Prevalence and Complications of Aberrant Subclavian Artery in Patients With Heritable and Nonheritable Arteriopathies.

BACKGROUND: An aberrant subclavian artery (ASA) (or lusoria) is the most common congenital anomaly of the aortic arch (0.5%-2.2%; female-to-male ratio 2:1 to 3:1). ASA can become aneurysmal and result in dissection, involving Kommerell's diverticulum when present and the aorta. Data of its significance in genetic arteriopathies are not available. OBJECTIVES: The purpose of this study was to assess the prevalence and complications of ASA in gene-positive and -negative nonatherosclerotic arteriopathies. MATERIALS: The series includes 1,418 consecutive patients with gene-positive (n = 854) and gene-negative arteriopathies (n = 564) diagnosed as part of institutional work-up for nonatherosclerotic syndromic and nonsyndromic arteriopathies. Comprehensive evaluation includes genetic counseling, next-generation sequencing multigene testing, cardiovascular and multidisciplinary assessment, and whole-body computed tomography angiography. RESULTS: ASA was found in 34 of 1,418 cases (2.4%), with a similar prevalence in gene-positive (n = 21 of 854, 2.5%) and gene-negative (n = 13 of 564, 2.3%) arteriopathies. Of the former 21 patients, 14 had Marfan syndrome, 5 had Loeys-Dietz syndrome, 1 had type-IV Ehlers-Danlos syndrome, and 1 had periventricular heterotopia type 1. ASA did not segregate with genetic defects. Dissection occurred in 5 of 21 patients with genetic arteriopathies (23.8%; 2 Marfan syndrome and 3 Loeys-Dietz syndrome), all with associated Kommerell's diverticulum. No dissections occurred in gene-negative patients. At baseline, none of the 5 patients with ASA dissection fulfilled criteria for elective repair according to guidelines. CONCLUSIONS: The risk of complications of ASA is higher in patients with genetic arteriopathies and is difficult to predict. In these diseases, imaging of the supra-aortic trunks should enter baseline investigations. Determination of precise indications for repair can prevent unexpected acute events such as those described.

Mid-term follow-up chest CT findings in recovered COVID-19 patients with residual symptoms.

OBJECTIVES: More than a year has passed since the initial outbreak of SARS-CoV-2, which caused many hospitalizations worldwide due to COVID-19 pneumonia and its complications. However, there is still a lack of information detailing short- and long-term outcomes of previously hospitalized patients. The purpose of this study is to analyze the most frequent lung CT findings in recovered COVID-19 patients at mid-term follow-ups. METHODS: A total of 407 consecutive COVID-19 patients who were admitted to the Fondazione IRCCS Policlinico San Matteo, Pavia and discharged between February 27, 2020, and June 26, 2020 were recruited into this study. Out of these patients, a subset of 108 patients who presented with residual asthenia and dyspnea at discharge, altered spirometric data, positive lung ultrasound and positive chest X-ray was subsequently selected, and was scheduled to undergo a mid-term chest CT study, which was evaluated for specific lung alterations and morphological patterns. RESULTS: The most frequently observed lung CT alterations, in order of frequency, were ground-glass opacities (81%), linear opacities (74%), bronchiolectases (64.81%), and reticular opacities (63.88%). The most common morphological pattern was the non-specific interstitial pneumonia pattern (63.88%). Features consistent with pulmonary fibrosis were observed in 32 patients (29.62%). CONCLUSIONS: Our work showed that recovered COVID-19 patients who were hospitalized and who exhibited residual symptoms after discharge had a slow radiological recovery with persistent residual lung alterations. ADVANCES IN KNOWLEDGE: This slow recovery process should be kept in mind when determining the follow-up phases in order to improve the long-term management of patients affected by COVID-19.

Role of Scar and Border Zone Geometry on the Genesis and Maintenance of Re-Entrant Ventricular Tachycardia in Patients With Previous Myocardial Infarction.

