Electrocardiogram analysis in Anderson-Fabry disease: a valuable tool for progressive phenotypic expression tracking.

Background: Electrocardiogram (ECG) has proven to be useful for early detection of cardiac involvement in Anderson-Fabry disease (AFD); however, little evidence is available on the association between ECG alterations and the progression of the disease. Aim and Methods: To perform a cross sectional comparison of ECG abnormalities throughout different left ventricular hypertrophy (LVH) severity subgroups, providing ECG patterns specific of the progressive AFD stages. 189 AFD patients from a multicenter cohort underwent comprehensive ECG analysis, echocardiography, and clinical evaluation. Results: The study cohort (39% males, median age 47 years, 68% classical AFD) was divided into 4 groups according to different degree of left ventricular (LV) thickness: group A ≤ 9 mm (n = 52, 28%); group B 10-14 mm (n = 76, 40%); group C 15-19 mm (n = 46, 24%); group D ≥ 20 mm (n = 15, 8%). The most frequent conduction delay was right bundle branch block (RBBB), incomplete in groups B and C (20%,22%) and complete RBBB in group D (54%, p < 0.001); none of the patients had left bundle branch block (LBBB). Left anterior fascicular block, LVH criteria, negative T waves, ST depression were more common in the advanced stages of the disease (p < 0.001). Summarizing our results, we suggested ECG patterns representative of the different AFD stages as assessed by the increases in LV thickness over time (Central Figure). Patients from group A showed mostly a normal ECG (77%) or minor anomalies like LVH criteria (8%) and delta wave/slurred QR onset + borderline PR (8%). Differently, patients from groups B and C exhibited more heterogeneous ECG patterns: LVH (17%; 7% respectively); LVH + LV strain (9%; 17%); incomplete RBBB + repolarization abnormalities (8%; 9%), more frequently associated with LVH criteria in group C than B (8%; 15%). Finally, patients from group D showed very peculiar ECG patterns, represented by complete RBBB + LVH and repolarization abnormalities (40%), sometimes associated with QRS fragmentation (13%). Conclusions: ECG is a sensitive tool for early identification and long-term monitoring of cardiac involvement in patients with AFD, providing "instantaneous pictures" along the natural history of AFD. Whether ECG changes may be associated with clinical events remains to be determined.

Lessons from peculiar cases of anaphylaxis: why allergists should be prepared for the unexpected.

Summary: Anaphylaxis is the most severe systemic hypersensitivity reaction, it can be caused by a number of well identified triggers such as foods, drugs, stinging insects and facilitated by predisposing clinical conditions. However, sometimes anaphylaxis shows up with uncommon or peculiar characteristics which could delay diagnosis and therapeutic treatment. In this report we aimed to describe less accounted / difficult-to-approach shapes of anaphylaxis to facilitate clinicians to suspect these severe reactions even in uncommon conditions. We choose to present data on anaphylaxis regarding simulation, mode of exposure to sensitizing agents, pregnancy, exposure to animals, intimate behaviour, psychological stress and other situations.

Allergy in adolescent population (14-18 years) living in Campania region (Southern Italy). A multicenter study.

Summary: Adolescents (Ad) constitute a difficult to manage population among individuals suffering from asthma. The aim of our study was to assess the prevalence, clinical characteristics and age of onset of allergic sensitization and clinical symptoms in a sample of atopic Ad living in the Campania region (Southern Italy). Sixteen Allergy units or Centers belonging to the Italian Association of Hospital and Territorial Allergologists (AAIITO, Campania region) participated in this cross-sectional study. A case report form (CRF) was specifically designed for this study and commercial allergen extracts used for screening SPTs were provided by ALK-Abelló Group (Milan, Italy). A total of 443 patients were examined (females, f 220, 49.6 %; males, m 223, 50.3%). Dust mites represent the most common sensitizing agents in allergic Ad living in Campania region (Dermatoph. pteronyssinus 67.4% and Dermatoph. farinae 66.5%), followed by Parietaria (58.9%), grasses (45.8%), Artemisia vulgaris (16.7%), Olea Europaea (32.2%), dog dander (17.1%), cat dander (20.0%), Alternaria alternata (8.1%), Cupressus sempervirens (4.9%), Betula pendula (4.7%), other allergens (19.4%). An interesting comparison has been made between clinical data of our Ad with data of elderly patients (E). The role of allergic sensitization is significantly higher in Ad compared to E. Dermatophagoides pteronyssinus is the first sensitizing allergen in Ad and the last in E. Parietaria constitutes the first sensitizing pollen both in Ad and E, the percentage of sensitization is higher in Ad. Another important difference is the higher prevalence of As, as only symptom, in E compared to Ad (19.7% versus 7.6%). In conclusion, our findings confirm the high prevalence and clinical significance of airway allergic sensitization in the adolescents living in Campania region.

