Project description:BackgroundDuring the COVID-19 outbreak, cardiovascular imaging, especially transoesophageal echocardiography (TOE), may expose healthcare personnel to virus contamination and should be performed only if strictly necessary. On the other hand, transthoracic echocardiography (TTE) and TOE represent the first-line imaging exams for the diagnosis of infective endocarditis (IE). To date, this is the first case of COVID-19 complicated by IE.Case summaryWe present the case of a 57-year-old man with severe COVID-19 pneumonia requiring mechanical ventilation. During the intensive care unit (ICU) stay, he developed fever and positive haemocoltures for methicillin-resistant Staphylococcus aureus infection. TTE did not identify endocardial vegetations. TOE was then performed and outlined IE of the aortic valve on the non-coronary cusp. Antibiotic therapy was given with progressive resolution of the septic state and improvement of inflammatory signs. After 30 days of ICU stay, the patient was transferred to the Sub-ICU and then to a rehabilitation hospital. A close follow-up has been scheduled: after full recovery, a new echocardiography will be performed (TTE and TOE, if the former is non-conclusive) to consider surgical valve repair in the case of persistence/progression of the valvular lesion or deterioration of the valve function.DiscussionIn COVID-19 patients, echocardiography remains the leading imaging exam for the diagnosis of IE. If the suspicion of IE is high, even in this setting of patients, TTE or TOE (if TTE is non-conclusive) are mandatory. A high degree of attention must be paid and appropriate preventive measures taken to avoid contamination of healthcare personnel.
Project description:BackgroundSince the onset of the COVID-19 pandemic, several cardiovascular manifestations have been described. Among them, venous thromboembolism (VTE) seems to be one of the most frequent, particularly in intensive care unit patients. We report two cases of COVID-19 patients developing acute pulmonary embolism (PE) after discharge from a first hospitalization for pneumonia of moderate severity.Case summaryTwo patients with positive RT-PCR test were initially hospitalized for non-severe COVID-19. Both received standard thromboprophylaxis during the index hospitalization and had no strong predisposing risk factors for VTE. Few days after discharge, they were both readmitted for worsening dyspnoea due to PE. One patient was positive for lupus anticoagulant.DiscussionWorsening respiratory status in COVID-19 patients must encourage physicians to search for PE since SARS-CoV-2 infection may act as a precipitant risk factor for VTE. Patients may thus require more aggressive and longer thromboprophylaxis after COVID-19 related hospitalization.
Project description:BackgroundReal-world studies on fremanezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention, are few and with limited follow-up.ObjectiveWe aimed to evaluate the long-term (up to 52 weeks) effectiveness and tolerability of fremanezumab in high-frequency episodic migraine and chronic migraine.MethodsThis s an independent, prospective, multicenter cohort study enrolling outpatients in 17 Italian Headache Centers with high-frequency episodic migraine or chronic migraine and multiple preventive treatment failures. Patients were treated with fremanezumab 225 mg monthly. The primary outcomes included changes from baseline (1 month before treatment) in monthly headache days, response rates (reduction in monthly headache days from baseline), and persistence in medication overuse at months 3, 6, and 12 (all outcome timeframes refer to the stated month). Secondary outcomes included changes from baseline in acute medication intake and disability questionnaires scores at the same timepoints. A last observation carried forward analysis was also performed.ResultsA total of 90 patients who received at least one dose of fremanezumab and with a potential 12-month follow-up were included. Among them, 15 (18.0%) patients discontinued treatment for the entire population, a reduction in monthly headache days compared with baseline was reported at month 3, with a significant median [interquartile range] reduction in monthly headache days (- 9.0 [11.5], p < 0.001). A statistically different reduction was also reported at month 6 compared with baseline (- 10.0 [12.0]; p < 0.001) and at 12 months of treatment (- 10.0 [14.0]; p < 0.001). The percentage of patients with medication overuse was significantly reduced compared with baseline from 68.7% (57/83) to 29.6% (24/81), 25.3% (19/75), and 14.7% (10/68) at 3, 6, and 12 months of treatment, respectively (p < 0.001). Acute medication use (days and total number) and disability scores were also significantly reduced (p < 0.001). A ≥ 50% response rate was achieved for 51.9, 67.9, and 76.5% of all patients at 3, 6, and 12 months, respectively. Last observation carried forward analyses confirmed these findings. Fremanezumab was well tolerated, with just one patient discontinuing treatment because of adverse events.ConclusionsThis study provides evidence for the real-world effectiveness of fremanezumab in treating both high-frequency episodic migraine and chronic migraine, with meaningful and sustained improvements in multiple migraine-related variables. No new safety issue was identified.
