Massive bone allograft engineered with autologous vessels: A new perspective for the future.

Reconstruction is very important to ensure good function and quality of life after bone tumor resection. For metacarpals and phalanges, amputation and toe transfer are the gold-standard indications; nevertheless, allograft reconstruction must also be taken into account. Unfortunately, because of its inert biological behavior, it undergoes progressive resorption, with frequent fracture. Several attempts have been made to induce new vascularization in massive bone allograft, with poor results. However, neo-angiogenesis was reported with vascular loops, and we therefore hypothesized that heterologous graft integration could be enhanced by creating a vascular loop through the graft. A 50-year-old male with chondrosarcoma of the ring finger of the left hand underwent wide resection. An allogenic middle phalanx of comparable size was then prepared to fill the defect. Two small windows were performed proximally and distally on the radial surface of the allogenic phalanx, and a 4 cm-long vein graft was inserted inside the medullary canal. Metacarpophalangeal joint stability was achieved by collateral ligament reconstruction with micro-anchors. The distal part of the allograft was then stabilized to the middle phalanx with a 1.5 mm-thick micro-plate and screws. The radial proper palmar digital artery was proximally and distally sutured end-to-end to the vein graft, under microscopy. At 12-month follow-up, the allograft was fused, and histology performed at plate removal at 18 months revealed viable spindle cells with osteoblastic differentiation, without evidence of atypia, in a dense fibrous stroma. At 22 months' follow-up, the patient was apparently disease-free, and satisfied with his manual function.

Italian SARS-CoV-2 patients in intensive care: towards an identikit for subjects at risk?

OBJECTIVE: To investigate patient characteristics and factors that increase the risk of being admitted to intensive care and that influence survival in cases of SARS-CoV-2 pneumonia. PATIENTS AND METHODS: One-hundred and ninety-one SARS-CoV-2 patients were admitted to the "Fondazione Poliambulanza di Brescia" Hospital (Brescia, Lombardy, Italy) in the period 1st March 2020 to 11th April 2020. Data on demographics, clinical presentation at admission, co-morbidities, pharmacological treatment, admission to intensive care and death was recorded. Logistic regression and survival analysis were carried out to investigate the risk of being admitted to intensive care and the risk of death. RESULTS: The mean age of the study cohort was 64.6±9.9 years (range 20-88). Median BMI was 28.5±5 kg/m2. Fever (81%) and dyspnea (65%) were the most common symptoms on admission. Most of patients (63%) had at least one co-existing disease. The 157 (82%) patients admitted to intensive care were more likely to be of intermediate age (60-69 years; OR 3.23, 95% CI 1.32-8.38), overweight (OR 2.66, 95% CI 1.02-7.07) or obese (OR 5.63, 95% CI 1.73-21.09) and with lymphocytopenia (OR 2.75, 95% CI 1.17-6.89) than the 34 patients admitted to the ordinary ward. During intensive care, 50% of patients died and their death was associated with older age (HR 2.06, 95% CI 1.07-3.97), obesity (HR 2.23, 95% CI 1.15-4.35) and male gender (HR 1.9, 95% CI 1.02-3.57). CONCLUSIONS: We found that admission to intensive care and poor survival were associated with advanced age and higher body mass index, albeit with differences in statistical significance. Pre-existing diseases and symptoms on admission were not associated with different clinical outcomes. Interestingly, male gender was more prevalent among SARS-CoV-2 patients and was related negatively to survival, but it was not associated with more frequent admission to intensive care.

Lifestyle changes in the management of adulthood and childhood obesity.

Adulthood and childhood obesity is rapidly becoming an epidemic problem and it has a short and long term impact on health. Short term consequences are mostly represented by psychological effects, in fact obese children have more chances to develop psychological or psychiatric problems than non--obese children. The main long term effect is represented by the fact that childhood obesity continues into adulthood obesity and this results in negative effects in young adult life, since obesity increases the risk to develop morbidity and premature mortality. The obesity--related diseases are mostly represented by hypertension, type 2 diabetes, dyslipidaemia, cardiovascular diseases. Medical treatment should be discouraged in childhood because of the side effects and it should be only reserved for obese children with related medical complications. Lifestyle changes should be encouraged in both adulthood and childhood obesity. This review focuses on the management of obesity both in adulthood and in childhood, paying particular attention to lifestyle changes that should be recommended.

HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNα2a and Ribavirin: a randomized controlled trial.

Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 µg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte proliferation assay (LPA) for E1E2-specific-CD4 + T cells were performed at week 0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and a sustained virological response (SVR) was achieved in 4 P/R + V and 2 P/R patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R + V as compared to P/R patients (P = 0.023 and 0.025, P = 0.019 and <0.001, respectively). Among the 22 patients with the strongest direct antiviral effects of IFN (ε ≥ 0.800), those treated with P/R + V (10) reached lower HCV-RNA levels (P = 0.026) at week 16. HCV E1E2MF59 vaccine in combination with Peg-IFNα2a + RBV was safe and elicited E1E2 neutralizing antibodies and specific CD4 + T cell proliferation. Upon early response to IFN, vaccinations were associated with an enhanced second phase viral load decline. These results prompt phase II trials in combination with new antiviral therapies.

Effects of physical exercise on the female reproductive system.

The excess in physical activity could be closely linked to considerable negative consequences on the whole body. These dysfunctions called as "female athlete triad"' by the American College of Sports Medicine (ACSM) include amenorrhea, osteoporosis and disorder eating. The female athlete triad poses serious health risks, both on the short and on the long term, to the overall well-being of affected individuals. Sustained low energy availability can impair health, causing many medical complications within skeletal, endocrine, cardiovascular, reproductive and central nervous system. On the contrary, several studies have shown, that physical activity improves cardiovascular risk factors, hormonal profile and reproductive function. These improvements include a decrease in abdominal fat, blood glucose, blood lipids and insulin resistance, as well as improvements in menstrual cyclicity, ovulation and fertility, decreases in testosterone levels and Free Androgen Index (FAI) and increases in sex hormone binding globulin (SHBG). Other studies reported that physical activity improved self-esteem, depression and anxiety. Thus, the aim of this review is to elucidate the effect of physical exercise on female reproductive system and viceversa the impact of hormonal status on physical activity and metabolism. In addition this review supports the idea that physical exercise is a helpful tool for the management of obesity, prevention of cardiovascular, metabolic diseases and female reproductive organs related diseases (e.g. breast cancer). When the excess in physical activity leads up to the female athlete triad, it is imperative to treat each component of the triad by employing both pharmacological and non pharmacological treatments.

Autonomic nervous system in the control of energy balance and body weight: personal contributions.

The prevalence of obesity is increasing in the industrialized world, so that the World Health Organization considers obesity as a "pandemia" in rich populations. The autonomic nervous system plays a crucial role in the control of energy balance and body weight. This review summarizes our own data and perspectives, emphasizing the influence exerted by autonomic nervous system on energy expenditure and food intake, which are able to determine the body weight. Activation of the sympathetic discharge causes an increase in energy expenditure and a decrease in food intake, while reduction of food intake and body weight loss determines a reduction of the sympathetic activity. On the other hand, pathophysiological mechanisms of the obesity involve alterations of the sympathetic nervous system in accordance with the "Mona Lisa Hypothesis," an acronym for "most obesities known are low in sympathetic activity." Furthermore, the parasympathetic influences on the energy expenditure are analyzed in this review, showing that an increase in parasympathetic activity can induce a paradoxical enhancement of energy consumption.

RANKL expression in a case of follicular lymphoma.

The TNF-family molecule, RANKL, is a key regulator of bone remodeling and essential for the development and activation of osteoclasis. Bone involvement signals diesease activity in non-Hodgkin's lymphoma and influences the progenesis. The molecular mechanism and soluble factors involved in osteoclastic activation in haematological malignancies remain unclear except for Multiple Myeloma and Adult T-cell Leukemia. The aim of this paper is to report the first case of Follicular Lymphoma with bone involvement displaying an aberrant expression of RANKL in malignant cells. The detection of RANKL in Follicullar Lymphoma may help to prevent bone lesion in patients by determining an appropriate treatment.

Non-alcoholic fatty liver disease in an area of southern Italy: main clinical, histological, and pathophysiological aspects.

BACKGROUND/AIMS: Studies on non-alcoholic fatty liver disease (NAFLD) have included chronic liver damage attributed to various causes. Our investigation was held to observe the main clinical, histological, and pathophysiological aspects of NAFLD in patients not exposed to any known cause of chronic liver disease. METHODS: We evaluated, in 84 in-patients (male/female, 66/18; median age, 36 years), the clinical and biochemical characteristics of NAFLD, and particularly its association with diabetes, dyslipidemia, hyperinsulinemia and/or with the increase of parameters of oxidative stress (blood levels of malonyldialdehyde, 4-hydroxynonenal and total plasma antioxidant capacity). RESULTS: Ninety percent of patients had an increased body mass index (BMI), 35% had dyslipidemia, 40% had sub-clinical diabetes (only 3% had overt diabetes), 60% had hyperinsulinemia, and more than 90% had enhanced levels of lipid peroxidation markers. In 48 patients who had consented to liver biopsy, we found: 14 with simple steatosis, 32 with steatohepatitis, and two with cirrhosis. CONCLUSIONS: Our data indicate that in our country, NAFLD may occur in young males with an increased BMI, with or without hyperinsulinemia, dyslipidemia and diabetes, generally associated with disorders of redox status, and that it may be differentiated from steatosis to steatohepatitis or cirrhosis only with a liver biopsy.

