Quality of life in Klinefelter patients on testosterone replacement therapy compared to healthy controls: an observational study on the impact of psychological distress, personality traits, and coping strategies.

PURPOSE: We aimed to verify if 1 year-testosterone-replacement therapy could produce a psychopathological recovery and a satisfactory quality of life in Klinefelter syndrome (KS) patients compared to matched healthy controls. Further, we analyzed personality traits and coping strategies, an issue not yet examined in androgen-treated KS patients. We also enquired whether any of the sociodemographic and psychological variables might predict a patient's general and sexual life satisfaction. METHODS: The Quality of Life Enjoyment and Satisfaction Questionnaire and the Temperament and Character Inventory-Revised were administered to both 23 KS patients and matched healthy subjects. Psychopathology was investigated by the Symptom Checklist-90-Revised (SCL-90-R) and the Mini-mental State Examination. The COPE Inventory was used to identify cognitive and behavioral strategies to manage disease-related distress. RESULTS: In testosterone-treated KS patients, when compared with controls, SCL-90-R subscales analysis evidenced high psychological distress, mainly presented as obsessive thoughts, hanger-hostility, phobias, and psychoticism. Self-directedness and self-transcendence, along with the prevalent use of emotion-focused coping strategies, outlined the personality of our KS patients. Depression and somatization proved to be predictors of general life dissatisfaction. Depression, anger-hostility, and paranoid ideation, instead, emerged as predictors of sexual life dissatisfaction. CONCLUSION: Endocrinologists should cooperate with mental health providers to foster a better outcome of the disease in KS patients.

Excisional haemorrhoidectomy: is it safe in patients with an ileal pouch-anal anastomosis?

AIM: Excisional haemorrhoidectomy in patients with ulcerative colitis (UC), especially those undergoing an ileal pouch-anal anastomosis (IPAA), remains controversial. The aim of our study was to determine the safety of excisional haemorrhoidectomy in UC patients with and without an IPAA. METHOD: A retrospective review of all adult UC patients undergoing excisional haemorrhoidectomy between 1 January 1995 and 1 January 2019 at a tertiary inflammatory bowel disease referral centre was performed. Data collected included patient demographics, clinical characteristics of UC, prior surgical intervention for UC (colectomy, IPAA) and complications after haemorrhoidectomy. RESULTS: Forty-one adult patients [50% male; median age 52 (range 25-79) years] with UC underwent excisional haemorrhoidectomy between 1 January 1995 and 1 January 2019. The majority (n = 23) had not previously undergone surgery for UC. However, eight had already undergone construction of an IPAA at the time of haemorrhoidectomy, seven had IPAA at the time of haemorrhoidectomy and three had an IPAA constructed subsequent to haemorrhoidectomy. Two (4.9%) patients need to go back to theatre for postoperative bleeding. There were no further 30-day complications or long-term nonhealing of the surgical site. There were no pouch complications in those who had haemorrhoidectomy at the time of IPAA construction or in the presence of an IPAA. CONCLUSION: Our data suggest that excisional haemorrhoidectomy may be performed safely in carefully selected UC patients with symptomatic haemorrhoids with or without IPAA and even at the time of IPAA construction.

Cardiovascular outcome trials and major cardiovascular events: does glucose matter? A systematic review with meta-analysis.

PURPOSE: We did a meta-analysis with meta-regression to evaluate the relationship between hemoglobin A1c (A1C) reduction and the primary CV outcome of cardiovascular outcome trials (CVOTs). METHODS: We used a random effects meta-analysis of the 12 CVOTs to quantify the effect of A1C reduction on major cardiovascular events (MACE) risk by stratifying the difference in achieved A1C (drug vs placebo) in three strata: A1c < 0.3%, A1c ≥ 0.3% and < 0.5%, and A1c ≥ 0.5%. RESULTS: We found a relation between the reduction in achieved A1C and the hazard ratio reduction for MACE (P = 0.002), explaining almost all (94.1%) the between-study variances: lowering A1C by 0.5% conferred a significant HRR of 20% (95% CI 4-33%) for MACE. CONCLUSIONS: Blood glucose reduction may play a more important role than previously thought in reducing the risk of MACE during treatment with the newer glucose-lowering drugs, including peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors.

