Characteristics and determinants of pulmonary long COVID.

BACKGROUNDPersistent cough and dyspnea are prominent features of postacute sequelae of SARS-CoV-2 (also termed "long COVID"); however, physiologic measures and clinical features associated with these pulmonary symptoms remain poorly defined. Using longitudinal pulmonary function testing (PFT) and CT imaging, this study aimed to identify the characteristics and determinants of pulmonary long COVID.METHODSThis single-center retrospective study included 1,097 patients with clinically defined long COVID characterized by persistent pulmonary symptoms (dyspnea, cough, and chest discomfort) lasting for 1 or more months after resolution of primary COVID infection.RESULTSAfter exclusion, a total of 929 patients with post-COVID pulmonary symptoms and PFTs were stratified as diffusion impairment and pulmonary restriction, as measured by percentage predicted diffusion capacity for carbon monoxide (DLCO) and total lung capacity (TLC). Longitudinal evaluation revealed diffusion impairment (DLCO ≤ 80%) and pulmonary restriction (TLC ≤ 80%) in 51% of the cohort overall (n = 479). In multivariable modeling regression analysis, invasive mechanical ventilation during primary infection conferred the greatest increased odds of developing pulmonary long COVID with diffusion impairment and restriction (adjusted odds ratio [aOR] = 9.89, 95% CI 3.62-26.9]). Finally, a subanalysis of CT imaging identified radiographic evidence of fibrosis in this patient population.CONCLUSIONLongitudinal PFTs revealed persistent diffusion-impaired restriction as a key feature of pulmonary long COVID. These results emphasize the importance of incorporating PFTs into routine clinical practice for evaluation of long COVID patients with prolonged pulmonary symptoms. Subsequent clinical trials should leverage combined symptomatic and quantitative PFT measurements for more targeted enrollment of pulmonary long COVID patients.FUNDINGNational Institute of Allergy and Infectious Diseases (AI156898, K08AI129705), National Heart, Lung, and Blood Institute (HL153113, OTA21-015E, HL149944), and the COVID-19 Urgent Research Response Fund at the University of Alabama at Birmingham.

Characteristics and Determinants of Pulmonary Long COVID.

RATIONALE: Persistent cough and dyspnea are prominent features of post-acute sequelae of SARS-CoV-2 (termed 'Long COVID'); however, physiologic measures and clinical features associated with these pulmonary symptoms remain poorly defined. OBJECTIVES: Using longitudinal pulmonary function testing (PFTs) and CT imaging, this study aimed to identify the characteristics and determinants of pulmonary Long COVID. METHODS: The University of Alabama at Birmingham Pulmonary Long COVID cohort was utilized to characterize lung defects in patients with persistent pulmonary symptoms after resolution primary COVID infection. Longitudinal PFTs including total lung capacity (TLC) and diffusion limitation of carbon monoxide (DLCO) were used to evaluate restriction and diffusion impairment over time in this cohort. Analysis of chest CT imaging was used to phenotype the pulmonary Long COVID pathology. Risk factors linked to development of pulmonary Long COVID were estimated using univariate and multivariate logistic regression models. MEASUREMENTS AND MAIN RESULTS: Longitudinal evaluation 929 patients with post-COVID pulmonary symptoms revealed diffusion impairment (DLCO ≤80%) and restriction (TLC ≤80%) in 51% of the cohort (n=479). In multivariable logistic regression analysis (adjusted odds ratio; aOR, 95% confidence interval [CI]), invasive mechanical ventilation during primary infection conferred the greatest increased odds of developing pulmonary Long COVID with diffusion impaired restriction (aOR=10.9 [4.09-28.6]). Finally, a sub-analysis of CT imaging identified evidence of fibrosis in this population. CONCLUSIONS: Persistent diffusion impaired restriction was identified as a key feature of pulmonary Long COVID. Subsequent clinical trials should leverage combined symptomatic and quantitative PFT measurements for more targeted enrollment of pulmonary Long COVID patients.

Routine Contrasted Chest CT Accurately Identifies Anatomic Variations of the Proximal Subscapular System.