Allergic sensitization to common pets (cats/dogs) according to different possible modalities of exposure: an Italian Multicenter Study.

BACKGROUND: The query "are there animals at home?" is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. METHODS: Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. RESULTS: A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150-20.75%) or indirect contact (103-14.25%), in 111 subjects (15.35%) any contact was reported. CONCLUSIONS: Only 213 patients (29.46%) would be classified as "exposed to animals" and 510 (70.54%) as "not exposed" according to usual query. Our classification has shown that many "not-exposed" subjects (399-55.19%) were "really exposed". The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals.

Allergy in urban elderly population living in Campania region (Southern Italy). A multicenter study.

Given the increasing life expectancy observed in Western countries, there is a marked interest to know more about how aging could influence respiratory health. The aim of our study was to assess the prevalence, clinical characteristics and age of onset of allergic sensitization and clinical symptoms in a sample of atopic elders living in Campania region area (Southern Italy). Fourteen Allergy units or Centres examined a total of 462 patients. In this context 215 (46.53%) had positive skin prick tests (SPTs) to at least one allergen and were diagnosed with respiratory allergy. Parietaria represents the most common sensitizing agent in elders living in Campania region, followed by dust mites, grass pollen and Olea europaea. A relatively high percentage of atopic subjects suffered from respiratory symptoms at a fairly advanced age, namely 8.3% at 60-64 years, 10.2% at 65-70 and 5.7% at > 70 years. In conclusion, the prevalence and clinical significance of airway allergic sensitization in the elderly living in Campania region is more significant than expected in latter stages of life. Physicians should not neglect the role of atopy as a risk factor for the onset of allergic respiratory symptoms even in elderly patients.

Sensitization to cockroach allergens in the urban atopic populations living in Campania district (southern Italy). A multicenter study.

BACKGROUND: Although cockroach (CR) is an important cause of allergic sensitization worldwide, only a few data are available in Italy and in a previous study we have observed, in Naples area, a low prevalence of CR sensitization. OBJECTIVES: We sought to perform a prospective study for assessing the prevalence of allergic sensitization to CR in a sample of atopic population living in Campania district area (Southern Italy). METHODS: Ten Allergy Units or Centres of Campania district participated in this cross-sectional study. Each centre was required to collect the results of at least 100 allergy consultations in consecutive outpatients referred for actual or suspected respiratory allergy. We registered demographic data, type and duration of respiratory symptoms, pets ownership, possible exposure to CR allergens, results of the skin prick tests (SPTs). RESULTS: A total of 1477 patients were examined, 985 (66.68%) had a SPTs positivity to at least one allergen. In this context, ninety were sensitized to CR, thus the overall sensitization prevalence in subjects with respiratory allergy was 6.09% ranging between 0-11% and only five patients were mono-sensitized. Thirteen patients reported rhinitis (R) + bronchial asthma (A), twenty-one R + A + conjunctivitis (C), thirty-seven R + C, five only A and eleven individuals only R. Sixty-seven patients exhibited persistent and twenty-three intermittent symptoms. Dust mite constituted the first cause of associated sensitization to CR. CONCLUSIONS: The prevalence of allergic sensitization to CR is not negligible in population living in Campania district and shows a higher trend in comparison to that found recently and some years ago in Naples area. Finally, we suggest atopic individuals and especially those highly sensitized to mite allergens or those living in low-income areas to be tested by SPTs / evaluation of serum specific IgE to CR allergens to exclude the occurrence of CR allergic sensitization.

Long-term outcome after radioiodine therapy with adjuvant rhTSH treatment: comparison between patients with non-toxic and pre-toxic large multinodular goitre.