Clinical inertia, reverse clinical inertia, and medication non-adherence in type 2 diabetes.

PURPOSE: Clinical inertia and medication non-adherence are thought to contribute largely to the suboptimal glycemic control in many patients with type 2 diabetes. The present review explores the relations between A1C targets, clinical inertia and medication non-adherence in type 2 diabetes. METHODS: We searched PubMed for English-language studies published from 2001 through June 1, 2018. We also manually searched the references of selected articles, reviews, meta-analyses, and practice guidelines. Selected articles were mutually agreed upon by the authors. RESULTS: Clinical inertia is the failure of clinicians to initiate or intensify therapy when indicated, while medication non-adherence is the failure of patients to start or continue therapy that a clinician has recommended. Although clinical inertia may occur at all stages of diabetes treatment, the longest delays were reported for initiation or intensification of insulin. Medication non-adherence to antidiabetic drugs may range from 53 to 65% at 1 year and may be responsible for uncontrolled A1C in about 23% of cases. Reverse clinical inertia can be acknowledged as the failure to reduce or change therapy when no longer needed or indicated. Clinical inertia and medication non-adherence are difficult to address: clinician-and patient-targeted educational programs, more connected communications between clinicians and patients, the help of other health professional figures (nurse, pharmacist) have been explored with mixed results. CONCLUSIONS: Both clinical inertia and medication non-adherence remain significant barriers to optimal glycemic targets in type 2 diabetes. Moreover, part of clinical inertia may be a way through which clinicians face current uncertainty in medicine, including some dissonance among therapeutic guidelines. Scientific associations should find an agreement about how to measure and report clinical inertia in clinical practice and should exhort clinicians to consider reverse clinical inertia as a cause of persisting inappropriate therapy in vulnerable patients.

Influence of occlusal characteristics, food intake and oral hygiene habits on dental caries in adolescents: a cross-sectional study.

AIM: Dental caries is one of the most common oral diseases affecting children. The complex multifactorial aetiology of caries involves host (saliva composition and tooth enamel characteristics), oral microflora and substrate (oral hygiene quality and dietary habits composition). Occlusal characteristics may be also a factor in dental caries development. The aim of this aepidemiologic study was to verify the association between DMFT (Decayed, Missed, Filled Teeth) index and occlusal characteristics, dietary habits, oral hygiene habits and parents' education level in a sample of 12-year-old schoolchildren from Southern Italy. MATERIALS AND METHODS: A sample of 536 children was examined to detect dental caries status and several occlusal variables (i.e. molar relationship, overjet and overbite, presence of crossbite, scissor bite, crowding, diastemas and/or midline deviation). A questionnaire to retrieve parents' educational level, patient's dietary and oral hygiene habits was administered. The associations among these variables were assessed statistically through the ?2 test. RESULTS: A positive association was found between caries, parents' social status and some occlusal disorders. va specificato, l'abstract non può essere una caccia al tesoro. In relation to occlusal variables, crossbite (?2=3.96, P=0.04) was significantly associated to caries. A significant association was also found between the education level of mothers (?2=7.74, P<0.01) and fathers (?2=6.35, P=0.01) and the presence of caries. Dietary habits, oral hygiene and remaining occlusal characteristics were not associated with caries presence (all P>0.05). CONCLUSIONS: Of the evaluated occlusal characteristics only posterior crossbite was associated with caries prevalence. Education level of the parents was the other factor significantly associated with caries. Dietary habits, oral hygiene frequency and the remaining occlusal characteristics were not associated with dental caries.

From inflammation to sexual dysfunctions: a journey through diabetes, obesity, and metabolic syndrome.

