Authorship of Italian medical literature on neuroendocrine neoplasms: any gender gap?

PURPOSE: While males have dominated the physician lines over the last decades the recent female doctors' number increasing might progressively reduce this gender gap. This might be not fully true in the academic/research area. We aimed to analyze the gender distribution of first/senior Italian authors on neuroendocrine neoplasm papers published on peer reviewed journals. METHODS: Publications from January 2019 to September 2023 were reviewed; only papers with first and/or senior Italian authors were included. First/senior author gender, type of article, co-authorship with foreign authors were the variable analyzed. RESULTS: 742 papers with Italian first and/or senior authors were retrieved, 449 (60.5%) multicentric, 285 (38.4%) original articles. A female author was first and senior author in 386/742 (52%) and in 228/742 (31%) papers, respectively. 150 (20.2%) papers included foreign coauthors, being an Italian female researcher first author in 50 papers (33%), senior author in 28 (18.6%). The number of Italian female first/senior authors has been increasing over the years (22 in 2019, 113 in 2022; 16 in 2019, 62 in 2022, respectively). The first/senior female authors were mainly Oncologists/Endocrinologists/Pathologists rather than Gastroenterologists/Nuclear Medicine doctors/Surgeons/Radiologists. CONCLUSION: There has been an increase in the prevalence of female authorship of published research in the neuroendocrine setting over the last 5 years, which partially reflects the current distributions in this field, taking into account that several specialties with different gender distribution are involved. However, senior authorship continues to be primarily men. Efforts should be made to improve proportionate gender representation in both clinical and academic/research setting.

Targeting neuroendocrine tumors with octreotide and lanreotide: Key points for clinical practice from NET specialists.

Octreotide and lanreotide are the two somatostatin analogs (SSA) currently available in clinical practice. They have been approved first to control the clinical syndrome (mainly carcinoid syndrome) associated with functioning neuroendocrine tumors (NET) and later for tumor growth control in advanced low/intermediate grade NET. Although evidence regarding their role, especially as antiproliferative therapy, has been increasing over the years some clinical indications remain controversial. Solicited by AIOM (Italian Association of Medical Oncology) a group of clinicians from various specialties, including medical oncology, endocrinology, and gastroenterology, deeply involved in NET for their clinical and research activity, addressed eight open questions, critically reviewing evidence and guidelines and sharing clinical take-home messages. The questions regarded the use of long-acting octreotide and lanreotide in the following settings: functioning and non-functioning NET refractory to label dose, first-line metastatic pulmonary NET, combination with other therapy with an antiproliferative intent, maintenance in NET responding to other therapies, adjuvant treatment, Ki-67-related cut-off, somatostatin receptor imaging, safety, and feasibility. The level of evidence is not absolute for the majority of these clinical contexts, so it is recommended to distinguish routine versus sporadic utilization in very selected cases. Mention of such specific issues by the main European guidelines (ENETS, European Neuroendocrine Tumor Society, and ESMO, European Society for Medical Oncology) was explored and their position reported. However, different clinical decisions on single patients could be made if the case is carefully discussed within a NET-dedicated multidisciplinary team.

Sporadic and MEN1-related gastrinoma and Zollinger-Ellison syndrome: differences in clinical characteristics and survival outcomes.

