Insights about urinary hippuric and citric acid as biomarkers of fruit and vegetable intake in patients with kidney stones: The role of age and sex.

OBJECTIVES: Urinary hippuric acid (HA) and citrate can represent useful biomarkers of fruit and vegetable (FAV) intake in nephrolithiasis. However, their clinical significance across the life span has been poorly investigated. The aim of this study was to investigate the association between the two biomarkers with FAV intake across different age groups and sexes in a large group of stone formers (SFs). METHODS: SFs undergoing baseline 24-h urinary collection for metabolic profile of lithogenic risk at our institution were consecutively enrolled for a 6-y time span (N = 1185; 625 men). HA and citrate excretions were determined by ion chromatography and ultraviolet method, respectively. SFs completed a food frequency questionnaire on the intake of FAV. Stepwise logistic regression was applied to investigate factors associated with very low FAV (≤1 servings/d) and analysis of covariance to compare citrate and HA excretion across age groups and sexes. RESULTS: Very low FAV intake prevalence declined with age (Ptrend < 0.001), and was inversely associated with HA and citrate excretion (P < 0.001) in a stepwise logistic regression model. A significant increasing trend was verified for both biomarkers across age groups until the age of 65 for HA (P < 0.001) and 55 for citrate (P < 0.001). Citrate excretion significantly declined after the age of 65, and was higher in women than men in adult age groups, regardless of FAV intake. CONCLUSIONS: Both urinary citrate and HA were positively associated with FAV intake in SFs. However, unlike HA, citrate excretion was significantly influenced by the female sex and by older age.

Short-Term Changes in Urinary Relative Supersaturation Predict Recurrence of Kidney Stones: A Tool to Guide Preventive Measures in Urolithiasis.

PURPOSE: Kidney stone disease is characterized by a relatively high rate of recurrence. In our study we analyzed the association between relative supersaturation and the risk of stone recurrence. Additionally, we examined the association between the risk of recurrence and changes in relative supersaturation and urinary composition after 1 week of medical treatment. MATERIALS AND METHODS: We performed a post hoc analysis of data from a previously published randomized controlled trial comparing the effect of 2 diets in 120 men with recurrent calcium oxalate stones and hypercalciuria. Baseline and followup 24-hour urine parameters were used to calculate the relative supersaturation of calcium oxalate, calcium phosphate and uric acid using the EQUIL2, JESS and LithoRisk computer programs. Cox models were used to calculate the estimated association between each baseline relative supersaturation, and 1-week changes and the risk of recurrence during followup. RESULTS: During a 5-year followup 35 patients (34%) experienced recurrence. A reduction in calcium oxalate relative supersaturation at 1 week was significantly associated with a lower risk of recurrence using the EQUIL2 calculation (for every 10% reduction from baseline HR 0.92, 95% CI 0.86-1.00, p = 0.044). However, there was no association for relative supersaturation calculated by other methods or for the relative supersaturation of other salts. Changes in the 24-hour urine excretion of citrate, potassium and magnesium were significantly associated with a risk of recurrence. CONCLUSIONS: In recurrent stone formers with hypercalciuria baseline values and changes in the relative supersaturation of calcium oxalate may be associated with the risk of recurrence. Changes in urinary citrate, potassium and magnesium following dietary intervention may also be predictive.

Determinants of calcium and oxalate excretion in subjects with calcium nephrolithiasis: the role of metabolic syndrome traits.

