Search

Background: Severely ill patients with coronavirus disease 2019 (COVID-19) show an increased risk of new-onset atrioventricular blocks (AVBs), associated with high rates of short-term mortality. Recent data suggest that the uncontrolled inflammatory activation observed in these patients, specifically interleukin (IL)-6 elevation, may play an important pathogenic role by directly affecting cardiac electrophysiology. The aim of our study was to assess the acute impact of IL-6 changes on electrocardiographic indices of atrioventricular conduction in severe COVID-19., Methods: We investigated (1) the behavior of PR-interval and PR-segment in patients with severe COVID-19 during active phase and recovery, and (2) their association with circulating IL-6 levels over time., Results: During active disease, COVID-19 patients showed a significant increase of PR-interval and PR-segment. Such atrioventricular delay was transient as these parameters rapidly normalized during recovery. PR-indices significantly correlated with circulating IL-6 levels over time. All these changes and correlations persisted also in the absence of laboratory signs of cardiac strain/injury or concomitant treatment with PR-prolonging drugs, repurposed or not., Conclusions: Our study provides evidence that in patients with severe COVID-19 and high-grade systemic inflammation, IL-6 elevation is associated with a significant delay of atrioventricular conduction, independent of concomitant confounding factors. While transient, such alterations may enhance the risk of severe AVB and associated short-term mortality. Our data provide further support to current anti-inflammatory strategies for severe COVID-19, including IL-6 antagonists., Competing Interests: Dr. Pietro Enea Lazzerini received a grant from Roche Italia S.p.A. outside the submitted work, in 2018. The other authors declare no competing interests., (© 2024 The Author(s). Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Background: Although accumulating data indicate that IL-6 (interleukin-6) can promote heart rate-corrected QT interval (QTc) prolongation via direct and indirect effects on cardiac electrophysiology, current evidence comes from basic investigations and small clinical studies only. Therefore, IL-6 is still largely ignored in the clinical management of long-QT syndrome and related arrhythmias. The aim of this study was to estimate the risk of QTc prolongation associated with elevated IL-6 levels in a large population of unselected subjects., Methods and Results: An observational study using the Veterans Affairs Informatics and Computing Infrastructure was performed. Participants were US veterans who had an ECG and were tested for IL-6. Descriptive statistics and univariate and multivariate regression analyses were performed to study the relationship between IL-6 and QTc prolongation risk. Study population comprised 1085 individuals, 306 showing normal (<5 pg/mL), 376 moderately high (5-25 pg/mL), and 403 high (>25 pg/mL) IL-6 levels. Subjects with elevated IL-6 showed a concentration-dependent increase in the prevalence of QTc prolongation, and those presenting with QTc prolongation exhibited higher circulating IL-6 levels. Stepwise multivariate regression analyses demonstrated that increased IL-6 level was significantly associated with a risk of QTc prolongation up to 2 times the odds of the reference category of QTc (e.g. QTc >470 ms men/480 ms women ms: odds ratio, 2.28 [95% CI, 1.12-4.50] for IL-6 >25 pg/mL) regardless of the underlying cause. Specifically, the mean QTc increase observed in the presence of elevated IL-6 was quantitatively comparable (IL-6 >25 pg/mL:+6.7 ms) to that of major recognized QT-prolonging risk factors, such as hypokalemia and history of myocardial infarction., Conclusions: Our data provide evidence that a high circulating IL-6 level is a robust risk factor for QTc prolongation in a large cohort of US veterans, supporting a potentially important arrhythmogenic role for this cytokine in the general population.

