The urgent need to extend the appropriate use of ultrasound in Africa and worldwide. Overview, experiences and perspectives.

It is known that in African countries the health condition is problematic, both from a diagnostic and therapeutic point of view. Patients have to travel long distances to access medical care. Many cannot afford the cost of transportation to a medical facility. Ultrasound its into the scenario of healthcare imaging with limited resources, as an effective, economical, repeatable diagnostic tool, requiring low maintenance. Ultrasound tools in fact are relatively cheap and machines are easy to move, making them adapt to be taken to a rural setting where they are most needed. However ultrasound exams are not easy to perform and they need an adequate training. The spread of POCUS (point-of-care "focused" ultrasound) worldwide could be useful in Africa to identify high-risk patients. These cases selected in rural setting by POCUS can be referred to hospitals for further treatment. To deal with these situations it is necessary to form doctors and/or paramedical staff capable of guaranteeing a qualitatively adequate service. Therefore the need for basic training is greater in developing countries. Sharing successful educational strategies should advance the integration of ultrasound into the university medical school curricula. This will ensure that recently qualified doctors can practice their basic skills accurately and independently.

Renal insufficiency in non-diabetic subjects: relationship of MTHFR C677t gene polymorphism and left ventricular hypertrophy.

BACKGROUND: Association of methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism with hyperhomocysteinemia, renal failure, and cardiovascular events is controversial. We investigated the relationship of MTHFR 677C>T polymorphisms with left ventricular hypertrophy (LVH) and renal insufficiency. METHODS: Glomerular filtration rate (GFR) and left myocardial ventricular mass/m2 were assessed in 138 non-diabetic subjects (age, 50.93 ± 14.85 years; body mass index, 27.95 ± 5.98 kg/m(2)), 38 no-mutation wild MTHFR C677CC, 52 heterozygous MTHFR C677CT, and 48 homozygous MTHFR C677TT, all with adequate adherence to current international healthy dietary guidelines. Serum homocysteine, insulin resistance, high-sensitivity C-reactive-protein (hsCRP), parathyroid hormone, and renal artery resistive index (RRI) were challenged by odds ratio analysis and multiple linear regression models. RESULTS: MTHFR 677C>T polymorphism showed higher GFR (73.8 ± 27.99 vs. 58.64 ± 29.95; p= 0.001) and lower renal failure odds (OR, 0.443; 95% confidence interval, 0.141-1.387) in comparison with wild MTHFR genotype. A favorable effect on GFR of MTHFR polymorphism is presented independently by the negative effects of LVH, increased intra-renal arterial resistance, and hyperparathyroidism; GFR is the significant predictive factor to LVH. CONCLUSIONS: Renal insufficiency in non-diabetic subjects is explained by interactions of MTHFR C677T polymorphism mutation with LVH, hsCRP, intact parathyroid hormone (iPTH), and RRI. Sign of these predictive effects is opposite: subjects with MTHFR 677C>T polymorphism have lower likelihood of renal insufficiency; differently, wild-type MTHFR genotype subjects have lower GFR and greater hsCRP, iPTH, RRI, and LVH.

Obesity-independent association of human adenovirus Ad37 seropositivity with nonalcoholic fatty liver disease.

OBJECTIVE: Adenoviruses Ad36 and Ad37 increase adiposity in animals and are associated with obesity in humans; effects on the liver have been reported. The association of Adenovirus Ad36 seropositivity (Ad36+) with obesity but not with the severity of nonalcoholic fatty liver disease (NAFLD) has been previously shown. We investigate whether nondiabetic Ad37+ patients show a different prevalence of NAFLD and ultrasound Bright Liver score. PATIENTS: A total of 268 adult nondiabetic patients (146 men, 122 women) were included after lifestyle counseling including a personalized Mediterranean diet, increase in physical activity, and smoking withdrawal. After an Ad37+/Ad36+ assay, overweight obesity, insulin resistance, C-reactive protein, and bright liver prevalence and severity were compared according to Ad37+. RESULTS: Sixty-five of 268 patients were Ad37+ and 82/268 patients were both Ad37 seronegative (Ad37-) and Ad36-. The prevalence of obesity, defined as body mass index≥30, was not significantly different in Ad37+ (11/65; 16.9%) vs. Ad37- (15/82; 18.2%) patients; Bright Liver was present in 22/65 (33.8%) Ad37+ patients vs. 13/82 (15.8%) Ad37- patients (P<0.019). By odds ratio (OR), a consistent risk for NAFLD was associated with Ad37+, greater insulin resistance, and C-reactive protein. By a predictive multiple linear regression model, 40.0% of variance toward NAFLD and 50.4% toward the severity of Bright Liver score was explained significantly and independently by Ad37+ and by body mass index. CONCLUSIONS: Ad37+ status in nondiabetic patients on an appropriate diet is significantly associated with NAFLD; because fatty liver improves even without weight loss by a "healthy" diet, and not only by lower food caloric intake, Ad37+ may be an adjunctive hallmark of an unfavorable clinical-metabolic profile, if not a causative factor of NAFLD.