Project description:PurposeEspecially in elderly and multimorbid patients, Coronavirus Disease 2019 (COVID-19) may result in severe pneumonia and secondary complications. Recent studies showed pneumothorax in rare cases, but tension pneumothorax has only been reported once.Case presentationA 47-year-old male was admitted to the emergency department with fever, dry cough and sore throat for the last 14 days as well as acute stenocardia and shortage of breath. Sputum testing (polymerase chain reaction, PCR) confirmed SARS-CoV-2 infection. Initial computed tomography (CT) showed bipulmonary groundglass opacities and consolidations with peripheral distribution. Hospitalization with supportive therapy (azithromycin) as well as non-invasive oxygenation led to a stabilization of the patient. After 5 days, sputum testing was negative and IgA/IgG antibody titres were positive for SARS-CoV-2. The patient was discharged after 7 days. On the 11th day, the patient realized pronounced dyspnoea after coughing and presented to the emergency department again. CT showed a right-sided tension pneumothorax, which was relieved by a chest drain (Buelau) via mini open thoracotomy. Negative pressure therapy resulted in regression of the pneumothorax and the patient was discharged after 9 days of treatment.ConclusionTreating physicians should be aware that COVID-19 patients might develop severe secondary pulmonary complications such as acute tension pneumothorax.Level of evidenceV.
Project description:BackgroundPatients with severe COVID-19 pneumonia are hypercoagulable and are at risk for acute pulmonary embolism. Timely diagnosis is imperative for their prognosis and recovery. This case describes an otherwise healthy 55-year-old man with respiratory failure requiring mechanical ventilatory support secondary to COVID-19 pneumonia. Massive acute pulmonary embolism with right heart failure complicated his course.CaseA healthy 55-year-old man presented to our emergency department (ED) with a sore throat, cough, and myalgia. A nasopharyngeal swab was obtained, and he was discharged for home quarantine. His swab turned positive for SARS-CoV-2 infection on real-time reverse transcriptase-polymerase chain reaction assay (RT-PCR) on day 2 of his ED visit. A week later, he represented with worsening shortness of breath, requiring intubation for hypoxic respiratory failure due to COVID-19 pneumonia. Initially, he was easy to oxygenate, had no hemodynamic compromise, and was afebrile. On day 3, he became febrile and developed significant hemodynamic instability requiring maximum vasopressor support and oxygenation difficulty. His ECG revealed sinus tachycardia with S1Q3T3 pattern. On bedside TTE, there was evidence of right heart strain and elevated pulmonary artery systolic pressure of 45 mmHg. All data was indicative of a massive APE as the etiology for his hemodynamic collapse. A decision was made to forgo computed tomography pulmonary angiography (CTPA), given his clinical instability, and systemic thrombolytic therapy was administered. Within the next 12-24 hours, his hemodynamic status significantly improved.ConclusionsThis case highlights the importance of considering massive APE in COVID-19 patients as a cause of the sudden and rapid hemodynamic decline. Furthermore, timely diagnosis can be made to aid in appropriate management with the help of bedside TTE and ECG in cases where CTPA is not feasible secondary to the patient's hemodynamic instability.
Project description:BackgroundSignificant coagulopathy and hyperinflammation are found in patients with coronavirus disease 2019 (COVID-19). Expert consensus has recommended prophylactic anticoagulation in COVID-19 patients due to the risk of thrombo-embolism. However, the use of therapeutic anticoagulation in these patients is still a matter of debate.Case summaryWe describe a patient with COVID-19 pneumonia and a clinical hyperinflammatory state. He developed early respiratory depression and required ventilation, and he subsequently developed haemodynamic instability. Point-of-care echocardiography demonstrated a right atrial thrombus and right ventricular dysfunction suggestive of acute massive pulmonary embolism. He was managed with veno-arterial extracorporeal membrane oxygenation and local thrombolysis.DiscussionCritical cases of COVID-19 pneumonia are associated with hypercoagulation, and these patients should be monitored closely for complications. Therapeutic anticoagulation may play a role in the management and prevention of thrombo-embolism.
