Electrocardiogram analysis in Anderson-Fabry disease: a valuable tool for progressive phenotypic expression tracking.

Background: Electrocardiogram (ECG) has proven to be useful for early detection of cardiac involvement in Anderson-Fabry disease (AFD); however, little evidence is available on the association between ECG alterations and the progression of the disease. Aim and Methods: To perform a cross sectional comparison of ECG abnormalities throughout different left ventricular hypertrophy (LVH) severity subgroups, providing ECG patterns specific of the progressive AFD stages. 189 AFD patients from a multicenter cohort underwent comprehensive ECG analysis, echocardiography, and clinical evaluation. Results: The study cohort (39% males, median age 47 years, 68% classical AFD) was divided into 4 groups according to different degree of left ventricular (LV) thickness: group A ≤ 9 mm (n = 52, 28%); group B 10-14 mm (n = 76, 40%); group C 15-19 mm (n = 46, 24%); group D ≥ 20 mm (n = 15, 8%). The most frequent conduction delay was right bundle branch block (RBBB), incomplete in groups B and C (20%,22%) and complete RBBB in group D (54%, p < 0.001); none of the patients had left bundle branch block (LBBB). Left anterior fascicular block, LVH criteria, negative T waves, ST depression were more common in the advanced stages of the disease (p < 0.001). Summarizing our results, we suggested ECG patterns representative of the different AFD stages as assessed by the increases in LV thickness over time (Central Figure). Patients from group A showed mostly a normal ECG (77%) or minor anomalies like LVH criteria (8%) and delta wave/slurred QR onset + borderline PR (8%). Differently, patients from groups B and C exhibited more heterogeneous ECG patterns: LVH (17%; 7% respectively); LVH + LV strain (9%; 17%); incomplete RBBB + repolarization abnormalities (8%; 9%), more frequently associated with LVH criteria in group C than B (8%; 15%). Finally, patients from group D showed very peculiar ECG patterns, represented by complete RBBB + LVH and repolarization abnormalities (40%), sometimes associated with QRS fragmentation (13%). Conclusions: ECG is a sensitive tool for early identification and long-term monitoring of cardiac involvement in patients with AFD, providing "instantaneous pictures" along the natural history of AFD. Whether ECG changes may be associated with clinical events remains to be determined.

Cardiovascular reflex tests detect autonomic dysfunction in symptomatic and pre-symptomatic subjects with hereditary transthyretin amyloidosis.

PURPOSE: Autonomic dysfunction is a distinctive but undervalued feature of hereditary transthyretin amyloidosis (ATTRv). It may predate the onset of polyneuropathy and cardiomyopathy, thereby providing crucial prognostic and therapeutic information. The objective of this study was to assess autonomic function by means of the standardized cardiovascular autonomic reflex tests (CRTs) in a cohort of subjects with genetically proven ATTRv from non-endemic areas who were in the symptomatic and pre-symptomatic stages. METHODS: All subjects enrolled in this cross-sectional study had genetically proven ATTRv. They underwent the head-up tilt test, Valsalva manoeuvre, deep breathing test, cold face test and handgrip test while under continuous blood pressure and heart rate monitoring. Based on the results of the nerve conduction study, the subjects were divided into two groups: those with polyneuropathy (ATTRv-wPN) and those without polyneuropathy (ATTRv-woPN). Age- and sex-matched healthy controls (HC) were used for comparison. RESULTS: Thirty-seven ATTRv subjects (19 with ATTRv-wPN, 18 with ATTRv-woPN) and 41 HC performed the CRTs. Of these 37 subjects with ATTRv, four (11%) presented neurogenic orthostatic hypotension the during head-up tilt test. Based on the results of the CRTs, autonomic dysfunction characterized by either sympathetic or parasympathetic impairment was detected in 37% and 63% of ATTRv-wPN subjects, respectively. Subjects with ATTRv-woPN presented a significant impairment of autonomic responses to the Valsalva manoeuvre compared to the HC (overshoot p = 0.004; Valsalva ratio p = 0.001). CONCLUSION: Autonomic dysfunctions are frequent in subjects with ATTRv when investigated by means of standardized CRTs, and are also relevant in the pre-symptomatic stage. Cardiovagal functions are the primary functions affected, among others. This may be crucial in defining the proper diagnostic workout for early diagnosis and improving the likelihood of providing the patient with prompt administration of disease-modifying treatments.

Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients.

Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with vs. patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels ≥140mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P<0.01). At admission, hyperglycaemic vs. normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P<0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P<0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P<0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset.

Management of pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a potentially lethal disease mainly affecting young females. Although the precise mechanism of PAH is unknown, the past decade has seen the advent of many new classes of drugs with improvement in the overall prognosis of the disease. Unfortunately the therapeutic options for PAH in South Africa are severely limited. The Working Group on PAH is a joint effort by the South African Heart Association and the South African Thoracic Society tasked with improving the recognition and management of patients with PAH. This article provides a brief summary of the disease and the recommendations of the first meeting of the Working Group.

[Extended lymphadenectomy for left NSLC--case report]. / Limfadenectomie extinsa in cancerul non small cells stâng--prezentare de caz.

The paper brings up a topical issue in the surgical treatment of non small lung cancer, namely optimal lymphadenectomy for tracking left, considering the anatomical features of specific drainage. This can be achieved by various methods recently introduced in the classical arsenal left lung cancer diagnosis. It's presented in detail a case of extended lymphadenectomy for lung cancer non small left to right paratraheal approach without ligament arterial section. The method allowed a correct staging and reporting of the case more accurate prognosis. The immediate goal of the authors is to discuss on this surgical technique and for long term to achieve a lot with statistical significance in order to assess the value of this method.

Densitometric CT evaluation of acute and chronic thromboembolic filling defects of the pulmonary arteries before and after contrast injection.

PURPOSE: The aim of this study was to assess the baseline computed tomography (CT) attenuation of acute and chronic pulmonary thromboemboli, their contrast enhancement (CE), correlation with haematocrit (Ht) levels and the presence of hypertrophic bronchial arteries. MATERIALS AND METHODS: From January 2006 to October 2009, we measured the baseline and postcontrast attenuation values of acute pulmonary thrombi emboli on CT angiograms of 86 patients with acute pulmonary embolism (PE) and those of chronic thrombi in 29 patients with pulmonary hypertension of various origins. The attenuation of acute thrombi was correlated with Ht and CE of chronic thrombi with the presence of hypertrophic bronchial arteries. RESULTS: Acute emboli had a mean baseline attenuation of 54.9 Hounsfield units (HU) and showed no CE. The attenuation of acute thrombi was not dependent on Ht. Chronic thrombi had a mean baseline attenuation of 33.8 HU, and 54% of thrombi showed significant CE. In 57% of cases, a collateral circulation had developed. In 76.5% of cases, CE and hypertrophic bronchial arteries coexisted (p=0.026). Neither thrombotic CE nor bronchial artery hypertrophy predominated in any one of the diseases associated with chronic thrombosis. CONCLUSIONS: Before contrast administration, acute emboli coare prevalently hyperattenuating and therefore more conspicuous. Only chronic thrombi exhibit CE, and CE is significantly associated with the development of collateral circulation, which may be involved in the process of thrombotic recanalisation.

Evaluation of mosaic pattern areas in HRCT with Min-IP reconstructions in patients with pulmonary hypertension: could this evaluation replace lung perfusion scintigraphy?

