Severe allergic asthma: Does alexithymia interfere with omalizumab treatment outcome?

BACKGROUND: Alexithymia is among psychological factors reported to interfere with asthma management. Severe allergic asthma (SAA) is characterized by uncontrolled asthma despite maximal standard pharmacological treatment which can benefit from an add-on treatment with Omalizumab, an anti-IgE monoclonal antibody. OBJECTIVE: To evaluate if alexithymia influences the efficacy of omalizumab in SAA. METHODS: The total alexithymia score 20 (TAS 20) questionnaire allowed to detect alexithymia. SAA was monitored recording number of exacerbations, asthma control test (ACT) and asthma quality of life questionnaire (AQLQ) scores, as well as forced expiratory volumes in 1 second % (FEV1%) levels before starting omalizumab, 1 and 2 years after. RESULTS: The study was conducted on 18 patients; Group 1, TAS 20 ≥ 61, was of 2 males and 4 females with SAA and alexithymia, while Group 2 , TAS 20 ≤ 51, was of 8 males and 4 females, without alexithymia. Group 1 had a statistically significant decrease in asthma exacerbations "p = 0.004", while ACT "p = 0.008" and AQLQ scores statistically increased. FEV1 values increased but not statistically significantly. Group 2 had a highly statistically significant decrease in the number of exacerbations and a highly statistically significant increase of ACT "p < 0.0001", FEV1 "p = 0.008" and AQLQ scores. CONCLUSIONS: Regardless the presence or not of alexithymia, all patients with SAA obtained a marked improvement after starting treatment with omalizumab. Therefore alexithymia does not seem to influence the treatment outcome of omalizumab.

Interleukin-33 serum levels in postmenopausal women with osteoporosis.

There are many cytokines involved in the pathogenesis of osteoporosis. So far IL-33 involvement in osteoporotic patients has not yet been studied. IL-33 is a pro-inflammatory cytokine which mediates several immune functions; its involvement in a wide range of diseases, such as atopic dermatitis, asthma, and rheumatoid arthritis, is now emerging. In view of the crucial role of this cytokine in inflammation and bone remodeling, we measured IL-33 levels in the serum of postmenopausal women with osteoporosis. In 50 postmenopausal osteoporotic patients and 28 healthy postmenopausal control women, serum IL-33 levels were measured by enzyme linked immunosorbent assay. In both patients and controls the bone mineral density (BMD) was measured by double-energy X-ray absorptiometry (DXA). Vitamin D, calcium, alkaline phosphatase (ALP), parathyroid hormone (PTH) serum levels, as well as bone turnover markers, such as C-terminal telopeptide of type 1 collagen (CTX) and N-terminal propeptide of type 1 procollagen (P1NP) were also evaluated. In postmenopausal osteoporotic women IL-33 levels were significantly lower compared to healthy controls (3.53 ± 2.45 vs. 13.72 ± 5.39 pg/ml; P = 0.009) and positively correlated respectively with serum PTH (rho = 0.314; P = 0.026) and P1NP (rho = 0.373; P = 0.011) levels, while a statistically significant inverse correlation was observed between serum IL-33 and CTX levels (rho = -0.455; P = 0.002). Our results thus suggest that IL-33 represents an important bone-protecting cytokine which may be of therapeutic benefit in treating bone resorption.

Involvement of new oxidative stress markers in chronic spontaneous urticaria.