BACKGROUND: The association of metabolic syndrome (MetS) traits with urinary calcium (UCE) or oxalate excretion (UOE) is uncertain in calcium stone formers (CSFs). Our aim was to investigate this association in a large group of Caucasian CSFs. METHODS: We retrospectively reviewed data of CSFs evaluated at our Kidney Stone Clinic from 1984 to 2015. Data on body mass index (BMI), MetS traits defined according to international consensus, family history of urolithiasis, anti-hypertensive treatments, calcemia, renal function, and 24-h urinary profile of lithogenic risk were collected. The association between MetS traits and UCE or UOE was tested with multivariate linear regression models accounting for a long list of potential confounders. RESULTS: We included 3003 CSFs, aged 44 ± 14 years. The prevalence of hypertension, diabetes, overweight (BMI ≥ 25 kg/m2) and dyslipidemia was 17, 2, 42 and 38%, respectively. Median values of UCE and UOE were 211 mg/24 h (IQR 143-296) and 28 mg/24 h (IQR 22-34), respectively. At a multivariate model, including age, sex, date of examination, drug treatments, family history, renal function, blood calcium and urinary factors as covariates, hypertension was a significant positive determinant of UCE (ß ± SE 0.23 ± 0.07, p = 0.003), but overweight, dyslipidemia and diabetes were not. No MetS trait was significantly associated with UOE in multivariate models. CONCLUSIONS: In a large group of Caucasian CSFs, hypertension was the only MetS trait significantly associated with UCE, while no MetS trait was associated with oxalate excretion.

Water and other fluids in nephrolithiasis: State of the art and future challenges.

Adequate hydration, as to maintain urinary volume over 2 L/day, has long been considered as the cornerstone medical prescription for preventing nephrolithiasis. However, scientific evidence about what kind of water stone formers should drink and about the effects of other beverages on urinary stone risk factors is sometimes unclear. Moreover, the recommendation that water therapy prevents kidney stone recurrence relies on only one randomized controlled trial, even if more epidemiologic and basic science studies seem to support this assumption. Therefore, in this review we analyze current evidence that support water therapy in nephrolithiasis and we highlight the possible effects of different types of water and other beverages on lithogenic risk, giving some practical recommendations for what stone formers should be advised to prevent recurrence.

Calcium urolithiasis course in young stone formers is influenced by the strength of family history: results from a retrospective study.

The role of the strength of family history of stones (FHS), i.e., degree of relatives with the disease, on the course of calcium urolithiasis (CU) is not fully understood, particularly in young patients where genetic background has the greatest influence on disease expression. Thus, with a retrospective cross-sectional design, we examined baseline clinical parameters and urinary chemistries of 369 subjects (196 M) with CU and 96 controls (41 M) aged between 15 and 25 at the time of the first visit at our stone clinic. Subjects with metabolic syndrome traits, known causes of CU or CU onset before the age of 15 were excluded. Clinical and metabolic parameters were compared among stone formers (SF) and controls, stratified by gender, the presence and type of FHS determined through the kinship coefficient of relatives with stones. No significant differences in clinical course were found between SF with and without FHS, except for the presence of bilateral stones (OR 2.01, 95% CI 1.20-3.39, p < 0.01). A significant age-, sex- and disease duration-adjusted trend for a higher number of colics (p for trend = 0.001), number of stones (p for trend = 0.002), stone rate (p for trend = 0.003) and the presence of retained stones (OR 1.60, 95% CI 1.14-2.21, p = 0.006) was detected with increasing FHS strength. Urinary chemistries were unaffected by FHS in both SF and controls, except for a higher calcium excretion in females with FHS (p < 0.05). The type of FHS, thus, significantly influences the clinical course of CU in young SF, mainly irrespective of urinary factors.

The influence of maternal and paternal history on stone composition and clinical course of calcium nephrolithiasis in subjects aged between 15 and 25.

