Are too many inferior vena cava filters used? Controversial evidences in different clinical settings: a narrative review.

The use of inferior vena cava filters to prevent pulmonary embolism is increasing mainly because of indications that appear to be unclearly codified and recommended. The evidence supporting this approach is often heterogeneous, and mainly based on observational studies and consensus opinions, while the insertion of an IVC filter exposes patients to the risk of complications and increases health care costs. Thus, several proposed indications for an IVC filter placement remain controversial. We attempt to review the proof on the efficacy and safety of IVC filters in several "special" clinical settings, and assess the robustness of the available evidence for any specific indication to place an IVC filter.

Papillary fibroelastoma, unusual cause of stroke in a young man: a case report.

BACKGROUND: Papillary fibroelastoma is the third most common primary benign tumor with an incidence of up to 0.33% in autopsy series; it accounts for approximately 75% of all cardiac valvular tumors. CASE PRESENTATION: We describe a rare case of a 28-Year-old man that while playing football, had a sudden onset of neurological deficit: aphasia, right hemiparesis and right facial numbness. Transthoracic echocardiography (TTE) showed a 10x10 mm mass attached to the anterior mitral valve leaflet. The patient was treated surgically for the prevention of further embolic complications. Histologic examination of the resected mass revealed a papillary fibroelastoma. It is the third most frequent primary cardiac tumor, after myxoma and fibroma, and the most common primary tumor of heart valves. Despite the benign nature of this tumor, it carries very high risk of embolic complications. The successful complete resection of the papillary fibroelastoma is curative and the long-term postoperative prognosis is excellent. CONCLUSIONS: Differential diagnosis of cardiac masses requires clinical informations, laboratory tests, blood cultures and appropriate use of imaging modalities. Papillary fibroelastoma is a potential cause of embolic stroke in the young. The prompt surgical excision of papillary fibroelastoma is curative and the long-term postoperative prognosis is excellent.

A Rare Case of Aortic Valve Thrombosis in Patient with Idiopathic Hypereosinophilic Syndrome.

Idiopathic hypereosinophilic syndrome (HES) is characterized by persistent eosinophilia and eosinophil-mediated organ-system damage. Cardiac thrombosis and thromboembolic complications represent common causes of morbidity and mortality and usually involve cardiac ventricles or mitral and prosthetic valves, while the involvement of the aortic valve is extremely rare in HES. Here we report peculiar multimodality images of an atypical case of extended thrombosis of the aortic valve, complicated by myocardial ischemia and asymptomatic cerebral ischemia, likely due to thrombus embolization, occurring in a 48-year-old man with HES. Prompt anticoagulant and steroid therapy lead to rapid and complete resolution of the thrombotic lesions, allowing preserving the native valve and preventing further embolic events.

From the Veins to the Heart: A Rare Cause of Varicose Veins.

The presence of pulsating varicous veins is an uncommon finding, generically attributed to right heart failure. The precise causes of this phenomenon have been poorly defined in the literature. The finding of this infrequent condition is important because it may be a sign of major diseases, often not known. Here we described a 75-year-old woman presented to the Angiology Unit for the presence of bilateral pulsatile swelling in her groin and along both lower limbs. A bedside ultrasound examination showed an arterial like pulsating flow both in the superficial and in the deep veins of the lower limbs due to a severe tricuspid regurgitation not previously known.

Clinical and pathological findings of a fatal systemic capillary leak syndrome (Clarkson disease): a case report.