Interactions between metabolic disorders (diabetes, gallstones, and dyslipidaemia) and the progression of chronic hepatitis C virus infection to cirrhosis and hepatocellular carcinoma. A cross-sectional multicentre survey.

BACKGROUND: Diabetes, gallstones and dyslipidaemia are widespread, metabolically related, disorders that can affect the liver, often in a clinically silent fashion. AIM: To investigate whether the presence of these disorders may worsen chronic viral disease by inducing additional liver damage, revealed by variations in serum increases of aminotransferase, alkaline phosphatase and gamma-glutamyl-transpeptidase activities. PATIENTS AND METHODS: This retrospective, cross-sectional study involved 1,195 patients with chronic hepatitis C virus infection: 47.2% chronic hepatitis, 45.2% cirrhosis, and 7.6% hepatocellular carcinoma. 14.9% of patients had enzymatic cholestasis, defined as combined increase of alkaline phosphatase and gamma-glutamyl-transpeptidase. A Log-linear statistical model was applied to the following variables: stages of liver disease, diabetes, cholelithiasis, hypertriglyceridaemia, hypercholesterolaemia, and enzymatic cholestasis. RESULTS: Log-linear analysis, applied to categorical variables, revealed, for the first time, a three-way interaction between the stages of chronic liver disease, diabetes, and enzymatic cholestasis. Two-way interactions demonstrated that liver disease stages correlated directly to the prevalence of cholelithiasis and inversely to hypercholesterolaemia. Irrespective of the liver disease stage, hypertriglyceridaemia correlated to hypercholesterolaemia. CONCLUSIONS: This study discloses a synergistic liver damaging effect of diabetes and hepatitis C virus. The three-way interaction obtained by our analysis suggests that diabetes is a risk factor for the progression of viral liver disease and that it contributes to disease evolution, at least in part, by induction of cholestasis.

Liver transplantation in Italy: current status. Study Group on Liver Transplantation of the Italian Association for the Study of the Liver (A.I.S.F.).

The first liver transplant in Italy was performed in 1982. With the improvement in results, the number of patients followed, in recent years, has substantially increased in all centres. In parallel, the indications for liver transplantation have expanded and have raised the need for more organized structures where patients can be referred for evaluation and transplantation. Indications and contraindications to liver transplantation in Italy, the role of retransplantation, paediatric liver transplantation, waiting list management, liver transplantation outside Italy and the new Italian laws on organ donation are discussed. The multidisciplinary Study Group on Liver Transplantation of the Italian Association for the Study of the Liver (AISF) has collected information from all the Italian centres to ascertain the degree of consistency in their methods.

Quantification of fecal neutrophils by MPO determination (myeloperoxidase) in patients with invasive diarrhea. Cuantificación de neutrofilos fecales mediante la determinación de MPO (Mieloperoxidasa) en pacientes con diarrea invasiva.

Myeloperoxidase (MPO), a specific polymorphonuclear leukocyte enzyme, has been used previously to quantify the number of neutrophils in tissue. MPO activity was found to be linearly related to the number of neutrophil cells. In an attempt to use this method in leukocytes measuring in stool, fecal MPO was solubilized with hexadecyltrimethylammonium bromide and the MPO activity was measured by a dianisidine-H2O2 assay. Stools from 10 normal subjects and 39 patients with diarrhea produced by enteropathogenic bacteria were examined for leukocytes by MPO activity as well as microscopically using methylene blue stain, MPO activity was positive in 36 patients (92%) and leukocytes were present by microscopic observation in 30 (77%). Fecal leukocytes were not found in healthy controls and the MPO activity was undectable. Stool MPO activity had a range of from 1.6 to 2,830.0 x 10(3) UMPO per gram of feces (median 460.0). The number of neutrophils obtained through MPO activity had a range of 6.0 to 13,216.0/ mm3 (median 1,261.0). Fecal MPO activity is a simple biochemical assay for the detection and quantification of fecal leukocytes.