In multinodular goitre (MNG), low radioiodine (RAI) activity after recombinant human (rh) TSH is able to reduce thyroid volume (TV) and improve symptoms. Our aim was to evaluate the long-term outcome of RAI after rhTSH treatment in patients who were divided according to their baseline TSH levels. Eighteen patients (69.2 ± 6.1 year) presented non-toxic (TSH >0.3 mIU/l) MNG (TV: 61.0 ± 3.8 ml; group 1), while 13 patients (74.1 ± 7.9 year) had non-autoimmune pre-toxic (TSH <0.3 mIU/l) MNG (TV: 82.6 ± 14.4 ml; group 2). TSH, thyroid hormones, TV (by ultrasonography), body mass index (BMI), symptoms and quality of life (QoL) were evaluated. Treatment induced short-term thyrotoxicosis in both groups, but this was slightly more marked in group 2 than in group 1. The number and severity of adverse events were similar. The follow-up period was 55.3 ± 4.1 months in group 1 and 57.2 ± 5.1 months in group 2. The final TV reduction was similar in groups 1 (63.4 ± 3.6%) and 2 (57.2 ± 4.6%) and TV reduction positively correlated only with initial TV. At the last examination, 14 group-1 subjects were on L-T4 therapy, while 2 group-2 subjects were on methimazole. An increase in BMI was noted only in group 2. MNG-related symptoms were significantly reduced in both groups. Symptoms related to sub-clinical hyperthyroidism improved in group 2, while no significant changes in QoL were noted in either group. This study confirms the effectiveness of rhTSH adjuvant treatment in reducing TV after low RAI activities, irrespective of baseline thyroid status. TSH levels <0.3 mIU/l proved to be predictive of a more severe thyrotoxic phase after rhTSH and RAI, while initial TSH levels >0.3 mIU/l were more frequently followed by a need for L-T4 therapy. Compressive symptoms improved in the majority of subjects.

Perioperative anaphylactic risk score for risk-oriented premedication.

Basing on the current knowledge, this paper is aimed to review the core characteristics of the most relevant therapeutic agents (steroids and antihistamines), administered to prevent perioperative anaphylaxis. Moreover, the Authors propose the validation of a Global Anaphylactic Risk Score, built up by recording the individual scores related to the most relevant anaphylaxis parameters (i.e. medical history, symptoms and medication for asthma, rhinitis and urticaria etc) and by adding them on all together; the score could be used in the preoperative phase to evaluate the global anaphylactic risk and to prescribe risk-oriented premedication protocols.

Radioiodine therapy of hyperfunctioning thyroid nodules: usefulness of an implemented dose calculation algorithm allowing reduction of radioiodine amount.

AIM: Radioiodine is a common option for treatment of hyperfunctioning thyroid nodules. Due to the expected selective radioiodine uptake by adenoma, relatively high "fixed" activities are often used. Alternatively, the activity is individually calculated upon the prescription of a fixed value of target absorbed dose. We evaluated the use of an algorithm for personalized radioiodine activity calculation, which allows as a rule the administration of lower radioiodine activities. METHODS: Seventy-five patients with single hyperfunctioning thyroid nodule eligible for 131I treatment were studied. The activities of 131I to be administered were estimated by the method described by Traino et al. and developed for Graves'disease, assuming selective and homogeneous 131I uptake by adenoma. The method takes into account 131I uptake and its effective half-life, target (adenoma) volume and its expected volume reduction during treatment. A comparison with the activities calculated by other dosimetric protocols, and the "fixed" activity method was performed. 131I uptake was measured by external counting, thyroid nodule volume by ultrasonography, thyroid hormones and TSH by ELISA. RESULTS: Remission of hyperthyroidism was observed in all but one patient; volume reduction of adenoma was closely similar to that assumed by our model. Effective half-life was highly variable in different patients, and critically affected dose calculation. The administered activities were clearly lower with respect to "fixed" activities and other protocols' prescription. CONCLUSION: The proposed algorithm proved to be effective also for single hyperfunctioning thyroid nodule treatment and allowed a significant reduction of administered 131I activities, without loss of clinical efficacy.

Sensitization to horse allergens in Italy: a multicentre study in urban atopic subjects without occupational exposure.