Systemic capillary leak syndrome (SCLS) is a rare disorder with episodes of hypotension, hypoalbuminemia, and hemoconcentration. During attacks endothelial hyperpermeability results in leakage of plasma proteins into the interstitial space. Attacks vary in severity and may be lethal.A 49-year-old previously healthy man was admitted to hospital for hypovolemic shock, anasarca with pleuropericardial effusion, muscle fatigue, and oliguria occurring after a flu-like syndrome. Laboratory data showed an increase in hematocrit (65%), leucocytes (24.590 µ/L), creatinine (2.5 mg/dL), creatine phosphokinase (10.000 U/L), and a decrease in serum albumin (17 g/L) without proteinuria. Immunoglobulins of class G/λ monoclonal gammopathy were detected (1.3 g/L). The initial suspicions addressed to a protein-loosing syndrome or to an effort-related rhabdomyolysis. Initial therapy was based on steroids, albumin, and high molecular weight plasma expanders (hydroxyethyl starch). Because of high hematocrit, phlebotomy was also performed. The patient had complete clinical remission and a diagnosis of SCLS was finally made. He received prophylactic therapy with verapamil and theophylline that was self-stopped for intolerance (hypotension and tachycardia). He had a new crisis 2 days after a physical effort, and was admitted in intensive care unit. The patient died for severe hypovolemic shock with multiorgan failure and sudden cardiac arrest 15 hours after hospital admission. Postmortem investigation revealed massive interstitial edema of main organs with myocardial hyperacute ischemia.Studies on SCLS are limited for the rarity of the disease and its unpredictable course. Both prophylactic and acute crisis treatments are empirical and optimal management of severe attacks is still lacking.

Myasthenia Gravis following Low-Osmolality Iodinated Contrast Media.

We describe the case of 79-year-old man admitted to our general hospital for a 6-week history of progressive dysphagia to solids and liquids associated with weight loss. To reach a diagnosis a total body CT scan with low-osmolality iodinate contrast agent was performed. Two hours later the patient developed an acute respiratory failure requiring orotracheal intubation and mechanical ventilation. The laboratory and neurological tests allow formulating the diagnosis of myasthenia gravis. In literature, other three case reports have associated myasthenic crisis with exposure to low-osmolality contrast media. This suggests being careful in administering low-osmolality contrast media in myasthenic patients.

Oral renin inhibitors in clinical practice: a perspective review.

Hypertension is an important risk factor for cardiovascular morbidity and mortality. The importance of the renin-angiotensin-aldosterone system (RAAS) in cardiovascular and renal diseases has long been recognized: for this reason the conventional therapies, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), ß-blockers, and aldosterone antagonists represent the backbone of current antihypertensive therapy. Aliskiren is the first direct renin inhibitor (DRI) suitable for oral administration. By achieving more complete renin-angiotensin system inhibition, direct renin inhibitors may afford greater protection from hypertensive complications. Present evidence indicates that aliskiren reduces baseline systolic and diastolic blood pressure greater than placebo and that it is as effective as other first-line antihypertensive agents. Extra advantages can be reached when it is used in combination therapy. Clinical trials and in vitro studies also suggest that aliskiren has several cardioprotective and renoprotective effects. Therapy with aliskiren is well tolerated, but recently some concerns have arisen because of the early termination of the ALTITUDE study due to an increased incidence of adverse effects.

The kidney in type 2 diabetes: focus on renal structure

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Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes.

Type 2 diabetes is frequently associated with an inflammatory status; the relationships between low-grade inflammation and diabetic nephropathy are still unclear. The aim of this study was to evaluate the relationships between acute-phase markers of inflammation, glomerular structure, and albumin excretion rate (AER) in type 2 diabetes. In 74 patients with type 2 diabetes (23 normoalbuminuric, 30 microalbuminuric, and 21 proteinuric) fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP), and IL-6 were determined. AER was measured on three 24-h urine collections; GFR was measured by 51Cr EDTA plasma clearance. A kidney biopsy was performed, and mesangial fractional volume [Vv(mes/glom)] and glomerular basement membrane (GBM) width were estimated by electron microscopic morphometric analysis. CRP, fibrinogen, SAA, and IL-6 differed among groups, with proteinuric patients having the highest levels. SAA and fibrinogen correlated with AER (P < 0.03 and P < 0.001, respectively). GBM width and Vv(mes/glom) increased from normoalbuminuric to proteinuric patients [P < 0.005 normoalbuminuric and microalbuminuric versus proteinuric for GBM, P < 0.01 normoalbuminuric versus proteinuric for Vv(mes/glom)]. In patients with increased GBM width (> 396 nm), CRP, SAA, and IL-6 were higher than in patients with normal GBM width (P < 0.003, P < 0.004, and P < 0.0004, respectively). GBM width was directly correlated with fibrinogen (r = 0.33, P < 0.002) and IL-6 (r = 0.25 P < 0.05). In conclusion, this study demonstrates that acute-phase markers of inflammation are associated with nephropathy status and GBM thickening, suggesting a role for inflammation in the pathogenesis of diabetic glomerulopathy.