Metabolic diseases are associated with chronic low-grade inflammation, which has been indicated as a potential mediator of endothelial dysfunction and cardiovascular disease. Visceral adiposity is thought to be the starting condition of the inflammatory state through the release of inflammatory cytokines, including TNF-alpha, CRP, and IL-6, which in turn promote endothelial dysfunction, endothelial expression of chemokines (IL-1) and adhesion molecules (ICAM-1, VCAM-1, and P-selectin), and the inhibition of anti-atherogenic factors (adiponectin). Obesity, metabolic diseases, and diabetes, all conditions characterized by abdominal fat, are well-recognized risk factors for sexual dysfunction in both sexes. Evidence from randomized-controlled trials supports the association between inflammatory milieau and erectile dysfunction in men suffering from metabolic diseases, whereas, in women, this has to be confirmed in further studies. A healthy lifestyle based on dietary pattern with high content of whole grain, fruit, nuts and seeds, and vegetables and low in sodium and saturated fatty acids plus regular physical activity may help to modulate the pro-inflammatory state associated with metabolic diseases and the related burden of sexual dysfunctions.

TSH oscillations in young patients with type 1 diabetes may be due to glycemic variability.

PURPOSE: A relationship between thyroid dysfunction and diabetes mellitus has been described by several authors but the role of glycemic variability is still unclear. We planned the present study to evaluate the influence of glycemic variability on thyroid hormones and TSH concentrations in patients with type 1 diabetes mellitus (T1DM). METHODS: Seventy-seven young patients with T1DM were enrolled and evaluated for basal glucose concentrations, HbA1c, thyroid hormones and TSH concentrations. Glucose variability was investigated by considering the standard deviation of blood glucose readings and by calculating the mean amplitude of glycemic excursions and continuous overlapping net glycemic action (CONGA). The low (LBGI) and high (HBGI) blood glucose indices were also calculated. The correlations between TSH, thyroid hormones, glycemia and HbA1c were studied in patients and in controls, whereas those between TSH, thyroid hormones and indices of glucose variability only in patients. RESULTS: No correlations were observed in T1DM patients between free thyroid hormones and glycemic values, HbA1c and indices of glucose variability, while an inverse correlation was observed between TSH levels and glycemic values (r = -0.27; p = 0.01), CONGA index (r = -0.35; p = 0.001) and HBGI (r = -0.28; p = 0.01) but not with HbA1c (r = -0.1; p = 0.47). CONCLUSIONS: Our results suggest a direct action of glycemic excursions on TSH secretion, regardless of variations of thyroid hormone concentrations. Thus, the evaluation of thyroid function through the assay of TSH concentrations in these patients should be made, if possible, by multiple samples on patients in euglycemic state to avoid underestimation or overestimation of thyroid dysfunction due to a wrong diagnosis of euthyroidism or dysthyroidism with consequent inappropriate choice of therapeutic options.

Do intraoperative pyloric interventions predict the need for postoperative endoscopic interventions after minimally invasive esophagectomy?

Intraoperative pyloric procedures are often performed during esophagectomies to reduce the rates of gastric conduit dysfunction. They include pyloroplasty (PP), pyloromyotomy (PM), and pylorus botulinum toxin type-A injections (BI). Despite these procedures, patients frequently warrant further endoscopic interventions. The aim of this study is to compare intraoperative pyloric procedures and the rates of postoperative endoscopic interventions following minimally invasive esophagectomy (MIE). We identified patients who underwent MIE for esophageal carcinoma and grouped them as 'None' (no intervention), 'PP', 'PM', or 'BI' based on intraoperative pyloric procedure type. The rates of endoscopic interventions for the first six postoperative months were compared. To adjust for variability due to MIE type, the rates of >1 interventions were compared using a zero-inflated Poisson regression analysis. Significance was established at P < 0.05. There were 146 patients who underwent an MIE for esophageal cancer from 2008 to 2015; 77.4% were three-hole MIE, and 22.6% were Ivor- Lewis MIE. BI was most frequent in Ivor-Lewis patients (63.5%), while PP was most frequent (46.9%) in three-hole patients. Postoperative endoscopic interventions occurred in 38 patients (26.0%). The BI group had the highest percentage of patients requiring a postoperative intervention (n = 13, 31.7%). After adjusting for higher rates of interventions in three-hole MIE patients, the BI and None groups had the lowest rates of >1 postoperative interventions. Our data did not show superiority of any pyloric intervention in preventing endoscopic interventions. The patients who received BI to the pylorus demonstrated a trend toward a greater likelihood of having a postoperative intervention. However when adjusted for type of MIE, the BI and None groups had lower rates of subsequent multiple interventions. Further research is needed to determine if the choice of intraoperative pyloric procedure type significantly affects quality of life, morbidity, and overall prognosis in these patients.