OBJECTIVE: The vascular anatomy of the proximal subscapular artery has been previously classified into 2 major types depending on the presence of a common subscapular trunk. The purpose of this study was to determine the utility, reliability, and cost of routine chest imaging to identify these anatomical variations. METHODS: Data were collected retrospectively at a tertiary medical center for patients who were undergoing CT chest for various indications between October 2019 and October 2020. Two independent and blinded readers interpreted CT chest with contrast of 52 patients for a total 104 sides. RESULTS: The proximal branching pattern of the subscapular system was identified to have a common trunk in 99 (95%) sides. The remaining five sides (5%) demonstrated two arterial pedicles; with one patient exhibiting the variant anatomy bilaterally. CONCLUSION: Preoperative CT chest with contrast can accurately identify anatomic variation of the subscapular vascular system. For complex reconstruction requiring a single anastomosis in the vessel depleted neck, preoperative imaging can assure selection of a type I vascular anatomy of the proximal subscapular system. Preoperative imaging with contrasted CT has value in assessing this anatomy when planning for chimeric flaps involving circumflex scapular and thoracodorsal arteries. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:684-687, 2024.

Interobserver agreement for the direct and indirect signs of pulmonary embolism evaluated using contrast enhanced magnetic angiography.

BACKGROUND: Accurate diagnosis of pulmonary embolism (PE) using contrast enhanced MRA (CE-MRA) requires awareness of both the direct and indirect findings of PE. PURPOSE: To evaluate reader agreement of the direct and indirect findings of PE on CE-MRA. METHODS: We evaluated pulmonary artery diameter, right ventricle/left ventricle ratio, and clot/vessel lumen signal intensity ratio. Also, eight direct and eight indirect findings of PE were interpreted twice by two radiologists with different experience levels. The prevalence, and intra- and inter-reader agreement for the direct and indirect findings of PE were recorded. Statistical analysis of the measurements was assessed using intraclass correlation while Cohen's kappa test determined inter- and intra-reader agreement. RESULTS: We reviewed 66 positive CE-MRA exams, 10 of which cases were used for training. The largest PE for each of the remaining 56 cases (40 woman) were included in this analysis (38.9 ± 19.7 (mean age (years) ± S.D.)). The highest interobserver agreement for the direct findings were vessel cutoff (κ = 0.52, 95 % CI = (0.30, 0.74), p < .0001) and bright clot (κ = 0.51, 95 % CI = (0.26, 0.78), p = .0001). The highest interobserver agreement for the indirect findings were for atelectasis (κ = 0.67, 95 % CI = (0.49, 0.87), p < .0001), pleural effusions (κ = 0.56, 95 % CI = (0.32, 0.79), p = 0001) and blank slate sing (κ = 0.56, 95 % CI = (0.18, 0.94), p < .0001). CONCLUSION: The indirect findings of atelectasis and pleural effusion had better interobserver reproducibility than the direct findings of vessel cutoff and bright clot. The intraobserver reproducibility of the direct and indirect findings is dependent on experience level. SUMMARY STATEMENT: Using contrast enhanced magnetic resonance angiography for the diagnosis of pulmonary embolism, the indirect findings of atelectasis and pleural effusion had better interobserver reproducibility than the direct findings of vessel cutoff and bright clot.

Magnetic Resonance Imaging for the Evaluation of Pulmonary Embolism.

Pulmonary embolism (PE) is a leading cause of acute cardiovascular death throughout the world. Although computed tomography angiography (CTA) is the primary imaging study used to diagnose acute PE, pulmonary magnetic resonance angiography (MRA) is increasingly being used in patients with contraindications for CTA. This manuscript reviews the MRA techniques used for the diagnosis of PE and discuss how these techniques can be implemented in routine clinical practice. In addition, the efficacy and effectiveness of these techniques will be compared to other modalities.

Contrast-enhanced pulmonary MRA for the primary diagnosis of pulmonary embolism: current state of the art and future directions.