In patients with healed myocardial infarction, the left ventricular ejection fraction is characterized by low sensitivity and specificity in the prediction of future malignant arrhythmias. Thus, there is the need for new parameters in daily practice to perform arrhythmic risk stratification. The aim of this study is to identify some features of proarrhythmic geometric configurations of scars and border zones (BZ), by means of numerical simulations based on left ventricular models derived from post myocardial infarction patients. Two patients with similar clinical characteristics were included in this study. Both patients exhibited left ventricular scars characterized by subendo- and subepicardial BZ and a transmural BZ isthmus. The scar of patient #1 was significantly larger than that of patient #2, whereas the transmural BZ isthmus and the subdendo- and subepicardial BZs of patient #2 were thicker than those of patient #1. Patient #1 was positive at electrophysiologic testing, whereas patient #2 was negative. Based on the cardiac magnetic resonance (CMR) data, we developed a geometric model of the left ventricles of the two patients, taking into account the position, extent, and topological features of scars and BZ. The numerical simulations were based on the anisotropic monodomain model of electrocardiology. In the model of patient #1, sustained ventricular tachycardia (VT) was inducible by an S2 stimulus delivered at any of the six stimulation sites considered, while in the model of patient #2 we were not able to induce sustained VT. In the model of patient #1, making the subendo- and subepicardial BZs as thick as those of patient #2 did not affect the inducibility and maintenance of VT. On the other hand, in the model of patient #2, making the subendo- and subepicardial BZs as thin as those of patient #1 yielded sustained VT. In conclusion, the results show that the numerical simulations have an effective predictive capability in discriminating patients at high arrhythmic risk. The extent of the infarct scar and the presence of transmural BZ isthmuses and thin subendo- and subepicardial BZs promote sustained VT.

Radiological differences between chronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH).

OBJECTIVES: The aim of this study was to describe the radiological features of chronic thromboembolic pulmonary disease (CTEPD), not yet systematically described in the literature. Furthermore, we compared vascular scores between CTEPD and chronic thromboembolic pulmonary hypertension (CTEPH) patients, trying to explain why pulmonary hypertension does not develop at rest in CTEPD patients. METHODS: Eighty-five patients (40 CTEPD, 45 CTEPH) referred to our centre for pulmonary endarterectomy underwent dual-energy computed tomography pulmonary angiography (DE-CTPA) with iodine perfusion maps; other 6 CTEPD patients underwent single-source CTPA. CT scans were reviewed independently by an experienced cardiothoracic radiologist and a radiology resident to evaluate scores of vascular obstruction, hypoperfusion and mosaic attenuation, signs of pulmonary hypertension and other CT features typical of CTEPH. RESULTS: Vascular obstruction burden was similar in the two groups (p = 0.073), but CTEPD patients have a smaller extension of perfusion defects in the iodine map (p = 0.009) and a smaller number of these patients had mosaic attenuation (p < 0.001) than CTEPH patients, suggesting the absence of microvascular disease. Furthermore, as expected, the two groups were significantly different considering the indirect signs of pulmonary hypertension (p < 0.001). CONCLUSIONS: CTEPD and CTEPH patients have significantly different radiological characteristics, in terms of signs of pulmonary hypertension, mosaic attenuation and iodine map perfusion extension. Importantly, our results suggest that the absence of peripheral microvascular disease, even in presence of an important thrombotic burden, might be the reason for the absence of pulmonary hypertension in CTEPD. KEY POINTS: • CTEPD and CTEPH patients have significantly different radiological characteristics. • The absence of peripheral microvascular disease might be the reason for the absence of pulmonary hypertension in CTEPD.

CT-guided biopsy in the differential diagnosis of Sjogren syndrome associated cystic lung disease: A case of lung nodular AL-k amyloidosis.

