SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial.

Despite advances, few therapeutics have shown efficacy in severe coronavirus disease 2019 (COVID-19). In a different context, virus-specific T cells have proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 trial to evaluate the safety and efficacy of off-the-shelf, partially human leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in combination with standard of care (SoC) in patients with severe COVID-19 compared to SoC during Delta variant predominance. After a dose-escalated phase 1 safety study, 90 participants were randomized to receive CoV-2-ST+SoC (n = 60) or SoC only (n = 30). The co-primary objectives of the study were the composite of time to recovery and 30-d recovery rate and the in vivo expansion of CoV-2-STs in patients receiving CoV-2-ST+SoC over SoC. The key secondary objective was survival on day 60. CoV-2-ST+SoC treatment was safe and well tolerated. The study met the primary composite endpoint (CoV-2-ST+SoC versus SoC: recovery rate 65% versus 38%, P = 0.017; median recovery time 11 d versus not reached, P = 0.052, respectively; rate ratio for recovery 1.71 (95% confidence interval 1.03-2.83, P = 0.036)) and the co-primary objective of significant CoV-2-ST expansion compared to SοC (CoV-2-ST+SoC versus SoC, P = 0.047). Overall, in hospitalized patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible and safe. Larger trials are needed to strengthen the preliminary evidence of clinical benefit in severe COVID-19. EudraCT identifier: 2021-001022-22 .

COVID-19-Associated Pulmonary Aspergillosis (CAPA) in Northern Greece during 2020-2022: A Comparative Study According to the Main Consensus Criteria and Definitions.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has emerged as an important complication among patients with acute respiratory failure due to SARS-CoV-2 infection. Almost 2.5 years since the start of the COVID-19 pandemic, it continues to raise concerns as an extra factor that contributes to increased mortality, which is mostly because its diagnosis and management remain challenging. The present study utilises the cases of forty-three patients hospitalised between August 2020 and February 2022 whose information was gathered from ten ICUs and special care units based in northern Greece. The main aim was to describe the gained experience in diagnosing CAPA, according to the implementation of the main existing diagnostic consensus criteria and definitions, and present the different classification of the clinical cases due to the alternative algorithms.

Dirofilariasis pulmonar: un reto diagnóstico en la práctica clínica / Pulmonary dirofilariasis: A diagnostic pitfall in clinical practice

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Atypical pattern of lung involvement in pacemaker endocarditis.

Pacemaker endocarditis has a high rate of morbidity and mortality and is associated with substantial health-care cost. To maximize the effectiveness of treatment, diagnosis of pacemaker endocarditis should be made as early as possible. Medical treatment alone is not successful, and the removal of the entire artificial pacing system is often required. We present a case of a female patient with a permanent transvenous pacemaker, recurring episodes of fever and chills, general malaise, and a computed tomography image of a solitary tumor-like lesion indicating pneumonia. The symptoms subsided with empirical antibiotics but without improvement in the radiologic images. A wedge resection of the lesion by thoracotomy was performed, revealing a necrotic lung lesion compatible with pulmonary infarct. Transesophageal echocardiography showed a mass that was adherent to the pacemaker lead. The therapeutic approach consisted of surgical removal of the complete pacing system along with long-term antibiotic therapy and implantation of a new device with an epicardial lead. Serial follow-up echocardiograms for a 1-y period did not show any recurrence, and the subsequent course was uneventful.

The base excess gap is not a valid tool for the quantification of unmeasured ions in cardiac surgical patients: a retrospective observational study.

BACKGROUND: The base excess gap (BE(gap)) method is commonly used for the quantification of unmeasured ions in critically ill patients. However, it has never been validated against the standard quantitative acid-base approach. OBJECTIVE: To compare the BE(gap) as a tool for the prediction of the excess of unmeasured ions with the offset of strong ion gap (SIG) from its reference value. DESIGN: A retrospective observational study. SETTING: Adult ICU in a tertiary hospital. PATIENTS: One hundred and thirty-five cardiac surgical patients admitted for postoperative care. INTERVENTIONS: None. MAIN OUTCOME MEASURES: BE(gap) was calculated as BE(gap) = SBE - BE(si) - BE(wa), where SBE is the standard base excess, BE(si) is the partition due to strong ions ([Na+]-[Cl-]-[lactate-] - 30.5) and BE(wa) is the partition due to weak acids [0.25×{42 - (albumin)}]. The deviation of the observed SIG (SIG(ob)) from its reference value was calculated as deltaSIG = 2.85 - SIG(ob). We used Bland-Altman and concordance correlation analysis to compare BE(gap) with deltaSIG. A bias of ±1 meq l(-1) with limits of agreement of ±2 meq l(-1) and a concordant correlation coefficient of more than 0.9 were considered to indicate a strong agreement. RESULTS: The concordant correlation coefficient between BE(gap) and deltaSIG was 0.702. The mean bias between the two variables was 1.8 meq l(-1), with a lower limit of agreement of -0.9 meq l(-1) and an upper limit of agreement of 4.4 meq l(-1). CONCLUSION: The BE gap method cannot reliably quantify the unmeasured ion excess in cardiac surgical patients. Clinicians should use the full Stewart-Figge model for quantitative acid-base assessments.

