Marfan syndrome and aortic involvement: a narrative review.

Marfan syndrome (MFS) is a systemic connective tissue disease that commonly and most severely affects the ocular, skeletal, and cardiovascular systems. The aim of the manuscript is to review the aortic involvement and complications in MFS, including aortal dissection, thoracic aortic aneurysm, abdominal aortic aneurysm, and acute aortic syndrome. Dissecting thoracic aortic aneurysm and progressing aortic root enlargement are the major causes of MFS morbidity and mortality. Guidelines on aortic disease endorsed by the American College of Cardiology, and the American Heart Association recommend the measurement of the external and internal aortic diameters perpendicular to the axis of blood flow when Computed Tomography, or Magnetic Resonance Imaging, or Cardiac Echography are performed. The pathophysiology, diagnosis, prevention, and medical and surgical treatments of MFS associated with aortic complications are reported in this narrative review. Development and strengthening of centers specialized in cardiovascular diseases and MFS, together with an improvement in the knowledge of its pathogenesis through genetics and proteomics investigations, can ameliorate the prognosis of this disease.

New York Heart Association class and pulmonary artery pressure as prognostic factors of interstitial lung disease survival.

OBJECTIVE: The aim of this study was to evaluate New York Heart Association (NYHA) class and systolic pulmonary artery pressure (sPAP) as survival predictors in major interstitial lung diseases (ILD) including idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP) and hypersensitivity pneumonitis (HP) and in other ILD like granulomatosis with polyangiitis (GPA). PATIENTS AND METHODS: We analyzed survival, NYHA class, sPAP, and Octreoscan uptake index (UI) in 104 ILD patients (59 IPF, 19 NSIP, 10 HP and 16 GPA; median age 60.5 years) all referred to a single centre. RESULTS: Median survival was 68 months, with 1- and 2-year survival of 91% and 78%, respectively. Survival was lower among IPF and NSIP vs. HP and GPA patients (p=0.01). NYHA class 3-4 was more frequent among IPF (76.3%) vs. NSIP patients (31.6%; p<0.001). HP and GPA had NYHA class 1-2. NYHA class was negatively associated with survival (class 1=90.3 months vs. class 3=18.3 months and class 4=5.1 months; p=0.001). sPAP was >55 mmHg in 76.3% of patients with IPF and 35-55 mmHg in 63.2% of patients with NSIP. Patients with HP and GPA had sPAP < 55 mmHg. Among patients with IPF, NYHA and sPAP were negatively associated with survival (p<0.01) both showed a parallel trend. High-resolution computed tomography and survival were worse among IPF and NSIP vs. HP and GPA patients (p<0.001). Octreoscan UI was <10, 10-12, and >12 in IPF, NSIP, HP and GPA, respectively. Octreoscan UI was negatively associated with survival (p=0.002). CONCLUSIONS: NYHA class and sPAP are comparable ILD survival predictors. NYHA class is correlated with worse prognosis for IPF and NSIP vs. HP and GPA patients.

Stem cells therapy in acute myocardial infarction: a new era?

Stem cells transplantation after acute myocardial infarction (AMI) has been claimed to restore cardiac function. However, this therapy is still restricted to experimental studies and clinical trials. Early un-blinded studies suggested a benefit from stem cell therapy following AMI. More recent blinded randomized trials have produced mixed results and, notably, the last largest pan-European clinical trial showed the inconclusive results. Furthermore, mechanisms of potential benefit remain uncertain. This review analytically evaluates 34 blinded and un-blinded clinical trials comprising 3142 patients and is aimed to: (1) identify the pros and cons of stem cell therapy up to a 6-month follow-up after AMI comparing benefit or no effectiveness reported in clinical trials; (2) provide useful information for planning future clinical programs of cardiac stem cell therapy.

New York Heart Association class associated with imaging is a prognostic mortality risk predictor in interstitial lung diseases.

