Anti-Müllerian hormone in pre-menopausal females after ablative radioiodine treatment for differentiated thyroid cancer.

PURPOSE: In recent years, anti-Mullerian hormone (AMH) has been considered a reliable index of ovarian reserve. There are few data on AMH values in thyroid cancer. The aim of this study was to evaluate AMH levels in pre-menopausal women with a history of low-risk thyroid cancer. METHODS: Thirty-four women (aged 40.7 ± 6.7 years) were studied 7.1 ± 0.9 years after surgery and at least one RAI treatment. A group of 23 thyroid cancer women (41.6 ± 7.4 years) who had undergone only thyroidectomy served as controls. AMH, follicle-stimulating hormone (FSH) and estradiol were assayed on days 2-3, and prolactin and progesterone levels on days 21-24 of the menstrual cycle. RESULTS: Pregnancy (RAI group 62%; control group 61%) and miscarriage rates (18% and 26%) were similar. AMH levels were similar in the RAI (10.7 ± 1.7 pmol/l) and control (17.5 ± 4.7 pmol/l) groups. Regular menses were reported in 41% and 52% of RAI and control subjects, respectively. Non-ovulatory cycles were noted in 26% and 35% of RAI and control women, respectively. AMH levels were found to be negatively correlated with age (RAI group P = 0.0003; control group P = 0.0001) and FSH, and positively correlated with progesterone, but not with the other hormonal parameters. CONCLUSIONS: AMH should replace FSH in the evaluation of gonadal reserve in pre-menopausal thyroid cancer women. At present, age is the only predictor of AMH levels. About one out of two women with a history of thyroid cancer suffers from menstrual dysregulation, but infertility must be considered a low risk.

A Real Life Comparison between Allergenic Extracts and Allergenic Molecules.

Serum IgE assay is a mainstay step in the allergy work up. Allergenic extracts and molecular components are available at present. This real life study compared the serum specific IgE levels against allergenic extracts with allergenic molecules in patients allergic to Parietaria, Betulaceae, and mites. This retrospective real life study included 489 subjects with respiratory allergy. Inclusion criteria were 1) documented diagnosis of allergic rhinitis (AR) and/or allergic asthma, and 2) documented allergy to Parietaria judaica (Par j) 2 (216 patients: 112 females, mean age 42 years), or to Betula verrucosa (Bet v) 1 (62 patients: 35 females, mean age 3 years), or Dermatophagoides pteronyssinus (Der p) 1 (211 patients: 107 females, mean age 34 years); and mono-allergy. Serum IgE, specific both for total/crude allergen extracts and individual purified/recombinant allergens, were assessed by ImmunoCap system. The serum IgE levels to birch extract were very strongly (R2=0.96) related to IgE to Bet v 1. There was a strong (R2=0.71) correlation between Dermatophagoides pteronyssinus IgE and Der p 1. A very strong (R2=0.87) correlation also existed between Parietaria extract IgE and Par j 2 IgE levels. However, there was discrepancy between percentages of positivity between allergenic extracts and molecules. Therefore, allergen molecular diagnostics may represent a useful way in allergy work up, but deserves caution in particular circumstances.

The impact of age on Pru p 3 IgE production in Italy.

BACKGROUND: Pollen allergy may be frequently associated with fruit-vegetables: the so-called pollen food syndrome. Pru p 3 is the most relevant peach allergen. Previously, it has been reported that serum specific IgE level to Pru p 3 depends on age in a limited geographic area. OBJECTIVE: This study aimed to to test the hypothesis about the differences of Pru p 3 sensitization across Italy, mainly concerning the impact of age. METHODS: The current study was retrospective and multicentre, involving 2 labs in Northern Italy (709 subjects), 1 in Genoa (1,040 subjects), and 1 in Southern Italy (2,188 subjects). All of them referred to labs for IgE testing because of suspected food allergy. Serum IgE to Pru p 3 was assessed in all subjects. RESULTS: Sixteen point seven percent (16.7%) of subjects were sensitized to Pru p 3. Sensitization percentage sigificantly decreased over time. The serum IgE levels increased up to young adulthood and then decreased until aging. CONCLUSION: Our experience demonstrates that Pru p 3 sensitization and production are closely age-dependent phenomena.

Can pan-allergens affect the sensitization pattern?

The present study tested the hypothesis that a pan-allergen sensitization may affect the sensitization pattern. For this reason, 22 sensitization pattern allergens (SPA), common in Genoa (Italy), were selected for analyses. Successively, five of them, such as Pru p 3 as representative for LTP family, Bet v 1 and Pru p 1 for PR-10, and Bet v 2 and Pru p 4 for Profilin, were used as target allergens (TA). This retrospective study included 1059 subjects, (396 males and 663 females, mean age 42.8 years). The current study showed that sensitization to a pan-allergen entails higher odds to have other sensitizations. In addition, the co-sensitization pattern depends on the basis of the sensitizing pan-allergen family. LTP-sensitization is strongly associated with peanut sensitization, PR10 and profiling sensitization with hazelnut positivity. This study shows that a pan-allergen sensitization is frequently associated with co-sensitizations and the sensitization pattern depends on the sensitizing pan-allergen.

