The Beneficial Effects of Bariatric-Surgery-Induced Weight Loss on Renal Function.

Obesity represents an independent risk factor for the development of chronic kidney disease (CKD), leading to specific histopathological alterations, known as obesity-related glomerulopathy. Bariatric surgery is the most effective means of inducing and maintaining sustained weight loss. Furthermore, in the context of bariatric-surgery-induced weight loss, a reduction in the proinflammatory state and an improvement in the adipokine profile occur, which may also contribute to the improvement of renal function following bariatric surgery. However, the assessment of renal function in the context of obesity and following marked weight loss is difficult, since the formulas adopted to estimate glomerular function use biomarkers whose production is dependent on muscle mass (creatinine) or adipose tissue mass and inflammation (cystatin-c). Thus, following bariatric surgery, the extent to which reductions in plasma concentrations reflect the actual improvement in renal function is not clear. Despite this limitation, the available literature suggests that in patients with hyperfiltration at baseline, GFR is reduced following bariatric surgery, whereas GFR is increased in patients with decreased GFR at baseline. These findings are also confirmed in the few studies that have used measured rather than estimated GFR. Albuminuria is also decreased following bariatric surgery. Moreover, bariatric surgery seems superior in achieving the remission of albuminuria and early CKD than the best medical treatment. In this article, we discuss the pathophysiology of renal complications in obesity, review the mechanisms through which weight loss induces improvements in renal function, and provide an overview of the renal outcomes following bariatric surgery.

Arterial Hypertension and Cardiopulmonary Function: The Value of a Combined Cardiopulmonary and Echocardiography Stress Test.

Arterial hypertension (AH) is a global burden and the leading risk factor for mortality worldwide. Haemodynamic abnormalities, longstanding neurohormonal and inflammatory activation, which are commonly observed in patients with AH, promote cardiac structural remodeling ultimately leading to heart failure (HF) if blood pressure values remain uncontrolled. While several epidemiological studies have confirmed the strong link between AH and HF, the pathophysiological processes underlying this transition remain largely unclear. The combined cardiopulmonary-echocardiography stress test (CPET-ESE) represents a precious non-invasive aid to detect alterations in patients at the earliest stages of HF. The opportunity to study the response of the cardiovascular system to exercise, and to differentiate central from peripheral cardiovascular maladaptations, makes the CPET-ESE an ideal technique to gain insights into the mechanisms involved in the transition from AH to HF, by recognizing alterations that might be silent at rest but influence the response to exercise. Identifications of these subclinical alterations might allow for a better risk stratification in hypertensive patients, facilitating the recognition of those at higher risk of evolution towards established HF. This may also lead to the development of novel preventive strategies and help tailor medical treatment. The purpose of this review is to summarise the potential advantages of using CPET-ESE in the characterisation of hypertensive patients in the cardiovascular continuum.

Predicting the transition to and progression of heart failure with preserved ejection fraction: a weighted risk score using bio-humoural, cardiopulmonary, and echocardiographic stress testing.

AIMS: Risk stratification of heart failure (HF) patients with preserved ejection fraction (HFpEF) can promote a more personalized treatment. We tested the prognostic value of a multi-parametric evaluation, including biomarkers, cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE), and lung ultrasound, in HFpEF patients and subjects at risk of developing HF (HF Stages A and B). BACKGROUND: Risk stratification of heart failure (HF) patients with preserved ejection fraction (HFpEF) can promote a more personalized treatment. DESIGN: We tested the prognostic value of a multi-parametric evaluation, including biomarkers, cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE), and lung ultrasound, in HFpEF patients and subjects at risk of developing HF (HF Stages A and B). METHODS AND RESULTS: We performed a resting clinical/bio-humoural evaluation and a symptom-limited CPET-ESE in 274 patients (45 Stage A, 68 Stage B, and 161 Stage C-HFpEF) and 30 age- and sex-matched healthy controls. During a median follow-up of 18.5 months, we reported 71 HF hospitalizations and 10 cardiovascular deaths. Cox proportional-hazards regression identified five independent predictors and each was assigned a number of points proportional to its regression coefficient: stress-rest ΔB-lines >10 (3 points), peak oxygen consumption <16 mL/kg/min (2 points), minute ventilation/carbon dioxide production slope ≥36 (2 points), peak systolic pulmonary artery pressure ≥50 mmHg (1 point) and resting N-terminal pro-brain natriuretic peptide (NT-proBNP) >900 pg/mL (1 point). The event-free survival probability for low risk (<3 points), intermediate risk (3-6 points), and high risk (>6 points) were 93%, 52%, and 20%, respectively. The area under the curve (AUC) for the scoring system to predict events was 0.92 (95% CI 0.88-0.96), with an accuracy significantly higher than the individual components of the score (all P < 0.01 vs. individual AUCs). CONCLUSION: A weighted risk score including NT-proBNP, markers of cardiopulmonary dysfunction and indices of exercise-induced pulmonary congestion identifies HFpEF patients at increased risk for adverse events and Stage A and B subjects more likely to progress towards more advanced HF stages.

