Microbiologic and clinical characteristics of biofilm-forming Candida parapsilosis isolates associated with fungaemia and their impact on mortality.

OBJECTIVES: Biofilm formation (BF) by fungal isolates may dramatically complicate infection. We determined the ability of Candida parapsilosis isolates from single fungaemia episodes to form biofilms and we analysed biofilm subgroups for antifungal susceptibility and pathogenic potential. We then correlated BF with clinical characteristics and outcomes of the episodes. METHODS: BF was measured using the crystal violet biomass assay. Antifungal susceptibility of preformed biofilms was assessed, and virulence was studied using the Galleria mellonella model. A retrospective analysis of patients' clinical records was performed. RESULTS: Of 190 patient-unique isolates, 84, 38 and 68 were identified as having high BF (HBF), moderate BF (MBF) or low BF (LBF), respectively. Among 30 randomly selected isolates, nine (eight HBF and one MBF), six (all HBF) and one (HBF) isolates had elevated sessile minimum inhibitory concentrations to fluconazole, anidulafungin or amphotericin B; all HBF and MBF isolates had elevated voriconazole sessile minimum inhibitory concentrations. G. mellonella killing rates of HBF isolates were significantly greater than MBF (or LBF) isolates (50% vs. 20%, 2 days from infection). By comparing HBF/MBF (106 patients) and LBF (84 patients) groups, we found that HBF/MBF patients had more central venous catheter-related fungaemias (62/106 (58.5%) vs. 29/84 (34.5%), p 0.001) and were more likely to die at 30 days from fungaemia onset (61/106 (57.5%) vs. 28/84 (33.3%), p 0.01). In the HBF/MBF group, azole antifungal therapy and central venous catheter removal were significantly associated with a higher and lower 30-day mortality rate, respectively. CONCLUSIONS: C. parapsilosis BF influences the clinical outcome in patients with fungaemia.

Risk factors for bloodstream infections due to colistin-resistant KPC-producing Klebsiella pneumoniae: results from a multicenter case-control-control study.

The increasing prevalence of colistin resistance (ColR) Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (Kp) is a matter of concern because of its unfavourable impact on mortality of KPC-Kp bloodstream infections (BSI) and the shortage of alternative therapeutic options. A matched case-control-control analysis was conducted. The primary study end point was to assess risk factors for ColR KPC-Kp BSI. The secondary end point was to describe mortality and clinical characteristics of these infections. To assess risk factors for ColR, 142 patients with ColR KPC-Kp BSI were compared to two controls groups: 284 controls without infections caused by KPC-Kp (control group A) and 284 controls with colistin-susceptible (ColS) KPC-Kp BSI (control group B). In the first multivariate analysis (cases vs. group A), previous colistin therapy, previous KPC-Kp colonization, ≥3 previous hospitalizations, Charlson score ≥3 and neutropenia were found to be associated with the development of ColR KPC-Kp BSI. In the second multivariate analysis (cases vs. group B), only previous colistin therapy, previous KPC-Kp colonization and Charlson score ≥3 were associated with ColR. Overall, ColR among KPC-Kp blood isolates increased more than threefold during the 4.5-year study period, and 30-day mortality of ColR KPC-Kp BSI was as high as 51%. Strict rules for the use of colistin are mandatory to staunch the dissemination of ColR in KPC-Kp-endemic hospitals.

Risk factors for carbapenem-resistant Klebsiella pneumoniae bloodstream infection among rectal carriers: a prospective observational multicentre study.

Knowledge of carbapenem-resistant Klebsiella pneumoniae (CR-KP) colonization is important to prevent nosocomial spread but also to start prompt adequate antibiotic therapy in patients with suspicion of infection. However, few studies have examined the incidence and risk factors for CR-KP bloodstream infection (BSI) among rectal carriers. To identify risk factors for CR-KP BSI among carriers, we performed a multicentre prospective matched case-control study of all adult CR-KP rectal carriers hospitalized in five tertiary teaching hospitals in Italy over a 2-year period. Carriers who developed CR-KP BSI were compared with those who did not develop subsequent BSI. Overall, 143 CR-KP BSIs were compared with 572 controls without a documented infection during their hospitalization. Multivariate analysis revealed that admission to the Intensive Care Unit (ICU) (OR, 1.65; 95% CI, 1.05-2.59; p 0.03), abdominal invasive procedure (OR, 1.87; 95% CI, 1.16-3.04; p 0.01), chemotherapy/radiation therapy (OR, 3.07; 95% CI, 1.78-5.29; p <0.0001), and number of additional colonization sites (OR, 3.37 per site; 95% CI, 2.56-4.43; p <0.0001) were independent risk factors for CR-KP BSI development among CR-KP rectal carriers. A CR-KP BSI risk score ranging from 0 to 28 was developed based on these four independent variables. At a cut-off of ≥2 the model exhibited a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 42%, 29% and 93%, respectively. Colonization at multiple sites with CR-KP was the strongest predictor of BSI development in our large cohort of CR-KP rectal carriers.