INTRODUCTION: Oxidative stress is a result of an imbalance between endogenous production of free reactive oxygen species and reduced effectiveness of antioxidant defence mechanisms. Advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs) are compounds formed by transformation of macromolecules, including proteins which can serve as markers of oxidative stress and inflammation in several diseases. AIM: To investigate the role of AGEs and AOPPs as new markers of oxidative stress and inflammation in patients with chronic spontaneous urticaria (CSU). MATERIAL AND METHODS: Advanced glycation end products and AOPP levels were determined in the sera of 85 patients with CSU and 64 healthy controls, using spectrofluorimetry and spectrophotometry, respectively. RESULTS: Advanced oxidation protein products levels in patients were statistically higher than those in controls. These levels were not affected by the presence of positive autologous serum test results or autologous plasma test results. No statistically significant differences were found between AGE levels in patients and controls. CONCLUSIONS: Formation of AGEs and AOPPs may be accelerated in immunological and allergic disorders. Depending on the sites evaluated, the presence or absence of oxidative stress in chronic urticaria is controversial. To our knowledge, this is the first study showing the possible involvement of AOPPs in CSU. The different behaviour observed for these two biomarkers is very likely due to the activation of specific related biochemical pathways associated with the condition under study.

Feasibility and Acceptability of Office-Based Polypectomy With a 16F Mini-Resectoscope: A Multicenter Clinical Study.

STUDY OBJECTIVE: To investigate the feasibility and acceptability of office hysteroscopic polypectomy using a novel continuous-flow operative 16F mini-resectoscope. DESIGN: Multicenter prospective case series (Canadian Task Force classification III). SETTING: "SS Antonio e Biagio" Hospital, Alessandria, and University "Federico II" of Naples. PATIENTS: One hundred eighty-two patients with endometrial polyps. INTERVENTIONS: Hysteroscopic polypectomy performed with 16F mini-resectoscope in an office setting, without analgesia and/or anesthesia. MEASUREMENTS AND MAIN RESULTS: Polypectomy was successfully performed in 175 patients in a single surgical step (96.15%), with only 1 patient (.54%) requiring a second office surgical step to complete the surgery. Seven patients (3.84%) were excluded from the analysis of operative parameters because of severe pelvic pain during the office procedure, which required a second inpatient surgical step. No major complications were recorded. CONCLUSION: Our findings demonstrate that removal of endometrial polyps using the 16F mini-resectoscope in an office setting is a feasible and safe surgical option. Outpatient see-and-treat polypectomy is an acceptable and effective alternative to inpatient resectoscopic polypectomy.

Is intravesical instillation of hyaluronic acid and chondroitin sulfate useful in preventing recurrent bacterial cystitis? A multicenter case control analysis.

OBJECTIVE: Urinary tract infections (UTIs) are common in the female population and, over a lifetime, about half of women have at least one episode of UTI requiring antibiotic therapy. The aim of the current study was to compare two different strategies for preventing recurrent bacterial cystitis: intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS), and antibiotic prophylaxis with sulfamethoxazole plus trimethoprim. MATERIALS AND METHODS: This was a retrospective review of two different cohorts of women affected by recurrent bacterial cystitis. Cases (experimental group) were women who received intravesical instillations of a sterile solution of high concentration of HA + CS in 50 mL water with calcium chloride every week during the 1(st) month and then once monthly for 4 months. The control group included women who received traditional therapy for recurrent cystitis based on daily antibiotic prophylaxis using sulfamethoxazole 200 mg plus trimethoprim 40 mg for 6 weeks. RESULTS: Ninety-eight and 76 patients were treated with experimental and control treatments, respectively. At 12 months after treatment, 69 and 109 UTIs were detected in the experimental and control groups, respectively. The proportion of patients free from UTIs was significantly higher in the experimental than in the control group (36.7% vs. 21.0%; p = 0.03). Experimental treatment was well tolerated and none of the patients stopped it. CONCLUSION: The intravesical instillation of HA + CS is more effective than long-term antibiotic prophylaxis for preventing recurrent bacterial cystitis.

Increased levels of interleukin 31 (IL-31) in osteoporosis.