Quantitave and qualitative changes in vascular endothelial growth factor gene expression in glomeruli of patients with type 2 diabetes.

OBJECTIVE: Vascular endothelial growth factor (VEGF) exists in three main splice variants, characterized by 121, 165 and 189 amino acids (VEGF 121, VEGF 165 and VEGF 189) and acts via two specific receptors: VEGF-R1 or Flt-1 and VEGF-R2 or KDR. VEGF plays an important role in the pathogenesis of diabetic retinopathy. This study examined the relationship between VEGF and its isoforms and the severity of diabetic nephropathy in type 2 diabetes. DESIGN: We evaluated the glomerular gene expression of VEGF and its receptors and studied the relationships with renal functional and structural parameters in type 2 diabetic patients. METHODS: Glomeruli from 17 kidney biopsies were microdissected; 14 out of 17 biopsies were also subjected to electron microscopic morphometric analysis to estimate glomerular structural parameters. VEGF mRNA was studied by comparative kinetic RT-PCR and real-time RT-PCR in order to identify the three different isoforms and to quantify VEGF, VEGF-R1 and VEGF-R2 mRNA levels. RESULTS: (i) Glomerular VEGF mRNA levels were inversely related to albumin excretion rate (r=-0.66, P=0.004); (ii) both the degree of mesangial and mesangial matrix expansion were inversely related to VEGF 165 mRNA levels (r=-0.73, P=0.005 and r=-0.64, P=0.017), and directly to VEGF 121 mRNA levels (r=0.74, P=0.003 and r=0.73, P=0.004); and (iii) VEGF and VEGF-R2 mRNA levels were directly related (r=0.62, P=0.033). CONCLUSIONS: These findings suggested that quantitative and qualitative changes in VEGF expression are present in type 2 diabetic patients with nephropathy and might be involved in the pathogenesis and progression of diabetic glomerulopathy.

PC-1 amino acid variant Q121 is associated with a lower glomerular filtration rate in type 2 diabetic patients with abnormal albumin excretion rates.

OBJECTIVE: To study the relationships between the PC-1 K121Q variant and diabetic nephropathy (DN) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 125 patients with type 2 diabetes and abnormal albumin excretion rate (AER) (range 20-5416 microg/min) were followed up for 4 years with repeated measurements of glomerular filtration rate (GFR). Genomic DNA was extracted from all patients, and the PC-1 K121Q polymorphism was determined by the PCR AvaII restriction enzyme. A subset of 64 patients underwent a percutaneous kidney biopsy at baseline, and glomerular structure was analyzed by electron microscopic morphometric analysis. At baseline, age (56 +/- 8 vs. 59 +/- 7 years), BMI (28.3 +/- 4.3 vs. 28.6 +/- 3.7 kg/m(2)), known duration of type 2 diabetes (11.1 +/- 7 vs. 11.9 +/- 8 years), and HbA(1c) (8.6 +/- 1.8 vs. 8.4 +/- 1.7%) were similar in K121K (KK, n = 87, 73 men/14 women) and XQ (35 K121Q + 3 Q121Q, n = 38, 27 men/11 women) patients. Baseline GFR was 96 +/- 28 ml. min(-1). 1.73 m(-2) and was related (P = 0.01-0.001) to age, known diabetes duration, and systolic blood pressure. RESULTS: XQ patients had lower GFR (P < 0.05) than KK patients (88 +/- 30 vs. 100 +/- 26 ml. min(-1). 1.73 m(-2)); this difference persisted also after factoring in age and known diabetes duration. The rate of progression of DN was similar in KK and XQ patients: %deltaGFR was 4.1/year (median, range: 22.9-30.6) vs. 4.2/year (9.8-26.7). Morphometric parameters of diabetic glomerulopathy were similar in the two genotype groups. CONCLUSIONS: Among patients with type 2 diabetes with abnormal AER, those carrying the Q PC-1 genotype have more severe DN but not a faster GFR decline than KK patients, thus suggesting faster DN development since diabetes diagnosis in XQ patients.

Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes.

Podocyte structural changes have been suggested to be involved in the pathogenesis of albuminuria in diabetes. We evaluated podocytes density, number, and structure in 67 white patients with type 2 diabetes: 21 normoalbuminuric (NA), 23 microalbuminuric (MA), and 23 proteinuric (P). Kidney function and biopsy studies were performed; 20 kidney donors served as control subjects. Electron microscopic morphometric analysis was used to estimate numerical density of podocytes per glomerulus [Nv(epi/glom)], filtration slit length density per glomerulus (FSLv/glom), and foot process width (FPW). The number of podocytes per glomerulus (Epi N/glom) was obtained by multiplying Nv(epi/glom) by mean glomerular volume. Nv(epi/glom) was significantly decreased in all type 2 diabetic groups compared with control subjects and was lower in MA and P than in NA (P < 0.0001, ANOVA). Epi N/glom was lower in MA and P patients compared with control subjects (P < 0.002, ANOVA); however, there were no significant differences among the type 2 diabetic groups. In addition, MA and P had decreased FSLv/glom and increased FPW compared with NA (P < 0.005 for both, ANOVA). The albumin excretion rate was inversely related to Nv(epi/glom) and FSLv/glom and directly to FPW (P < 0.0005 for all), whereas there was no correlation with Epi N/glom. In conclusion, changes in podocyte structure and density occur since the early stages of diabetic nephropathy and might contribute to increasing albuminuria in type 2 diabetic patients. These findings also suggest that in white type 2 diabetic patients, the density of podocytes may be functionally more relevant than the absolute number.

Effects of cigarette smoking on glomerular structure and function in type 2 diabetic patients.

Prospective studies have established smoking as an independent risk factor for diabetic nephropathy, suggesting an adverse effect of smoking on glomerular structure and function. To test this hypothesis, this study evaluated GFR, metabolic profile, and smoking habits in 96 patients with type 2 diabetes and abnormal albumin excretion rate (AER). All patients underwent percutaneous kidney biopsy: mesangial fractional volume [Vv (mes/glom)] and glomerular basement membrane (GBM) width were estimated by electron microscopic morphometric analysis; interstitial fibrosis was estimated semiquantitatively by light microscopy. Forty-eight patients were smokers. Compared with nonsmokers, smokers had higher values of HbA(1c) (P = 0.002), AER (P = 0.026), GFR (P = 0.004), and GBM width (P = 0.002); moreover, GFR was higher in current smokers than in former smokers (P = 0.001), and GBM width was related to heavy smoking (F = 5.4; P = 0.006). Multiple linear regression analyses revealed that HbA(1c) was associated with fasting blood glucose (beta coef = 0.52; P < 0.001), smoking habit (beta coef = 0.31; P < 0.001), insulin therapy (beta coef = 0.22; P = 0.012), and male gender (beta coef = -0.20; P = 0.020); AER was related to Vv (mes/glom) (beta coef = 0.32; P = 0.003), GBM width (beta coef = 0.28; P = 0.016), and interaction between smoking habit and HbA(1c) (beta coef = 0.24; P = 0.040). GFR was negatively correlated with Vv (mes/glom) (beta coef = -0.57; P < 0.001) and age (beta coef = -0.29; P = 0.001) and positively correlated with GBM width (beta coef = 0.27; P = 0.012), heavy current smoking (beta coef = 0.24; P = 0.028), and HbA(1c) (beta coef = 0.28; P = 0.040); GBM width was explained by Vv (mes/glom) (beta coef = 0.53; P < 0.001), interaction between heavy smoking and HbA(1c) levels (beta coef = 0.25; P = 0.003), and diabetes duration (beta coef = 0.23; P = 0.010). Smoking habit did not affect the index of interstitial fibrosis. In conclusion, cigarette smoking affects glomerular structure and function in type 2 diabetes and may be an important factor for the onset and progression of diabetic nephropathy.

