Fatty liver, carotid disease and gallstones: A study ofage-related associations

AIM: To evaluate carotid intima-media thickening (IMT)and plaques, gallstone disease (GD) and fatty liver (FL)as a function of age.METHODS: In 449 subjects, FL and carotid diseasewere assessed ultrasonographically. In a subgroup of65/449 patients with non-alcoholic fatty liver disease(NAFLD), carotid disease, GD and associated factorswere determined.RESULTS: FL of unspecifi ed etiology was more commonin younger and GD in older individuals. FL subjectshad an increased prevalence of IMT and a decreasedprevalence of plaques and manifested carotid diseaseearlier. Plaques were more common in subjects with GD.Age was an independent predictor of carotid diseaseoutcome and FL was a protective factor for plaques. InNAFLD, there was an inverse correlation between bodyweight and age and the latter independently predictedcarotid fi ndings.CONCLUSION: Cardiovascular risk in patients with FLand NAFLD needs to be assessed as a function of ageand body weight

Is nonalcoholic steatohepatitis associated with a high-though-normal thyroid stimulating hormone level and lower cholesterol levels?

Hypothyroidism is associated with the risk of development of the metabolic syndrome (MS) and hypercholesterolemia. Direct evidence that hypothyroidism might be associated with advanced chronic liver disease via nonalcoholic steatohepatitis (NASH) is limited. We studied the relationship between thyroid hormones, thyroid stimulating hormone (TSH), cholesterol, and NASH. In consecutive euthyroid patients with biopsy-proven nonalcoholic fatty liver disease, TSH and thyroid hormone (FT3 and FT4) concentrations were compared in 25 patients with steatosis and 44 non-cirrhotic NASH patients featuring concurrent ballooning, lobular inflammation and steatosis. The MS was diagnosed according to ATP III criteria. A meta-analysis of previously published studies was performed to evaluate whether NASH, compared to simple steatosis, is associated with lower cholesterol levels. At univariate analysis, compared to those with steatosis, patients with NASH have a wider waist, elevated levels of BMI, ALT, AST, fasting insulin, HOMA-IR, ferritin, TSH and a lower serum cholesterol. At stepwise multivariable logistic regression analysis, the independent predictors of NASH are high HOMA and TSH and lower total cholesterol (Model 1); MS and high TSH (Model 2). At meta-analysis, serum total cholesterol levels are significantly lower in predominantly non-cirrhotic NASH than in simple steatosis. This study provides cross-sectional and meta-analytic evidence that, in euthyroid patients, high-though-normal TSH values are independently associated with NASH. Further work is needed to ascertain the role, if any, of lower cholesterol serum levels in assisting in the diagnosis of NASH

Efficacy, safety, and drug survival of IL-23, IL-17, and TNF-alpha inhibitors for psoriasis treatment: a retrospective study

Background Real-life studies in psoriasis are lacking. Many monoclonal antibodies targeting tumor-necrosis factor (TNF)-alpha, interleukin 17, and 23 are approved drugs for psoriasis treatment. Objectives To compare the short and long-term efficacy, safety, and drug survival of anti TNF-alpha, anti-IL-17, and anti-IL-23 in a large case series. Methods Psoriasis area severity index (PASI) and retention rates for adalimumab, secukinumab, guselkumab, ixekizumab, and brodalumab were analised. Results A total of 263 patients were randomly selected among the five drugs register of the patients attending the Psoriasis Unit at the Turin University Hospital. The mean PASI at baseline was 14.3. Ixekizumab showed a significantly higher efficacy profile compared to other drugs in terms of PASI90 and PASI100 at week 12, 24, and week 48 even when adjusted for other confounding factors. This superiority was not followed by an expected higher drug survival. On the contrary, secukinumab was the only drug that showed a higher drug survival among bio-naïve patients

O6-methylguanine-DNA methyltransferase promoter hypermethylation in colorectal carcinogenesis

Epigenetic alterations have been reported in colorectal neoplasia which can either complement or in some cases be predisposed to genetic alterations such as K-ras mutations. We examined the promoter methylation status of the CDKN2A and O6-methylguanine-DNA methyltransferase (MGMT) genes, after sodium bisulfite conversion and DNA amplification with methylation specific PCR. Moreover, we searched for G to A transitions in codons 12 and 13 of the K-ras oncogene in normal colorectal mucosae, aberrant crypt foci (ACF, early premalignant lesions) and carcinomas. CDKN2A hypermethylation was an infrequent event in ACF (2 of 26, 7.7%). On the contrary, MGMT hypermethylation was found in the normal mucosae (3 of the 12 samples, 25%), in 14 of the 26 ACF (53.8%) and in 7 of the 9 (77.8%) carcinomas examined. K-ras mutations were evident in 6 ACF (23%) and in 3 carcinomas (33.3%), mostly associated with MGMT promoter hypermethylation. These findings strongly support the hypothesis that epigenetic mechanisms play an important role in the early steps of colorectal carcinogenesis