PURPOSE: The aim of this study is to evaluate a possible correlation between areas of lung attenuation, found in minimum intensity projection (Min-IP) reconstruction images performed with high resolution computed tomography without contrast medium (HRCT), and areas of lung perfusion alteration, found in lung perfusion scintigraphy (LPS). MATERIALS AND METHODS: Two independent radiologists, unaware of LPS results, evaluated retrospectively a group of 113 patients affected by pulmonary hypertension (HP) of different aetiology. These have been examined in a period of two years in our centre both by spiral computed tomography (CT) with and without contrast-medium and by LPS. The final diagnosis was determined on clinical data, right heart catheterisation and contrast enhanced CT in angiographic phase (CTPA). We reconstructed the Min-IP images of lung parenchyma in all the cases both in HRCT without contrast-medium, and in contrast enhanced CT in angiographic phase (CTPA) in axial, sagittal and coronal planes. The obtained images were qualitatively graded into three categories of pulmonary attenuation: homogeneous, inhomogeneous with non-segmental patchy defects, inhomogeneous with segmental defects. The same criteria of classification were used also for LPS images. In the group of patients with chronic thromboembolic pulmonary hypertension (CTEPH) we also compared the number of areas of lung attenuation found in Min-IP images in HRCT without contrast-medium, and their exact localization, with not perfused areas in LPS. Gold standard for the diagnosis of pulmonary embolism was spiral contrast enhanced CT in angiographic phase (CTPA). RESULTS: In all cases we found exact correspondence between the Min-IP images in HRCT with and without contras agent. The attenuation pattern seen on Min-IP images was concordant with those of LPS in 96 out of 113 patients (85%). In the remaining 17 cases (15%) it was discordant: in 12 cases inhomogeneous in Min-IP images (7 with non-segmental patchy defects, 5 with segmental defects) and homogeneous in LPS, in 5 cases inhomogeneous (1 with non-segmental patchy defects, 4 with segmental defects) in LPS images and homogeneous in Min-IP. In a general view, Min-IP reconstruction without contrast-medium showed a sensitivity of 100% and specificity of 96.1%, positive predictive value (PPV) of 92.3% and negative predictive value (NPV) of 100%, to recognize a pattern of lung attenuation inhomogeneous with segmental defects correspondent to a chronic thromboembolic condition, no false negative cases and three false positive cases; on the other hand LPS, on its own, showed a sensitivity of 91.67% and specificity of 93.51%, positive predictive value (PPV) of 86.84% and negative predictive value (NPV) of 96%, 3 false negative cases and 5 false positive cases. CONCLUSION: Min-IP obtained in HRCT without contrast-medium and in CTPA were equivalent. Min-IP images generally showed a higher sensitivity and specificity than LPS in the evaluation of lung perfusion regarding patients with pulmonary hypertension caused by different etiology, particularly in CTEPH patients. These results can be completed with the evaluation of HRCT and CTPA basal scans, providing more informations than ventilation/perfusion lung scintigraphy. HRCT images integrated by Min-IP reconstruction can represent the first step in the diagnostic algorithm of patients affected by dyspnoea and pulmonary hypertension of unknown causes, reserving the use of contrast-medium only in selected patients and reducing the patients' X-ray-exposition.

The role of the right ventricle in pulmonary arterial hypertension.

Although changes in the pulmonary vasculature are the primary cause of pulmonary arterial hypertension (PAH), severity of symptoms and survival are strongly associated with right ventricular function, and right heart failure is the main cause of death in patients with PAH. Echocardiography and cardiac magnetic resonance imaging allow noninvasive evaluation of right ventricular function and structure, and a number of indices have been shown to have potential prognostic value in PAH. Given the importance of the right ventricle in PAH, preservation and improvement of its function should be important aspects of therapy; however, there are currently few data specifically related to this aspect of treatment response. Simple, reproducible, noninvasive measures of right ventricular function would help to improve the management of patients with PAH, and to provide tools with which to help establish the optimal therapeutic approach to manage not only the effects of the disease on the pulmonary vasculature, but also to support and improve right ventricular function.

Application of a new pulmonary artery obstruction score in the prognostic evaluation of acute pulmonary embolism: comparison with clinical and haemodynamic parameters.