Cardiac Reserve and Exercise Capacity: Insights from Combined Cardiopulmonary and Exercise Echocardiography Stress Testing.

BACKGROUND: Cardiopulmonary exercise testing (CPET) represents the gold standard to estimate peak oxygen consumption (VO2) noninvasively. To improve the analysis of the mechanisms behind effort intolerance, we examined whether exercise stress echocardiography measurements relate to directly measured peak VO2 during exercise in a large cohort of patients within the heart failure (HF) spectrum. METHODS: We performed a symptom-limited graded ramp bicycle CPET exercise stress echocardiography in 30 healthy controls and 357 patients: 113 at risk of developing HF (American College of Cardiology/American Heart Association stage A-B) and 244 in HF stage C with preserved (HFpEF, n = 101) or reduced ejection fraction (HFrEF, n = 143). RESULTS: Peak VO2 significantly decreased from controls (23, 21.7-29.7 mL/kg/minute; median, interquartile range) to stage A-B (18, 15.4-20.7 mL/kg/minute) and stage C (HFpEF: 13.6, 11.8-16.8 mL/kg/minute; HFrEF: 14.2, 10.7-17.5 mL/kg/minute). A regression model to predict peak VO2 revealed that peak left ventricular (LV) systolic annulus tissue velocity (S'), peak tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (right ventricle-pulmonary artery coupling), and low-load left atrial (LA) reservoir strain/E/e' (LA compliance) were independent predictors, in addition to peak heart rate, stroke volume, and workload (adjusted R2 = 0.76, P < .0001). The model was successfully tested in subjects with atrial fibrillation (n = 49) and with (n = 224) and without (n = 163) beta-blockers (all P < .01). Peak S' showed the highest accuracy in predicting peak VO2 < 10 mL/kg/minute (cut point ≤ 7.5 cm/sec, area under the curve = 0.92, P < .0001) and peak VO2 > 20 mL/kg/minute (cut point > 12.5 cm/sec, area under the curve = 0.84, P < .0001) in comparison with the other cardiac variables of the model (P < .05). CONCLUSIONS: Peak VO2 is directly related to measures of LV systolic function, LA compliance, and right ventricle-pulmonary artery coupling, in addition to heart rate and stroke volume and independently of workload, age, and sex. The evaluation of cardiac mechanics may provide more insights into the causes of effort intolerance in subjects from HF stages A-C.

The Complex Relationship Between Serum Uric Acid, Endothelial Function and Small Vessel Remodeling in Humans.