Pulmonary involvement in Sjogren syndrome (SS) could manifest as cystic lung disease (CLD). CLD in SS includes lymphocytic interstitial pneumonia (LIP) and pulmonary amyloidosis. Differential diagnosis usually requires surgical lung biopsy, whereas CT-guided percutaneous fine needle aspiration biopsy (CT-FNAB) has not yet explored. We describe the case of a 63-year-old never smoker Caucasian female with a SS diagnosis who displayed a newly detected diffuse CLD at high-resolution computed tomography, though totally asymptomatic. Given the favorable location of one big lesion at the superior left lobe, a CT-FNAB was proposed instead of a more invasive SLB. At histology examination a diagnosis of pulmonary nodular AL kappa amyloidosis in the context of SS was established. In conclusion, CT-FNAB might represent an alternative and less invasive diagnostic procedure than SLB in the differential diagnosis of CLD, even if further research is needed. Moreover, this case presents an unusual association between SS and pulmonary nodular AL kappa amyloidosis, with pulmonary nodules and cysts without systemic manifestations.

Radiographic findings in 240 patients with COVID-19 pneumonia: time-dependence after the onset of symptoms.

OBJECTIVE: To analyze the most frequent radiographic features of COVID-19 pneumonia and assess the effectiveness of chest X-ray (CXR) in detecting pulmonary alterations. MATERIALS AND METHODS: CXR of 240 symptomatic patients (70% male, mean age 65 ± 16 years), with SARS-CoV-2 infection confirmed by RT-PCR, was retrospectively evaluated. Patients were clustered in four groups based on the number of days between symptom onset and CXR: group A (0-2 days), 49 patients; group B (3-5), 75 patients; group C (6-9), 85 patients; and group D (> 9), 31 patients. Alteration's type (reticular/ground-glass opacity (GGO)/consolidation) and distribution (bilateral/unilateral, upper/middle/lower fields, peripheral/central) were noted. Statistical significance was tested using chi-square test. RESULTS: Among 240 patients who underwent CXR, 180 (75%) showed alterations (group A, 63.3%; group B, 72%; group C, 81.2%; group D, 83.9%). GGO was observed in 124/180 patients (68.8%), reticular alteration in 113/180 (62.7%), and consolidation in 71/180 (39.4%). Consolidation was significantly less frequent (p < 0.01). Distribution among groups was as follows: reticular alteration (group A, 70.9%; group B, 72.2%; group C, 57.9%; group D, 46.1%), GGO (group A, 67.7%; group B, 62.9%; group C, 71%; group D, 76.9%), and consolidation (group A, 35.5%; group B, 31.4%; group C, 47.8%; group D, 38.5%). Alterations were bilateral in 73.3%. Upper, middle, and lower fields were involved in 36.7%, 79.4%, and 87.8%, respectively. Lesions were peripheral in 49.4%, central in 11.1%, or both in 39.4%. Upper fields and central zones were significantly less involved (p < 0.01). CONCLUSIONS: The most frequent lesions in COVID-19 patients were GGO (intermediate/late phase) and reticular alteration (early phase) while consolidation gradually increased over time. The most frequent distribution was bilateral, peripheral, and with middle/lower predominance. Overall rate of negative CXR was 25%, which progressively decreased over time. KEY POINTS: • The predominant lung changes were GGO and reticular alteration, while consolidation was less frequent. • The typical distribution pattern was bilateral, peripheral, or both peripheral and central and involved predominantly the lower and middle fields. • Chest radiography showed lung abnormalities in 75% of patients with confirmed SARS-CoV-2 infection, range varied from 63.3 to 83.9%, respectively, at 0-2 days and > 9 days from the onset of symptoms.

Multidisciplinary Approach in the Early Detection of Undiagnosed Connective Tissue Diseases in Patients With Interstitial Lung Disease: A Retrospective Cohort Study.