[Giovanni Gigli. The Nephrological School of Pisa from Tuscany to Umbria]. / Giovanni Gigli. La Scuola Nefrologica Pisana tra la Toscana e l'Umbria.

Giovanni Gigli (1913-1988) can be considered one of the pioneers of Italian nephrology. Years before the foundation of the Italian Society of Nephrology (SIN), Gigli was engaged in research into renal function and renal disease. He published an important monograph on the study of renal function in 1953. In addition to his scientific interests, Gigli was involved in the clinical aspects of renal disease and in popularizing the new concepts in this field. Of particular value in his career were the foundation of a school of nephrology and the introduction of a chronic dialysis treatment program at the Institute of Medical Pathology in Perugia.

[Historical Archives of Italian Nephrology. "Le Giornate Mediche Triestine del 1952" the first nephrological international meeting held in Italy]. / Archivi storici della Nefrologia Italiana. Le Giornate Mediche Triestine del 1952, il primo Convegno Nefrologico Internazionale in Italia.

The author came recently across the proceedings volume of a forgotten meeting on renal disease, held in Trieste in 1952. The invited speakers came from Italy, France and Switzerland, and were prominent figures of the European medicine. They dealt with various topics: renal pathophysiology, pathology, diagnosis, and treatment of renal disease. The analysis of the proceedings shows that most of the chosen topics were "hot" for that time and that the papers presented by Italian and foreign speakers were absolutely up-to-date. The discovery of the proceedings of this meeting, followed by other international renal meetings all over Europe, shows that, in spite of the lack of international recognition, Italian nephrologists were active at an early time and maintained a scientific relationship with their foreign counterpart.

3 R study: renal outcome in renal ischemia: revascularisation or medical treatment.

Ischemic nephropathy refers to the kidney damage following stenosis or an obstructive lesion in the main kidney arteries. This disorder has been overlooked in the past and a more rational and specific use of clinical criteria, and the development of not very invasive techniques with a good diagnostic accuracy such as spiral CT angiography, NMR angiography and echo-colour-Doppler have improved our ability to identify these patients. It is therefore likely that, in the next few years, we will find ourselves treating an increasing number of patients with renovascular ischemic disorders. Transluminal angioplasty and, more recently, the use of endovascular stents, have led to a marked improvement in the treatment of stenoses and, together with vascular surgery, allow to treat almost all patients with this disorder. There is, however, a lack of prospective and controlled studies, which demonstrate the long term benefit of revascularization treatment, as compared with optimum conservative treatment in reducing cardiovascular mortality, cardiovascular events and preserving renal function. The Ischemic Nephropathy Study Group of the Italian Society of Nephrology has organized a prospective, controlled study over a period of three years, aimed at comparing the effect of revascularization versus medical therapy in 300 patients with renal artery stenosis, ranging between 50 and 90 per cent, who will be randomly assigned to the two treatments. End point will be cardiovascular mortality and morbidity and need for renal replacement therapy.

Angiotensin-converting enzyme gene I/D polymorphism and carotid artery disease in renovascular hypertension.