Adenovirus-36 seropositivity enhances effects of nutritional intervention on obesity, bright liver, and insulin resistance.

BACKGROUND: Obesity and liver steatosis are both currently attributed to inappropriate lifestyle and nutrition. Higher prevalence of human adenovirus Ad36 seropositivity (Ad36+) is reported only in obesity. AIMS: To investigate whether a lifestyle-nutritional intervention achieves different outcomes in NAFLD patients, i.e., if is blunted or enhanced according to Ad36 seropositivity status. METHODS: One-year nutritional intervention was planned and accomplished for 62 non-alcoholic fatty liver disease overweight-obese patients, studied by liver ultrasound, evaluating Bright Liver Score (BLS), by Homeostatic Model assessment of Insulin Resistance (HOMA), by body composition and Ad36+ assay. Lower salt/lower calories Mediterranean diet, physical activity increase, smoking withdrawal and lifestyle counseling, provided by a health psychologist, were given. RESULTS: Ad36 seropositive patients have baseline greater BMI with the same level of BLS. Different prevalence of post-interventional response, significantly greater among Ad36+ patients, is observed: greater decrease of obesity, assessed by BMI, greater reduction of insulin resistance, assessed by HOMA and higher prevalence of bright liver disappearance. A BMI-adjusted multiple linear regression model explains significantly 23.8% (p < 0.04) of the variance; significant predictive variables are Ad36 seropositivity (p < 0.012) and fat mass loss (p < 0.011) accounting for the variance of the occurrence of bright liver disappearance. CONCLUSIONS: Ad36 previous infection is significantly associated with enhanced weight loss, bright liver disappearance, and recovery of insulin sensitivity through the chosen tailored nutritional interventional treatment. Nonetheless, Ad36 seronegative NAFLD patients' fatty liver pattern improves, at a lower extent, also without significant weight loss: an effect of dietary changes profile, Mediterranean diet, not only of lowered food caloric intake, is conceivably operating.

Renal resistive index and parathyroid hormone relationship with renal function in nondiabetic patients.

INTRODUCTION: The renal resistive index (RRI) reflects intrarenal vascular resistance and stiffness, which are associated with chronic kidney disease. The links connecting renal function, intrarenal arterial resistance, and parathyroid hormone (PTH) with hypertension and metabolic factors remain elusive. The aim of this study is to investigate the possible relationship of RRI with glomerular filtration rate, PTH, hypertension, obesity (body mass index and waist-to-hip ratio), bioelectrical impedance analysis in body composition assessment, serum lipids, and insulin resistance assessed by homoeostasis model insulin resistance index. PATIENTS AND METHODS: This study was carried out on 387 (246 women, 141 men) nondiabetic patients, between >25 and <75 years, referred to an Internal Medicine Clinic and Day Hospital for essential hypertension, overweightness-obesity, and/or dyslipidemia. Lower salt/lower calorie Mediterranean diet, physical activity increase, smoking withdrawal, and lifestyle counseling, provided by a health psychologist support, were prescribed. RESULTS: Higher hypertension risk, present in 42.5% of the overall group of eligible patients (164/387), is associated with high PTH and high RRI, along with greater renal insufficiency, insulin resistance, and obesity. There is a straight linear relationship of RRI to PTH (0.202; p=0.009) in arterial hypertension, which is not observed in normal blood pressure patients. By gender-adjusted multiple linear regression analysis, it was found that fat mass, waist-to-hip ratio, and PTH account significantly for 62.3% of the variance to RRI in hypertensive patients. CONCLUSION: Increased arterial stiffness and intrarenal arterial resistance are associated with higher PTH in arterial hypertension; obesity (defined by greater fat mass and waist-to-hip ratio) and PTH are the independent conditions that account significantly for higher RRI.

Ad36 adipogenic adenovirus in human non-alcoholic fatty liver disease.