BACKGROUND: Horses play a significant role in people's leisure time in Italy and other countries, but few data are available on IgE-mediated sensitization to horse allergens in patients without occupational exposure. We assessed, in a multicentric survey, the prevalence of horse sensitization in atopic subjects and its clinical characteristics. METHODS: Allergists from the whole Italian territory were required to collect the results of skin prick tests from at least 100 consecutive subjects. Those patients with a positive skin test to horse dander underwent a detailed interview concerning clinical history, pet ownership and possible exposure. RESULTS: Data from 3,235 outpatients were collected and 2,097 had at least 1 skin positivity. Among them, 113 (5.38%) were sensitized to horse dander (9 monosensitized). Thirty patients reported direct horse contact (4 owners and 26 for riding or occasional contact), 23 patients were sometimes in contact with horse owners and 60 subjects denied any direct or indirect exposure. Among 9 horse monosensitized patients, 6 had intermittent and mild rhinitis and 3 persistent moderate/severe rhinitis plus asthma. Three of them were horse owners or riders and the remaining had no contact with the animal. CONCLUSIONS: Our data evidence that the rate of sensitization to horse dander is not negligible and probably underestimated. In susceptible, not occupationally exposed individuals, horse contact, but also indirect or no apparent exposure, may induce sensitization. We recommend inclusion of horse allergen in the routine panel for the diagnosis of respiratory allergy.

A study of the efficacy of radioiodine therapy with individualized dosimetry in Graves' disease: need to retarget the radiation committed dose to the thyroid.

Although Iodine-131 (131I) therapy is fully validated for Graves' disease (GD), there is debate about radioiodine amount to be administered (prescribed activity), as well as the use of individualized dosimetry vs fixed 131I activity. The clinical outcome of 119 GD patients treated with 131I from 2003 to 2008 has been evaluated. The prescribed activity was calculated according to a dosimetric protocol taking into account several variables, including thyroid volume reduction during treatment. In addition, we performed a simulation according to other dosimetric protocols, by calculating the corresponding prescribed activities. The patients were followed up for at least 12 months after treatment. In the first period of observation (2003), a 120-200 Gray (Gy) radiation dose to the thyroid was prescribed, according to the guidelines published by the Italian Societies of Endocrinology, Nuclear Medicine and Medical Physics: hyperthyroidism cure with a single radioiodine administration was obtained in 53% of patients. This outcome raised up to 89% when a higher radiation dose to the target (200- 250 Gy) was prescribed, although the administered activities were still lower, as a rule, than the most commonly employed fixed activities (400-600 Mega-Becquerel--MBq). Our method showed a high level of individual dose optimisation, particularly when compared to simplified methods. In conclusion, the protocol adopted in this study ensures a satisfactory rate of hyperthyroidism cure, while administering quite low 131I activities, provided that an adequate committed radiation dose to the thyroid is prescribed. In this context, the dose indication given by the aforementioned guidelines should probably be revised.

Thyrotropin receptor autoantibody measurement following radiometabolic treatment of hyperthyroidism: comparison between different methods.

BACKGROUND: TSH receptor antibodies (TRAb) play a crucial role in the pathogenesis of Graves' disease (GD). The use of human recombinant TSH-receptor far improved the analytical performance of TRAb assays (2nd-generation assays). The 3rd-generation assay is based on the inhibition of binding of a human biotin-labeled monoclonal thyroid- stimulating antibody (M22) to TSH-receptor by the autoantibodies present in the serum. AIM: We aimed to assess the ability of the 2nd- and 3rd-generation assays to detect serum TRAb following radioiodine therapy for hyperthyroidism. METHODS: Sera from 47 hyperthyroid (25 autoimmune, 22 non-autoimmune) patients were tested using the two different assays before and at different time intervals after radioiodine therapy. The modifications of TRAb were evaluated, as well as the correlation between the two methods. RESULTS: The results obtained by the two methods proved to be closely correlated. A rise in TRAb was invariably observed in GD patients following radioiodine, with a median peak at 6 months, irrespective of their initial clinical status, presence of ophthalmopathy, smoking habits or other variables. Such a rise was nearly superimposable using both methods. No TRAb appearance was observed in patients with non-autoimmune hyperthyroidism. CONCLUSIONS: The use of methods of higher sensitivity with respect to that formerly used indicate that nearly all GD patients develop TRAb following radioiodine, and that this phenomenon is transient and not related to baseline conditions and clinical outcome/efficacy of treatment.