AIMS: The relationship between serum uric acid (SUA) and microvascular remodeling in humans remains largely unexplored. We assessed whether SUA provides additional information on the severity of microvascular remodeling than that obtained from the European Heart Score (HS), the patterns of microvascular remodeling associated with changes in SUA levels and the mediation by endothelial function and nitric oxide (NO) availability on this relationship. METHODS: A total of 162 patients included in the microvascular dataset of the Italian Society of Hypertension with available information on SUA, media-to-lumen (M/L) ratio, media cross-sectional area (MCSA), endothelial function, NO availability and HS were included in the analysis. The top tertile of M/L ratio and MCSA were used to define severe microvascular remodeling. RESULTS: A U-shaped association was observed between SUA and both M/L ratio and MCSA. Adjustment for HS did not affect these associations. SUA was able to reclassify a significant number of subjects without, and with, severe M/L ratio and MCSA remodeling over the HS alone. The microvascular remodeling associated with SUA levels presented a predominant hypertrophic pattern. SUA was inversely associated with endothelial function and NO availability. Structural equation modeling analysis controlling for the HS suggested that the association of SUA with M/L ratio and MCSA was mediated through changes in endothelial function and NO availability. CONCLUSIONS: The addition of SUA to the HS improves the identification of subjects with greater microvascular remodeling. The relationship between SUA and microvascular remodeling is mediated by endothelial function and NO availability.

Painless lymphadenopathy, eosinophilia and nephrotic syndrome: a diagnostic challenge in an era of increased migration.

Kimura's disease is a rare chronic inflammatory condition of unknown cause that most frequently affects Asian adults. It is characterized by painless lymphadenopathy in the head and neck region and eosinophilia, often associated with nephrotic syndrome. Α young Asian male presented to our Department with œdema at the lower limbs and scrotum, retroauricular masses, eosinophilia and proteinuria. Diagnosis was reached by a combination of the clinical picture, the patient's origin and a histological examination, which revealed well-developed lymph follicles with increased numbers of eosinophils and fibrosis, a finding typical of Kimura's disease. In case of a young Asian male who is otherwise healthy, but presents head/neck masses and/or unexplained eosinophilia associated with nephrotic syndrome, consider Kimura's disease in the differential diagnosis.

Inflammation and Vascular Ageing: From Telomeres to Novel Emerging Mechanisms.

Cardiovascular disease (CVD) remains the leading cause of morbility and mortality worldwide. The identification of common cardiovascular risk factors has led to the development of effective treatments that enabled a significant reduction of the global cardiovascular disease burden. However, a significant proportion of cardiovascular risk remains unexplained by these risk factors leaving many individuals at risk of cardiovascular events despite good control of the risk factors. Recent randomized clinical trials and Mendelian randomization studies have suggested that inflammation explains a significant proportion of the residual cardiovascular risk in subjects with good control of risk factors. An accelerated process of vascular ageing is increasingly recognized as a potential mechanism by which inflammation might increase the risk of CVD. In turn, cellular ageing represents an important source of inflammation within the vascular wall, potentially creating a vicious cycle that might promote progression of atherosclerosis, independently from the individual cardiovascular risk factor burden. In this review, we summarise current evidence suggesting a role for biological ageing in CVD and how inflammation might act as a key mediator of this association.

Protocols cure diseases, not patients: flaccid paresis in post-NSTEMI statin treatment.

An 82-year-old white woman presented at our Internal Medicine ward with flaccid tetraparesis. Two months earlier, she had suffered a non-ST elevation myocardial infarction treated with percutaneous coronary intervention (PCI) and stenting, and she had been prescribed the classical post-PCI therapy (ß-blockers, statins and antiplatelet agents). At admission, she was haemodynamically stable and the physical examination revealed reduced reflexes in the four limbs. Urgent laboratory findings revealed mild hypokalaemia. Considering the high statin doses she was taking, we also performed an urgent creatine phosphokinase test, which indicated rhabdomyolysis. Statin therapy was immediately stopped and aggressive fluid treatment begun, supplemented with potassium for increased urinary potassium losses. The patient progressively regained muscle strength.

[Atrial fibrillation and thyroid nodules]. / Fibrillazione atriale e noduli tiroidei.