OBJECTIVE: Mortality risk factors as forced vital capacity, diffuse lung capacity for carbon monoxide, and 6-minutes' walk test were studied in clinical trials monitoring patients affected by interstitial lung diseases (ILD). However, these parameters showed scarce accuracy. Our aim was to identify New York Heart Association (NHYA) class, in association with high resolution computed tomography (HRCT) and somatostatin receptor scintigraphy (Octreoscan), as a prognostic mortality risk factor in ILD patients. PATIENTS AND METHODS: Study population comprised 128 ILD patients (78 Males and 50 Females). Histological diagnosis was usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP) and granulomatous lung disease in 59, 19 and 50 patients, respectively. Patients were monitored by NYHA class, HRCT and Octreoscan at baseline and every 3 years up to a 10-year follow up. Overall survival was calculated from the date of diagnosis until death or last follow-up update. Statistical analysis was performed using Kaplan-Meier, log-rank test (LRT), multivariate analysis with Cox proportional hazard regression model, and log-likelihood ratio test. RESULTS: Overall median survival was 89.3 months (7.4 years) with the poorer survival rate observed in UIP patients. NYHA class came out as a reliable prognostic mortality risk factor in each group of patients and prognosis was progressively worse with NYHA class increase (LRT p<0.001). A strong correlation was found between NYHA class and age, CT-score, and Octreoscan in UIP patients (p<0.001). CONCLUSIONS: The determination of NYHA class can therefore be recommended as an additional prognostic mortality risk factor in ILD patients.

Cardiovascular risk in patients without known cardiovascular disease.

Understanding the risks of atherosclerotic cardiovascular disease (CVD) allows for better patient education and management. Multiple risk models have been validated in large patient populations and provide insights into the risks associated with CVD. When assessing such risks, we suggest using a model that predicts myocardial infarction, cardiovascular death, and/or cerebrovascular events. In this review, we analyze several risk models and stratify the risks associated with CVD. We suggest that appropriate profiling of patients at-risk of CVD will lead to better physician recognition and treatment of modifiable risk factors, appropriate application of ATP III treatment for hyperlipidemia, and achieving optimal blood pressure control.

Nail disorders in patients with chronic renal failure and undergoing haemodialysis treatment: a case-control study.

BACKGROUND: Few controlled studies have compared nail disorders in patients with chronic renal failure (CRF) and haemodialysis (HD)-dependent individuals with a healthy population. OBJECTIVE: The aim of this study was to compare the prevalence of nail disorders in patients with CRF and patients undergoing HD treatment with a healthy population, and evaluate the relationship between nail changes and various demographic, medical and laboratory parameters in these groups. METHODS: In this case-control study we recruited 73 patients affected with CRF, 77 patients undergoing regular HD and 77 healthy individuals. All patients were examined for the presence of nail disorders. Various parameters [age, gender, type of kidney disease, regular medications, duration of renal failure and HD, dialysis efficacy (Kt/v), haemoglobin, neutrophil count, calcium, phosphorus, albumin, creatinine, urea, alkaline phosphatase and parathyroid hormone (PTH) levels] of the patients were determined by multivariate analysis and compared. RESULTS: Forty-four patients (60.3%) with CRF and 48 patients (62.3%) undergoing HD treatment had at least one type of nail pathology. The most common nail alterations found in patients with CRF and those undergoing HD were absence of lunula (AL) and half-and-half nails (HHN), respectively. Prevalence of nail disorders among patients with CRF was influenced significantly by PTH level (P = 0.03). In the HD group, male sex, age above 65 years and comorbidities (diabetes mellitus, hypertension and heart failure) were significantly associated with nail pathologies. CONCLUSION: Patients with CRF and those undergoing HD therapy have higher rates of nail disorders when compared to a healthy population. Efficient HD does not improve nail changes.

Anti-Saccharomyces cerevisiae antibodies in Behçet's disease--a familial study.