Comparative facile methods for preparing graphene oxide-hydroxyapatite for bone tissue engineering.

Motivated by the success of using graphene oxide (GO) as a nanofiller of composites, there is a drive to search for this new kind of carbon material as a bioactive component in ceramic materials. In the present study, biomineralized GO was prepared by two different approaches, represented by in situ sol-gel synthesis and biomimetic treatment. It was found that in the biocomposites obtained by the sol-gel approach, the spindle-like hydroxyapatite nanoparticles, with a diameter of ca. 5 ± 0.37 nm and a length of ca. 70 ± 2.5 nm, were presented randomly and strongly on the surface. The oxygen-containing functional groups, such as hydroxyl and carbonyl, present on the basal plane and edges of the GO sheets, play an important role in anchoring calcium ions, as demonstrated by FT-IR and TEM investigations. A different result was obtained for biocomposites after biomimetic treatment: an amorphous calcium phosphate on GO sheet was observed after 5 days of treatment. These different approaches resulted in a diverse effect on the proliferation and differentiation of osteogenic mesenchymal stem cells. In fact, in biocomposites prepared by the sol-gel approach the expression of an early marker of osteogenic differentiation, ALP, increases with the amount of GO in the first days of cell culture. Meanwhile, biomimetic materials sustain cell viability and proliferation, even if the expression of alkaline phosphatase activity in a basal medium is delayed. These findings may provide new prospects for utilizing GO-based hydroxyapatite biocomposites in bone repair, bone augmentation and coating of biomedical implants and broaden the application of GO sheets in biological areas. Copyright © 2016 John Wiley & Sons, Ltd.

Erectile dysfunction in young men with type 1 diabetes.

Erectile dysfunction (ED) is a common comorbidity of diabetes mellitus, but few studies investigated its prevalence in type 1 diabetes. The objective of this study was to evaluate the prevalence and correlates of ED in young men with type 1 diabetes treated with different intensive insulin regimens. The study population included 151 type 1 diabetic men, aged 18-35 years, and 60 healthy age-matched controls. Ninety-four men were treated with multiple daily injections of insulin (MDI), and the remaining 71 with continuous subcutaneous insulin infusion (CSII). All participants in the study completed the International Index of Erectile function (IIEF-5), and other validated multiple-choice questionnaires assessing quality of life, physical activity, depressive symptoms and diabetes-related problems. The overall prevalence of ED was higher in diabetic men (37%), as compared with controls (6%, P<0.001). ED prevalence rates were similar in both MDI (36%) and CSII (39%) groups (P=0.326); both were higher compared with controls (P<0.001 for both). More than half of diabetic men (58%) had mild ED. Compared with men without ED, diabetic men with ED showed lower weight, body mass index, fasting glucose, insulin dose and high-density lipoprotein cholesterol levels, and higher self-rating depression score (SRDS). In the multiple regression analysis only the SRDS (P=0.032) were independent predictors of IIEF-5 score in the overall diabetic men. Young men with type 1 diabetes treated with MDI or CSII show a higher prevalence of ED, as compared with healthy age-matched men. Depression was associated with ED in diabetic population.

Influence of short-term selenium supplementation on the natural course of Hashimoto's thyroiditis: clinical results of a blinded placebo-controlled randomized prospective trial.

BACKGROUND: The real efficacy of selenium supplementation in Hashimoto's thyroiditis (HT) is still an unresolved issue. OBJECTIVES: We studied the short-term effect of L-selenomethionine on the thyroid function in euthyroid patients with HT. Our primary outcome measures were TSH, thyroid hormones, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) levels and thyroid echogenicity after 6 months of L-selenomethionine treatment. The secondary outcome measure was serum CXCL10 levels. METHODS: In a placebo-controlled randomized prospective study, we have enrolled untreated euthyroid patients with HT. Seventy-six patients were randomly assigned to receive L-selenomethionine 166 µg/die (SE n = 38) or placebo (controls n = 38) for 6 months. TSH, free T4 (FT4), free T3 (FT3), TPOAb and CXCL10 serum levels were assayed at time 0, after 3 and 6 months. An ultrasound examination of the left and right thyroid lobe in transverse and longitudinal sections was performed. A rectangular region, the region of interest, was selected for analysis. RESULTS: TSH, FT4, FT3, TPOAb, thyroid echogenicity and CXCL10 were not statistically different between SE and control groups at time 0, after 3 and 6 months. In the SE group, FT4 levels were significantly decreased (P < 0.03) after 3 months, while FT3 increased (P < 0.04) after 3 and 6 months versus baseline values. In the control group, the FT3 decreased after 3 and 6 months (P < 0.02) compared to baseline. CONCLUSION: The short-term L-selenomethionine supplementation has a limited impact on the natural course in euthyroid HT. Our results tip the balance toward the ineffectiveness of short-term L-selenomethionine supplementation in HT.