Gender differences in genital lichen sclerosus: data from a multicenter Italian study on 729 consecutive cases

BACKGROUND: Studies specifically conducted to assess gender differences in genital lichen sclerosus (GLS) are not available. This multi- center study aimed to identify possible gender-related differences on GLS clinical features, history and course, through collecting data from a large mixed-sex sample of patients. METHODS: This was a cross-sectional study on 729 subjects (53.8% females, 46.2% males) affected with GLS, consecutively observed within a network of 15 Italian dermatology units. The following information was specifically collected: clinical features and severity of symptoms re- lated to GLS, extragenital involvement, previous therapies, diagnostic suspicion at referral, type of referring physicians, development of genital squamous-cell carcinoma (SCC). RESULTS: Females complained of symptoms more frequent and severe than men; pallor and scarring-sclerosis-atrophy were the most frequent features without gender differences; itching-related signs were more frequent in females than in males as well as extragenital involvement; prior to receiving a definitive diagnosis, females received treatment more frequently than males; 40% of patients were referred with a misdiagnosis; the highest rate of correct suspected diagnosis at referral came from dermatologists than from other physicians; duration of the disease was found to predispose to SCC development. CONCLUSIONS: Our findings highlighted several gender differences on clinical presentation and symptom profile of GLS. In spite of some characteristic features, misdiagnosis at referrals was frequent

Gender differences in genital lichen sclerosus: data from a multicenter Italian study on 729 consecutive cases

BACKGROUND Studies specifically conducted to assess gender differences in genital lichen sclerosus (GLS) are not available. This multicenter study aimed to identify possible gender-related differences on GLS clinical features, history and course, through collecting data from a large mixed-sex sample of patients. METHODS This was a cross-sectional study on 729 subjects (53.8% females, 46.2% males) affected with GLS, consecutively observed within a network of 15 Italian dermatology units. The following information was specifically collected: clinical features and severity of symptoms related to GLS, extragenital involvement, previous therapies, diagnostic suspicion at referral, type of referring physicians, development of genital squamous-cell carcinoma (SCC). RESULTS Females complained of symptoms more frequent and severe than men; pallor and scarring-sclerosis-atrophy were the most frequent features without gender differences; itching- related signs were more frequent in females than in males as well as extragenital involvement; prior to receiving a definitive diagnosis, females received treatment more frequently than males; 40% of patients were referred with a misdiagnosis; the highest rate of correct suspected diagnosis at referral came from dermatologists than from other physicians; duration of the disease was found to predispose to SCC development. CONCLUSIONS Our findings highlighted several gender differences on clinical presentation and symptom profile of GLS. In spite of some characteristic features, misdiagnosis at referrals was frequent

Long-term proactive management of psoriasis with calcipotriol and betamethasone dipropionate foam: an Italian consensus through a combined nominal group technique and Delphi approach