Our aim was to compare the influence of maternal history of stones (MHS) and paternal history of stones (PHS) on composition of calculi and disease course in a group of patients with calcium nephrolithiasis (CN) aged between 15 and 25, the age range with the maximal influence of family history on disease expression. One-hundred thirty-five patients (68 F) with CN and one stone-forming parent were retrospectively selected from the database of our outpatient stone clinic, and categorized according to MHS or PHS. Data about stone disease course and composition of passed calculi, determined by chemical analysis or Fourier-transformed infrared spectrophotometry, were collected together with information on blood chemistry and 24-h urinary profile of lithogenic risk. The characteristics of disease course and stone composition were compared using logistic regression tests adjusted for age, sex, and BMI or analysis of covariance where appropriate. Patients with MHS (n = 46) had significantly higher urinary calcium/creatinine ratio and ammonium, a higher prevalence of urological treatments (57 vs 27 %, p < 0.001) and mixed calcium oxalate/calcium phosphate stone composition (69 vs 35 %, p = 0.002) than those with PHS. At multivariate logistic regression models, MHS was independently associated with urological treatments (OR 4.5, 95 %CI 1.9-10.7, p < 0.001) and the formation of calculi with mixed calcium oxalate/calcium phosphate composition (OR 5.8, 95 %CI 1.9-17.9, p = 0.002). The method of stone analysis did not affect this result. In conclusion, in subjects aged 15-25, MHS is associated with mixed calcium stones and with a higher risk for urological procedures, and should be, therefore, considered in the management of urolithiasis.

A novel organizational model to face the challenge of multimorbid elderly patients in an internal medicine setting: a case study from Parma Hospital, Italy.

Continuous increase of elderly patients with multimorbidity and Emergency Department (ED) overcrowding are great challenges for modern medicine. Traditional hospital organizations are often too rigid to solve them without consistently rising healthcare costs. In this paper we present a new organizational model achieved at Internal Medicine and Critical Subacute Care Unit of Parma University Hospital, Italy, a 106-bed internal medicine area organized by intensity of care and specifically dedicated to such patients. The unit is partitioned into smaller wards, each with a specific intensity level of care, including a rapid-turnover ward (mean length of stay <4 days) admitting acutely ill patients from the ED, a subacute care ward for chronic critically ill subjects and a nurse-managed ward for stable patients who have socio-economic trouble preventing discharge. A very-rapid-turnover ("come'n'go") ward has also been instituted to manage sudden ED overflows. Continuity, effectiveness, safety and appropriateness of care are guaranteed by an innovative figure called "flow manager," with skilled clinical experience and managerial attitude, and by elaboration of an early personalized discharge plan anticipating every patient's needs according to lean methodology principles. In 2012-2014, this organizational model, compared with other peer units of the hospital and of other teaching hospitals of the region, showed a better performance, efficacy and effectiveness indexes calculated on Regional Hospital Discharge Records database system, allowing a capacity to face a massive (+22 %) rise in medical admissions from the ED. Further studies are needed to validate this model from a patient outcome point of view.

Spring season birth is associated with higher emergency department admission for acute allergic reactions.

BACKGROUND: Acute allergic reactions are important causes of emergency department (ED) admission, imposing a significant clinical and organizational burden. Since the season of birth is linked with early exposure to allergens, this study was aimed to establish whether an association exists between season of birth and incidence and severity of acute allergic reactions in the ED. METHODS: The electronic hospital database was searched to identify all consecutive adult patients who were admitted to the ED for acute allergic reactions (acute urticaria, acute angioedema, urticaria-angioedema and anaphylaxis) during a 1-year period. RESULTS: The final study population consisted in 588 patients (328 women and 260 men; mean age 43 ± 18 years, range 16-96 years). Increased frequency of ED admission was observed for patients born in spring, whereas the lowest frequency was found for those born in autumn. Patients born in spring exhibited 1.19 and 1.12 higher risk of ED admission for acute allergic reactions compared to those born in autumn and in all other seasons, respectively. This difference remained significant in patients with allergic reaction attributable to drugs and in those with unknown triggers, whereas no pattern of seasonality was observed in patients with allergic reactions attributable to aliments, hymenoptera, chemicals or inhalants. Patients born in spring also exhibited 1.86 and 1.52 higher risk of being admitted to the ED for severe acute allergic reactions compared to those born in autumn and in all other seasons, respectively. CONCLUSIONS: Patients born in spring appear particularly vulnerable to allergic reactions requiring ED visit.

Idiopathic Calcium Nephrolithiasis and Hypovitaminosis D: A Case-control Study.