Sexual function in young women with type 1 diabetes: the METRO study.

PURPOSE: The aim of this study was to evaluate the prevalence and risk factors associated with female sexual dysfunction (FSD) in young women with type 1 diabetes treated with different intensive insulin regimens. METHODS: Type 1 diabetic women aged 18-35 years were included in this study if they had stable couple relationship and no oral contraceptive use. All women were asked to complete the Female Sexual Function Index (FSFI) and other validated multiple-choice questionnaires assessing sexual-related distress (Female Sexual Distress Scale, FSDS), quality of life (SF-36 Health Survey), physical activity (International Physical Activity Questionnaire), depressive symptoms (Zung Self-Rating Depression Scale, SRDS) and diabetes-related problems (Diabetes Integration Scale ATT-19). FSD was diagnosed according to a FSFI score higher than 26.55 and a FSDS score lower than 15. RESULTS: The overall prevalence of FSD in diabetic and control women was 20 and 15 %, respectively (P = 0.446). Compared with the continuous subcutaneous insulin infusion group and control women, diabetic women on multiple daily injections (MDI) had lower global FSFI score (P = 0.007), FSDS score (P = 0.045) and domains such as arousal (P = 0.006), lubrication and satisfaction scores (P < 0.001 for both). In the multiple regression analysis, only the mental component summary (P = 0.047) and the SRDS score (P = 0.042) were independent predictors of FSFI score in the overall diabetic women. CONCLUSION: Young women with type 1 diabetes wearing an insulin pump show a prevalence of sexual dysfunction similar to that of healthy age-matched women, but sexual function was significantly impaired in diabetic women on MDI therapy. Depression and the mental health status were independent predictors for FSD in diabetic women.

Efficacy and safety of insulin-GLP-1 receptor agonists combination in type 2 diabetes mellitus: a systematic review.

INTRODUCTION: Attaining optimal glycemic targets in patients with type 2 diabetes is often hard and compromised by the shortcomings of the several treatments. Areas covered: When glycemic levels are not adequately controlled, an association of GLP-1 receptor agonists and insulin therapy can be adopted. In order to assess the benefit/risk profile of this combination therapy, a literature search of randomized clinical trials was performed.Eighteen trials matched the inclusion criteria. In 10 studies, GLP-1 receptor agonists were added on to an existing regimen, whereas insulin added to an existing GLP-1 receptor agonists regimen occurred in 2 studies. Six studies compared GLP-1 receptor agonists with short acting insulin as a treatment strategy to intensify basal insulin therapy. Expert opinion: Clinical trials herein reviewed demonstrated the safety and the efficacy of combining GLP-1 receptor agonists with basal insulin, with most studies showing equal or slightly superior efficacy, as compared with the addition of prandial insulin, associated with weight loss and less hypoglycemia.

Personalized intensification of insulin therapy in type 2 diabetes - does a basal-bolus regimen suit all patients?