Our previous papers reported an association between atrial fibrillation and supracentimeter thyroid nodules. Recently we noticed that the number of patients admitted to our ward presenting this relationship, was higher than average data relating to whole world's population. In this study we tried to prove the existence of this association in a selected group of inpatients aged between 71 and 80. This to rule-out any age-related confounding factor. We enrolled one hundred inpatients, aged between 71-80. Each patient underwent TSH, FT3, FT4 determination, ECG and thyroid ultrasound examination. 55 males and 45 females: 25 with atrial fibrillation (group A) and 75 without atrial fibrillation (group B). In group A, 80% had supracentimeter thyroid nodules, whereas in group B, only the 6.7% showed supracentimeter thyroid nodules. The rate of supracentimeter thyroid nodules in inpatients without atrial fibrillation (group B) was in line with that found in many studies about whole world's population (4-10%). On the contrary, subjects with atrial fibrillation (group A) showed a rate of supracentimeter thyroid nodules significantly higher (p < 0.001). These findings confirm our previous studies even in more age homogeneous peoples. Moreover, they suggest a link between atrial fibrillation and thyroid nodules. Cytokines and growth factors (IGF-1, EGF, FGF) might act like a connection between nodule goitre and atrial fibrillation.

[Celiac disease and myelodysplastic syndrome. A case report]. / Un paziente con malattia celiaca e sindrome mielodisplastica.

Celiac disease is an immune-mediated disorder induced by the intake of gluten proteins involving primarily the gastrointestinal tract. Myelodysplastic syndromes are clonal hematologic disorders, expanded from myeloid stem cells of uncertain pathogenesis. Anaemia is a common finding in patients with celiac disease. Frequently it is secondary to malabsorption of iron, folic acid or vitamin B12 and usually disappears completely with a strict adherence to a gluten-free diet and supplement of deficient factors. To the best of our knowledge, in medical literature only two cases of myelodysplastic syndrome associated with celiac disease have been described. Here we describe the case of a patient affected by adult celiac disease who went into remission following a gluten free diet. Later a macrocytic anaemia without vitamin B12 or folate deficiency appeared. Hematologic tests showed findings consistent with refractory anemia with ring sideroblasts. The association of celiac disease with myelodysplastic syndromes seems not to be casual. It raises the hypothesis of a primitive immunological disorder in both diseases.

[Hypokalemia from ectopic ACTH secretion and hypothiroidism in patient affected by small cell lung cancer]. / Ipokaliemia da produzione ectopica di ACTH ed ipotiroidismo in paziente affetto da microcitoma.

Endocrin paraneoplastic syndromes are characterized by an ectopic hormonal production. The ectopic adrenocorticotropic hormone (ACTH) secretion is often associated with small cell lung cancer. We report the case of 64-years-old man with persistent hypokalemia in Cushing's syndrome due to ectopic ACTH secretion. The patient was affected by small cell lung cancer and presented an hypothiroidism too. A proper chemotherapy resulted in remission of the hypokalemia, but the hypothiroidism was not influenced during our observation period.

[Pure red cell anaemia secondary to medullary B cell chronic lymphoproliferative disorders. A rare case]. / Aplasia eritroide pura secondaria a disturbo linfoproliferativo cronico midollare primario a cellule B. Un caso inusuale.

Acquired erythroblastopenia is rather rare, more frequent in adult or old male. In absence of anti EPO antibody, it's associate to inhibition of the erythroid growth mediated by suppressive T lymphocytes, generally T8 or NK or mediated by IgG antibody in association with timoma, lymphoproliferative or immunological disorders, and other diseases. The course usually is chronic and follows that of the associate pathology. We report a case with pure red cell anaemia associated to non classified medullary B cell lymphoproliferative disorder in an old woman with complete remission after steroid therapy.

[New therapeutic strategies to the advanced non small cell lung cancer]. / Nuove strategie terapeutiche nel carcinoma polmonare non a piccole cellule metastatico.

Lung cancer is an elevated mortality disease in spite of conventional therapy. Today it is possible to identify some molecules, as the epidermal growth factor receptor, involved in the earliest molecular alterations ofcancerogenesis. Here we show the inhibitors of the epidermal growth factor receptor as a therapeutic mean.

[Incidence of thyroid nodules in patients with and without atrial fibrillation]. / Incidenza di noduli tiroidei in pazienti con e senza fibrillazione atriale.

In one of our previous articles we noted that many patients affected by atrial fibrillation had more thyroid nodules > or = 10mm (38%) than general population (10%). These data are confirmed by a same number of patients without atrial fibrillation admitted to our Department of Internal Medicine. The high incidence of low-T3 syndrome is confirmed too.