PURPOSE: Evaluation of computed tomography (CT) pulmonary angiography parameters revealing pulmonary embolism (PE) severity with particular attention to pulmonary obstruction indexes. Comparison with clinical and hemodynamic data and determination of predictive role in the development of chronic pulmonary heart disease. MATERIALS AND METHODS: This retrospective study analyzes 45 not consecutive patients from November 2007 to December 2008 with CT angiography diagnosis of acute PE. Included in the study are patients at the first documented episode of acute PE, with 6 month follow-up. Patients with severe pre-existent cardiopulmonary pathology or neoplastic diseases were excluded from the study. CT angiography evaluated right ventricular (RV)/left ventricular (LV) ratio, obstruction index according to Qanadli and Total Clot Burden (Ghanima score). PE indexes were compared with Troponin I measurement and echocardiography result; at last hospitalization and intensive care time were reported. RESULTS: A significant association was found between Ghanima and Qanadli score: the two indexes are equivalent in quantification of pulmonary arterial obstruction (p<0.001). Among others CT parameters, the new Ghanima score evidenced the best accuracy to detect patients evolving to chronic pulmonary heart disease (76%). This value is higher than that of echocardiography (71%). Troponins showed highest accuracy (82%). CONCLUSIONS: Ghanima score can be used in emergency CT angiography diagnosis as prognostic marker for a quickly risk stratification of pulmonary heart disease or death in patients with acute PE. This approach allows to obtain, with just one test, both the diagnosis and a rather accurate acute PE risk stratification.

Treat-to-target strategies in pulmonary arterial hypertension: the importance of using multiple goals.

Major advances have occurred in the treatment of pulmonary arterial hypertension (PAH) over the past decade. The advent of PAH-specific pharmacological treatments has offered hope to patients with a debilitating, progressive disease and a poor prognosis. Combined drug treatment offers improved benefits over monotherapy, and current treatment guidelines for PAH recommend a sequential add-on approach to combination therapy for patients in New York Heart Association (NYHA)/World Health Organization functional class (WHO FC) II-IV. Goal-oriented therapy determines the timing of treatment escalation by inadequate response to known prognostic indicators. Close monitoring of patients aids the early identification of inadequate response, so that treatment can be escalated promptly and before the patient's condition deteriorates further. Existing treatment goals are based on baseline values of prognostic indicators, but it is vital to identify risk factors that are both relevant during treatment and that can be assessed during follow-up appointments. Data from different PAH aetiologies indicate that NYHA/WHO FC is the most appropriate prognostic marker, with 6-min walk distance and several haemodynamic parameters representing alternatives. Future refinement of goal-oriented therapy could include the use of multiple prognostic markers, while additional, large clinical trials will answer questions concerning choice and combination of treatment goals.

[Pulmonary vein anomaly in a patient with pulmonary aspergillosis]. / Anomalie venoasa pulmonara la un pacient cu aspergilom pulmonar.

Vein pulmonary anomalies are seldom met. They have a prevalence of 0.4-0.7% of the cases (according to the American authors). The case under discussion is a 68-year-old patient, who was admitted in the hospital for hemoptysis in low quantity but recurrent, physical asteny, fever and weight loss. The onset had been two months before admission to the hospital. The thoracic X-ray shows opacity at the left apex with marked subcostal and costal intensity, with a homogenous area of 5/6 cm. The thoracic CT exam shows multiple bilateral fibronodular images and the left upper lobe shows a cavitary image with regular and thin walls; intracavitary there is an oval formation with mixed densities of approximate 3.5/4/4.5 cm, which suggests a lung aspergilloma. Surgery will be performed--left upper lobectomy associated with atypical resection from the left Fowler segment. During the surgery it is noticed that the left upper pulmonary vein is abnormaly in the left pulmonary hilum. It has a cranial trajectory, runs in parallel with the left phrenic nerve on the mediastinal surface of the left upper lobe then goes in the mediastinum and pours into the left vein branchocefalic trunk. The post-surgery recovery was slowly favourable with complete pulmonary re-expansion, but with the persistence of the aerial losses which imposed pleural drainage for a period of over 2 weeks.

[Superior vena cava syndrome--surgical solution--case report]. / Sindromul de vena cava superioara--varianta terapeutica.

