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.     

Endocarditis after mitral valve repair

Background. Native valve endocarditis is frequently managed with antibiotics alone, but prosthetic valve endocarditis usually requires an early operation. What is the best treatment of endocarditis after mitral valve repair?

Methods. From 1986 to 2000, 22 patients were treated for endocarditis affecting a previously repaired mitral valve. Causes of mitral valve dysfunction that led to repair were degenerative (11 patients), ischemic (5 patients), endocarditic (3 patients), rheumatic (2 patients), and functional (1 patient). Endocarditis was active in 21 patients and healed in 1. Interval from initial mitral valve repair to onset of endocarditis ranged from 1 week to 10.3 years (median, 6 months). Pathology included leaflet vegetation (15), annuloplasty vegetation (4), leaflet perforation (5), and abscess (3). Mean follow-up was 3.9 ± 3.3 years.

Results. Fifteen patients underwent repeat mitral valve operations with freedom from mitral valve reoperation of 65%, 41%, and 26% at 30 days, 1 year, and 5 years after onset of endocarditis. After a high early hazard, risk of reoperation fell to 10.8% per year. Seven patients, all with a leaflet vegetation, were treated with antibiotics alone. Antibiotics eradicated infection in all; however all had mitral regurgitation 2+ to 4+. Survival was 96%, 74%, and 68% at 30 days, 1 year, and 5 years. Endocarditis recurred in 1 patient (92% free of event).

Conclusions. Most patients that have endocarditis develop after mitral valve repair require reoperation. However if infection is limited to a leaflet, early reoperation may be unnecessary because antibiotics alone can eradicate infection.     

Changes in bone mineral density, lean body mass and fat content as measured by dual energy x-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation therapy

PURPOSE: We characterize the consequences of androgen deprivation therapy on body composition in elderly men. MATERIALS AND METHODS: Using a dual energy x-ray absorptiometry instrument, we determined the changes in bone mineral density, bone mineral content, fat body mass and lean body mass in 35 patients with prostate cancer without bone metastases who received luteinizing hormone releasing hormone analogue for 12 months. RESULTS: At baseline conditions 46% of cases were classified as osteopenic and 14% as osteoporotic at the lumbar spine and 40% were osteopenic and 4% osteoporotic at the hip. Androgen deprivation significantly decreased bone mineral density either at the lumbar spine (mean gm./cm.2 [SD] 1.00 [0.194], 0.986 [0.172] and 0.977 [0.182] at baseline, and 6 and 12 months, respectively, p <0.002) or the hip (0.929 [0.136], 0.926 [0.144] and 0.923 [0.138], p <0.03). A more than 2% decrease in bone mineral density was found at the lumbar spine in 19 men (54.3%) and at the hip in 15 (42.9%). Bone mineral content paralleled the bone mineral density pattern. Lean body mass decreased (mean gm. [SD] 50,287 [6,656], 49,296 [6,554] and 49,327 [6,345], p <0.003), whereas fat body mass consistently increased (18,115 [6,209], 20,724 [6,029] and 21,604 [5,923] p <0.001). CONCLUSIONS: Serial bone densitometry evaluation during androgen deprivation therapy may allow the detection of patients with prostate cancer at risk for osteoporotic fractures, that is those with osteopenia or osteoporosis at baseline and fast bone loss. The change in body composition may predispose patients to accidental falls, thus increasing the risk of bone fracture.     

Hip fractures in Italy: 2000–2005 extension study

Summary

A total of 507,671 people ≥65 experienced hip fractures between 2000 and 2005. In 2005, 94,471 people ≥65 were hospitalized due to hip fractures, corresponding to a 28.5% increase over 6 years. Most fractures occurred in patients ≥75 (82.9%; n?=?420,890; +16% across 6 years), particularly in women (78.2%; n?=?396,967).

Introduction

We aimed to analyze incidence and costs of hip fractures in Italy over the last 6 years.

Methods

We analyzed the national hospitalization and DRG databases concerning fractures occurred in people ≥65 between 2000 and 2005.