OBJECTIVE: To evaluate the rate and clinical correlations of antibodies against saccharomyces cerevisiae (ASCA) among healthy family members of patients with Behçet's disease (BD). METHODS: Twenty-one BD patients and 52 healthy family members (HFM) were studied. Data from medical files and from patients' interviews was collected, regarding the entire spectrum of disease manifestations. Each family member was personally interviewed and a questionnaire composed of BD symptoms and their temporal relation was compiled. IgA- and IgG-ASCA levels, determined by ELISA, were studied in all BD patients and their family members, the results were compared to a group of 23 healthy controls (HC). RESULTS: Eight (38.1%) BD patients were ASCA positive, compared to five among HFM (9.6%) and none among healthy unrelated controls (p=0.001). Mean IgG and IgA-ASCA levels were significantly higher in BD patients compared with HFM and HC groups (p = 0.002 and p = 0.03, respectively). No correlation was found between positive ASCA tests and any of BD-related manifestations. Mean IgG-ASCA levels were significantly lower in HFM compared to BD patients (p = 0.03), yet IgA-ASCA levels were similar in HFM and BD. Mean IgG and IgA-ASCA levels were higher in HFM compared with healthy unrelated controls (p=0.09 and p=0.03). No difference was found in ASCA rates between relatives of BD patients who had positive or negative ASCA tests, or between spouses of BD patients and genetically related relatives. In HFM with recurrent oral ulcers there was a positive correlation between titers of IgA-ASCA and the yearly number of oral ulcers episodes (p = 0.01), and mean ulcers healing time (p = 0.01). IgG-ASCA titers correlated with yearly number of aphtae episodes (p = 0.03). CONCLUSION: The results of this study confirm our previous observation on a high prevalence of ASCA in BD. ASCA levels are also increased in healthy family members of BD patients, and are probably influenced by genetic as well as environmental factors. ASCA in HFM were significantly associated with a more severe oral ulcer disease. The role of ASCA as a marker for predisposition to develop future BD remains to be evaluated.

Bronchial hyperresponsiveness in asthmatic adults--a long-term correlation study.

BACKGROUND: Bronchial hyper responsiveness (BHR), is a risk factor for asthma. It is a state in which excessive narrowing of the airways occurs in response to varying stimuli. BHR seems to be due to the interaction of multiple factors and its relation to asthma is complex. Asthma without BHR is unusual. Indeed, patients who show a higher degree of symptoms have higher levels of BHR. To date no study has investigated the correlation between BHR in mild persistent asthmatic adults and a long-term therapy of five years. The aim of this study is to evaluate (i) the role of BHR in the clinical evaluation of asthma, (ii) the correlation between BHR and therapy in asthma. METHODS: Seventy patients (were recruited 34 men, age 21-55 years) suffering from: (a) mild seasonal allergic asthma (17/70), (b) mild perennial allergic asthma (34/70) and (c) mild non-allergic [corrected] asthma (19/70). 14 patients from group (a) and 28 patients from group (b) were treated with inhaled beta2-agonists, beclomethasone, disodiumcromoglycate and immunotherapy. 14 patients from group (c) underwent the same treatment regimen without immunotherapy. All patients were evaluated with a metacholine challenge test. The BHR (PD20 FEV1) was calculated at baseline and after a two-year symptom free period. Fifteen pts were followed-up for five years with an evaluation every year. All other patients did not receive any treatment. The results (expressed as mean +/- SE) were evaluated. RESULTS: Fourteen pts and three pts from group (a) showed a mean BHR value of 984 +/- 3.66 and 674 +/- 2.06; 343 +/- 7.60 and 208 +/- 7.70 respectively. The results were not statistically significant Twenty-eight and six pts from group (b) showed mean values of 685 +/- 1.45 and 1405 +/- 5.65; 856 +/- 7.09 and 435 +/- 2.20 with apparent improvement for the former. Five pts and fourteen pts from group (c) showed mean value of 2682 +/- 7.85 and 2099 +/- 6.82; 816 +/- 2.53 and 877 +/- 4.78 respectively. As for the 5-yr follow up ten pts and five pts from group (b) showed mean values of 705 +/- 1.6 and 861 +/- 7.15; 911 +/- 7.3 and 457 +/- 2.3 respectively. CONCLUSIONS: Although the clinical picture improved with therapy, BHR was not significantly affected in any patient group, at two and five years of follow-up. Furthermore, no correlation was found between the clinical picture and PD20 FEV1 values. BHR seems to result from the interaction of multiple factors that are worth further investigating. BHR cannot be considered a marker of disease activity in asthma and therefore is not a useful tool for guiding asthma therapy.