Nitric oxide modulation of renal and cardiac hemodynamics in type 2 diabetes.

OBJECTIVE: To evaluate endothelial function in type 2 diabetic patients with and without diabetic nephropathy. METHODS: We studied the effects of systemic infusion of the nitric oxide (NO) synthase inhibitor NG-monomethyl-l-arginine (L-NMMA) on cardiovascular and renal hemodynamics in six type 2 diabetic patients with microalbuminuria (D2-MA), six type 2 diabetic patients with normoalbuminuria (D2-NA) and five control subjects. Both type 2 diabetic patients and control subjects had mild arterial hypertension. RESULTS: L-NMMA infusion decreased the cardiac index in all groups. A reduction in glomerular filtration rate (GFR) and an increase in filtration fraction were observed only in controls. Renal plasma flow decreased in controls and D2-NA patients and renal vascular resistance increased in all groups. CONCLUSIONS: The effect of L-NMMA on cardiac output was similar in controls and type 2 diabetic patients with and without diabetic nephropathy. In contrast, the effect on GFR was impaired in both diabetic groups, suggesting that glomerular NO homeostasis is altered in type 2 diabetes. Moreover the discrepancy, in diabetic patients, between cardiac and renal effects during L-NMMA infusion suggests that the modulation of glomerular hemodynamics is independent from NO-regulated cardiac output.

Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients.

BACKGROUND: Glomerular filtration rate (GFR) is the best overall index of renal function in health and disease. Inulin and 51Cr-EDTA plasma clearances are considered the gold standard methods for estimating GFR. Unfortunately, these methods require specialized technical personnel over a period of several hours and high costs. In clinical practice, serum creatinine is the most widely used index for the noninvasive assessment of GFR. Despite its specificity, serum creatinine demonstrates an inadequate sensitivity, particularly in the early stages of renal impairment. Recently, cystatin C, a low molecular mass plasma protein freely filtered through the glomerulus and almost completely reabsorbed and catabolized by tubular cells, has been proposed as a new and very sensitive serum marker of changes in GFR. This study was designed to test whether serum cystatin C can replace serum creatinine for the early assessment of nephropathy in patients with type 2 diabetes. METHODS: The study was performed on 52 Caucasian type 2 diabetic patients. Patients with an abnormal albumin excretion rate (AER) were carefully examined to rule out non-diabetic renal diseases by ultrasonography, urine bacteriology, microscopic urine analysis, and kidney biopsy. Serum creatinine, serum cystatin C, AER, serum lipids, and glycosylated hemoglobin (HbA1c) were measured. GFR was estimated by the plasma clearance of 51Cr-EDTA. In addition the Cockcroft and Gault formula (Cockcroft and Gault estimated GFR) was calculated. RESULTS: Cystatin C serum concentration progressively increased as GFR decreased. The overall relationship between the reciprocal cystatin C and GFR was significantly stronger (r = 0.84) than those between serum creatinine and GFR (r = 0.65) and between Cockcroft and Gault estimated GFR and GFR (r = 0.70). As GFR decreased from 120 to 20 mL/min/1.73 m2, cystatin C increased more significantly that serum creatinine, giving a stronger signal in comparison to that of creatinine over the range of the measured GFR. The maximum diagnostic accuracy of serum cystatin C (90%) was significantly better than those of serum creatinine (77%) and Cockcroft and Gault estimated GFR (85%) in discriminating between type 2 diabetic patients with normal GFR (>80 mL/min per 1.73 m2) and those with reduced GFR (<80 mL/min/1.73 m2). In particular, the cystatin C cut-off limit of 0.93 mg/L corresponded to a false-positive rate of 7.7% and to a false-negative rate of 1.9%; the serum creatinine cut-off limit of 87.5 micromol/L corresponded to a false-positive rate of 5.8% and to a false-negative rate of 17.0%. CONCLUSIONS: Cystatin C may be considered as an alternative and more accurate serum marker than serum creatinine or the Cockcroft and Gault estimated GFR in discriminating type 2 diabetic patients with reduced GFR from those with normal GFR.