There is evidence linking the activation of the renin-angiotensin system (RAS) with target organ damage in renovascular hypertension (RVH). A genetic association of the DD genotype of the angiotensin-converting enzyme (ACE) gene with cardiovascular complications has been found in various clinical conditions. The aim of our study was to determine whether the insertion/deletion (I/D) polymorphism of the ACE gene is associated with the high prevalence of target organ damage reported in RVH. A total of 65 atherosclerotic patients (age 68.2 +/- 5.2 years) with RVH and 49 atherosclerotic patients (age 68.0 +/- 6.3 years) with essential hypertension (EH) were sequentially enrolled when attending the outpatient clinic for specialist assessment of their vascular disorder. Cardiac, renal, and vascular involvement were assessed in both groups and blood was taken for genetic analysis. Patients with RVH had a higher prevalence of left ventricular hypertrophy (LVH), carotid artery disease, and albuminuria than those with EH. In RVH, but not in EH, the DD genotype was significantly associated with severe arterial disease. In RVH, carotid disease (lumen narrowing >60%) was present in 62% of DD patients versus 25% of the other genotypes (OR = 4.90, 95% CI: 1.70-14.13). Such an association was also present in peripheral vascular disease: 72.4% in DD patients versus 41.6% in the other genotypes (OR = 3.67, 95% CI = 1.29-10.36). Logistic regression analysis showed that the DD genotype was the strongest predictor of risk of severe carotid disease. We conclude that, in atherosclerotic RVH, there is an association of the severity of vascular disease with the DD genotype of the ACE gene.

ACE gene polymorphism and survival in atherosclerotic renovascular disease.

Renovascular disease (RVD) is an important cause of end-stage renal disease and is associated with a high mortality rate, mostly because of coexisting cardiovascular and cerebrovascular disease. The deletion (DD) polymorphism of the angiotensin-converting enzyme (ACE) gene has been described in association with severe vascular disease affecting major organs. To investigate whether DD genotype is a risk factor for mortality in RVD, we performed a follow-up study of 61 patients with this disease. Patients (age, 68.0 +/- 6.5 years) affected by atherosclerotic vascular disease were enrolled after angiographic demonstration of a renal artery stenosis. The average follow-up was 48.1 +/- 14.9 months. Genotype was insertion/deletion (I/D) in 30 patients, DD in 27 patients, and II in 4 patients. At enrollment, a complete assessment of heart, blood vessels, and renal function was performed. During the follow-up period, 13 patients died (9 DD, 4 ID) and 7 patients evolved into end-stage renal failure. The cumulative survival rate at 5 years was 45.4% +/- 13.4%. Factors associated with mortality were analyzed with Cox proportional hazard regression. The multivariate analysis showed that DD genotype, severe carotid disease, and smoking were independent predictors of mortality. The multivariate analysis of predictors of renal failure showed that the only significant association was found with baseline serum creatinine level of 265 micromol/L or greater. We conclude that the DD genotype of the ACE gene is a marker for mortality in RVD.

Survival of patients with renovascular disease and ACE inhibition.

AIM: Renovascular hypertension (RVH) is associated with a high prevalence of target organ damage and a high mortality. We have undertaken this follow-up study to assess the role played by comorbid conditions, and pharmacological treatment on survival, and on renal function in 64 patients with diffuse atherosclerotic vascular and renovascular disease (RVD). PATIENTS AND METHODS: The patients were followed for an average period of 37.3+/-20.4 months. RESULTS: At the end of the follow-up we found a cumulative survival at 5 years of 60%+/-10. Cerebrovascular and cardiovascular disease were responsible for 92% of deaths. A decrease in creatinine clearance >10 ml/min at 5 years was found in 65% of patients, 3 of whom ended in dialysis. Multivariate analysis of predictors of survival showed that treatment with angiotensin converting enzyme inhibitors (ACEi) was significantly associated with a favourable outcome (p = 0.019). Conversely, proteinuria had a negative effect. Renal survival was best predicted by the level of renal function at entry (p = 0.02), and was not influenced by pharmacological treatment. CONCLUSION: We conclude that ACEi exerts a beneficial effect on survival without affecting renal function in patients with RVD due to unilateral renal stenosis.

Comparison of target organ damage in renovascular and essential hypertension.

In many reports, the prevalence of target organ damage in renovascular hypertension (RVH) appears to be higher than in essential hypertension (EH). Since in most studies the renal artery stenosis is part of a diffuse atherosclerotic disease, it is not known whether these complications are due to RVH itself or to the vascular disease. We have undertaken a case control study of 92 patients divided into two groups (46 in each), one with RVH and the other with EH and abdominal aortic aneurysm, with a comparable degree of diffuse atherosclerotic vascular disease. The vascular state of the extracranial carotid arteries and abdominal and inferior limb districts was investigated with angiography and sonography. The prevalence of left ventricular hypertrophy (LVH) and ischemic heart disease (IHD) were assessed by electrocardiography. Serum creatinine and urinary protein excretion were employed in the renal evaluation. While the analysis of the results confirmed an even diffusion of atherosclerotic vascular disease between the two groups, a significant difference was found in the prevalence of heart and renal damage. LVH was present in 32.6% of RVH patients versus 10.8% in EH (P = .02). Serum creatinine > 1.4 mg/dL was found in 50% of RVH and in 23.9% of EH, (P = .01). The prevalence of proteinuria in RVH was also higher although not reaching the statistical significance. The results suggest that, in patients with comparable degrees of atherosclerotic vascular disease, RVH is responsible for the higher prevalence of target organ damage in this condition compared to those with EH.