Interstitial lung disease (ILD) encompasses a wide range of parenchymal lung pathologies with different clinical, histological, radiological, and serological features. Follow-up, treatment, and prognosis are strongly influenced by the underlying pathogenesis. Considering that an ILD may complicate the course of any connective tissue disease (CTD) and that CTD's signs are not always easily identifiable, it could be useful to screen every ILD patient for a possible CTD. The recent definition of interstitial pneumonia with autoimmune features is a further confirmation of the close relationship between CTD and ILD. In this context, the multidisciplinary approach is assuming a growing and accepted role in the correct diagnosis and follow-up, to as early as possible define the best therapeutic strategy. However, despite clinical advantages, until now, the pathways of the multidisciplinary approach in ILD patients are largely heterogeneous across different centers and the best strategy to apply is still to be established and validated. Aims of this article are to describe the organization of our multidisciplinary group for ILD, which is mainly focused on the early identification and management of CTD in patients with ILD and to show our results in a 1 year period of observation. We found that 15% of patients referred for ILD had an underlying CTD, 33% had interstitial pneumonia with autoimmune feature, and 52% had ILD without detectable CTD. Furthermore, we demonstrated that the adoption of a standardized strategy consisting of a screening questionnaire, specific laboratory tests, and nailfold videocapillaroscopy in all incident ILD proved useful in making the right diagnosis.

The growth of non-solid neoplastic lung nodules is associated with low PD L1 expression, irrespective of sampling technique.

BACKGROUND: Few data are known regarding the molecular features and patterns of growth and presentation which characterize those lung neoplastic lesions presenting as non-solid nodules (NSN). METHODS: We retrospectively reviewed two different cohorts of NSNs detected by CT scan which, after transthoracic fine-needle aspiration (FNA) and core needle biopsy (CNB) received a final diagnosis of malignancy. All the enrolled patients were then addressed to surgical removal of lung cancer nodules or to exclusive radiotherapy. Exhaustive clinical and radiological features were available for each case. RESULTS: In all 62 analysed cases the diagnosis of adenocarcinoma (ADC) was reached. In cytologic samples, EGFR activating mutations were identified in 2 of the 28 cases (7%); no case showed ALK/EML4 or ROS1 translocations. In the histologic samples EGFR activating mutation were found in 4 out of 25 cases (16%). PD-L1 immunostains could be evaluated in 30 cytologic samples, while the remaining 7 did not reach the cellularity threshold for evaluation. TPS was < 1% in 26 cases, > 1% < 50% in 3, and > 50% in 1. All surgical samples showed TPS < 1%. Of the 17 cases that could be evaluated on both samples, 15 were concordantly TPS 0, and 2 showed TPS > 1% < 50 on the biopsy samples. TPS was < 1% in 14 cases, > 1%/< 5% in 4 cases, > 5%/< 50% in 2 cases, > 50% in 1 case. CONCLUSIONS: Overall PD-L1 immunostaining documented the predominance of low/negative TPS, with high concordance in FNA and corresponding surgical samples. It can be hypothesized that lung ADC with NSN pattern and predominant in situ (i.e. lepidic) components represent the first steps in tumor progression, which have not yet triggered immune response, and/or have not accumulated a significant rate of mutations and neoantigen production, or that they belong to the infiltrated-excluded category of tumors. The negative prediction of response to immunomodulating therapy underlines the importance of rapid surgical treatment of these lesions. Notably, cell block cytology seems to fail in detecting EGFR mutations, thus suggesting that this kind of sampling technique should be not adequate in case of DNA direct sequencing.

Pulmonary emphysema not combined with lung fibrosis in systemic sclerosis.

Interstitial Lung Disease (ILD) is a common finding of Systemic Sclerosis (SSc) mainly presenting in the form of Nonspecific Interstitial Pneumonia (NSIP) and deeply affecting patients' prognosis. Beside NSIP, other types of ILD have been reported. The most recently described pattern is the so-called Combined-pulmonary emphysema and lung fibrosis, characterized by the coexistence of both upper lobes centrilobular and paraseptal emphysema and lower lobes ILD. We presented three cases of patients with SSc, in which High Resolution Computed Tomography examinations showed emphysema with atypical distribution and radiological presentation, without or with mild signs of fibrosing lung disease, that stabilized after immunosuppressive treatment.