Maternal and fetal outcome of lupus pregnancy: a prospective study of 29 pregnancies.

The aim of this study was to analyse pregestational and pregnancy risk factors for adverse fetal and maternal outcome in lupus pregnancy. Twenty women with systemic lupus erythematosus (SLE) (29 pregnancies) were prospectively evaluated. Mean patient age was 29.5+/-4.7 years, and mean disease duration, 6.3+/-6.5 years. Twenty-two pregnancies (75.9%) ended in live births; preterm delivery occurred in 17.4%, intrauterine growth restriction in 50%, preeclampsia in 3.7%, and gestational hypertension in 8%. Six pregnancies (20.7%) ended in spontaneous abortions. Adverse live-birth outcome was significantly associated with low pregestational serum albumin level, elevated gestational anti-dsDNA antibody, and diabetes mellitus. Spontaneous abortion was directly associated with low levels of pregestational serum albumin, positive anticardiolipin IgA, anti-beta2-glycoprotein I IgM, and anti-La antibodies, and inversely associated with number of patients' children. Postgestational lupus flare-up was noted in six pregnancies. Risk factors included high pregestational SLE Disease Activity Index (SLEDAI), lower serum albumin, elevated serum antibody to dsDNA, proteinuria, and use of prednisone and hydroxychloroquine. We conclude that despite high rate of obstetrical complications and postpartum lupus flare-up, pregnancy poses low risk for the majority of women with SLE.

Secondary pulmonary hypertension--diagnosis and management.

Secondary pulmonary hypertension (SPHtn) is generally attributable to abnormalities in structure or function of the heart or lung parenchyma. While often defined as a physiologic parameter, pulmonary hypertension (PHtn) can be a major contributor to death and disability in cardiopulmonary diseases. Both detection and management are a challenge. We will review the pathophysiology, diagnostic tools, and treatment strategies in SPHtn with an emphasis on cor pulmonale associated with chronic obstructive pulmonary disease (COPD), pulmonary vasculopathies, and pulmonary embolus. The pathophysiology and common etiologies of SPHtn can be divided into three major categories: (1) elevated pulmonary venous pressure (LV failure and mitral valve disease), (2) pulmonary vascular occlusive disease with or without pulmonary parenchymal disease (pulmonary emboli, COPD, connective tissue diseases), and (3) hypoxemia (sleep apnea). The echo-Doppler is a simple cost-effective tool for detecting PHtn, evaluating right ventricular function, and distinguishing common etiologies such as abnormal systolic and diastolic left ventricular function and mitral valve disease. The ventilation-perfusion radionuclide scan can be used to exclude thromboembolic PHtn, but a helical computer tomography with contrast or pulmonary angiography are necessary to distinguish patients that may benefit from a pulmonary thromboendarterectomy. The six minute walk oxygen saturation test is useful as a quantitative measure of functional capacity, prognosis, response to therapy, and oxygen requirement. Treatment strategies in cor pulmonale are tailored to the specific diagnosis, but generally include proper nutrition, exercise, oxygen supplementation, medications such as digoxin, diuretics, anti-coagulation, and pulmonary vasodilator therapy in selected patients.

A case of cellulitis complicating Campylobacter jejuni subspecies jejuni bacteremia and review of the literature.

Infection with Campylobacter species is a predominant cause of food-borne gastroenteritis in the industrialized world. Bacteremia is detected in <1% of patients with diarrhea, mainly in immunocompromised hosts or those in the extremes of age. Reported here is the case of a 78-year-old, immunocompromised male patient with Campylobacter jejuni subsp. jejuni bacteremia complicated by cellulitis. The infection was characterized by a protracted course with several recurrences and refractoriness to multiple antibiotic regimens, responding only to a prolonged course of meropenem treatment. The frequency of cellulitis as reflected in previously reported series of Campylobacter bacteremia and the clinical characteristics of this difficult-to-treat infection are reviewed.

Neurotensin pulmonary metabolism in normal and asthmatic subjects.