OBJECTIVE: To investigate the association between vitamin D deficiency (25-hydroxyvitamin D <20 ng/mL) and idiopathic calcium nephrolithiasis (ICN). METHODS: A total of 884 patients with ICN (363 males, mean age of 51 ± 14) and 967 controls (162 males, mean age of 59 ± 15) from an area with no food fortification policy were considered following a case-control study design. Patients were enrolled at a third-level outpatient stone clinic. Controls were selected from a laboratory database after exclusion of those with nephrolithiasis, bone, endocrine, liver, and kidney diseases. Serum 25-hydroxyvitamin-D (25-OH-D), date of test, presence/history of diabetes, and cardiovascular disease including hypertension were recorded for all subjects. Serum parathormone, calcium, phosphorus, and urinary factors of lithogenic risk were available in stone formers (SF). After univariate statistical analysis, propensity score matching with conditional logistic regression was used to control for the possible effects of covariates. RESULTS: The prevalence of 25-OH-D <20 ng/mL was 56% in SF and 44% in controls (P <.001), with median levels of 18 ng/mL [interquartile range (IQR) of 12-24)] versus 23 ng/mL (IQR of 14-30) (age and sex adjusted P <.001). After a fully adjusted conditional logistic regression analysis, performed on propensity-matched cohorts (442 SF, 442 controls), there was a statistically significant association between vitamin D deficiency and odds of nephrolithiasis (estimated odds ratio of 2.29, confidence interval 95% 1.74-3.02, P <.001). 25-OH-D levels were not different in hypercalciuric and normocalciuric SF (median and IQR of 18 ng/mL and 13-23 vs 19 ng/mL and 13-26, respectively, P = .2). CONCLUSIONS: SF have lower serum 25-OH-D levels than controls. The role of hypovitaminosis D in the onset of ICN should be better reconsidered.

Salt and nephrolithiasis.

Dietary sodium chloride intake is nowadays globally known as one of the major threats for cardiovascular health. However, there is also important evidence that it may influence idiopathic calcium nephrolithiasis onset and recurrence. Higher salt intake has been associated with hypercalciuria and hypocitraturia, which are major risk factors for calcium stone formation. Dietary salt restriction can be an effective means for secondary prevention of nephrolithiasis as well. Thus in this paper, we review the complex relationship between salt and nephrolithiasis, pointing out the difference between dietary sodium and salt intake and the best methods to assess them, highlighting the main findings of epidemiologic, laboratory and intervention studies and focusing on open issues such as the role of dietary salt in secondary causes of nephrolithiasis.

Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group.

OBJECTIVE: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. MATERIALS AND METHODS: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. RESULTS: Evidence from the selected studies were used to form evidence-based guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. CONCLUSIONS: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. HYPERCALCIURIA: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content ≥ 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. HYPEROXALURIA: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. HYPERURICOSURIA: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. HYPOCITRATURIA: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels. CHILDREN: There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein (< 20 g/day) low-salt (< 2 g/day) diet with high hydration (> 3 liters/day) is strongly advised in children with cystinuria. ELDERLY: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved.

Mean platelet volume is significantly associated with serum levels of thyroid-stimulating hormone in a cohort of older euthyroid subjects.

PURPOSE: This retrospective and observational study aimed to establish whether any relationship exists between the values of serum thyroid-stimulating hormone (TSH) and those of the mean platelet volume (MPV) in a large cohort of older euthyroid Italian subjects. MATERIALS AND METHOD: The study population was represented by a cohort of 1,050 ostensibly healthy and euthyroid patients aged 50 years and older, who were referred for screening of thyroid disorders over a 1-year period. RESULTS: A significant association was found between MPV and TSH values in both simple (r = 0.12; p < 0.001) and multivariable regression analysis (beta coefficient, 0.07; p < 0.001) after adjustment for age, sex, free thyroxin values and platelet count. After stratification of the study population according to quartiles of serum TSH levels, a graded increase of MPV values was found from the first to the fourth quartile of TSH (p = 0.013). The odds ratio for an increased MPV value of the fourth versus the first quartile of TSH was 1.54 (95% CI, 1.08-2.20; p = 0.017). CONCLUSIONS: The results of this investigation demonstrate that a significant, positive and independent association exists between MPV and serum TSH values in a large cohort of older euthyroid Italian subjects.