Background: In ∼50% of severe atrioventricular blocks (AVBs) occurring in adults <50 years, the underlying etiology remains unknown. Preliminary evidence from case reports suggests that autoimmunity, specifically the presence of circulating anti-Ro/SSA antibodies in the patient (acquired form), in the patient's mother (late-progressive congenital form), or in both (mixed form), could be involved in a fraction of idiopathic AVBs in adults by possibly targeting the L-type calcium channel (Ca v 1.2) and inhibiting the related current (I CaL )., Objectives: The purpose of this study was to evaluate whether anti-Ro/SSA antibodies are causally implicated in the development of isolated AVBs in adults., Methods: Thirty-four consecutive patients with isolated AVB of unknown origin and 17 available mothers were prospectively enrolled in a cross-sectional study. Anti-Ro/SSA antibodies were assessed by fluoroenzyme-immunoassay, immuno-Western blotting, and line-blot immunoassay. Purified immunoglobulin-G (IgG) from anti-Ro/SSA-positive and anti-Ro/SSA-negative subjects were tested on I CaL and Ca v 1.2 expression using tSA201 and HEK293 cells, respectively. Moreover, in 13 AVB patients, the impact of a short course of steroid therapy on AV conduction was evaluated., Results: Anti-Ro/SSA antibodies, particularly anti-Ro/SSA-52kD, were found in 53% of AVB-patients and/or in their mothers, most commonly an acquired or mixed form (two-thirds of cases) without history of autoimmune diseases. Purified IgG from anti-Ro/SSA-positive but not anti-Ro/SSA-negative AVB patients acutely inhibited I CaL and chronically down-regulated Ca v 1.2 expression. Moreover, anti-Ro/SSA-positive sera showed high reactivity with peptides corresponding to the Ca v 1.2 channel pore-forming region. Finally, steroid therapy rapidly improved AV conduction in AVB-patients with circulating anti-Ro/SSA antibodies but not in those without., Conclusions: Our study points to anti-Ro/SSA antibodies as a novel, epidemiologically relevant and potentially reversible cause of isolated AVB in adults, via an autoimmune-mediated functional interference with the L-type calcium channels. These findings have significant impact on antiarrhythmic therapies by avoiding or delaying pacemaker implantation., Competing Interests: Funding Support and Author Disclosures This work was supported by Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR), Progetti di Rilevante Interesse Nazionale (PRIN), and Bando 2017, protocollo 2017XZMBYX (to Dr Lazzerini and Dr Capecchi); a Merit Review grant I01 BX002137 from Biomedical Laboratory Research & Development Service of Veterans Affairs Office of Research and Development (to Dr Boutjdir); National Heart, Lung, and Blood Institute grant 1R01HL164415-01 (to Dr Boutjdir); and U.S. Department of Defense award number W81XWH-21-1-0424 (to Dr Boutjdir). Dr Lazzerini has received a grant from Roche Italia S.p.A. outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Heart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly via direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms., Methods: We investigated the following mechanisms: (1) the QTc duration in patients with COVID-19 during the active phase and recovery, and its association with C-reactive protein (CRP) and IL-6 levels; (2) the acute impact of IL-6 administration on QTc in an in vivo guinea pig model; and (3) the electrophysiological effects of IL-6 on ventricular myocytes in vitro ., Results: In patients with active severe COVID-19 and elevated IL-6 levels, regardless of acute myocardial injury/strain and concomitant QT-prolonging risk factors, QTc was significantly prolonged and rapidly normalized in correlation with IL-6 decrease. The direct administration of IL-6 in an in vivo guinea pig model acutely prolongs QTc duration. Moreover, ventricular myocytes incubated in vitro with IL-6 show evident prolongation in the action potential, along with significant inhibition in the rapid delayed rectifier potassium current (I Kr )., Conclusion: For the first time, we demonstrated that in severe COVID-19, systemic inflammatory activation can per se promote QTc prolongation via IL-6 elevation, leading to ventricular electric remodeling. Despite being transitory, such modifications may significantly contribute to arrhythmic events and associated poor outcomes in COVID-19. These findings provide a further rationale for current anti-inflammatory treatments for COVID-19, including IL-6-targeted therapies., Competing Interests: PL received a grant from Roche Italia S.p.A. outside the submitted work in 2018. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lazzerini, Accioli, Acampa, Zhang, Verrengia, Cartocci, Bacarelli, Xin, Salvini, Chen, Salvadori, D’errico, Bisogno, Cevenini, Marzotti, Capecchi, Laghi-Pasini, Chen, Capecchi and Boutjdir.)

Background Recent data suggest that systemic inflammation can negatively affect atrioventricular conduction, regardless of acute cardiac injury. Indeed, gap-junctions containing connexin43 coupling cardiomyocytes and inflammation-related cells (macrophages) are increasingly recognized as important factors regulating the conduction in the atrioventricular node. The aim of this study was to evaluate the acute impact of systemic inflammatory activation on atrioventricular conduction, and elucidate underlying mechanisms. Methods and Results We analyzed: (1) the PR-interval in patients with inflammatory diseases of different origins during active phase and recovery, and its association with inflammatory markers; (2) the existing correlation between connexin43 expression in the cardiac tissue and peripheral blood mononuclear cells (PBMC), and the changes occurring in patients with inflammatory diseases over time; (3) the acute effects of interleukin(IL)-6 on atrioventricular conduction in an in vivo animal model, and on connexin43 expression in vitro. In patients with elevated C-reactive protein levels, atrioventricular conduction indices are increased, but promptly normalized in association with inflammatory markers reduction, particularly IL-6. In these subjects, connexin43 expression in PBMC, which is correlative of that measured in the cardiac tissue, inversely associated with IL-6 changes. Moreover, direct IL-6 administration increased atrioventricular conduction indices in vivo in a guinea pig model, and IL-6 incubation in both cardiomyocytes and macrophages in culture, significantly reduced connexin43 proteins expression. Conclusions The data evidence that systemic inflammation can acutely worsen atrioventricular conduction, and that IL-6-induced down-regulation of cardiac connexin43 is a mechanistic pathway putatively involved in the process. Though reversible, these alterations could significantly increase the risk of severe atrioventricular blocks during active inflammatory processes.