[Gastric localization of sarcoidosis]. / Localizzazioni gastriche in corso di sarcoidosi.

Sarcoidosis is a systemic granulomatous disease of unknown etiology, characterized by an immunological disorder with accumulation of activated lymphocytes and macrophages in all the organs and apparatus. The intrathoracic lymphnodes and the lung remain the most common sites of such disease. The gastrointestinal sarcoidosis, particularly of the stomach, is very rare. The stomach may be the primitive or the secondary (systemic sarcoidosis) site of sarcoid granuloma. The endoscopic aspects of the gastric mucosa are variable: localized or diffused hyperemia, single or multiple ulcers, aspects of atrophic gastritis with easy bleeding during contact, rigid mucosa and so on. Generally asymptomatic, the disease may show symptoms as pain in the epigastrium, nausea, vomiting, haematemesis and so on. The wide range of gastric pathologies resembling sarcoidosis both on a histological level and on a clinic-endoscopical one (syphilis, histoplasmosis, Crohn's disease, stomach cancer) require an extremely accurate diagnosis above all for the setting out of the therapy with steroids which are the most appropriate drugs (prednisone). Three out of thirty-two patients observed for respiratory problems, already affected by cutaneous and pulmonary sarcoidosis, started suffering from gastric symptoms of different kind: pain in the epigastrium, haematemesis, weight loss, nausea and post-prandial vomiting. Gastroscopy and biopsy, with histopathologic examination of gastric mucosal specimens taken from the most suspicious sites, confirmed the diagnosis of sarcoidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Derotation osteotomy in the treatment of congenital dislocation of the hip: a review of long-term results.

The authors clinically and radiographically evaluate the long-term results of 257 femoral derotation osteotomies performed between 1959 and 1970 for congenital dysplasia and dislocation of the hip. Tracing the patients was very difficult because of the prolonged follow-up, yet a group of 36 patients was finally gathered. These patients were then uniformly studied and classified through precise quantification, with a numeric reference value, of clinical deficits and radiographic changes. The evaluation of the results confirmed that the effectiveness of femoral derotation osteotomy depends upon its timeliness, correct execution, and potential association with corrective surgery of the acetabular dome. Finally, both preexistent joint damage and the presence of genetic factors in the disease, which often causes relapse in spite of a technically perfect operation, are very important in determining the final result.

The kidney in essential hypertension.

With the effectiveness of today's antihypertensive agents, it is possible to reduce blood pressure without harming the kidney, and also to improve renal function, thus delaying the otherwise unavoidable decline that follows organ damage induced by hypertension.

Impaired renal functional reserve and albuminuria in essential hypertension.

The stimulatory effects of an infusion of amino acids on glomerular filtration rate has previously been used to measure renal functional reserve and detect glomerular hyperfiltration. Thirty four patients with mild to moderate essential hypertension and seemingly normal renal function and 22 healthy controls were given infusions of amino acids to investigate whether renal functional reserve is reduced in essential hypertension and to detect patients at risk of renal damage. Although basal creatinine clearance increased after the infusion of amino acids in the controls (mean 27.9 ml/min; 95% confidence interval 18.2 to 37.6), the overall change was lower in the patients (mean 13.4 ml/min; 8.3 to 18.5), 11 of the 34 showing no increase at all. In these 11 non-responders the mean systolic blood pressure was higher than that in the 23 others (178.5 mmHg v 157 mmHg, respectively). Mean urinary albumin excretion was abnormal in the patients (93.3 mg/24 h; 44.2 to 142.4); eight of the 11 non-responders had an albumin excretion above the normal range (greater than 20 mg/24 h). In the 11 patients without renal functional reserve a positive correlation was found between basal creatinine clearance and albumin excretion (r = 0.695). As consumed renal reserve and albuminuria are markers of glomerular hyperfiltration studying renal function before and after infusion of amino acids can detect hypertensive patients at risk of progressive renal damage.