AIMS: Infection with specific pathogens may lead to increased adiposity. The human adenovirus 36 (Ad36) is a relatively new factor in promoting adipogenesis. It seems to improve the metabolic profile, expanding adipose tissue and enhancing insulin sensitivity in animal models. The aim of this study was to investigate whether any association or predictor effect of Ad36 seropositivity is present in non-alcoholic fatty liver disease (NAFLD), a condition associated with obesity and insulin resistance (IR). METHODS: Sixty-five NAFLD patients and 114 controls were investigated. Ultrasound bright liver score (BLS), body composition, IR evaluated by homeostasis model assessment of insulin resistance index (HOMA or HOMA-IR) and serum neutralization assay for antibodies to Ad36 were assessed. RESULTS: Ad36-seropositive patients have a lower risk of bright liver [OR 0.505 (95% confidence interval (CI) 0.265-0.962)]; greater IR leads to a higher risk of bright liver [OR 9.673 (95% CI 4.443-21.058)]. Among NAFLD, Ad36-seropositive vs. Ad36-seronegative patients did not show a significant IR difference. Ad36-seropositive NAFLD patients, with the same levels of HOMA and BLS, had greater body mass index and body fat mass, in comparison with seronegative NAFLD patients. By a multiple linear regression model, BLS was explained by HOMA (beta 0.513; P<0.0001), high density lipoprotein cholesterol (beta-0.219, P<0.006) and Ad36 seropositivity (beta-0.202, P<0.005); Ad36 seropositivity did not explain HOMA in the other multiple logistic regression model. CONCLUSIONS: Ad36 seropositivity is not associated with a significant difference of IR in NAFLD patients, but is associated with a greater adiposity. Ad36 seropositivity is associated with a lower occurrence of NAFLD and bright liver, which, conceivably, is not directly mediated by IR.

Protective role of coffee in non-alcoholic fatty liver disease (NAFLD).

AIM: The benefits of coffee on abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma have been reported, but there is a lack of satisfactory explanation. Thus, this study aims to investigate if coffee use has any relationship with bright liver, measured by ultrasound bright liver score (BLS), in patients with non-alcoholic fatty liver disease (NAFLD), and which relationship, if any, is present with BMI and insulin resistance. METHODS: This study was performed on 245 patients, 137 with NAFLD and 108 controls. Coffee drinking was defined according to the absolute number of cups of coffee (only espresso coffee), and also graded as 1 (0 cups of coffee/day), 2 (1-2 cups of coffee/day) 3 (≥3 cups of coffee/day). Insulin resistance was assessed by homoeostasis model-insulin resistance index (HOMA). RESULTS: Less fatty liver involvement is present in coffee vs. non-coffee drinkers. Odds ratios show that obesity, higher insulin resistance, lower HDL cholesterol, older age and arterial hypertension are associated with a greater risk of more severe BLS; to the contrary, coffee drinking is associated with less severe BLS. In the multiple logistic regression (MLR) model, number of cups of coffee, HOMA and BMI account for 35.8% of the variance to BLS. Coffee use is inversely associated with the degree of bright liver, along with insulin resistance and obesity, which, to the contrary, are directly associated with greater likelihood and severity of bright liver appearance. CONCLUSIONS: A possible opposite, if not antagonistic, role of coffee with regard to overweightness and insulin resistance, similar to that reported in hepatocarcinoma and cirrhosis, is envisaged in the natural history of NAFLD.

Elective coronary stent patients: preinterventional functional status and clinical-instrumental assessment.

The functional status of ischemic heart disease (IHD) is currently assessed using the Seattle Angina Questionnaire (SAQ), a tool for monitoring and predicting the patient's prognosis. Illness perceptions (IP) are associated with IHD behavioral risk factors. The aim of the study was to find whether different IP, as evaluated by the IP Questionnaire (IPQr), can predict any of the features of the SAQ, i.e., to determine whether the SAQ is influenced and/or biased by illness perceptions. Moreover, whether New York Heart Association class and Ejection Fraction (EF%) are predictors of IHD severity measured as need of subsequent stenting procedures was also assessed. Eighty IHD patients eligible for percutaneous coronary intervention (PCI) and drug-eluting stent implant were asked to complete the IPQr and the SAQ. Laboratory analyses, echocardiography, and coronary diagnostic and interventional procedures were performed concurrently. Physical limitations of the SAQ are predicted by IPQr emotional representation. Ischemic heart disease functional status is regulated by illness perceptions and beliefs. Thus, some of the inferences drawn from the SAQ regarding IHD prognosis and even interventional indications may be biased and compromise the prognostic reliability of the SAQ information on physical function. This can also have consequences for therapeutic indications.

Lifestyle interventions, insulin resistance, and renal artery stiffness in essential hypertension.