Quantification of fecal neutrophils by MPO determination (myeloperoxidase) in patients with invasive diarrhea. Cuantificación de neutrofilos fecales mediante la determinación de MPO (Mieloperoxidasa) en pacientes con diarrea invasiva

Myeloperoxidase (MPO), a specific polymorphonuclear leukocyte enzyme, has been used previously to quantify the number of neutrophils in tissue. MPO activity was found to be linearly related to the number of neutrophil cells. In an attempt to use this method in leukocytes measuring in stool, fecal MPO was solubilized with hexadecyltrimethylammonium bromide and the MPO activity was measured by a dianisidine-H2O2 assay. Stools from 10 normal subjects and 39 patients with diarrhea produced by enteropathogenic bacteria were examined for leukocytes by MPO activity as well as microscopically using methylene blue stain, MPO activity was positive in 36 patients (92

) and leukocytes were present by microscopic observation in 30 (77

). Fecal leukocytes were not found in healthy controls and the MPO activity was undectable. Stool MPO activity had a range of from 1.6 to 2,830.0 x 10(3) UMPO per gram of feces (median 460.0). The number of neutrophils obtained through MPO activity had a range of 6.0 to 13,216.0/ mm3 (median 1,261.0). Fecal MPO activity is a simple biochemical assay for the detection and quantification of fecal leukocytes.

Quantification of fecal neutrophils by MPO determination (myeloperoxidase) in patients with invasive diarrhea. Cuantificación de neutrofilos fecales mediante la determinación de MPO (Mieloperoxidasa) en pacientes con diarrea invasiva.

Myeloperoxidase (MPO), a specific polymorphonuclear leukocyte enzyme, has been used previously to quantify the number of neutrophils in tissue. MPO activity was found to be linearly related to the number of neutrophil cells. In an attempt to use this method in leukocytes measuring in stool, fecal MPO was solubilized with hexadecyltrimethylammonium bromide and the MPO activity was measured by a dianisidine-H2O2 assay. Stools from 10 normal subjects and 39 patients with diarrhea produced by enteropathogenic bacteria were examined for leukocytes by MPO activity as well as microscopically using methylene blue stain, MPO activity was positive in 36 patients (92

) and leukocytes were present by microscopic observation in 30 (77

). Fecal leukocytes were not found in healthy controls and the MPO activity was undectable. Stool MPO activity had a range of from 1.6 to 2,830.0 x 10(3) UMPO per gram of feces (median 460.0). The number of neutrophils obtained through MPO activity had a range of 6.0 to 13,216.0/ mm3 (median 1,261.0). Fecal MPO activity is a simple biochemical assay for the detection and quantification of fecal leukocytes.

Gross pathologic types of hepatocellular carcinoma in Italy.

The prevalence and independent predictors of the different macroscopic types of hepatocellular carcinoma (HCC) were assessed in 1,073 unselected patients of 14 hospitals in Italy from May 1996 to May 1997. Solitary HCC was the most common cancer type (44.6%), followed by multinodular (44.2%), diffuse (8.4%) and massive (2.8%) types. After adjustment for the influence of confounders by multiple logistic regression analysis, Child-Pugh grades B and C were found to be independent predictors of multinodular (odds ratio, OR, 2.0; 95% confidence interval (CI) = 1.5-2.6) and diffuse (OR 2.6; 95% CI = 1.6-4.4) HCC types. These findings indicate that the majority of HCC cases are not detected at a potentially treatable stage. Delayed detection of HCC is associated with a higher likelihood of the multinodular or diffuse gross pathologic type.

Efficacy of high dose of recombinant alpha 2b interferon on long term response in chronic hepatitis C and cirrhosis: prospective randomized multicentre study.

BACKGROUND/AIMS: The long-term response to alpha-Interferon in HCV-related chronic liver diseases is disappointing. A randomized controlled trial was conducted to investigate: 1) if doubling the standard regimen of 3 MU recombinant alpha 2b-interferon thrice weekly for one year could improve the long-term response, and 2) the efficacy of these two schedules in cirrhotic patients. PATIENTS AND METHODS: A series of 80 anti-HCV positive patients with biopsy proven liver disease (52 chronic hepatitis and 28 cirrhosis) were randomized to receive either 3 MU or 6 MU alpha 2b-interferon. RESULTS: Based on "intention-to-treat analysis", 38% in the 3 MU group and 53% in the 6 MU group had end-of-treatment response. After 24 months, 18% had long-term response: 5% in 3 MU group and 30% in 6 MU group (p < 0.008). HCV genotype had no influence on the response rate. Thirty-eight percent of the cirrhotics treated with 6 MU had long-term response, while none of those treated with 3 MU had long-term response (difference 38%; 95% confidence internal 10%-67%; p = 0.03). At the end of treatment, 38% of patients lost HCV-RNA. After 24 months only 19% remained HCV-RNA negative: 12 patients (31%) in the 6 MU group and 2 (6%) in the 3 MU group (p < 0.05). CONCLUSIONS: 6 MU of alpha 2b-interferon thrice weekly for 12 months is significantly better than 3 MU in inducing a long-term response and permanent loss of HCV-RNA. This result is particularly striking in the subgroup of cirrhotics.