BACKGROUND: Several inflammatory cytokines play a key part in the induction of osteoporosis. Until now, involvement of the Th2 cytokine interleukin-31 (IL-31) in osteoporosis hadn't yet been studied. IL-31 is a proinflammatory cytokine mediating multiple immune functions, whose involvement in a wide range of diseases, such as atopic dermatitis, inflammatory bowel diseases and cutaneous lymphomas, is now emerging. Given the important role of IL-31 in inflammation, we measured its serum levels in postmenopausal osteoporotic patients. METHODS AND RESULTS: In fifty-six postmenopausal females with osteoporosis and 26 healthy controls, bone mineral density (BMD) measurements were performed by using calcaneal quantitative ultrasound (QUS) technique, confirmed at the lumbar spine and hip by dual energy X-ray absorptiometry (DXA). Both patients and controls were divided according to age (less or more than 65 years) and disease severity (T-score levels and presence of fractures). Serum IL-31 levels were measured by ELISA technique. Osteoporotic patients exhibited elevated levels of serum IL-31 compared with healthy controls (43.12 ± 6.97 vs 29.58 ± 6.09 pg/ml; p < 0.049). IL-31 expression was higher in over 65 years old patients compared to age-matched controls (45 ± 11.05 vs. 17.92 ± 5.92; p < 0.01), whereas in younger subjects no statistically significant differences were detected between patients and controls (37.91 ± 6.9 vs 32.08 ± 8.2). No statistically significant differences were found between IL-31 levels in patients affected by mild (T-score > -3) compared to severe (T-score < -3) osteoporosis (59.17 ± 9.22 vs 37.91 ± 10.52), neither between fractured and unfractured osteoporotic women (33.75 ± 9.16 vs 51.25 ± 8.9). CONCLUSIONS: We showed for the first time an increase of IL-31 serum levels in postmenopausal women with decreased BMD. Although they did not reflect the severity of osteoporosis and/or the presence of fractures, they clearly correlated with age, as reflected by the higher levels of this cytokine in aged patients.

Gonadotrophin-releasing hormone analogue or dienogest plus estradiol valerate to prevent pain recurrence after laparoscopic surgery for endometriosis: a multi-center randomized trial.

OBJECTIVES: To evaluate the efficacy of dienogest + estradiol valerate (E2V) and gonadotrophin-releasing hormone analogue (GnRH-a) in reducing recurrence of pain in patients with chronic pelvic pain due to laparoscopically diagnosed and treated endometriosis. DESIGN: Multi-center, prospective, randomized study. SETTING: Three university departments of obstetrics and gynecology in Italy. POPULATION: Seventy-eight women who underwent laparoscopic surgery for endometriosis combined with chronic pelvic pain. METHODS: Post-operative administration of dienogest + E2V for 9 months (group 1) or GnRH-a monthly for 6 months (group 2). MAIN OUTCOME MEASURES: A visual analogue scale was used to test intensity of pain before laparoscopic surgery at 3, 6 and 9 months of follow up. A questionnaire to investigate quality of life was administered before surgery and at 9 months of follow up. RESULTS: The visual analogue scale score did not show any significant differences between the two groups (p = 0.417). The questionnaire showed an increase of scores for all women compared with pre-surgery values, demonstrating a marked improvement in quality of life and health-related satisfaction with both treatments. No significant differences were found between the groups. The rate of apparent endometriosis recurrence was 10.8% in group 1 and 13.7% in group 2 (p = 0.962). CONCLUSION: Both therapies seemed equally efficacious in preventing endometriosis-related chronic pelvic pain recurrence in the first 9 months of follow-up.

Vulvo-vaginal atrophy: a new treatment modality using thermo-ablative fractional CO2 laser.