Project description:IntroductionNumerous agents for prophylaxis of SARS-CoV-2-induced diseases are currently registered for the clinical use. Formation of the immunity happens within several weeks following vaccine administration which is their key disadvantage. In contrast, drugs based on monoclonal antibodies, enable rapid passive immunization and therefore can be used for emergency pre- and post-exposure prophylaxis of COVID-19. However rapid elimination of antibody-based drugs from the circulation limits their usage for prolonged pre-exposure prophylaxis.MethodsIn current work we developed a recombinant adeno-associated viral vector (rAAV), expressing a SARS-CoV-2 spike receptor-binding domain (RBD)-specific antibody P2C5 fused with a human IgG1 Fc fragment (P2C5-Fc) using methods of molecular biotechnology and bioprocessing.Results and discussionsA P2C5-Fc antibody expressed by a proposed rAAV (rAAV-P2C5-Fc) was shown to circulate within more than 300 days in blood of transduced mice and protect animals from lethal SARS-CoV-2 virus (B.1.1.1 and Omicron BA.5 variants) lethal dose of 105 TCID50. In addition, rAAV-P2C5-Fc demonstrated 100% protective activity as emergency prevention and long-term prophylaxis, respectively. It was also demonstrated that high titers of neutralizing antibodies to the SARS-CoV-2 virus were detected in the blood serum of animals that received rAAV-P2C5-Fc for more than 10 months from the moment of administration.Our data therefore indicate applicability of an rAAV for passive immunization and induction of a rapid long-term protection against various SARS-CoV-2 variants.
Project description:IntroductionEarly discontinuation and poor adherence are common limitations of conventional preventive migraine medications that limit their long-term efficacy. Therefore, a migraine preventive medication with favorable long-term safety is warranted.ObjectiveThis study aimed to evaluate the long-term safety and tolerability of fremanezumab for the preventive treatment of chronic or episodic migraine in Japanese patients.MethodsIn this 52-week, randomized, open-label, parallel-group study, fremanezumab monthly or quarterly was administered in newly enrolled Japanese patients with chronic migraine or episodic migraine. Safety was assessed by monitoring of treatment-emergent adverse events, including injection-site reactions, laboratory and vital sign assessments. Newly enrolled patients and rollover patients from previous phase IIb/III trials who did not receive fremanezumab in this study were included in the immunogenicity testing cohort (n = 587). Efficacy outcomes included changes from baseline in the average monthly migraine days and headache days of at least moderate severity. Other efficacy outcomes included changes in disability scores.ResultsA total of 50 patients were enrolled with chronic migraine (monthly, n = 17; quarterly, n = 17) or episodic migraine (monthly, n = 8; quarterly, n = 8). The most commonly reported treatment-emergent adverse events were nasopharyngitis (64.0%) and injection-site reactions (erythema, 24.0%; induration, 10.0%; pain, 8.0%; pruritus, 6.0%). The discontinuation rate was low (4.0% from adverse events, 2.0% from a lack of efficacy) and no deaths were reported. The incidence of anti-drug antibody development was low (2.4%). Fremanezumab reduced monthly migraine days and headache days of at least moderate severity from 1 month after initial administration, and this effect was maintained with no worsening throughout 12 months. Fremanezumab also led to sustained reductions in any acute headache medication use and headache-related disability at 12 months.ConclusionsFremanezumab administered monthly and quarterly was well tolerated in patients with chronic migraine and episodic migraine and led to sustained improvements in monthly migraine days and headache days of at least moderate severity throughout 12 months.Clinical trial registrationClinicalTrials.gov Identifier: NCT03303105.
Project description:BACKGROUND:Coronavirus disease 2019 (COVID-19), a highly contagious viral disease has spread from Wuhan, Hubei Province, China to all over the world from its first recognition on December 2019. To date, only a few neonatal early-onset sepsis by SARS-COV-2 has been reported worldwide. CASE PRESENTATION:In this report, we present two seriously ill neonates who were born from mothers with stablished COVID-19 pneumonia. Laboratory tests showed lymphopenia with high LDH and hypocalcemia right after the birth. They had fever for days without responding to antibiotics and despite ruling out other potential causes. Both patients had positive RTPCR for SARS-COV-2 in the second round of testing but the first assay tested was negative. Hydroxychloroquine was used to treat both patients; the first patient was treated with it over a period of 14?days before showing signs of improvement. The second patient responded to the treatment over a period of 5 days. CONCLUSION:Although based on the available evidences, vertical transmission of COVID-19 is less likely, many aspects of pathogenesis and transmission of this novel virus are still unclear. Therefore we cannot rule out the vertical transmission totally. Further investigations are warranted to determine the exact mechanisms and routes of transmission.