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.

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.

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.

[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.

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.

[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.

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.

Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial.

BACKGROUND: Treatments for pulmonary arterial hypertension have been mainly studied in patients with advanced disease (WHO functional class [FC] III and IV). This study was designed to assess the effect of the dual endothelin receptor antagonist bosentan in patients with WHO FC II pulmonary arterial hypertension. METHODS: Patients with WHO FC II pulmonary arterial hypertension aged 12 years or over with 6-min walk distance of less than 80% of the normal predicted value or less than 500 m associated with a Borg dyspnoea index of 2 or greater were enrolled in this double-blind, placebo-controlled, multicentre trial. 185 patients were randomly assigned to receive bosentan (n=93) or placebo (n=92) for the 6-month double-blind treatment period via a centralised integrated voice recognition system. Primary endpoints were pulmonary vascular resistance at month 6 expressed as percentage of baseline and change from baseline to month 6 in 6-min walk distance. Analyses of the primary endpoints were done with all randomised patients who had a valid baseline assessment and an assessment or an imputed value for month 6. This trial was registered with ClinicalTrials.gov, number NCT00091715. FINDINGS: Analyses were done with 168 patients (80 in the bosentan group, 88 in the placebo group) for pulmonary vascular resistance and with 177 (86 and 91) for 6-min walking distance. At month 6, geometric mean pulmonary vascular resistance was 83.2% (95% CI 73.8-93.7) of the baseline value in the bosentan group and 107.5% (97.6-118.4) of the baseline value in the placebo group (treatment effect -22.6%, 95% CI -33.5 to -10.0; p<0.0001). Mean 6-min walk distance increased from baseline in the bosentan group (11.2 m, 95% CI -4.6 to 27.0) and decreased in the placebo group (-7.9 m, -24.3 to 8.5), with a mean treatment effect of 19.1 m (95% CI 3.6-41.8; p=0.0758). 12 (13%) patients in the bosentan group and eight (9%) in the placebo group reported serious adverse events, the most common of which were syncope in the bosentan group and right ventricular failure in the placebo group. INTERPRETATION: Bosentan treatment could be beneficial for patients with WHO FC II pulmonary arterial hypertension.

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.

Reversing the tuberculosis upwards trend: a success story in Romania.

At present, no published evidence is available on the effectiveness of the DOTS (directly observed treatment, short-course) strategy in reducing the incidence of tuberculosis (TB) within a country in the European "hot spots". The present study aimed to demonstrate the effectiveness of the strategy implementation in reversing the epidemiological TB trend in Romania based on programmatic data analysis. Key programme indicators were analysed from 1998 to 2007, and included DOTS coverage, case-detection rate, treatment success and overall incidence of notified cases. Internationally agreed definitions were used. The key programme indicators began declining and the World Health Assembly targets were reached (79% case-detection of new sputum-smear positive cases and 85.5% success rate in new culture-positive TB cases), 7 yrs after initiation of the DOTS expansion. The success story in Romania suggests that other middle-income, high-incidence countries (i.e. those belonging to the former Soviet Union) might be able to reach the World Health Assembly Targets and curb the burden of tuberculosis.

[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.

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.

[Particular localisation of hydatic disease--sternum]. / Localizare particulara a bolii hidatice la om--sternul.

Bones localization of hydatic disease is extremely rare (0.5-2.5 %). In approximative 50% of the cases of bones hydatidosis, the cysts are localized at spines vertebrae, broad bones and mandible. We present a case of a 38 years old female. The patient related an insidious beginning of symptoms, about 3-4 years before, with anterior chest pain, and 3-4 month before hospitalization, the presence of a sternal tumor, in upper portion of the bone. Clinical examination of the patient showed a sternal tumor, at manubrium, painful at palpation, increased consistency, with local inflammation signs. Also, the patient related pain at sterno-clavicular articulation, increased by left upper limb motions, but without mobility restriction. Biochemical analysis revealed an moderate inflammatory syndrome: blood cell sedimentation speed = 40 mm/h, WBC = 9600/mmc, E = 3%, Hb = 11.8g/100ml, alcaline and acid phosphatase - normal range. Thoracic scan: sternal tumor at manubrium with invasion at sternoclavicular joint and bone destruction. Intraoperative we discovered that the sternal tumor was in fact an hydatic cysts, confirmed by the anatomo-pathological exam; we performed cysts removal and resection of osteitic bone. Postoperative outcome was favorable, with antiparasitic treatment after surgery; no recurrence of the hydatic disease or secondary localization.

Pulmonary hypertension in primary Sjögren's syndrome: report of a case and review of the literature.

A 61-year-old female with a history of vaginal dryness, Raynaud's phenomenon, xerostomia and xerophthalmia presented with exertional dyspnoea and weakness. Laboratory and instrumental examinations enabled us to make the diagnosis of primary Sjögren's syndrome, while cardiologic and imaging investigations evidenced isolated pulmonary hypertension and ruled out pulmonary fibrosis. Oral anticoagulant and furosemide therapy induced a partial improvement of exertional dyspnoea and weakness.

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.