The study investigates lifestyle and effective anti-hypertensive intervention in overweight-obese patients can influence insulin-resistance (HOMA-IR) and US Renal-Resistive-Index (RRI). After a 1-year interventional program (including a personalized Mediterranean diet, physical activity increase, smoking withdrawal counseling), 156 Essential Hypertension (EH) patients still have abnormal HOMA-IR, significantly higher in comparison to 159 control group patients. Body mass index (BMI) and cholesterol-high-density-lipoprotein improvement are the best predictors of a HOMA-IR decrease; RRI improves in EH according to lifestyle interventions, but no predictor to RRI is identified. Persistence of IR can be tentatively assumed as a steady sign, persistent also after extended lifestyle intervention in EH, further warranting more intensive dietary interventions.

Coffee, nutritional status, and renal artery resistive index.

BACKGROUND: The relationship between nutrition and atherosclerosis is known, even dissociated from protein malnutrition. Cardiovascular impact of several nutrients is known; among them the action of coffee is still debated and cardiovascular effect of caffeine has been investigated without definite results. OBJECTIVE: The aim of this study is to investigate whether coffee habits, and/or quantity of coffee consumption, have any relationship with renal resistive index (RRI), a hallmark of arterial stiffness (AS). The relationship of AS with nutritional status assessed by body composition and serum albumin, insulin resistance (assessed by HOMA), and renal function assessed by glomerular filtration rate (GFR) is concurrently investigated. METHODS: This study was done with 221 consecutive patients, without diabetes, cancer, liver, renal, and heart disease, referred for clinical noninvasive assessment and nutritional counseling: 124 essential hypertensive and 97 nonhypertensive patients were eligible. Personalized Mediterranean diet, physical activity increase, and smoking withdrawal counseling were provided. RESULTS: By multiple linear regression, fat-free mass (FFM), HOMA (positive relationship), and number of cups of coffee/day (negative relationship) account for 17.2% of the variance to RRI. By odds ratios lower risk to increased RRI is associated with higher serum albumin, higher hemoglobin, and FFM; greater risk is associated with hypertension, insulin resistance (HOMA ≥ 3.0), and renal insufficiency (GFR ≤ 90); coffee, assessed by number of cups/day, reduces risk. CONCLUSION: Coffee use is inversely associated with RRI. Habitual coffee users have risk protection to higher RRI; lower serum albumin, insulin resistance, and renal insufficiency are associated with greater RRI.

Echocardiography and NAFLD (non-alcoholic fatty liver disease).

UNLABELLED: Non-alcoholic-fatty-liver-disease (NAFLD) is associated with atherosclerosis, increased cardiovascular risks and mortality. We investigated if, independently of insulin resistance, diet, physical activity and obesity, fatty liver involvement has any relationship with echocardiographic measurements in NAFLD. PATIENTS AND METHODS: 660 NAFLD and 791 non-NAFLD subjects, referred to the same out-patients medical unit for lifestyle-nutritional prescription, were studied. Congestive heart failure, myocardial infarction, malignancies, diabetes mellitus, extreme obesity, underweight-bad-nourished subjects and renal insufficiency were exclusion criteria. Liver steatosis was assessed by Ultrasound-Bright-Liver-Score (BLS), left ventricular ejection fraction (LVEF), trans-mitral E/A doppler ratio (diastolic relaxation) and left ventricular myocardial mass (LVMM/m(2)) by echocardiography. Doppler Renal artery Resistive Index (RRI), insulin resistance (HOMA) and lifestyle profile were also included in the clinical assessment. RESULTS: LVMM/m(2) is significantly greater in NAFLD, 101.62±34.48 vs. 88.22±25.61, p<0.0001 both in men and in women. Ejection fraction is slightly smaller only in men with NAFLD; no significant difference was observed for the E/A ratio. BMI (30.42±5.49 vs. 24.87±3.81; p<0.0001) and HOMA (2.90±1.70 vs. 1.85±1.25; p: 0.0001) were significantly greater in NAFLD patients. By Multiple-Linear-Regression, NAFLD and unhealthy dietary profile are associated also in lean non-diabetic subjects with lower systolic function, independently of BMI, dietary profile, physical activity, RRI and insulin resistance. CONCLUSION: NAFLD may be a meaningful early clue suggestive of diminishing heart function, with similar determining factors. NAFLD is amenable to management and improvement by lifestyle change counseling, addressing a dual target: reducing fatty liver, which is easily monitored by ultrasound, and, independently, maintaining a normal heart function.

Relationship of MTHFR gene polymorphisms with renal and cardiac disease.