Purpose: To define the indications, technical limitations and diagnostic yeld of small bowel transbuccal enema in the follow-up of surgical jejunoileal shunting in patients with complicated severe essential obesity., Material and Methods: Three patients were submitted to surgical diversion: two of them underwent an intestinal bypass after Payne-De Wind (isoperistaltic end-to-side jejunoileostomy) and the other after Scott (end-to-end jejunoileostomy). The latter refers to intestinal recanalization and antiperistaltic lower end-to-side gastroenteric restoration., Results: Radiologic studies are the only means to depict the surgical small bowel. Radiographic follow-up needs barium sulfate administration and therefore cannot be performed any sooner than 30 days postoperatively. In the last three years the classic transbuccal enema has been performed with a Rollandi tube (with a terminal opening and a balloon). Both the anastomosis and the blind loop are difficult to demonstrate., Conclusions: Jejunoileal bypass can be used to treat severe obsity uncontrollable otherwise, to reduce food absorption. Different severe complications may result and small bowel studies may permit to show late local complications. Small bowel enema is also indispensable in bypass reversal. There are no alternatives to this radiologic examination which is however very difficult to perform, because of the changes made by previous operation(s), and to interpret because the anastomosis, the sutured loop and wall changes are often poorly demonstrated.

Introduction: Diagnostic imaging in emergency rooms may be inadequate and delayed, which makes chest traumas in children more severe and difficult to treat. We carried out a retrospective study on adults and children who had survived major chest traumas involving the respiratory tract to assess the differences between the two age groups and the role of emergency CT., Material and Methods: Our series consisted of fourteen children admitted to the emergency department for various accidents. Home accidents prevailed (9/14 = 64.3%). On admission, chest radiography was performed in most cases (11/14 = 78.6%); CT was carried out in 21.4% (3/14 patients)., Results: Trauma involved more organs in pediatric patients (11/14 = 78.6%) and lung involvement was always associated with other types of injury, namely contusion (14/14 = 100%), pneumothorax (11/14 = 78.6%), hemothorax (10/14 = 71.4%), tear (4/14 = 28.6%). CT corrected or integrated the radiographic findings of contusion focus in 67% (8/14) and that of pneumothorax in 63.6%; both patterns cannot be demonstrated otherwise., Discussion: Mixed and multiple posterior parenchymal injuries with no rib fractures prevail in young subjects because their bones and ligaments are more elastic, which may lead to trauma underestimation. Tracheobronchial ruptures and pneumomediastinum are much more severe in children than in adults. Chest plain film is often the only diagnostic tool used, despite its major technical and interpretative limitations, also because skull and abdomen are the most investigated regions. Executive limitations are stronger in childhood, increasing the margin of error and the risk of delayed treatment. CT is as cost-effective as radiography and shows even the injuries missed or poorly depicted on conventional images; CT also gives accurate information on damage severity and nature., Conclusions: Traumatic injuries are more severe in pediatric patients due to their build and to biomechanical, clinical and management factors. Spiral CT should be considered the examination of choice to be performed in the emergency department equipped also for pediatric re-animation.