Birch allergy and oral allergy syndrome: The practical relevance of serum immunoglobulin E to Bet v 1.

BACKGROUND: Birch allergy (BA) may frequently be associated with fruit-vegetables oral allergy syndrome (OAS). Bet v 1 is the major birch allergen. Previously, it was reported that serum-specific immunoglobulin E (IgE) level could differentiate allergy from sensitization. Thus, this study aimed to investigate the practical role of Bet v 1 IgE. METHODS: A total of 245 subjects (128 women, 117 men; mean age, 41 years) with suspected allergic rhinitis and sensitization to Bet v 1 were evaluated. Serum IgE to Bet v 1 was assessed by using immuno-enzymatic. BA and OAS were diagnosed according to validated criteria. Symptom severity perception was measured by the visual analog scale. RESULTS: A total of 158 patients (64.5%) had BA. Patients with BA had higher serum Bet v 1 IgE levels than subjects who were sensitized (p < 0.0001). A cutoff value of 8.94 kUA/L predicted BA (area under the curve, 0.76; odds ratio, 6.18). Fifty-three patients with BA (33.5%) had OAS. Patients positive for OAS had higher Bet v 1 levels (p < 0.0001) and more-severe symptoms (p < 0.0001) than patients with BA and negative for OAS. A cutoff value of 17.4 kUA/L predicted OAS (area under the curve, 0.59; odds ratio, 3.19). CONCLUSIONS: The present study demonstrated that serum IgE levels to Bet v 1 could be a useful marker for differentiating between different birch pollen sensitization phenotypes.

Can serum white birch (Betula verrucosa) pollen antigen (Bet v 1) immunoglobulin E measurement distinguish between sensitization and allergy?

BACKGROUND: In clinical practice, it is fundamental to distinguish between sensitization and allergy, mainly with respect to polysensitized patients. The aim of this study was to evaluate whether serum immunoglobulin E (IgE) to white birch (Betula verrucosa) pollen antigen (Bet v 1) assessment might be able to differentiate simple sensitization from true allergy. METHODS: In total, 197 subjects (100 females; mean age 44.9 years) with serum Bet v 1 IgE positivity and history of nasal symptoms were evaluated. Subjects were subdivided in 2 groups: allergic and sensitized. RESULTS: Allergic patients were 58.4% of the total; they had higher serum Bet v 1 IgE levels than sensitized subjects (p < 0.001). A serum IgE to Bet v 1 value >8.94 kilo units of allergen per liter (kUA/L) was able to differentiate between sensitization and allergy (area under the receiver operating characteristic curve [AUC] = 0.76; diagnostic odds ratio, ie, degree of agreement between health status and dichotomized IgE levels [DOR] = 6.5). Gender and season when the blood was drawn influenced IgE levels. CONCLUSION: Serum Bet v 1 IgE measurement may be able to differentiate sensitization from allergy in subjects with sensitization to Betulaceae pollen allergens. Thus, Bet v 1 IgE measurement should be considered a useful step in the management of patients with allergic rhinitis due to Betulaceae pollen allergens.

Soluble CD14 subtype (sCD14-ST) presepsin in premature and full term critically ill newborns with sepsis and SIRS.

Neonatal sepsis still remains a major cause of morbidity and mortality in neonatal intensive care unit (NICU). Recently, soluble CD14 subtype (sDC14-ST) also named presepsin, was proposed as an effective biomarker for diagnosing, monitoring, and assessing the risk of neonatal sepsis and septic shock. The aim of this study was to investigate the diagnostic accuracy of sCD14-ST presepsin in diagnosing neonatal bacterial sepsis and in discriminating non-bacterial systemic inflammatory response syndrome (SIRS) from bacterial sepsis. This study involved 65 critically ill full-term and preterm newborns admitted to the neonatal intensive care unit (NICU), divided into three groups: 25 newborns with bacterial neonatal sepsis (group A); 15 newborns with a diagnosis of non-bacterial SIRS and with no localizing source of bacterial infection (group B); and 25 babies with no clinical or bacteriological signs of systemic or local infection receiving routine NICU care, most of them treated with phototherapy for neonatal jaundice (group C). A total of 102 whole blood samples were collected, 40 in group A, 30 in group B and 32 in group C. In 10 babies included in group A, sCD14-ST presepsin was also measured in an additional second blood sample collected 3 days after the start of antibiotic treatment. sCD14-ST presepsin was measured by a commercially available chemiluminescent enzyme immunoassay (CLEIA) optimized on an automated immunoassay analyzer. Statistical analysis was performed by means of MedCalc® statistical package; receiver operating characteristic (ROC) analysis was computed, and the area under the ROC curve (AUC) was used to evaluate the ability of sCD14-ST to discriminate neonatal bacterial sepsis from non-bacterial SIRS. Blood sCD14-ST presepsin levels were found significantly higher in bacterial sepsis when compared with controls (p<0.0001); similarly, they were higher in non-bacterial SIRS when compared with controls (p<0.0001). However, no statistically significant difference was found between bacterial sepsis and non-bacterial SIRS (p=0.730). In our population, CRP and sCD14-ST did not correlate with each other. ROC analysis revealed that sCD14-ST presepsin has an area under the curve (AUC) of 0.995 (95% C.I.: 0.941-1.00) greater than that of CRP (0.827; 95% C.I.: 0.72-0.906). Similarly, in the group of babies with non-infectious SIRS, sCD14-ST AUC was greater than CRP AUC (0.979; 95% C.I.: 0.906-0.999 versus 0.771; 95% C.I.: 0.647-0.868). In controls, preliminary reference intervals for sCD14-ST ranged 223.4-599.7 ng/L, being significantly different from those previously published elsewhere. In conclusion, sCD14-ST presepsin could be introduced in clinical practice as a diagnostic tool for improving the management of neonatal sepsis and non-bacterial SIRS.