[Long-term results of laparoscopic retroperitoneal lymph node dissection (RPLND) in low-stage nonseminomatous germ-cell testicular tumors (NSGCTT) performed by a senior surgeon: 1999-2003]. / Risultati a lungo termine della linfadenectomia retroperitoneale laparoscopica nei tumori germinali non seminomatosi del testicolo; esperienza di un chirurgo anziano: 1999-2003.

BACKGROUND: Laparoscopic RPLND for low-stages NSGCTT is controversial: it is performed and recommended by excellent laparoscopic surgeons, but it is not widely used. The aim of this paper is to evaluate the results achieved by a senior surgeon, expert in open RPLND, who was introduced to laparoscopic surgery by excellent laparoscopists (LN, CU, GJ). PATIENTS AND METHODS: of the 48 operated patients, 36 had primary RPLND for clinical stage I disease (22 TIN0, 7 TxN0, 5 T2-3 N0 and 2 TIS1 N0) and 12 had post-chemotherapy surgery for IIA and IIB retroperitoneal nodes with normalized AFP and HCG. L-RPLND was performed with 4 ports and the en bloc removal of unilateral retroperitoneal nodes with the spermatic vessels. No post-operative adjuvant chemotherapy was planned for patients with documented nodal metastases as for open RPLND since 1985. RESULTS: Average operative time was 3.30' for the 36 clinical stage I patients and 4 hours for post-chemotherapy surgery. Blood loss was minimal in all cases, because of early conversion to open surgery in all patients with no immediate hemostasis at L-RPLND. Metastases were found in 6 (17%) out of the 36 clinical stage I patients: none in the 22 pTI, 1 in the 7 Tx, 3 in the 5 pT2-3 and in 2 of the 2 pT1S1 patients. Residual teratoma was found in 6 of the 12 patients who received neo-adjuvant chemotherapy for clinical stage IIA or IIB disease. The other 6 had fibrosis-necrosis. Further metastases developed in 2 of the 30 patients with negative nodes: 1 in the lung in a pT1, and 1 in a pT2 patient with increasing markers. Surprisingly, the first two pT2-3 patients with positive nodes developed liver metastases in a few months after L-RPLND. Consequently, all following patients with active metastases at L-RPLND received 2 courses of adjuvant PEB. All 4 patients who relapsed were cured, are alive and disease-free. CONCLUSIONS: L-RPLND is a very demanding operation, which appears to be more a staging procedure than a curative operation. It is ideal for pT1 clinical stage I and for post-chemotherapy stages IIA& B with residual teratoma and normalized markers, but wait & see in good risk and open RPLND in high risk patients are very competing. Only few reports compared laparoscopic versus open RPLND, but not in a randomized study.

Prevalence of post-partum thyroiditis in Liguria (Italy): an observational study.

BACKGROUND: Post-partum thyroiditis (PPT) is an autoimmune disorder occurring within the first year following delivery. A variable prevalence has been reported in different surveys. We prospectively evaluated PPT prevalence and outcome in a cohort of pregnant women living in a well-defined geographic area. AIM: A subset from a group of healthy women consecutively evaluated for thyroid function and thyroid autoimmunity during pregnancy, referring to the same obstetric unit, were followed up at 4-6 months and 1 yr after delivery. MATERIALS/SUBJECTS AND METHODS: Follow-up for PPT was performed in 258 pregnant women. Control data were obtained in a comparable group of healthy non-pregnant women. Free T3 (fT3), free T4 (fT4), TSH thyroglobulin/thyroid peroxidase autoantibodies (TgAb/TPOAb), and urinary iodine excretion were measured. RESULTS: Autoantibody positivity was observed in 9.3% of pregnant, similar to control women. Forty-three out of 59 autoantibody-positive women were followed up; 23 showed PPT at the first control, 18 had hypothyroidism at 1 yr (5 had not shown PPT at the first control). Among 215 out of 584 autoantibody-negative women followed up, 27 developed PPT (15 of them without thyroid autoantibodies); 16 developed thyroid autoantibodies without PPT. After 1 yr, 9 women had hypothyroidism: only 1 of them was autoantibody-negative at the former control. Urinary iodine was increased in several pregnant women. CONCLUSIONS: An overall PPT prevalence of about 18% may be estimated. PPT was also observed in autoantibody- negative women. Differences with other surveys may be related to both study protocol and characteristics of the population studied.