BACKGROUND: The role of pulmonary metabolism of endogenous neurotensin (NT) in asthma is still unclear. Information on this subject in humans is scarce. OBJECTIVES: Evaluation of the pulmonary metabolism of the endogenous NT in asthmatic subjects during symptom-free periods and after a methacoline challenge test and in healthy individuals. METHODS: Ten asthmatic subjects (aged 34 to 70 years), diagnosed with extrinsic (n = 5), atopic (n = 3), and mixed asthma (n = 2), were compared to a group of 10 healthy individuals (aged 45 to 69 years). The asthmatic group of patients was evaluated with a PD20-FEV1 methacoline challenge test 3 days after a washout period from cessation of their regular medications. Two catheters were inserted in order to draw blood samples for the evaluation of NT concentration: one was inserted into the pulmonary artery and the other into the radial artery. The mean concentration of NT in pulmonary and systemic arterial blood, as well as the arteriovenous difference of NT and the absolute value of production rate [PR/m'], PR/m'/kg and PR/m'/m2 were calculated for each participant. RESULTS: The mean neurotensin concentration in normal subjects was higher in mixed venous blood (pulmonary artery) than in systemic arterial blood (p < 0001). Similarly, mean NT mixed venous levels in asthmatic subjects was shown to be higher than mean NT levels in systemic arterial blood, before and after the bronchoconstriction with methacoline (p = 0.05 and p = 0.02, respectively). In contrast, the arterovenous difference and the mean values of PR of NT were similar in both groups. CONCLUSIONS: Our findings suggest that (1) NT concentration in mixed venous blood changes in transit through the pulmonary parenchyma, indicating that the pulmonary parenchyma is an important site of NT metabolism; (2) Pulmonary clearance of NT is unaffected by cholinergic bronchoconstriction. Further clinical studies are needed in order to improve both the understanding and the therapeutic approach of the neurogenic process in asthmatic subjects.

Octreoscan perspectives in sarcoidosis and idiopathic interstitial pneumonia.

STUDY OBJECTIVES: Clinical, radiological, and serological tests have been proven to be unsatisfactory as markers of activity in sarcoidosis and idiopathic interstitial pneumonia (IIP). We investigated 111In-Octreotide (Octreoscan) scintigraphy as a tool for classifying and assessing disease activity in sarcoidosis and IIP, in comparison of the radiological imaging and dyspnea symptom scores. PATIENTS: Thirty-three patients (pts) of which 16 with sarcoidosis (mean age 43.6, range 30-58 years) and 17 with histologically diagnosed IIP (mean age 62.2, range 35-79 years), were enrolled in the study. Clinical history was taken as well as, physical examination, chest X-ray and pulmonary function tests were assessed. A high-resolution computed tomography scan (HRCT) was carried out in-patients affected by sarcoidosis, who had a normal chest X-ray, and in IIP patients. Both groups were evaluated with the Octreoscan uptake index (U.I.; normal value: < or = 10). RESULTS: In patients affected with sarcoidosis, the Octreoscan U.I. was significantly higher than in patients with IIP (16.35 +/- 3.1 and 10.06 +/- 0.8, respectively; p < 0.01) and was correlated with the radiographic staging (p < 0.01) and with the degree of dyspnea (p < 0.01). In-patients with IIP the Octreoscan uptake index was slightly above the normal limit (range 10.3-11.7) in non-specific interstitial pneumonia (NSIP) and desquamative interstitial pneumonia (DIP), whereas in usual interstitial pneumonia (UIP) Octreoscan uptake index was always within normal limit (< or = 10 U.I.). A negative correlation was observed with histological findings (p < 0.01) and with HRCT appearance (p < 0.01). CONCLUSIONS: Octreoscan U.I. is correlated with the degree of dyspnea in patients affected by sarcoidosis and can quantify more accurately the degree of pulmonary involvement, as compared to radiological assessment. Further studies are necessary to evaluate Octreoscan as an early test for predicting disease progression. Octreoscan U.I. could be helpful in monitoring IIP in specific histological subsets (NSIP and DIP) and substitute HRCT in the assessment of UIP for its excellent accuracy.