AIM: To investigate the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial. METHODS: We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677T and A1298C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677T is present independently of the negative effects of left ventricular hypertrophy, increased Intra-Renal arterial Resistance and hyperparathyroidism. CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism.

ADV36 adipogenic adenovirus in human liver disease.

Obesity and liver steatosis are usually described as related diseases. Obesity is regarded as exclusive consequence of an imbalance between food intake and physical exercise, modulated by endocrine and genetic factors. Non-alcoholic fatty liver disease (NAFLD), is a condition whose natural history is related to, but not completely explained by over-nutrition, obesity and insulin resistance. There is evidence that environmental infections, and notably adipogenic adenoviruses (ADV) infections in humans, are associated not only with obesity, which is sufficiently established, but also with allied conditions, such as fatty liver. In order to elucidate the role, if any, of previous ADV36 infection in humans, we investigated association of ADV36-ADV37 seropositivity with obesity and fatty liver in humans. Moreover, the possibility that lifestyle-nutritional intervention in patients with NAFLD and different ADV36 seropositive status, achieves different clinical outcomes on ultrasound bright liver imaging, insulin resistance and obesity was challenged. ADV36 seropositive patients have a more consistent decrease in insulin resistance, fatty liver severity and body weight in comparison with ADV36 seronegative patients, indicating a greater responsiveness to nutritional intervention. These effects were not dependent on a greater pre-interventional body weight and older age. These results imply that no obvious disadvantage - and, seemingly, that some benefit - is linked to ADV36 seropositivity, at least in NAFLD. ADV36 previous infection can boost weight loss and recovery of insulin sensitivity under interventional treatment.

Contrast enhanced ultrasound of sentinel lymph nodes.

Sentinel lymph nodes are the first lymph nodes in the region that receive lymphatic drainage from a primary tumor. The detection or exclusion of sentinel lymph node micrometastases is critical in the staging of cancer, especially breast cancer and melanoma because it directly affects patient's prognosis and surgical management. Currently, intraoperative sentinel lymph node biopsies using blue dye and radioisotopes are the method of choice for the detection of sentinel lymph node with high identification rate. In contrast, conventional ultrasound is not capable of detecting sentinel lymph nodes in most cases. Contrast enhanced ultrasound with contrast specific imaging modes has been used for the evaluation and diagnostic work-up of peripherally located suspected lymphadenopathy. The method allows for real-time analysis of all vascular phases and the visualization of intranodal focal "avascular" areas that represent necrosis or deposits of neoplastic cells. In recent years, a number of animal and human studies showed that contrast enhanced ultrasound can be also used for the detection of sentinel lymph node, and may become a potential application in clinical routine. Several contrast agents have been used in those studies, including albumin solution, hydroxyethylated starch, SonoVue(®), Sonazoid(®) and Definity(®). This review summarizes the current knowledge about the use of ultrasound techniques in detection and evaluation of sentinel lymph node.

Renal function and severity of bright liver. Relationship with insulin resistance, intrarenal resistive index, and glomerular filtration rate.

AIMS: Relationships of renal function and liver disease are described in acute and chronic liver failure. The aim of the study is to investigate which relationship, if any, is present between severity of non-alcoholic fatty liver disease (NAFLD), assessed by bright liver score (BLS) versus mild-moderate renal insufficiency assessed by glomerular filtration rate (GFR) and by ultrasound intra-renal arterial resistive index (RRI). Moreover, which difference, if any, can be found in NAFLD patients with normal versus increased transaminases. PATIENTS: The study enrolled 323 NAFLD and 176 non-NAFLD consecutive patients, comparable for age, gender distribution, GFR, and RRI referred to a university clinical day hospital after an ultrasound diagnosis of bright liver, for clinical-nutritional counselling. Personalized computerized mediterranean diet, physical activity increase, and smoking withdrawal integrated counselling were provided. RESULTS: In NAFLD patients, homoeostasis model (HOMA) has a significant correlation with BLS. According to the severity of BLS, grade II-III versus grade I patients have significantly higher values of HOMA, body mass index (BMI), triglycerides, and longitudinal right liver length. By odds ratio, more severe BLS, increased HOMA, and transaminases are associated with lower GFR. Increased transaminases are associated with higher grades of BLS, HOMA, and BMI. By multiple linear regression waist-to-hip ratio, RRI, and BLS, as significant independent factors (p < 0.0001), explain significantly variance to GFR. This is not observed in normal control group, in which only RRI is a factor explaining GFR. CONCLUSION: Greater RRI, abdominal obesity, and greater BLS account for a lower GFR in NAFLD patients suggesting the hypothesis that inter-related factors can be operating early in the natural history of obesity-related kidney and liver disease.