Many patients with type 2 diabetes mellitus (T2DM) require insulin therapy. If basal insulin fails to achieve glycemic control, insulin intensification is one possible treatment intensification strategy. We summarized clinical data from randomized clinical trials designed to compare the efficacy and safety of basal-bolus and premixed insulin intensification regimens. We defined a between-group difference of ≥0.3% in end-of-study glycated hemoglobin (HbA1c) as clinically meaningful. A PubMed database search supplemented by author-identified papers yielded 15 trials which met selection criteria: randomized design, patients with T2DM receiving basal-bolus (bolus injection ≤3 times/day) vs. premixed (≤3 injections/day) insulin regimens, primary/major endpoint(s) HbA1c- and/or hypoglycemia-related, and trial duration ≥12 weeks. Glycemic control improved with both basal-bolus and premixed insulin regimens with - in most cases - acceptable levels of weight gain and hypoglycemia. A clinically meaningful difference between regimens in glycemic control was recorded in only four comparisons, all of which favored basal-bolus therapy. The incidence of hypoglycemia was significantly different between regimens in only three comparisons, one of which favored premixed insulin and two basal-bolus therapy. Of the four trials that reported a significant difference between regimens in bodyweight change, two favored basal-bolus therapy and two favored premixed insulin. Thus, on a population level, neither basal-bolus therapy nor premixed insulin showed a consistent advantage in terms of glycemic control, hypoglycemic risk, or bodyweight gain. It is therefore recommended that clinicians should adopt an individualized approach to insulin intensification - taking into account the benefits and risks of each treatment approach and the attitude and preferences of each patient - in the knowledge that both basal-bolus and premixed regimens may be successful.

Properties of carbon nanotube-dispersed Sr-hydroxyapatite injectable material for bone defects.

This study concerns the synthesis of gel materials based on carbon nanotubes dispersed strontium-modified hydroxyapatite (Sr-HA) at different compositions obtained by sol-gel technology and their influence on human-bone-marrow-derived mesenchymal stem cells. Furthermore, an evaluation of the influence of nanotubes and Strontium on physico-chemical, morphological, rheological and biological properties of hydroxyapatite gel was also performed. Morphological analysis (scanning electron microscopy) shows a homogeneous distribution of modified nanotubes in the ceramic matrix improving the bioactive properties of materials. The biological investigations proved that Sr-HA/carbon nanotube gel containing 0-20 mol (%) of Sr showed no toxic effect and promote the expression of early and late markers of osteogenic differentiation in cell culture performed in basal medium without osteogenic factors. Finally, the SrHA/carbon nanotube gels could have a good potential application as filler in bone repair and regeneration and may be used in the osteoporotic disease treatment.

Increased platelet reactivity in Klinefelter men: something new to consider.

Patients with Klinefelter syndrome (KS) exhibit an increased cardiovascular risk, but underlying mechanisms are largely unknown. The present cross-sectional study has been conducted to evaluate platelet reactivity and the expression of platelet activation markers (8-iso-prostaglandin F2α[8-iso-PGF2α] and 11-dehydro-thromboxane-B2[11-dehydro-TXB2]) in KS patients and healthy controls. Twenty-three consecutive KS patients under testosterone replacement therapy have been included as case group and 46 age-matched healthy males recruited among hospital staff served as controls. Light transmission aggregometry was performed in both cases and controls and maximal platelet aggregation (max-A%) was defined as maximal light transmittance reached within 5 min after the addition of 0.2 or 0.4 mm arachidonic acid (AA). A ≥ 50% irreversible light transmittance (LT-50%) following platelet stimulation defined an adequate platelet aggregation and AC-50% was defined as the minimal agonist concentration needed to achieve LT-50%. The AC-50% was 0.26 mm AA for KS and 0.36 mm for controls (p < 0.001). Whereas AA (0.2 mm) induced LT-50% in 69.6% of KS and in 15.2% of controls (p < 0.001), the stimulation with AA (0.4 mm) determined LT-50% in all cases and controls. However, max-A% was higher in KS than in controls both after AA (0.2 mm) (65.61% vs. 46.30%, p = 0.002,) and after AA (0.4 mm) (96.43% vs. 81.04%, p < 0.001). 8-iso-PGF2α and 11-dehydro-TXB2 were higher in KS than in controls (446.54 pg/mg creatinine vs. 230.00 pg/mg creatinine, p < 0.001 and 1278.36 pg/mg creatinine vs. 595.08 pg/mg creatinine, p = 0.001, respectively) and AC-50% inversely correlated with 8-iso-PGF2α (ρ = -0.548, p < 0.001) and with 11-dehydro-TXB2 (ρ = -0.523, p < 0.001). In a linear regression model, KS independently predicted a lower AC-50% (ß = -0.597, p < 0.001) and higher levels of 8-iso-PGF2α (ß = 0.709, p < 0.001) and 11-dehydro-TXB2 (ß = 0.605, p < 0.001). In contrast, no correlation has been found between max-A%, testosterone and estradiol levels in KS. We observed increased platelet reactivity in KS. This might, at least in part, explain the increased thrombotic risk associated with this disease.