OBJECTIVE: To evaluate the efficacy and feasibility of thermo-ablative fractional CO2 laser for the treatment of symptoms related to vulvo-vaginal atrophy (VVA) in post-menopausal women. METHODS: From April 2013 to December 2013, post-menopausal patients who complained of one or more VVA-related symptoms and who underwent vaginal treatment with fractional CO2 laser were enrolled in the study. At baseline (T0) and 30 days post-treatment (T1), vaginal status of the women was evaluated using the Vaginal Health Index (VHI), and subjective intensity of VVA symptoms was evaluated using a visual analog scale (VAS). At T1, treatment satisfaction was evaluated using a 5-point Likert scale. RESULTS: During the study period, a total of 48 patients were enrolled. Data indicated a significant improvement in VVA symptoms (vaginal dryness, burning, itching and dyspareunia) (P<0.0001) in patients who had undergone 3 sessions of vaginal fractional CO2 laser treatment. Moreover, VHI scores were significantly higher at T1 (P<0.0001). Overall, 91.7% of patients were satisfied or very satisfied with the procedure and experienced considerable improvement in quality of life (QoL). No adverse events due to fractional CO2 laser treatment occurred. CONCLUSION: Thermo-ablative fractional CO2 laser could be a safe, effective and feasible option for the treatment of VVA symptoms in post-menopausal women.

Oxidative stress markers in patients with hymenoptera venom allergy.

Oxidative stress occurs in many allergic and immunologic disorders as a result of the imbalance between the endogenous production of free reactive oxygen species (ROS) and/or the reduction of antioxidant defense mechanisms. Advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), and nitrosylated proteins (NPs) can be used as markers of oxidative stress and inflammation. Our objective was to examine the serum levels of AGEs, AOPPs, and NPs in patients with allergic reactions to hymenoptera venom before and after ultrarush venom immunotherapy (VIT). The study included two groups of patients: 30 patients allergic to yellow jacket or honey bee venom and treated by aqueous preparation of Vespula spp (26 patients) or Apis mellifera (four patients) VIT, and 30 healthy donors as controls. Blood samples were collected to measure serum levels of AGEs, AOPPs, and NPs at baseline (T1), at the end of the incremental phase of the VIT protocol (T2), and after 15 days (T3). Serum AOPP levels at T1 were significantly higher in comparison with controls (p = 0.001), whereas serum levels of NPs at T1 were significantly lower than those in controls (p < 0.0001). No significant difference in circulating levels of AOPPs, AGEs, and NPs was found during immunotherapy. These findings suggest that, although hymenoptera venom allergy (HVA) is characterized by isolated episodes of reactions to stinging insect venom and is not included among chronic inflammatory diseases, an oxidative stress status occurs in patients suffering from this kind of allergy. Furthermore, VIT does not modify serum levels of these oxidative stress biomarkers.

Interleukin-10 involvement in exposure to low dose of benzene.

OBJECTIVE: To establish if serum levels of interleukin-10 (IL-10) in subjects exposed to benzene are connected with age, working years, and employment age. METHODS: We evaluated serum levels of IL-10 in 51 employees working in oil refinery (group A) and in 16 office workers who resided in the same area (group B). RESULTS: There was no statistically significant difference between serum concentrations of IL-10 in groups A and B. There was a statistically significant dependent relationship in group A between age, working years, and serum concentration of IL-10. There was a statistically significant and positive dependent relationship in group A between serum concentration of IL-10 and employment age. CONCLUSIONS: The role played by IL-10 in benzene immune suppression may be relevant and attention should be directed toward assessment of age, working years, and employment age in benzene-exposed populations.

Effect of therapeutic plasma exchange on plasma levels of oxidative biomarkers in a patient with thrombotic thrombocytopenic purpura.