Cystic Echinococcosis of the Bone: A European Multicenter Study.

Cystic echinococcosis (CE) is a zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus. In humans, the infection induces the formation of parasitic cysts mostly in the liver and lungs, but virtually any organ can be affected. CE of the bone is one of the rarest forms of the disease, yet it is also extremely debilitating for patients and hard to manage for clinicians. Unlike abdominal CE, there is currently no expert consensus on the management of bone CE. In this study, we conducted a survey of the clinical records of seven European referral centers for the management of patients with CE and retrieved data on the clinical management of 32 patients with a diagnosis of bone CE. Our survey confirmed that the patients endured chronic debilitating disease with a high rate of complications (84%). We also found that diagnostic approaches were highly heterogeneous. Surgery was extensively used to treat these patients, as well as albendazole, occasionally combined with praziquantel or nitaxozanide. Treatment was curative only for two patients, with one requiring amputation of the involved bone. Our survey highlights the need to conduct systematic studies on bone CE, both retrospectively and prospectively.

A second case of pericardial mesothelioma mimicking systemic lupus erythematosus in the literature in over 30 years: a case report.

BACKGROUND: Mesothelioma is a rare neoplasm which commonly develops in the pleura of people exposed to asbestos. Pericardial mesothelioma accounts for only 0.7 % of all malignant mesotheliomas and it usually presents with pericardial effusion, mimicking serositis. To date, there are approximately 200 cases of pericardial mesothelioma described in the medical literature, and little knowledge exists about the systemic manifestations of this pathology. The first and only described case of pericardial mesothelioma with autoimmune features dates back to 1984 and, in our case report, we describe the second. CASE PRESENTATION: We report a case of a 45-year-old white woman whose pericardial mesothelioma was initially misdiagnosed as pericardial involvement of an autoimmune disease (systemic lupus erythematosus). After several relapses of pericardial effusion, a computed tomography scan and a biopsy with histological analysis were performed revealing neoplastic growth. CONCLUSIONS: We describe a rare case of pericardial mesothelioma in a patient with a clinical presentation compatible with lupus serositis. Clinicians should consider malignant mesothelioma in the differential diagnosis of pericardial effusion, especially when it is recurrent and not clearly explained by other causes. Cytological samples should always be obtained and, if imaging tools are suggestive for solid processes, histological confirmation is mandatory.

Lung disease recalling paraseptal emphysema in a patient with Goltz syndrome.

BACKGROUND: Goltz syndrome is a rare, genetic disorder mainly occurring in female patients. CASE PRESENTATION: The case presented here is, to the best of our knowledge, the first description of the occurrence of lung parenchymal alterations in a young female patient affected by Goltz syndrome. Although pulmonary involvement is not known in patients affected by X-linked Goltz syndrome, the case here described is related to the even rarer autosomal form of the disease, as in this case. It is thus conceivable that in such different genetic setting the involvement of lung parenchyma may be unveiled through atypical emphysematous lesions. CONCLUSION: This report suggested - for the first time time - a rationale for a lung function and imaging screening in patients affected by Goltz syndrome at least in its autosomal form.

Under-reporting of cardiovascular findings on chest CT.