Prognostic Value of Preoperative Serum Levels of Periostin (PN) in Early Breast Cancer (BCa).

PN is a secreted cell adhesion protein critical for carcinogenesis. Elevated serum levels of PN have been implicated as playing an important role in different types of cancer, and a few reports suggest a potential role as a prognostic marker. We evaluated the prognostic significance of preoperative serum PN concentration in patients with BCa receiving curative surgery. Enzyme-Linked Immunosorbent Assay (ELISA) was performed to determine the preoperative serum PN level in 182 patients. The correlations between serum PN concentration with clinical pathological features and PN expression in primary tumor samples were analyzed. The prognostic impact of serum PN levels with all-cause and BCa-specific mortality was also investigated. Appropriate statistics were used. Elevated serum PN levels were significantly associated with patient age (p = 0.005), adjuvant systemic therapy (p = 0.04) and progesterone receptor (PgR) status (p = 0.02). No correlation between PN preoperative serum levels and other clinical-pathological parameters, including either the epithelial or the stromal PN expression of primary tumor or the combination of the two, was found. Similarly, no association between serum PN levels and either all-cause or BCa-specific mortality was found. However, subgroup analysis revealed a correlation between higher PN serum levels and all-cause mortality in patients with node-negative disease (p = 0.05) and in those with a low PgR expression (p = 0.03). Higher levels of serum PN were also found to correlate with BCa-specific mortality in the subgroup of patients who did not receive any adjuvant systemic therapy (p = 0.04). Our findings suggest that PN was detectable in the serum of early BCa patients before surgery and increased base-line serum levels predicted worse long-term survival outcomes in specific subgroups of patients.

Borrelia burgdorferi, a great chameleon: know it to recognize it!

Borrelia burgdorferi is a spirochaete that can penetrate the blood-brain barrier in early infection and can cause endothelial damage other than central nervous system lesions. We describe a clinical case of neuroborreliosis that occurred in the absence of classical erythema migrans or arthralgia. Magnetic resonance imaging findings compatible with simil-vasculitis and demyelinating lesions associated with the presence of anti-B. burgdorferi antibodies in the plasma or cerebrospinal liquid is an indication for antimicrobial treatment against B. burgdorferi. An early diagnosis and a prompt establishment of an adequate antibiotic treatment is needed for a successful recovery.

Cell cycle/apoptosis molecule expression correlates with imatinib response in patients with advanced gastrointestinal stromal tumors.

PURPOSE: Altered expression of cell cycle/apoptosis key regulators may promote tumor progression, reflect secondary genetic/epigenetic events, and impair the effectiveness of therapy. Their expression pattern might then identify gastrointestinal stromal tumor (GIST) patient subgroups with different response to imatinib and elucidate novel therapeutic targets. EXPERIMENTAL DESIGN: Immunohistochemical evaluation of expression of p53, p16, p21, CHK2, CCND1, BCL2, CDK4, and MDM2 was done on 353 histologically validated GIST patients enrolled into a European/Australasian phase III trial. TP53 was screened for mutations in cases with presumptive nonfunctional protein; that is, high p53 and low expression of the two downstream molecules p21 and MDM2. Results were correlated with clinicopathologic data, KIT/PDGFRA mutation status, and imatinib dosage. RESULTS: Frequent impaired expression was found for BCL2 (78%), CHK2 (53%), p53 (50%), and p16 (47%). Stomach-originating GISTs showed significantly lower expression of p21, p16, and BCL2. KIT/PDGFRA wild-type GISTs had significant lower expression of CDK4. Eighty-eight percent of the high p53 expressers show low downstream target activation, indicating a nonfunctional p53 route. Of these high p53 expressers, 16.4% harbor a detectable TP53 mutation. Multivariate analysis, including previously identified markers, showed an independent effect of p53 and p16 on progression-free survival (PFS). Patients with high level of CHK2 and p21 showed significantly better PFS upon a high-dose regimen. CONCLUSIONS: Impaired p53, p16, BCL2, and CHK2 expression is common in advanced GISTs. Distinct patterns of expression correlate with tumor site, genotype, and PFS. Cell cycle/apoptosis maintenance is instrumental for optimal response to imatinib.