Spread of hepatitis C virus infection within families. Investigators of an Italian Multicenter Group.

In 1995, the intrafamilial spread of hepatitis C virus (HCV) was evaluated among 1379 household contacts of 585 HCV antibody-positive HCV RNA-positive subjects (index cases) in Italy. All index cases were patients with histologically proven chronic liver disease. The presence of antibodies to HCV (anti-HCV) was assessed by third-generation enzyme-linked immunosorbent assay (ELISA); the polymerase chain reaction (PCR) was used to test for HCV RNA. The overall anti-HCV prevalence among household contacts of index cases was 7.3% (101/1379); it was 15.6% in spouses and 3.2% in other relatives (P < 0.05; odds ratio (OR), 6.5; 95% confidence interval (CI), 3.5-8.6). Spouses married to index cases for longer than 20 years had a significantly higher anti-HCV prevalence than those married 20 years or less (19.8% vs 8.0%; P< 0.05; OR, 2.8; 95% CI, 1.5-5.3). Parenteral risk factors were more likely to be reported in anti-HCV positive than in anti-HCV negative household contacts. After adjustment for confounders by multiple logistic regression analysis, age greater than 4 5 years (OR, 3.1; 95% CI, 1.6-5.3) and any parenteral exposure (OR, 3.7; 95% CI, 1.7-8.1), were the only independent predictors of the likelihood of anti-HCV positivity among household contacts. Spouses versus other relatives and length of marriage were both no longer associated. These findings suggest that sexual transmission does not seem to play a role in the intrafamilial spread of HCV infection.

Characteristics of hepatocellular carcinoma in Italy.

BACKGROUND/AIMS: This study aimed to assess the main features of hepatocellular carcinoma at the time of diagnosis in Italy, particularly in relation to the presence or absence of underlying cirrhosis, hepatitis virus marker patterns, age of the subjects and alpha-foetoprotein values. METHODS: A total of 1148 patients with hepatocellular carcinoma seen at 14 Italian hospitals in the 1-year period from May 1996 to May 1997 were the subjects of this prevalence study. Both newly diagnosed cases (incident cases) and cases diagnosed before May 1996 but still attending the hospitals during the study period (prevalent cases) were included. RESULTS: We found that 71.1% of cases were positive for hepatitis C virus antibodies but negative for HBsAg; in contrast, 11.5% were negative for anti-HCV but positive for HBsAg; 5.3% were positive for both markers; and 12.1% were negative for both viruses. The mean age of detection was over 60 years, with a younger mean age in HBsAg-positive compared to anti-HCV-positive patients (59.3 years vs. 65.6 years, p<0.01). The male-to-female ratio among HBsAg-positive patients was 10.4:1, in contrast to 2.8:1 among anti-HCV-positive patients (p<0.01). The majority of cases (93.1%) had underlying cirrhosis. Cirrhotic patients were more likely to be anti-HCV positive than non-cirrhotic cases (73.2% vs 43.9%; p<0.01); conversely, absence of hepatitis virus markers was more frequently observed in the non-cirrhotic than in the cirrhotic population (40.9% vs. 10.0%; p<0.01). Overall, the alpha-foetoprotein level was altered (>20 ng/ml) in 57.9% of patients; only 18% of cases presented diagnostic (>400 ng/ml) values. Anti-HCV positivity (O.R. 2.0; CI 95%=1.3-3.1) but not HBsAg positivity (O.R. 1.0; CI 95%=0.6-1.8) was shown to be an independent predictor of the likelihood of altered alpha-foetoprotein values by multivariate analysis. CONCLUSIONS: These findings point to differences in the characteristics of the populations infected by hepatitis B and hepatitis C. Factors other than the hepatitis viruses are important in non-cirrhotic patients. A change in the relative prevalence of hepatitis virus markers among hepatocellular carcinoma cases was demonstrated, reflecting a significant change in the rate of HBV endemicity in the Italian population. Finally, the increased trend in the mortality rate from liver cancer in Italy from 4.8 per 100,000 in 1969 to 10.9 in 1994 may reflect the large cohort of subjects infected with HCV via the iatrogenic route during 1950s and 1960s when glass syringes were commonly used for medical treatment.