BACKGROUND: The role of oxidative stress in the initiation and progression of endothelial damage in thrombotic thrombocytopenic purpura (TTP) syndrome has been the subject of much speculation in the recent past. OBJECTIVES: The aim of this study was to measure the concentration of plasma advanced oxidation protein products (AOPPs), advanced glycation end products (AGEs), and carbonyl groups (CG) as markers of oxidative stress in plasma of a patient with TTP during the course of the disease until recovery and to evaluate the effect of plasmapheresis (PE) on these biomarkers. MATERIALS AND METHODS: The study consisted of plasma analysis of the patient, and 23 healthy subjects served as controls. In the patient with TTP, AOPP, AGE, and CG analysis was performed before and after each PE at the days +1 (Tα), +2, +4, +6, +10, +9, and +17 after the last plasmapheresis (Tω). RESULTS: Plasma concentrations of AOPPs were increased in the acute phase of TTP, and at Tα, the patient had AOPPs levels higher than 99°‰ of controls. AOPPs decreased in the recovery phase, and at Tω, their values were between 84° and 85°‰ of controls. No significant difference was found in AOPP levels before and after each PE. No significant differences for AGEs or CG concentrations were found at Tα with respect to the control group, while only a trend was observed for reduction of plasma AGEs after each plasmapheresis. CONCLUSION: Our data seem to confirm the hypothesis that oxidative stress is a critical component of the pathogenesis of TTP.

Erythropoiesis-stimulating agents: dose and mortality risk.

Hypo-responsiveness to erythropoiesis-stimulating agents (ESAs) has been associated with increased mortality in end-stage renal disease patients. It is not clear if this effect is related to the elevated ESAs dosage for targeting hemoglobin levels or underlying morbid conditions that lead to ESA resistance. We retrospectively evaluated from 2008 to death or December 2011, 28 consecutive incident hemodialysis patients. We identified 2 cohort of patients based on their mean annual ESAs dosage. The correlation between data was evaluated with the Spearman's rho test. Kaplan-Meier curves were generated to assess survival in subjects with high and low ESAs mean dose. Median ESAs dosage, used as a cutoff point between patients at high and low ESAs dose, was at 11.000 IU/week for epoetin alfa and beta, 55 mcg/week for darbopoietin, and 220 mcg/month for cera. Mean hemoglobin (Hb) level was 10.58 ± 0.13 g/dL. Of 28 patients, during follow-up, 6 (21,4%) died of all causes. High-dose ESA therapy was associated with increased all-cause mortality (P = .047). Moreover, there was a negative correlation between ESAs dose and Hb levels (rho = -0.825; P < .001). Higher ESAs dose for the treatment of anemia in incident hemodialysis patients was associated with higher mortality risk. ESAs and Hb serum levels were inversely correlated with mortality. Together, these findings suggest that ESAs dosage and Hb level may play a role through an independent manner or an interactive effect that adversely affects mortality.

Serum interleukin-22 (IL-22) is increased in the early stage of Hashimoto's thyroiditis compared to non-autoimmune thyroid disease and healthy controls.

OBJECTIVE: Hashimoto's thyroiditis (HT) is considered to be a Th1-related autoimmune disease (AID). Recent studies revealed that Th17 lymphocytes (producing mostly IL-17, IL-21 and IL-22) play a major role in numerous AIDs commonly thought to be Th1 diseases. More recently, another subset of Th cells, which produce IL-22 and thus so-called Th-22, have been identified. Few data are available in the literature on the role of IL-22, the main soluble mediator of both Th17 and Th22 cells, in HT. DESIGN: Using IL-22 Quantikine ELISA Kit (lower limit of detection 0.7 pg/ml), we assayed serum levels of IL-22 in three groups of subjects: newly diagnosed HT patients (n=55, 5 males and 50 females, age 38±17 years), non-HT patients with nodular goiter (n=30, 4 males and 26 females, age 43±14 years) and an age- and sex-matched group of healthy individuals. HT patients were euthyroid and were not receiving any treatment. RESULTS: HT patients showed significantly higher levels of serum IL-22 (group A, 42±34 pg/ml) as compared to non-HT-goitrous patients (18±15 pg/ml; P<0.001) and healthy controls (20±13 pg/ml; P=0.014). Serum IL-22 levels did not differ between non-HT-goitrous patients and healthy controls (p=0.496). No significant correlation was found between serum levels of IL-22 and Tg-Ab, TPO-Ab or TSH in the HT patients. CONCLUSIONS: Serum IL-22 is increased in newly diagnosed, untreated HT patients, as compared to thyroid autoimmune disease-free individuals. Our data suggest that IL-22 could play some role in the development of HT.