The patient of 52-year-old smoker was admitted in emergency with headaches, dyspnea, oedema and cyanosis of the cephalic extremity and of the superior members. This signs and symptoms suggest a superior vena cava sindrom. Thoracic CT scan shows the thrombosis of the superior vena cava and a tumor localized in the Bariety's Lodge of about 30/40 mm witch is around the right lateral wall of the traheea.This tumor is also tangent to the superior the superior vena cava. The patient was operated by total median sternotomy. By this approach we performed a complete excision of the mediastinal tumor mass. After that we effected a longitudinal cavotomy, we took out the endoluminal clot and we sutured the superior vena cava. The histological diagnosis of the mediastinal tumor was adenocarcinoma tubular-papillary moderately differentiated. The evolution post operative period was favorable the superior vena cava sindrom was a complet remission. The thoracic CT scan control after 9 months later didn't show a local relapse and blood flow was normally throw the superior vena cava.

[Clinical and therapeutical considerations regarding odontogenic acute mediastinitis]. / Consideratii clinico-terapeutice în mediastinitele acute de cauza dentara.

Odontogenic acute mediastinitis is an polymicrobial infections caused in most cases by gram negative and anaerobic germs. The odontogenic origin of the cases in this study was based on anamnestic inquiry of the patients, which reveales a dental treatment 7-15 days before the diagnosis of acute mediastinitis was established. Clinical features are often nonspecific at the debut of this affection; septic shock could appear suddenly associated with multiple systems and organs failure. This is the explication why, some of these patients presented septic shock when are diagnosed. In this situations, when acute mediastinitis is suspected, based on clinical and imaging findings, it must be confirmed by surgical exploration and perioperative bacteriological evaluations. Positive diagnosis is based on clinical features associated with labs and imaging studies. Surgery plays an important role in therapy of acute mediastinitis: debridement and drainage of mediastinum with subsequently lavage of it, using antiseptic solutions. Broad spectrum antibiotherapy should be administrated immediately, before antibiogram is ready.

End-points and clinical trial design in pulmonary arterial hypertension: have we made progress?

There is enormous interest in the treatment of pulmonary arterial hypertension (PAH), so it is appropriate to consider the design of trials of new therapies and the end-points to be measured when trying to decide whether or not a therapy is effective. In May 2003, the first meeting devoted solely to the discussion of end-points and trial design in PAH was held in Gleneagles, UK. At that time, most of the randomised controlled trials in PAH had used 6-min walking distance and/or resting haemodynamics as their primary end-points. The present article considers the progress that has been made since 2003. It deals with aspects of clinical trial design (such as noninferiority, superiority and withdrawal trials), considers end-points used in previous and current studies (such as 6-min walking distance, time to clinical worsening, haemodynamics, imaging and plasma brain natriuretic peptide), and considers what end-points might be used in the future. The second end-points meeting was held in Turnberry, UK, in June 2007. It had a similar format to the first meeting. Much of what is presented here is a summary of the workshops from that meeting. An attempt has been made to both summarise the current state of end-points and trial design and suggest new ways in which they could be improved. The present article forms one of a series being published in the European Respiratory Journal on pulmonary hypertension.

Evaluation of dental and maxillary development in patients with cleft lip alveolus.

Our purpose was to determine in 20 unilateral cleft lip and alveolus subjects characteristics of the maxillary permanent teeth and maxillary arch development. Clinical and radiographic examinations have been carried out to identify congenitally missing teeth and sagittal skeletal patterns. Study cast assessment was undertaken to evaluate mesiodistal widths of individual teeth, intercanine and intermolar distances for the maxillary arch, as well as dental relationships. We observed that the congenital absence of the upper incisors was higher on the cleft side than on the non-cleft side. There was a statistically significant difference between the mesiodistal widths of cleft-side permanent upper lateral incisors, and their antimeres (p<0.05). Most of the patients presented a class II dental relationship on the affected side comparing to class I/class III Angle on the unaffected side. We concluded that patients with isolated cleft lip and alveolus present perturbations in dental and maxillary arch development, a more severe disruption being recorded on the cleft side.