Purpose: To assess the role and the diagnostic yield of CT and of endoscopic retrograde cholangiopancreatography (ERCP) in the study of emergency pancreatic injuries from blunt abdominal trauma., Material and Methods: January, 1992, to December, 1996, eleven subjects with pancreatic trauma were operated on. The patients were 8 men and 3 women (mean age: 28.4 years, range: 15-47 years) with pancreatic traumas of different severity but all with gland fracture and severe ductal injuries. Direct radiography was performed in all cases in different projections: CT with 1 cm slice thickness and feed was also performed. A contrast agent was administered orally in 8/11 patients and i.v. in 11/11. ERCP was performed in supine recumbency within 12 hours of trauma; a hypotonic agent was administered i.v. in 5 cases. The examination was successful in 10 patients. Wirsung duct studies were extended to the biliary tract in 6 cases., Results: Pancreatic traumas were never isolated and usually associated with other abdominal injuries in the liver, spleen, small intestine, kidneys (by frequency) and with injuries in other body regions--the chest in 8/9 cases, limbs in 7/9, the spine in 4/9 and the skull-brain in 3/9 cases. Pancreatic fractures were mostly cervical and 3 of them were bifocal. The radiologic findings of pneumoperitoneum (4 cases), sentinel loop (3), paralytic ileum (11), air-fluid levels (9) were always aspecific. CT had 66.7% sensitivity, with over-all accuracy of pancreatic involvement by trauma in 5/11 cases and specific findings of fracture in 1/11 cases. CT showed associated parenchymal injuries in both the abdomen and other sites. ERCP diagnostic accuracy and sensitivity topped 100% in the demonstration of ductal injuries., Discussion: Pancreatic traumas are usually a rather uncommon event. They are classified as major and minor according to the extent and severity of ductal involvement. Injury site corresponds to the direction of impact force, but the neck is the preferential site for fractures because it is compressed within the spine and extended. Clinical findings are usually aspecific and questionable and diagnostic imaging, especially CT, plays therefore a major role in treatment planning. However, CT provides mainly indirect signs and fails to depict ductal rupture. Despite its difficult technical execution in emergency, ERCP shows ductal injuries with extreme accuracy and specificity, which finding is indispensable for treatment planning., Conclusions: Both CT and ERCP are necessary tools to diagnose pancreatic fractures: the former because it provides indispensable panoramic findings and the latter because it is the only method showing ductal involvement. Therefore, both techniques should be used for accurate surgical planning, which is a crucial step for the prognosis of these injuries. Cost-effectiveness and safe execution are well balanced.

Purpose: We investigated the frequency, clinical features, diagnostic course and therapy of congenital and acquired seminal vesicle cysts., Material and Methods: Seven vesicular cysts were found in adult subjects in 1995-1996. All diagnoses were made with suprapubic and transrectal US, CT and MRI. Vesiculo-deferentography was never used for diagnosis. Patient age and symptoms, cyst site, structure and dysembryogenetic associations were considered for diagnosis., Results: All the patients were adult and all but one fertile. Age ranges were IV (43%), III and V (28.5%) decades. The cyst was congenital in 5 patients, associated with other dysplasias in 60% of them, and acquired in 2 patients. 57% of patients had urogenital symptoms and 2 patients (28.5%) had no clinical signs. US was performed for fertility tests in one patient. The left gland was always and exclusively involved; its size ranged 3.2 to 5.8 cm and its shape was characteristic only in 2 acquired cysts., Discussion: Both abdominal and rectal US examinations were always performed and always reliably showed cyst site, origin, size and components. CT confirmed local findings and was also used to study the abdomen assessing renal presence and function. MRI permitted the best anatomical study with the multiplanar demonstration of the relationships between small pelvis structures., Conclusions: Congenital cysts and acquired distension of the seminal vesicles are uncommon findings also because they are difficult to diagnose. Diagnostic imaging reliably differentiates vesicular cysts from other cystic collections in that region, providing enough information to distinguish acquired from congenital forms, the former curable with drug treatment and the latter requiring more invasive therapy. Relative to site prevalence (100% in the left gland), we do not know if this was an aleatory finding or it indicated an actual congenital predisposition. US yields the indispensable diagnostic findings, but MRI should be always performed to ensure diagnosis, to study the abdomen and to plan possible surgery.

We investigated the diagnostic efficacy of the i.v. administration of a sonography (US) contrast agent to study eye and orbit tumors at different stages. We administered Levovist (Schering), an air microbubble stabilized by fatty acid, which is specific for angiographic indications. Baseline color Doppler US was performed on 24 selected patients and tumor vascularization patterns were classified into three classes. Color Doppler signal enhancement was assessed after contrast agent administration and the signal-to-noise ratio (SNR) was improved in 70% of cases, which helped identify vascular patterns and improved flowmetric accuracy. The Doppler effect was also improved and vascular signal was always enhanced. The SNR was improved also by the postcontrast detection of small vessels missed on baseline scans. Doppler signal enhancement was proportional to precontrast vascularization and depended on tumor size, with poor results in lesions < 5 mm. In contrast, vascular signal spots with increased postcontrast echogenicity sometimes caused excessive noise affecting the results. No correlation was found between signal enhancement and lesion histotype or between signal and lesion site. Treated lesions exhibited poorer contrast agent enhancement. The examination technique must be accurate and the various parameters set optimally, especially the velocity scale, gain and filtration; the unit must feature adequate recording capabilities (mm/s). To conclude, we believe that the routine use of i.v. US contrast agents will play a major role in improving diagnostic imaging in oculistics also thanks to the lack of untoward reactions and to the ease of contrast agent preparation.