The management of post-intubation tracheal stenoses with self-expandable stents: early and long-term results in 11 cases.

OBJECTIVE: The optimal management of post-intubation tracheal stenoses is surgical reconstruction of the airway. Stenting of the trachea using silastic T-tubes or one of the various types of tracheal stents are the alternative ways to surgical reconstruction for the management of post-intubation tracheal stenoses. The early and long-term results of 11 patients with post-intubation tracheal stenosis, who underwent tracheal stenting with self-expandable metallic stents (SEMSs), are presented. METHODS: Twelve patients (10 men, mean age: 47.8±20.4 years) with post-intubation tracheal stenosis were referred for tracheal stenting with SEMS (2000-2004). In three cases, the upper tracheal stenosis extended within the subglottic larynx. Stenting was successful in 11 patients, while, in one patient with involvement of the subglottic larynx, the attempt to insert the stent failed. Follow-up time varied from 6 to 96 months, and it was made with virtual and fiberoptic bronchoscopy. RESULTS: Immediate relief of obstructive symptoms was observed in all the 11 patients, where an SEMS was successfully inserted. Stent dislodgement occurred shortly after the procedure in two patients, and it was treated with insertion of a new stent in the first case and a stent-on-stent insertion in the second. Good patency of the stent was observed in three patients for 60-96 months. Three patients with good patency of the stent died from other reasons 24-48 months after stent insertion. Four patients developed obstructive granulation tissue at the ends of the stent after 12-43 months, requiring further treatment with thermal lasers and/or tracheostomy. One patient underwent stent removal and successful laryngotracheal reconstruction 6 months after stent insertion. CONCLUSIONS: The application of SEMS in post-intubation tracheal stenoses results in immediate improvement of obstructive symptoms without significant perioperative complications. SEMSs have the potential risks of migration and of granulation tissue formation at the end of the stent. SEMS should be applied only in strictly selected patients with post-intubation tracheal stenosis, who are considered unfit for surgery and/or with limited life expectancy.

Primary intrathoracic goiter: a rare and potentially serious entity.

BACKGROUND: Here we review primary intrathoracic goiter (P-ITG), a rare but potentially serious congenital entity that is distinct from the much more common secondary intrathoracic goiter. The latter is an extension of cervical thyroid that descends within the mediastinum. In contrast, P-ITGs lack a connection with the cervical thyroid and their blood supply comes from intrathoracic vessels. SUMMARY: P-ITGs can coexist with a normal or goitrous thyroid gland. When they coexist, either or both may be independently affected by neoplastic, infectious, or infiltrative processes. P-ITGs are mainly located in the anterosuperior mediastinum. Location in posterior or middle mediastinum is observed in 15% of cases, making the diagnosis challenging. Although P-ITGs are rare, they are important because they may reach large dimensions with serious consequences. Compression of the trachea is the most common clinical finding, but compression of other mediastinal organs is also observed. Computerized axial tomography (CT) and radionuclide imaging can suggest or make the diagnosis in most cases. The differential diagnosis includes other mediastinal tumors that show high attenuation on unenhanced CT. The treatment of choice is surgical resection of the goiter through a thoracic approach. Thoracic surgery for resection of a small primary mediastinal goiter is considered to be a relatively safe procedure. Long-standing P-ITGs may cause pressure on the trachea, however, resulting in tracheomalacia. This development is serious in its own right and complicates thoracic surgery. CONCLUSIONS: Resection through a thoracic approach is the appropriate treatment for a P-ITG. Surgical intervention is usually indicated without delay upon the establishment of the diagnosis because these goiters exhibit progressive growth. When P-ITGs are small, this approach should prevent the development of tracheomalacia and other serious complications.

Serum uric acid as an independent predictor of early death after acute stroke.

BACKGROUND: The prognostic significance of uric acid (UA) levels in acute stroke is unclear, so the objective of this study was to determine the association between levels of serum UA (SUA) and mortality in acute stroke. METHODS AND RESULTS: Consecutive patients (n=435) presenting with ischemic stroke and intracerebral hemorrhage were included in the study. The length of stay in hospital and the occurrence of death were recorded. On univariate analysis, the occurrence of death was associated with older age, smoking, presence of congestive heart failure or atrial fibrillation, absence of hyperlipidemia, and intracerebral hemorrhage as the index event. Furthermore, glucose, urea, creatinine and SUA at admission were significantly higher in patients who died, whereas total and high-density-lipoprotein cholesterol were significantly lower. On multiple logistic regression analysis, the independent relationship between higher SUA levels and death was confirmed (odds ratio (OR), 1.37; 95%confidence interval (CI), 1.13-1.67; p=0.001). The only other variables independently associated with the occurrence of death were urea concentration and presence of atrial fibrillation. If urate was >7.8 mg/dl (0.47 mmol/L), then there would be a high probability of early death (87%). CONCLUSIONS: Elevated levels of SUA are independently associated with an increased risk of early death in acute stroke.