none85Background: Although long-term management of psoriasis is paramount, this approach is challenging in clinical practice. In the recent PSO-LONG trial, a fixed-dose combination of betamethasone dipropionate (BD) and calcipotriol (Cal) foam applied twice a week on non-consecutive days for 52 weeks (proactive treatment) reduced the risk of relapse. However, the role of Cal/BD foam in the long-term management of psoriasis needs further clarifications. The ProActive Management (PAM) program, a nationwide Italian project, aims at reaching a consensus on the role of proactive management of psoriasis. Methods: A steering committee generated some statements through the nominal group technique (NGT). The statements were voted by an expert panel in an adapted Delphi voting process. Results: Eighteen statements were proposed, and the majority of them (14/18) reached a consensus during the Delphi voting. The need to provide long-term proactive topical treatment to reduce the risk of relapse for the treatment of challenging diseases sites or in patients where phototherapy or systemic therapies are contraindicated/ineffective was widely recognized. A consensus was reached about the possibility to associate the proactive treatment with systemic and biological therapies, without the need for dose intensification, thus favoring a prolonged remission. Moreover, the proactive treatment was recognized as more effective than weekend therapy in increasing time free from relapses. Approaches to improve adherence, on the other hand, need further investigation. Conclusions: The inclusion in guidelines of a proactive strategy among the effective treatment options will be a fundamental step in the evolution of a mild-moderate psoriasis therapeutic approach.noneDe Simone, Clara; Dapavo, Paolo; Malagoli, Piergiorgio; Martella, Alessandro; Campanati, Anna; Campione, Elena; Errichetti, Enzo; Franchi, Chiara; Gambardella, Alessio; Megna, Matteo; Osti, Federica; Ribero, Simone; Zagni, Giovanni; Calzavara-Pinton, Piergiacomo; Fabbrocini, Gabriella; Amoruso, Giuseppe Fabrizio; Baglieri, Francesco; Biamonte, Anna Silvia; Bianchelli, Tommaso; Bigi, Laura; Bortoli, Jarno; Brunetti, Bruno; Buligan, Cinzia; Cagni, Elisabetta; Calderoni, Ombretta; Calzavara-Pinton, Piergiacomo; Campanati, Anna; Caputo, Alighiero; Carrera, Carlo Giovanni; Carugno, Andrea; Chersi, Karin; Cicchelli, Stefano; De Natale, Flora; De Simone, Clara; Dapavo, Paolo; Di Maria, Domenico; Errichetti, Enzo; Fabbrocini, Gabriella; Ferrari, Angelo Salvatore; Fogli, Emanuela; Forconi, Riccardo; Franchi, Chiara; Galeazzi, Augusto; Gambardella, Alessio; Giovannini, Andrea; Giura, Maria Teresa; Iuculano, Massimo; Lazzaretti, Giuseppe; Leporati, Claudia; Magnanini, Massimiliano; Malagoli, Piergiorgio; Marconi, Barbara; Martella, Alessandro; Maruccia, Adriana; Megna, Matteo; Miglietta, Roberta; Minuti, Anna; Mocci, Luigi; Modica, Sonia; Narcisi, Alessandra; Odorici, Giulia; Osti, Federica; Pazzaglia, Massimiliano; Peila, Rossana; Pertusi, Ginevra; Pezza, Michele; Pezzullo, Elio; Puccia, Nunzio; Raulo, Umberto; Ribero, Simone; Rossi, Mariateresa; Rusignuolo, Sergio; Sapienza, Giada; Savarese, Catello; Scalisi, Mariaelena; Strippoli, Davide; Stroppiana, Elena; Tiberio, Rossana; Trischitta, Antonino; Tucci, Maria Giovanna; Vaira, Fabrizio; Verrone, Anna; Villa, Lucia; Zagni, Fabio; Zoccali, AndreaDe Simone, Clara; Dapavo, Paolo; Malagoli, Piergiorgio; Martella, Alessandro; Campanati, Anna; Campione, Elena; Errichetti, Enzo; Franchi, Chiara; Gambardella, Alessio; Megna, Matteo; Osti, Federica; Ribero, Simone; Zagni, Giovanni; Calzavara-Pinton, Piergiacomo; Fabbrocini, Gabriella; Amoruso, Giuseppe Fabrizio; Baglieri, Francesco; Biamonte, Anna Silvia; Bianchelli, Tommaso; Bigi, Laura; Bortoli, Jarno; Brunetti, Bruno; Buligan, Cinzia; Cagni, Elisabetta; Calderoni, Ombretta; Calzavara-Pinton, Piergiacomo; Campanati, Anna; Caputo, Alighiero; Carrera, Carlo Giovanni; Carugno, Andrea; Chersi, Karin; Cicchelli, Stefano; De Natale, Flora; De Simone, Clara; Dapavo, Paolo; Di Maria, Domenico; Errichetti, Enzo; Fabbrocini, Gabriella; Ferrari, Angelo Salvatore; Fogli, Emanuela; Forconi, Riccardo; Franchi, Chiara; Galeazzi, Augusto; Gambardella, Alessio; Giovannini, Andrea; Giura, Maria Teresa; Iuculano, Massimo; Lazzaretti, Giuseppe; Leporati, Claudia; Magnanini, Massimiliano; Malagoli, Piergiorgio; Marconi, Barbara; Martella, Alessandro; Maruccia, Adriana; Megna, Matteo; Miglietta, Roberta; Minuti, Anna; Mocci, Luigi; Modica, Sonia; Narcisi, Alessandra; Odorici, Giulia; Osti, Federica; Pazzaglia, Massimiliano; Peila, Rossana; Pertusi, Ginevra; Pezza, Michele; Pezzullo, Elio; Puccia, Nunzio; Raulo, Umberto; Ribero, Simone; Rossi, Mariateresa; Rusignuolo, Sergio; Sapienza, Giada; Savarese, Catello; Scalisi, Mariaelena; Strippoli, Davide; Stroppiana, Elena; Tiberio, Rossana; Trischitta, Antonino; Tucci, Maria Giovanna; Vaira, Fabrizio; Verrone, Anna; Villa, Lucia; Zagni, Fabio; Zoccali, Andre