PURPOSE: It is unclear whether (and, to what extent) radiologists look at and report cardiovascular abnormalities on non-cardio-synchronized standard chest computed tomography (CT). In this study, the frequency and the reporting rate of cardiovascular findings in chest CT examinations were retrospectively assessed. MATERIALS AND METHODS: This study was approved by the institutional review board of each participating center. Four academic centers provided data on 447 subjects who underwent non-ECG-synchronized chest CT examinations for evaluating pulmonary fibrosis (161/447, 36 %), suspected pulmonary embolism (140/447, 31.3 %), or lung cancer staging (146/447, 32.7 %). A total of 220/447 (53.7 %) and 227/447 CT (46.3 %) examinations were evaluated and reported by junior and senior chest radiologists, respectively. Two radiologists with training in cardiac imaging reviewed the same chest CT images looking for the presence of incidental cardiovascular abnormalities using a preformatted score sheet. Inter-observer agreement was assessed using the kappa coefficient of agreement (k). RESULTS: Inter-observer agreement between the study reviewers was moderate to good (0.4-0.73) for most of the incidental cardiovascular findings. At least one incidental cardiovascular finding not documented in the original report was identified by the study reviewers in 225/409 (55 %) of chest CT examinations. A total of 168/266 (63.2 %) potentially clinically significant cardiovascular findings were unreported in the original reports of 177/447 (39.6 %) subjects (p < 0.0001). Senior radiologists tended to more frequently report coronary artery calcification (p = 0.0006), cardiac valves calcification (p = 0.0003), and ascending aorta enlargement (p = 0.01) compared to junior radiologists. CONCLUSIONS: Several cardiovascular abnormalities can be reliably identified on standard chest CT. Yet, they are often under-reported, even when they might be relevant to the patient's work-up.

Anatomical mapping for atrial fibrillation ablation: a head-to-head comparison of ultrasound-assisted reconstruction versus fast anatomical mapping.

BACKGROUND: Accuracy in left atrial (LA) anatomical reconstruction is crucial to the safe and effective performance of catheter ablation of atrial fibrillation (AF). The aim of this study was to evaluate the accuracy of LA reconstruction performed with intracardiac echocardiography (ICE) as compared to fast anatomical mapping (FAM) both integrated in the CARTO mapping system (Biosense Webster, Diamond Bar, CA, USA). METHODS: A multislice computed tomography (MSCT) was preacquired from 29 patients with AF who underwent catheter ablation and 3D-LA geometry was reconstructed using both ICE and FAM separately. The accuracy of the LA anatomical definition was evaluated by comparing LA volumes, LA and pulmonary vein (PV) diameters obtained using ICE and FAM versus MSCT (gold standard). RESULTS: Anterior-posterior and superior-inferior LA diameters were shorter in ICE versus MSCT (32 ± 10 vs 46 ± 9 mm and 48 ± 7 vs 53 ± 7 mm, P < 0.01) but similar in FAM versus MSCT (45 ± 9 vs 46 ± 9 mm and 52 ± 10 vs 53 ± 7 mm). Latero-septal LA diameter was similar in ICE versus MSCT (63 ± 11 vs 63 ± 9 mm) but larger in FAM versus MSCT (69 ± 9 vs 63 ± 9 mm, P < 0.001). LA volume was lower in ICE versus MSCT (73 ± 30 mL vs 116 ± 45 mL, P < 0.0001) and slightly larger in FAM versus MSCT (132 ± 45 vs 116 ± 45 mL, P = 0.06). PV diameters were similar in FAM versus MSCT but significantly underestimated with ICE. CONCLUSIONS: Overall accuracy in the LA and PV anatomical reconstruction was found to be superior with FAM compared to ICE-guided approach. ICE resulted in a significant underestimate of both LA and PV dimensions, while FAM slightly overestimated LA geometry.

Unexpected responses to EGFR inhibition in NSCLC.

The presence of activating mutations of the epidermal growth factor receptor (EGFR)-gene identifies a distinct and clinically relevant molecular subset of non-small-cell lung cancer. It is now well demonstrated that EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib are superior to standard chemotherapy in this subset of tumors. Nevertheless, in many cases, responses are not durable and last for 6-12 months due to the occurrence of secondary or acquired resistance. Here we present three cases of EGFR-mutant lung adenocarcinomas (ADC), that showed an unexpected response to anti-EGFR small molecules. The first patient presented a continued 89 month-long response to erlotinib in a tumor recurred after surgery and conventional chemotherapy. In the other cases, subclinically persistent tumor in the lung tissue was documented histologically in lung resections performed after partial response to TKI treatment. The persistence of interstitial and endolymphatic tumor cells after TKI treatment might explain the common observation of tumor relapse after TKI discontinuation, and sustain the decision to continue treatment in responsive patients as in our first case.