CT pulmonary angiography (CTPA) is currently considered the imaging standard of care for the diagnosis of pulmonary embolism (PE). Recent advances in contrast-enhanced pulmonary MR angiography (MRA) techniques have led to increased use of this modality for the detection of PE in the proper clinical setting. This review is intended to provide an introduction to the state-of-the-art techniques used in pulmonary MRA for the detection of PE and to discuss possible future directions for this modality. This review discusses the following issues pertinent to MRA for the diagnosis of PE: (1) the diagnostic efficacy and clinical effectiveness for pulmonary MRA relative to CTPA, (2) the different pulmonary MRA techniques used for the detection of PE, (3) guidance for building a clinical service at their institution using MRA and (4) future directions of PE MRA. Our principal aim was to show how pulmonary MRA can be used as a safe, effective modality for the diagnosis of clinically significant PE, particularly for those patients where there are concerns about ionizing radiation or contraindications/allergies to the iodinated contrast material.

An alternating focused ultrasound system for thermal therapy studies in small animals.

PURPOSE: To develop an alternating focused ultrasound system (AFUS) for preclinical studies of thermal and acoustic responses of tumors in small animal models. This work was motivated by the need of noninvasively creating relatively small spheroidal thermal lesions in small targets (e.g., a murine tumor) without damaging the surrounding tissues. METHODS: The AFUS consists of two lead zirconate titanate (PZT-4) spherically curved ultrasound transducers with focal zones crossing each other at a 90 degrees angle. The transducers were independently powered following a programed alternating firing scheme. Before the device design and construction, an acoustic and biothermal model was developed to simulate the ultrasound pressure field and the resulting temperature and thermal dose distributions. A shape factor, sphericity, to quantify the roundness of the lesions was calculated based on the 240 equivalent minutes at 43 degrees C thermal dose contours. A prototype of the AFUS was constructed with two identical transducers of an operating frequency of 2.25 MHz, 38 mm in diameter, and F-number equal to 1.33. To evaluate the performance of the AFUS experimentally, a series of heating in polyacrylamide phantoms, ex vivo porcine liver tissues, and in implanted mouse tumors fibrosarcoma (FSaII) in vivo was conducted. In these experimental cases, the sphericity was calculated and compared based on the visible lesion (a marked change in coloration). RESULTS: As shown in the simulations, the lesions induced in polyacrylamide phantoms, ex vivo porcine liver tissues, and in vivo mouse tumors, the sphericities of the lesions yielded by AFUS heating were approximately 50% higher than those of single focused ultrasound heating as long as moderate intensities were used and the duty cycle pulses were distributed equally among the transducers. CONCLUSIONS: The AFUS is a device capable of noninvasively creating spheroidal thermal lesions in small targets such as murine tumors.

Phase I trial of low dose decitabine targeting DNA hypermethylation in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: dose-limiting myelosuppression without evidence of DNA hypomethylation.

Targeting aberrant DNA hypermethylation in chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL) with decitabine may reverse epigenetic silencing in B-cell malignancies. Twenty patients were enrolled in two phase I trials to determine the minimum effective pharmacological dose of decitabine in patients with relapsed/refractory CLL (n = 16) and NHL (n = 4). Patients received 1-3 cycles of decitabine. Dose-limiting toxicity (DLT) was observed in 2 of 4 CLL and 2 of 2 NHL patients receiving decitabine at 15 mg/m(2) per d days 1-10, consisting of grade 3-4 thrombocytopenia and hyperbilirubinaemia. Six patients with CLL received decitabine at 10 mg/m(2) per d days 1-10 without DLT; however, re-expression of methylated genes or changes in global DNA methylation were not observed. Therefore, a 5-day decitabine schedule was examined. With 15 mg/m(2) per d decitabine days 1-5, DLT occurred in 2 of 6 CLL and 2 of 2 NHL patients, consisting of grade 3-4 neutropenia, thrombocytopenia, and febrile neutropenia. Eight patients had stable disease. In 17 patients, there were no significant changes in genome-wide methylation or in target gene re-expression. In conclusion, dose-limiting myelosuppression and infectious complications prevented dose escalation of decitabine to levels associated with changes in global methylation or gene re-expression in CLL and NHL.