Interstitial pregnancy: a 'road map' of surgical treatment based on a systematic review of the literature.

An electronic search concerning the surgical approach in cases of interstitial pregnancy from January 2000 to May 2013 has been carried out. Fifty three studies have been retrieved and included for statistical analysis. Conservative and radical surgical treatments in 354 cases of interstitial pregnancy are extensively described. Hemostatic techniques have been reported as well as clinical criteria for the medical approach. Surgical outcome in conservative versus radical treatment were similar. When hemostatic techniques were used, lower blood losses and lower operative times were recorded. Conversion to laparotomy involved difficulties in hemostasis and the presence of persistent or multiple adhesions. Laparoscopic injection of vasopressin into the myometrium below the cornual mass was the preferred approach.

Serum interleukin-23 (IL-23) is increased in Hashimoto's thyroiditis.

Recent studies have demonstrated that T-helper 17 lymphocytes (Th17), which produce mostly IL-17, play a major role in several autoimmune diseases commonly thought to be Th1-related, including Hashimoto's thyroiditis (HT). IL-23, a member of the IL-12 cytokine family, is known to guide T cells toward the Th17 phenotype and its serum levels are increased in several autoimmune disease. Few data are available in the literature on IL-23 in HT. Using IL-23 Quantikine ELISA Kit (lower limit of detection 2.7 pg/mL) we analyzed the serum levels of IL-23 in 81 HT patients (75 females and 6 males, aged 14-70; mean age 39±17 years), and an age- and sex-matched group of 80 healthy persons. Both patients and controls did not receive any treatment. The positive detection rates of serum IL-23 were significantly higher in patients with HT: 56% of HT patients had detectable IL-23 in serum compared to 36% of healthy subjects (Chi χ² test, p=0.014). Moreover, HT patients had significantly higher serum concentrations of IL-23 (157.38 ± 17.92 pg/mL) in comparison with healthy controls (21.46 ± 5.4 pg/mL; p <0.0001). No significant correlation was found between serum levels of IL-23 and Tg-Ab or TPO-Ab levels, as well as with TSH values, in HT patients. In conclusion, serum IL-23 is increased in euthyroid and untreated HT patients, as compared to healthy subjects. Our data suggest that IL-23 would play a role in the pathogenesis of HT.

Oral contraceptives in the prevention of endometrioma recurrence: does the different progestins used make a difference?

OBJECTIVE: The primary aim of the study was to analyze the endometrioma recurrence rate in patients who underwent laparoscopic excision followed by postoperative long-term regimen of oral contraceptives (OCs). MATERIALS AND METHODS: 168 patients who underwent a conservative laparoscopic surgery for endometrioma, during the period between September 2009 and August 2010 in three university hospitals were studied. A long-term OCs therapy was offered to all women following surgery. Patients were randomly divided into three groups according to different progestins used (desogestrel, gestodene, dienogest). Women who refused a postoperative hormonal therapy served as control. Follow-up visits and transvaginal scan were planned at 1, 3, 6, 12, and 24 months after surgery. All patients who showed an ultrasound persistence of the endometrioma at 1 month follow-up were excluded from clinical analysis. RESULTS: Of the 168 patients, 131 completed the 24 months follow-up. Endometrioma recurrence was found in 21 (12.5 %) of all patients, it was unilateral in 17 cases while bilateral in 4 cases. The rate of recurrent endometrioma was statistically significant in non-users compared to the long-term OCs treated patients. CONCLUSION: The current data suggest the usefulness of long-term OCs regimen after conservative surgery for the prevention of ovarian endometrioma recurrence. As a statistical significant difference could not be observed between OCs groups, further study on the individual molecules is required in order to really understand the effect of each of them.