Results

A total of 507,671 people ≥65 experienced hip fractures across 6 years, resulting in about 120,000 deaths. In year 2005 94,471 people aged ≥65 were hospitalized due to hip fractures, corresponding to a 28.5% increase over 6 years. The majority of hip fractures occurred in patients ≥75 (82.9%; n?=?420,890; +16% across 6 years) and particularly in women (78.2%; n?=?396,967). Among women, 84.2% of fractures (n?=?334,223; +28.0% over 6 years) were experienced by patients ≥75, which is known to be the age group with the highest prevalence of osteoporosis, accounting for 68.6% of the overall observed increase in the total number of fractures. Hip fractures in men ≥75 increased by 33.1% (up to 16,540). Hospitalization costs increased across the six examined years (+36.1%) reaching 467 million euros in 2005, while rehabilitation costs rose up to 531 million in the same year.

Conclusions

Hip fractures of the elderly are increasing and represent a major health problem in industrialized countries such as Italy.     

Adenocarcinoma of the Ampulla of Vater: T-Stage,Chromosome 17p Allelic Loss,and Extended Pancreaticoduodenectomy are Relevant Prognostic Factors

Objective To evaluate the prognostic significance of different clinico-pathological and molecular factors, and to compare survival after standard and extended pancreaticoduodenectomy (PD) in ampulla of Vater adenocarcinoma (AVAC). Summary Background Data There are discordant data on factors affecting prognosis, and hence therapeutic choices, in AVAC. Patients and Methods Clinical-pathological factors were evaluated in 59 patients, subjected to PD for AVAC; in 42 subjects information on chromosome 17p and 18q allelic losses (LOH) and microsatellite instability (MSI) was also available. The association between survival and type of PD was investigated in the 25 patients operated between 1990 and 2001 (16 standard and nine extended). Results The overall 5- and 10-year tumor-related survival rates were 46% and 33%, respectively. Sixteen patients had T-stages 1–2, 14 T-stage 3, and 29 T-stage 4 cancers. Chromosome 17p and 18q LOH were detected in 23 (55%) and 15 cases (36%), respectively, and in 12 cases (29%) coexisted. Five cases were MSI-positive (12%). At univariate analysis, poor survival was associated with cancer ulceration (P = 0.051), poor differentiation (P = 0.008), T-stage 4 (P < 0.001), nodal metastases (P = 0.004), chromosome 17p (P < 0.001) and 18q LOH (P = 0.002), and absence of MSI (P = 0.009). At multivariate analysis, only T-stage (P = 0.002) and 17p LOH (P = 0.001) were independent predictors of survival. All patients with MSI-positive cancers were long-survivors (>12 yrs), whereas only 30% of MSI-negative cancer patients survived at 5 years. Extended pancreaticoduodenectomy was associated with a 3-year disease-related survival higher than standard resection (83% vs 31%; P = 0.018). Conclusion MSI and chromosome 17p status allow to better define prognosis within ampullary cancers at the same stage. Surgery alone resulted curative in MSI-positive cancer patients, whereas it was inadequate in patients showing allelic losses, who might benefit from adjuvant therapy. In this observational study, extended PD was associated with increased survival compared to standard procedures. Presented at the 2006 Annual Meeting of the American Hepato-Pancreato-Biliary Association, Miami Beach, Florida, March 9–12, 2006     

Levetiracetam: an improvement of attention and of oral fluency in patients with partial epilepsy

PURPOSE: The aim of the present study is to verify whether patients with partial epilepsy receiving levetiracetam (LEV) as an add-on treatment show an improvement in cognitive function. METHODS: A neuropsychological battery of tests was administered to 35 patients with partial epilepsy before the assumption of LEV and after the achievement of the therapeutical dose of this drug, 7 weeks later. A control group of 35 patients with partial epilepsy was administered the same battery of tests twice, at the same time interval as the LEV group. The controls were administered the same pharmacological treatment, which did not include LEV in either of the two sessions. RESULTS: We found a statistically significant improvement in cognitive functioning, i.e. in attention and oral fluency, in patients receiving LEV compared to the controls. The responders to LEV were 28.6%. CONCLUSIONS: LEV as an add-on therapy improved attention level and verbal fluency in our sample of patients with partial epilepsy. It is reasonable to assume that LEV may influence the metabolism of attention and of language area, as already suggested for piracetam (PIR) from which LEV derives. Further studies are needed to confirm these findings.     