The mean platelet volume is significantly associated with higher glycated hemoglobin in a large population of unselected outpatients.

AIMS: To examine the association between mean platelet volume (MPV) and glycated hemoglobin (HbA1c) in a large cohort of unselected outpatients. METHODS: We retrospectively reviewed combined results of complete blood count (CBC) and hemoglobin A1c (HbA1c) performed in all outpatients aged 18 years or older, who were referred to the outpatient clinic of our hospital for routine health check-up during the year 2013. RESULTS: Cumulative results of both CBC and HbA1c could be retrieved for 4072 male and female outpatients aged 18 years or older. There were significant associations between HbA1c and both MPV (r=0.10; p<0.001) and platelet count (r=0.05; p<0.001), that remained statistically significant after adjusting for age and sex. After stratifying the whole sample of patients for MPV quartiles, there was a significant, positive trend of HbA1c across quartiles of MPV (p<0.001). Similar findings were found when the whole sample was stratified by clinical thresholds of HbA1c (p<0.001), with values of MPV gradually increasing from subjects with normal glucose homeostasis, pre-diabetes and diabetes. CONCLUSIONS: The results of our investigation, which is supposed to be the largest cohort study on unselected outpatients assessing the relationship between HbA1c and platelets number or size, indicate that elevated MPV is significantly associated with higher HbA1c levels and vice versa.

Comorbidities and disease severity as risk factors for carbapenem-resistant Klebsiella pneumoniae colonization: report of an experience in an internal medicine unit.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging multidrug-resistant nosocomial pathogen, spreading to hospitalized elderly patients. Risk factors in this setting are unclear. Our aims were to explore the contribution of multi-morbidity and disease severity in the onset of CRKP colonization/infection, and to describe changes in epidemiology after the institution of quarantine-ward managed by staff-cohorting. METHODS AND FINDINGS: With a case-control design, we evaluated 133 CRKP-positive patients (75 M, 58 F; mean age 79 ± 10 years) and a control group of 400 CRKP-negative subjects (179 M, 221 F; mean age 79 ± 12 years) admitted to Internal Medicine and Critical Subacute Care Unit of Parma University Hospital, Italy, during a 10-month period. Information about comorbidity type and severity, expressed through Cumulative Illness Rating Scale-CIRS, was collected in each patient. During an overall 5-month period, CRKP-positive patients were managed in an isolation ward with staff cohorting. A contact-bed isolation approach was established in the other 5 months. The effects of these strategies were evaluated with a cross-sectional study design. CRKP-positive subjects had higher CIRS comorbidity index (12.0 ± 3.6 vs 9.1 ± 3.5, p < 0.0001) and CIRS severity index (3.2 ± 0.4 vs 2.9 ± 0.5, p < 0.0001), along with higher cardiovascular, respiratory, renal and neurological disease burden than control group. CIRS severity index was associated with a higher risk for CRKP-colonization (OR 13.3, 95% CI6.88-25.93), independent of comorbidities. Isolation ward activation was associated with decreased monthly incidence of CRKP-positivity (from 16.9% to 1.2% of all admissions) and infection (from 36.6% to 22.5% of all positive cases; p = 0.04 derived by Wilcoxon signed-rank test). Mortality rate did not differ between cases and controls (21.8% vs 15.2%, p = 0.08). The main limitations of this study are observational design and lack of data about prior antibiotic exposure. CONCLUSIONS: Comorbidities and disease severity are relevant risk factors for CRKP-colonization/infection in elderly frail patients. Sanitary measures may have contributed to limit epidemic spread and rate of infection also in internal medicine setting.