Vitamin D and autoimmunity: what happens in autoimmune polyendocrine syndromes?

PURPOSE: To evaluate the Vitamin D status of patients with a single autoimmune disease and of patients with several autoimmune diseases. METHODS: We enrolled 35 patients with isolated type 1 diabetes mellitus (T1DM), 60 with autoimmune polyendocrine syndromes (APS) including T1DM and 72 control subjects. Among patients with APS, 10 were classified as type 2 (Addison's disease + T1DM), whereas the other 50 as type 3 (autoimmune thyroid disease + T1DM + other autoimmune diseases). Vitamin D (25-OHD) levels were assessed by a chemiluminescent immunoassay in all patients and controls on samples drawn in the morning of the same months. RESULTS: Both groups of APS and T1DM patients showed 25-OHD levels significantly lower than healthy controls (p < 0.001 for both vs controls), without any significant difference between the two groups (p = 0.80). The highest prevalence of vitamin D deficiency (values <20 ng/ml) was observed in APS type 3 subgroup (8 out of 50 patients, 16%). CONCLUSIONS: Patients with APS present reduced vitamin D circulating levels, but the vitamin D status is not different between patients with single or multiple autoimmune diseases. The kind of autoimmune disease, rather than the association of several autoimmune diseases, may influence negatively the levels of vitamin D. Further prospective studies are needed to clarify if impaired vitamin D level is a causal factor in the pathogenesis of autoimmune diseases or a consequence of them.

Effect of citric acid crosslinking cellulose-based hydrogels on osteogenic differentiation.

Understanding the relationships between material surface properties and cellular responses is essential to designing optimal material surfaces for implantation and tissue engineering. In this study, cellulose hydrogels were crosslinked using a non-toxic and natural component namely citric acid. The chemical treatment induces COOH functional groups that improve the hydrophilicity, roughness, and materials rheological properties. The physiochemical, morphological, and mechanical analyses were performed to analyze the material surface before and after crosslinking. This approach would help determine if the effect of chemical treatment on cellulose hydrogel improves the hydrophilicity, roughness, and rheological properties of the scaffold. In this study, it was demonstrated that the biological responses of human mesenchymal stem cell with regard to cell adhesion, proliferation, and differentiation were influenced in vitro by changing the surface chemistry and roughness.

Characterization of pituitary cells targeted by antipituitary antibodies in patients with isolated autoimmune diseases without pituitary insufficiency may help to foresee the kind of future hypopituitarism.

PURPOSE: Detection of antipituitary antibodies (APA) at high levels and with a particular immunofluorescence pattern in patients with autoimmune polyendocrine syndromes may indicate a possible future autoimmune pituitary involvement. This longitudinal study was aimed at characterizing in patients with a single organ-specific autoimmune disease the pituitary cells targeted by APA at start, verifying whether this characterization allows to foresee the kind of possible subsequent hypopituitarism. METHODS: Thirty-six APA positive and 40 APA negative patients with isolated autoimmune diseases participated in the study. None of them had pituitary dysfunction at entry. Characterization by four-layer immunofluorescence of pituitary cells targeted by APA in APA positive patients at entry and study of pituitary function in all patients were performed every 6 months during a 5 year follow-up. RESULTS: Antipituitary antibodies immunostained selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group 1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2). All patients in group 1 showed subsequently a pituitary insufficiency, corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8 out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7 and combined in the other one. None of APA negative patients showed hypopituitarism. CONCLUSIONS: The characterization of pituitary cells targeted by APA in patients with isolated autoimmune diseases, when the pituitary function is still normal, may help to foresee the kind of subsequent hypopituitarism, especially when APA immunostained selectively only one type of pituitary cells. A careful follow-up of pituitary function in these patients is advisable to allow an early diagnosis of hypopituitarism, even in subclinical phase and a consequent timely replacement therapy.