Stress fractures are ubiquitary and most often caused by the subject's activities. In the past they occurred mostly in recruits, but today they are frequent in sportsmen. Stress fractures most frequently occur in the lower limbs, especially in the distal leg. We reviewed 32 injuries observed January, 1993, to June, 1995, and found that 25% of them had been misdiagnosed as stress fractures: in the cases where the diagnosis was correct, fatigue fractures (32%) were less frequent than insufficiency fractures (68%) and occurred in young subjects (mean age: 24 years), usually sportsmen (2/3 of cases). Insufficiency fractures may occur in people aged 8 to 81 years (mean: 61 years) and in subjects with metabolic disorders (45.5%). Considering the injury biomechanics and the patient history and symptoms, these lesions appear a rather uncommon event, whose radiologic diagnosis must be confirmed by clinical findings, since radiology mostly (81.6% of cases) showed only the repair process, rather than the fracture itself. The radiologic patterns were classified into three groups: the fracture margin was not shown in 70% of cases (group I), where however intraperiosteal reaction and/or soft tissue effusion were found; bone fracture was shown in 3 cases (group II) and fracture sequels in 4 (group III), where bone thickening (3 cases) or abnormal consolidation (1 case) was found. There are several synonyms of "stress fracture" and confusion is increased because stress lines and other not necessarily abnormal signs such as Park or Harris lines, reinforcement or calcification lines, are often grouped together with stress fractures. Only accurate clinical examination and laboratory findings permit to distinguish fatigue from insufficiency stress fractures and the latter are also very difficult to differentiate from pathologic fractures. The differentiation of fatigue from insufficiency fractures, originally made by English speaking authors, may be confusing because the definition "pathologic fractures" should be reserved only to focal injuries while in the past it included also insufficiency fractures. Thus, only (bone) fatigue injuries in patients exercising intensely and constantly should be considered stress fractures. Conventional radiography is an indispensable tool and MRI is used in selected cases where the former method is negative and in the patients needing early mobility to go back to work. If radiographic findings are questionable for metastases, nuclear medicine is the method of choice and CT and/or MRI may be indicated as second-line diagnostic imaging tools.

Common bile duct (CBD) diameter was measured with ultrasonography in 396 patients (131 had previous cholecystectomy) before and 40 minutes after the ingestion of a fatty meal. CBD diameter reduced in 177 cases, remained unchanged in 175, increased in 44. The increasing of CBD diameter always means obstructive choledochal pathology, caused by stones or other pathologic conditions. Caliber reduction or other pathologic conditions. Caliber reduction is physiologic. When CBD remains unchanged, in 10% of the cases there are stones in the duct.

The Authors verified the diagnostic incremental data furnished by computerized tomography in respect to traditional tomography in assessing and staging lung cancer. This comparative study was based on eight diagnostic parameters, analysed in 150 strongly suspected patients. It is concluded that computerized tomography allows to give a very accurate judgement about the stage of the cancer, reducing the need of diagnostic thoracotomies.

One hundred fifty six telethermographic exams, carried our for scrotal pathology (testicular and extratesticular), have been analyzed. In 80% of cases the pathological area has determined a remarkable hyperthermic thermographic pattern. On the contrary, in the remaining 20% of cases, the affected area has resulted iso- or hypothermic. In this work the eventual pathologic substrate, responsible of the different thermographic patterns, is discussed, also taking into account the echographic results.

Authors analyze clinical possibilities offered by the combination of pulsed Doppler/B mode in automatic ultrasound equipment in evaluating portal vein flow. In 60% of cases the system gave informations about flow in right (452 +/- 21 cm3/min) and in left (348 +/- 27 cm3/min) portal vein branches. Measurement failure causes and methods to avoid them are discussed.

The authors compared the diagnostic accuracy of pharmacologic double contrast, conventional barium meal and oesophago-gastro-duodenoscopy of the stomach in 922 selected patients. The agreement rate between conventional investigation and endoscopy was 70.3%, while it was 83.7% between double contrast studies and endoscopy. Double contrast false positives percentage (48.7%) is bigger than that for conventional technique (38.3%), whilst the latter has a much bigger number of false negatives, both absolutely (169 cases) and relatively (61.7%). Furthermore the association of double contrast and endoscopy was compared with the anatomo-pathological diagnosis in 335 cases. The agreement rate was 94.6%.