Fiber type-related changes in rat skeletal muscle calcium homeostasis during aging and restoration by growth hormone

The mechanisms by which aging induces muscle impairment are not well understood yet. We studied the impact of aging on Ca2+ homeostasis in the slow-twitch soleus and the fast-twitch extensor digitorum longus (EDL) muscles of aged rats by using the fura-2 fluorescent probe. In both muscles aging increases the resting cytosolic calcium concentration ([Ca2+]i). This effect was independent on calcium influx since a reduced resting permeability of sarcolemma to divalent cations was observed in aged muscles likely due to a reduced activity of leak channels. Importantly the effects of aging on resting [Ca2+]i, fiber diameter, mechanical threshold and sarcolemmal resting conductances were less pronounced in the soleus muscle, suggesting that muscle impairment may be less dependent on [Ca2+]i in the slow-twitch muscle. The treatment of aged rats with growth hormone restored the resting [Ca2+]i toward adult values in both muscles. Thus, an increase of resting [Ca2+]i may contribute to muscle weakness associated with aging and may be considered for developing new therapeutic strategies in the elderly.     

Do phonologic and rapid automatized naming deficits differentially affect dyslexic children with and without a history of language delay? A study of Italian dyslexic children.

OBJECTIVE: The study aims to verify whether phonologic and rapid automatized naming (RAN) deficits are present and associated in Italian dyslexic children and whether they differentially affect dyslexics with and without a history of previous language delay (LD). BACKGROUND: According to the phonologic core deficit hypothesis, dyslexia may stem from impairment of the representation and manipulation of phonemes and may be closely associated with oral language deficits. However, deficits in tasks not requiring fine-grained phonologic representations, such as RAN, have also been described in dyslexic children. METHODS: Thirty-seven children were selected on the basis of a reading deficit and were assigned to 2 groups according to whether or not they had a history of early LD as determined retrospectively by parental report. A battery of reading and writing, verbal working memory, metaphonologic, RAN, and visual search tests were administered. RESULTS: RAN deficits were shared by most dyslexics (with and without a history of LD), whereas phonologic deficits were mainly associated with a previous LD. This last condition did not result in a more profound impairment of reading and writing decoding skills. CONCLUSION: In a shallow orthography such as Italian, RAN, not phonologic deficits, may represent the main cognitive marker of developmental dyslexia.     

Sentinel Node Biopsy in Squamous-Cell Carcinoma of the Anal Canal

Background

Radiochemotherapy is the standard treatment for patients with carcinoma of the anal canal. Therefore, a surgical specimen is not usually obtained. Inguinal lymph node metastases cannot be accurately predicted by either clinical examination or imaging techniques. In this study, we applied the sentinel node technique in patients with anal canal squamous-cell carcinoma to determine whether this provided more reliable staging of tumors.

Methods

From May 2007 to May 2009, we enrolled 11 patients (7 women) with a mean age 65 (range 39–80) years with squamous-cell carcinoma of the anal canal and clinically and radiologically negative groin lymph nodes. The patients were staged with endorectal ultrasound, computed tomographic scan, magnetic resonance imaging of the pelvis, and positron emission tomography. There were two T1, four T2, and five T3 tumors (International Union Against Cancer classification). Lymphoscintigraphy with peritumoral 99mTc colloid injection was performed 16 to 18 h before surgery. During the surgery, patent blue dye was injected peritumorally, and the sentinel inguinal node was identified by a handheld gamma probe and dye visualization.

Results

The sentinel lymph node was detected in all 11 patients by scintigraphy; in 9 cases, the lymph node was in the inguinal region. All of these patients underwent radioguided node biopsy, and a total of 12 lymph nodes were removed. The average diameter of the resected nodes was 8 (range 4–20) mm. No serious complications occurred. In three patients, metastases were identified in the lymph node.

Conclusions

Sentinel node biopsy is a more accurate method than clinical or radiological techniques to stage the disease of patients with anal carcinoma.