triggered by the PVB19 infection with acute myocarditis. The clinical conditions further deteriorated with rhabdomyolysis and acute kidney injury: we started continuous veno-venous haemofiltration adding a cytokines adsorber. In the following hours, we observed a significant clinical improvement. The patient was discharged 1 month later and 5 months after discharge he experienced a new attack of SCLS, this time without myocardial involvement and with prompt symptoms resolution. Conclusion: Systemic capillary leak syndrome is a potentially fatal disorder: early recognition of this entity and prompt initiation of supportive therapy are warranted, therefore, it is paramount that an emergency physician thinks of SCLS in patients with signs of cardiogenic shock and the classical triad of hypotension, hypoalbuminia, and haemoconcentration.
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BACKGROUND: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.
Subject(s)
COVID-19 , Pandemics , COVID-19/therapy , Critical Illness/epidemiology , Critical Illness/therapy , Female , Humans , Intensive Care Units , Middle Aged , Prospective Studies , RegistriesABSTRACT
BACKGROUND: Autoptic pulmonary findings have been described in severe COVID-19 patients, but evidence regarding the correlation between clinical picture and lung histopathologic patterns is still weak. METHODS: This was a retrospective cohort observational study conducted at the referral center for infectious diseases in northern Italy. Full lung autoptic findings and clinical data of patients who died from COVID-19 were analyzed. Lung histopathologic patterns were scored according to the extent of tissue damage. To consider coexisting histopathologic patterns, hierarchical clustering of histopathologic findings was applied. RESULTS: Whole pulmonary examination was available in 75 out of 92 full autopsies. Forty-eight hospitalized patients (64%), 44 from ICU and four from the medical ward, had complete clinical data. The histopathologic patterns had a time-dependent distribution with considerable overlap among patterns. Duration of positive-pressure ventilation (p < 0.0001), mean positive end-expiratory pressure (PEEP) (p = 0.007), worst serum albumin (p = 0.017), interleukin 6 (p = 0.047), and kidney SOFA (p = 0.001) differed among histopathologic clusters. The amount of PEEP for long-lasting ventilatory treatment was associated with the cluster showing the largest areas of early and late proliferative diffuse alveolar damage. No pharmacologic interventions or comorbidities affected the lung histopathology. CONCLUSIONS: Our study draws a comprehensive link between the clinical and pulmonary histopathologic findings in a large cohort of COVID-19 patients. These results highlight that the positive end-expiratory pressures and the duration of the ventilatory treatment correlate with lung histopathologic patterns, providing new clues to the knowledge of the pathophysiology of severe SARS-CoV-2 pneumonia.
Subject(s)
COVID-19 , Lung , Autopsy , Humans , Lung/pathology , Patient Acuity , Retrospective StudiesABSTRACT
OBJECTIVE: The term Idiopathic Systemic Capillary Leak Syndrome (ISCLS) refers to an uncommon condition of severe distributive shock, resulting from an abrupt shift of fluids and proteins from the intravascular to the interstitial compartment. We hypothesise that the autonomic nervous system (ANS) fails in regulating the response to hypovolemia in acute ISCLS and that ANS variables characterise the progression to the recovery. DESIGN: Prospective cohort study of patients admitted to ICU for severe ISCLS flares. SETTING: Single, referral center in Italy for ISCLS. PATIENTS: Analysis of cardiovascular signals recorded during seven severe ISCLS attacks and one prodromal period in five patients. INTERVENTIONS: ANS was studied non-invasively by means of heart rate variability (HRV) and blood pressure variability analysis, as an estimation of vagal and sympathetic modulation directed to the heart and vessels. Heart rate and systolic arterial pressure (SAP) variability were also used to assess baroreflex sensitivity. ANS variables were measured during the subsequent phases which characterise ISCLS flares, namely the acute phase, the post-acute phase, and the recovery phase. MEASUREMENTS AND MAIN RESULTS: HRV was severely depressed during the acute phase accounting for the loss of ANS modulation during massive capillary extravasation. This phase was characterised by shock and impaired baroreflex control, which allowed SAP to oscillate driven by respiratory activity. Impending shock and transition from shock to a post-acute phase were marked by change of baroreflex spectral variables. The baroreflex control was fully restored during recovery. CONCLUSIONS: ANS modulation and baroreflex control are severely impaired during the acute haemodynamic instability which characterises ISCLS crises and their progressive restoration may be a clue of improvement. ANS indices during ISCLS flares might serve as useful biomarkers, able to timely announce the transition from one phase to the subsequent one, thus helping to adapt therapy accordingly.
Subject(s)
Autonomic Nervous System/physiopathology , Capillary Leak Syndrome/physiopathology , Adult , Biomarkers/metabolism , Blood Pressure , Female , Heart Rate , Humans , Male , Middle AgedABSTRACT
INTRODUCTION: Among the multiple complex pathophysiological mechanisms underlying COVID-19 pneumonia, immunothrombosis has been shown to play a key role. One of the most dangerous consequences of the prothrombotic imbalance is the increased incidence of micro- and macrothrombotic phenomena, especially deep vein thrombosis (DVT) and pulmonary embolism (PE). METHODS: We investigated the correlation between radiological and clinical-biochemical characteristics in a cohort of hospitalised COVID-19 patients. RESULTS: PE was confirmed in 14/61 (23%) patients, five (35.7%) had DVT. The radiographic findings, quantified by Qanadli score calculated on CT angiography, correlated with the clinical score and biochemical markers. The ratio between the right and left ventricle diameter measured at CT angiography correlated with the length of hospital stay. CONCLUSION: In our cohort radiological parameters showed a significant correlation with clinical prognostic indices and scores, thus suggesting that a multidisciplinary approach is advisable in the evaluation of PE in COVID-19 patients.
Subject(s)
COVID-19 , Pulmonary Embolism , Venous Thromboembolism , Computed Tomography Angiography , Humans , Pulmonary Embolism/diagnostic imaging , Risk Factors , SARS-CoV-2 , Venous Thromboembolism/diagnostic imaging , Venous Thromboembolism/etiologyABSTRACT
Urticaria and angioedema are experienced by up to 1 in 5 people, usually the result of common allergen or medication triggers and infections. Similarly, the majority of recurrent angioedema has an exogenous trigger, for example, angiotensin converting enzyme inhibitors, or is hereditary (type 1 and 2 hereditary angioedema); chronic spontaneous urticaria are most often autoimmune or autoallergic in routine clinical practice. There are, however, several skin and systemic conditions that can imitate the clinical appearance of either angioedema or urticaria, whereas there are several uncommon conditions that have chronic urticaria and/or recurrent angioedema as part of their disease manifestations. Correct diagnosis is paramount to ensuring subsequent tailored therapy for many of these conditions, and in many instances, diagnostic delay can be several years with morbid consequence. In this grand rounds article, we present 2 illustrative clinical cases as the backdrop to discussing a practical diagnostic approach for clinicians to recognize copycat phenotypes and "red flags" that should prompt further investigation of several uncommon mimics. We highlight key diagnostic features, epidemiology, and management for mimics where treatment is distinct from the common phenotypes of recurrent angioedema and chronic urticarias.