[Clinical differences between heart failure versus ischemic patients]. / Pazienti a confronto: il malato scompensato e quello ischemico.

Heart failure represents a very common disease with high mortality, despite therapeutic and preventive measures. In order to evaluate the characteristics of heart failure patients, a case-control study was carried out, comparing sixty heart failure patients versus sixty patients who presented an evident atherosclerotic disease, but not heart failure. Among the differences we found, a higher heart rate, reduced levels of free-triiodothyronine and increased levels of serum uric acid in heart failure patients might directly contribute to its pathophysiology and represent potential therapeutic targets.

Relationship between low T3 syndrome and NT-proBNP levels in non-cardiac patients.

OBJECTIVES: A low T3 syndrome was described in patients with heart failure (HF), and it appears to be associated with adverse outcome, representing an independent predictor of mortality. However, it is not known if low T3 levels contribute to the pathophysiology of HF. On the other hand, it has been seen that an elevation of brain natriuretic peptides (BNP and NT-proBNP) may represent a warning signal for future cardiovascular disease and may be an early marker of diastolic dysfunction. Therefore we tested the hypothesis that low levels of free-triiodothyronine (FT3) are sufficient to determine an increased concentration of the amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP), as the result of an initial and asymptomatic cardiac impairment. METHODS: A total of 52 consecutive non-cardiac patients underwent thyroid function profile evaluation and NT-proBNP determination. On the basis of FT3 values they were divided in two subgroups: a low T3 group (19 patients) and a normal T3 group (33 patients). RESULTS: The median NT-proBNP concentration of patients with low T3 syndrome was significantly higher than in those with normal FT3 (370 vs. 120 pg/ml, P = 0.002). There is a strong and inverse correlation between FT3 and Log NT-proBNP (R = -0.47, P < 0.001); this relation persists in a multivariable regression analysis, after adjustment for other potentially confounding variables (P = 0.008). CONCLUSION: In absence of overt cardiovascular disease, patients with low T3 syndrome present an increased concentration of NT-proBNP. These data suggest that low FT3 levels may be a contributing factor for the development of cardiac dysfunction.

Systolic blood pressure response to exercise in type 1 diabetes families compared with healthy control individuals.

OBJECTIVE: Oxidative stress is increased in type 1 diabetes families. Since oxidative damage is a mediator of vascular injury and familial predisposition to hypertension increases the risk of hypertension and diabetic nephropathy, we studied blood pressure responses to exercise and cardiovascular risk factors in type 1 diabetes families. METHODS: Thirty-five type 1 patients, 74 first-degree relatives, and 95 healthy individuals without established coronary heart disease underwent a cycle ergometer test. Examination included medical history, lifestyle questionnaire, body weight, blood pressure, and laboratory tests [fasting plasma glucose and insulin, haemoglobin A1c (HbA1c), plasma lipids, C-reactive protein, fibrinogen, folate, plasma thiols, and albumin excretion rate]. RESULTS: Diabetic patients had higher plasma glucose, HbA1c, folate, and albuminuria, while lower plasma thiols than controls; relatives differed from controls in higher plasma total cholesterol and albuminuria, lower plasma thiols. No patient presented exercised-induced angina. Diabetic patients achieved a higher maximal exercise systolic blood pressure (similar workload); systolic pressure remained high during recovery. Relatives showed higher values of systolic pressure at peak exercise (same workload). The following were associated with an abnormal blood pressure response to exercise: diastolic blood pressure and HbA1c in the control sample; disease duration and fibrinogen in the diabetic group; plasma low-density lipoprotein (LDL) cholesterol, body mass index (BMI), housework, and plasma thiols among relatives. CONCLUSION: An abnormal blood pressure response to exercise testing has been identified for the first time in asymptomatic normotensive non-diabetic relatives of type 1 diabetics, which was associated with indices of metabolic syndrome and oxidative damage. Moreover, in healthy normotensive non-diabetic control individuals (without a family history of type 1 diabetes), the systolic blood pressure response to exercise was significantly correlated with HbA1c levels.