Hippuric acid in 24 h urine collections as a biomarker of fruits and vegetables intake in kidney stone formers.

This work aimed to underline the prospects of hippuric acid, a product of the metabolism of polyphenols, as a new biomarker of fruits and vegetables intake associated with lithogenic risk. Biochemical parameters of lithogenic risk and hippuric acid were measured in the 24 h urine collections of a cohort of 696 Italian kidney stone formers divided into two subgroups according to their different dietary habits. The link between lithogenic risk parameters and hippuric acid was assessed and this compound was revealed as a valuable biomarker of fruits and vegetables intake in kidney stone formers. A cut-off value of urinary excretion of hippuric acid, 300 mg/24 h, was set as the threshold of discrimination between low and high intake of fruits and vegetables for these patients. These results highlight the importance of monitoring of the excretion hippuric acid in urine to address proper dietary guidelines for the management of stone former patients.

Neutrophil gelatinase-associated lipocalin in cancer.

Neutrophil gelatinase-associated lipocalin (NGAL), also known as lipocalin-2, is a 178-amino acid protein which exists in three molecular forms, including a 25-kDa monomer, a 45-kDa homodimer, and a 135-kDa heterodimer complexed with matrix metalloproteinase 9 (MMP-9). Polymorphonuclear neutrophils and tubular cells of the kidney are the most representative cellular sources. As such, NGAL is now considered the biochemical gold standard for early diagnosis of acute kidney injury. Recent evidence suggests, however, that ectopic or enhanced expression of NGAL may occur in many other pathologic conditions including cancer. Several epidemiologic studies, as reviewed in this chapter, showed that a variety of malignant tumors consistently overexpressed NGAL with increased concentration in blood, urine, and other biologic fluids. In addition, NGAL was frequently associated with tumor size, stage, and invasiveness. These features thus make it a potential biomarker for malignancy. A number of experimental studies also demonstrated that the ability to bind MMP-9, to scavenge iron into cancer cells along with the effect on subcellular localization of transmembrane proteins such as cadherins and catenins, confers this protein the potential to enhance can cer aggressiveness and makes it an appealing target of future anticancer research.

Dizziness and syncope in young people: keep your mind open! Case report of the challenging differentiation between arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) and catecholaminergic polymorphic ventricular tachycardia (CPVT).

A paradigmatic case of aborted sudden cardiac death (SCD) in a young man is discussed, mirroring the challenge of diagnosing the various conditions potentially underlying this dramatic condition. Based on the clinical characteristics of our case, presenting some overlapping clinical features common to both the diseases, the discussion will be focused on Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) and Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D). Epidemiological, genetic, diagnostic and therapeutic aspect will be discussed.

Do clinicians decide relying primarily on Bayesians principles or on Gestalt perception? Some pearls and pitfalls of Gestalt perception in medicine.

Clinical judgment is a foundation of medical practice and lies at the heart of a physician's knowledge, expertise and skill. Although clinical judgment is an active part of all medical fields, thus including diagnosis and therapy, communication and decision making, it is still poorly defined. It can be considered a synthesis of intuition (mainly based on Gestalt principles) and an analytical approach. Gestalt perception finds its rationale in the evidence that perception of any given object or experience exhibits intrinsic qualities that cannot be completely reduced to visual, auditory, tactile, olfactory, or gustatory components. Thus, perceptions are not constructed in a "bottom-up" fashion from such elements, but are instead globally perceived, in a more "top-down" fashion. Gestalt perception, if cautiously and carefully combined with structured (techno)logical tools, would permit one to defoliate the often too-many-branches built diagnostic trees, and help physicians to better develop their competency. On the other hand, the practice of evidence-based medicine lies in the integration of individual clinical expertise and judgment with the best available external clinical evidence from systematic research. This article is aimed at providing some general concepts about Gestalt perception, and to discuss some aspects of clinical practice potentially influenced by this approach.