BackgroundHere we study the effect of type 2 diabetes (T2DM) on bone cell precursors, turnover and cytokines involved in the control of bone cell formation and activity.MethodsWe enrolled in the study 21 T2DM women and 21 non diabetic controls matched for age and body mass index (BMI). In each subject we measured bone cell precursors, Receptor Activator of Nuclear Factor κB (RANKL), Osteoprotegerin (OPG), Sclerostin (SCL) and Dickoppf-1 (DKK-1) as cytokines involved in the control of osteoblast and osteoclast formation and activity, bone density (BMD) and quality trough trabecular bone score (TBS) and bone turnover. T2DM patients and controls were compared for the analyzed variables by one way ANOVA for Gaussian ones and by Mann-Whitney or Kruskal-Wallis test for non-Gaussian variables.ResultsRANKL was decreased and DKK-1 increased in T2DM. Accordingly, patients with T2DM have lower bone turnover compared to controls. BMD and TBS were not significantly different from healthy controls. Bone precursor cells were more immature in T2DM. However the number of osteoclast precursors was increased and that of osteoblasts decreased.ConclusionsPatients with T2DM have more immature bone cells precursors, with increased number of osteoclasts and decreased osteoblasts, confirming low bone turnover and reduced cytokines such as RANKL and DKK-1. BMD and TBS are not significantly altered in T2DM although, in contrast with other studies, this may be due to the match of patients and controls for BMI rather than age.

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Aim Anal stenosis (AS) is a rare but disabling disorder that often represents a complication of anorectal surgery. The aim of our study was to assess the safety and functional outcome of a modified rhomboid flap (MRF) in the treatment of moderate and severe AS. Methods Between January 2002 and September 2017, 50 consecutive patients with moderate and severe AS who underwent an MRF were retrospectively included. Anal continence (Cleveland Clinic Incontinence Score) and symptoms (Obstructed Defaecation Syndrome Score) were assessed preoperatively and postoperatively at 12 months. Furthermore, anal calibre was measured both preoperatively and postoperatively at 1, 6 and 12 months. Results The mean follow-up period was 97 AE 48.3 (33-180) months. The main aetiology was a previous excisional haemorrhoidectomy (N = 23; 46%). The mean preoperative anal calibre was 9.96 AE 2.68 (5-15) mm and there was a statistically significant improvement in all three periods (P < 0.0001) of postoperative evaluation (1, 6 and 12 months) with a mean difference, obtained comparing preoperative and 12 months anal calibre, of 14.1 AE 2.72 (P < 0.0001). Statistically significant improvement in both Cleveland Clinic Incontinence Score and Obstructed Defaecation Syndrome Score was observed in all patients at 12 months. The overall success rate was 96% (48/50 patients). Conclusion The use of an MRF is a safe and suitable option for the treatment of moderate and severe AS. The possibility of tailoring the flap, based on the degree as well as the level of AS, is the key.

BackgroundMyofibroblasts contribute to fibrosis through the overproduction of extracellular matrix (ECM) proteins, primarily type I collagen (COL-1) and fibronectin (FN), a process which is mediated in systemic sclerosis (SSc) by the activation of fibrogenic intracellular signaling transduction molecules, including extracellular signal-regulated kinases 1 and 2 (Erk1/2) and protein kinase B (Akt). Selexipag is a prostacyclin receptor agonist synthesized for the treatment of pulmonary arterial hypertension. The study investigated the possibility for selexipag and its active metabolite (ACT-333679) to downregulate the profibrotic activity in primary cultures of SSc fibroblasts/myofibroblasts and the fibrogenic signaling molecules involved.MethodsFibroblasts from skin biopsies obtained with Ethics Committee (EC) approval from patients with SSc, after giving signed informed consent, were cultured until the 3rd culture passage and then either maintained in normal growth medium (untreated cells) or independently treated with different concentrations of selexipag (from 30 μM to 0.3 μM) or ACT-333679 (from 10 μM to 0.1 μM) for 48 h. Protein and gene expressions of α-smooth muscle actin (α-SMA), fibroblast specific protein-1 (S100A4), COL-1, and FN were investigated by western blotting and quantitative real-time PCR. Erk1/2 and Akt phosphorylation was investigated in untreated and ACT-333679-treated cells by western botting.ResultsSelexipag and ACT-333679 significantly reduced protein synthesis and gene expression of α-SMA, S100A4, and COL-1 in cultured SSc fibroblasts/myofibroblasts compared to untreated cells, whereas FN was significantly downregulated at the protein level. Interestingly, ACT-333679 significantly reduced the phosphorylation of Erk1/2 and Akt in cultured SSc fibroblasts/myofibroblasts.ConclusionsSelexipag and mainly its active metabolite ACT-333679 were found for the first time to potentially interfere with the profibrotic activity of cultured SSc fibroblasts/myofibroblasts at least in vitro, possibly through the downregulation of fibrogenic Erk1/2 and Akt signaling molecules.

Background: Hemorrhoids are vascular cushions underlying the distal rectal mucosa and contributing for approximately 15–20% of the resting anal pressure with a complete closure of the anal canal. They can become pathological (hemorrhoidal disease, HD) being the most common cause of painless rectal bleeding during defecation with or without prolapsing anal tissue. The treatment of HD must be tailored to both the severity of disease and patient’s expectation. Methods: A narrative review of all the most relevant papers present on Pubmed was conducted. Results: Conservative treatment is effective in managing the majority of patients complaining of early stages of the disease. Dietary and lifestyle modifications to achieve regular defecation and soft stool are the first therapeutic step. Oral phlebotonic drugs can help to control symptoms. The use of topical medications, particularly during the acute phase or in the post-hemorrhoidectomy period can also be beneficial for all patients complaining of HD. Conclusion: Despite a large number of available products on the market and the high incidence of HD, very few randomized controlled trials have been carried out and most of the studies are uncontrolled case series. Larger and better designed trials are necessary to establish the real benefit of all types of drugs in the treatment of early stages of HD.