PURPOSE: Gastrinoma with Zollinger-Ellison syndrome (ZES) may occur sporadically (Sp) or as part of the inherited syndrome of multiple endocrine neoplasia 1 (MEN-1). Data comparing Sp and MEN-1/ZES are scanty. We aimed to identify and compare their clinical features. METHODS: Consecutive patients with ZES were evaluated between 1992 and 2020 among a monocentric Italian patient cohort. RESULTS: Of 76 MEN-1 patients, 41 had gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), 18 of whom had ZES; of 320 Sp-GEP-NEN, 19 had Sp-ZES. MEN-1/ZES patients were younger (p = 0.035) and the primary MEN-1/ZES gastrinoma was smaller than Sp-ZES (p = 0.030). Liver metastases occurred in both groups, but only Sp-ZES developed extrahepatic metastases. 13 Sp-ZES and 8 MEN-1/ZES underwent surgery. 8 Sp-ZES and 7 MEN-1/ZES received somatostatin analogs (SSAs). Median overall survival (OS) was higher in MEN-1/ZES than in Sp-ZES (310 vs 168 months, p = 0.034). At univariate-logistic regression, age at diagnosis (p = 0.01, OR = 1.1), G3 grading (p = 0.003, OR = 21.3), Sp-ZES (p = 0.02, OR = 0.3) and presence of extrahepatic metastases (p = 0.001, OR = 7.2) showed a significant association with OS. At multivariate-COX-analysis, none of the variables resulted significantly related to OS. At univariate-logistic regression, age (p = 0.04, OR = 1.0), size (p = 0.039, OR = 1.0), G3 grade (p = 0.008, OR = 14.6) and extrahepatic metastases (p = 0.005, OR = 4.6) were independently associated with progression-free survival (PFS). In multivariate-COX-analysis, only extrahepatic metastases (p = 0.05, OR = 3.4) showed a significant association with PFS. Among SSAs-treated patients, MEN-1/ZES showed better PFS (p = 0.0227). After surgery, the median PFS was 126 and 96 months in MEN-1 and Sp, respectively. CONCLUSION: MEN-1/ZES patients generally show better OS and PFS than Sp-ZES as well as better SSAs response.

Second primary neoplasms in patients with lung and gastroenteropancreatic neuroendocrine neoplasms: Data from a retrospective multi-centric study.

BACKGROUND: Patients with sporadic neuroendocrine neoplasms may exhibit a higher risk of a second primary tumor than the general population. AIM: This study aimed to analyze the occurrence of second primary malignancies. METHODS: A retrospective cohort of 2757 patients with sporadic lung and gastro-entero-pancreatic neuroendocrine neoplasms, managed at eight Italian tertiary referral Centers, was included. RESULTS: Between 2000 and 2019, a second primary malignancy was observed in 271 (9.8%) neuroendocrine neoplasms patients with 32 developing a third tumor. There were 135 (49.8%) females and the median age was 64 years. The most frequent locations of the second tumors were breast (18.8%), prostate (12.5%), colon (9.6%), blood tumors (8.5%), and lung (7.7%). The second primary tumor was synchronous in 19.2% of cases, metachronous in 43.2%, and previous in 37.6%. As concerned the neuroendocrine neoplasms, the 5- and 10-year survival rates were 87.8% and 74.4%, respectively. PFS for patients with a second primary malignancy was shorter than for patients without a second primary malignancy. Death was mainly related to neuroendocrine neoplasms. CONCLUSION: In NEN patients the prevalence of second primary malignancies was not negligible, suggesting a possible neoplastic susceptibility. Overall survival was not affected by the occurrence of a second primary malignancy.

Risk of preoperative understaging of duodenal neuroendocrine neoplasms: a plea for caution in the treatment strategy.

PURPOSE: Pretreatment staging is the milestone for planning either surgical or endoscopic treatment in duodenal neuroendocrine neoplasms (dNENs). Herein, a series of surgically treated dNEN patients was evaluated to assess the concordance between the pre- and postsurgical staging. METHODS: Retrospective analysis of patients with a histologically confirmed diagnosis of dNENs, who underwent surgical resection observed at eight Italian tertiary referral centers. The presurgical TNM stage, based on the radiological and functional imaging, was compared with the pathological TNM stage, after surgery. RESULTS: From 2000 to 2019, 109 patients were included. Sixty-six patients had G1, 26 a G2, 7 a G3 dNEN (Ki-67 not available in 10 patients). In 46/109 patients (42%) there was disagreement between the pre- and postsurgical staging, being it understaged in 42 patients (38%), overstaged in 4 (3%). As regards understaging, in 25 patients (22.9%), metastatic loco-regional nodes (N) resulted undetected at both radiological and functional imaging. Understaging due to the presence of distal micrometastases (M) was observed in 2 cases (1.8%). Underestimation of tumor extent (T) was observed in 12 patients (11%); in three cases the tumor was understaged both in T and N extent. CONCLUSIONS: Conventional imaging has a poor detection rate for loco-regional nodes and micrometastases in the presurgical setting of the dNENs. These results represent important advice when local conservative approaches, such as endoscopy or local surgical excision are considered and it represents a strong recommendation to include endoscopic ultrasound in the preoperative tools for a more accurate local staging.

Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids.

BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS: Bibliographical searches were carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review of the relevant literature was carried out, followed by expert review. RESULTS: PCs are well-differentiated neuroendocrine tumors and include low- and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs, but pathology examination is mandatory for their correct classification. Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease. Plasma chromogranin A can be increased in PCs. Surgery is the treatment of choice for PCs with the aim of removing the tumor and preserving as much lung tissue as possible. Resection of metastases should be considered whenever possible with curative intent. Somatostatin analogs are the first-line treatment of carcinoid syndrome and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however, temozolomide has shown most clinical benefit. CONCLUSIONS: PCs are complex tumors which require a multidisciplinary approach and long-term follow-up.

The additional values of microarray allergen assay in the management of polysensitized patients with respiratory allergy.

BACKGROUND: The IgE response is directed against specific components from an allergenic source. The traditional diagnostic methods use whole extracts, containing allergenic, nonallergenic and cross-reactive molecules. This may pose diagnostic challenges in polysensitized patients. Microarray techniques detect specific IgE against multiple molecules, but their value in term of additional information and economic saving has not been yet defined. OBJECTIVE: We assessed the additional diagnostic information provided by an allergen microarray in a large population of polysensitized subjects. METHODS: In this multicentre study, allergists were required to carefully record diagnosis and treatment of consecutive patients referred for asthma/rhinitis, using the standard methodology (history, skin prick test, IgE assay). Then, a microarray allergen assay was carried out. Clinicians were required to review their diagnosis/treatment according to microarray results. RESULTS: 318 allergic patients (30% reporting also nonrespiratory symptoms) and 91 controls were enrolled. The clinicians reported at least one additional information from the microarray in about 60% of patients, this resulting in therapeutic adjustments. In 66% of patients IgE to pan-allergens were detectable, being this clinically relevant in 38% of patients with polysensitization to pollens. CONCLUSION: Microarray IgE assay represents an advancement in allergy diagnosis, as a third-level approach in polysensitized subjects, when the traditional diagnosis may be problematic.

Sensitization profiles in polysensitized patients from a restricted geographical area: further lessons from multiplexed component resolved diagnosis.

BACKGROUND: The micro-array techniques for the detection of specific IgE has improved the diagnostic procedures for allergic diseases. This method also allows to define sensitisation profiles from an epidemiological point of view. We studied the sensitisation pattern in a population of polysensitized patients with respiratory allergy, living in a restricted geographical area in the north-west Italy. METHODS: Consecutive patients with asthma/rhinitis, living in the province of Cuneo, and having at least two positive skin prick test for non related aeroallergens were studied by a microarray (Phadia, Milan Italy) which allowed to detect specific IgE against 103 different allergen components. RESULTS: The 70 patients included had specific IgE towards a mean of 4.3 allergens/patient (range 2-12 allergens). Concerning pollens, 63 (90%) had specific IgE to at least one genuine grass pollen allergen, 32 (45.7%) had Ole e 1 specific IgE antibodies, although olive tree is not present in the area. A relevant percentage of sensitisation to mite was found (47,1%). True co-sensitisation to grass-pollen allergens/Bet v 1/Ole e 1 was observed in 15 individuals (21.4%). Prup 1, resulted to be a sensitising allergen in 23 patients (32.85%), 4 of whom were co-sensitised to Prup 3 and/or Art v 3. CONCLUSION: A detailed knowledge of the sensitisation pattern may have relevant implications for the prescription of specific immunotherapy. Moreover, sensitisation to PR-10 (or profilin), frequently associated to oral allergy syndrome, in some cases could hide the sensitisation to LTPs which are clinically more relevant.

Unreliable measurement of basophil maximum leukotriene release with the Bühlmann CAST 2000 enzyme-linked immunosorbent assay kit.

The Bühlmann CAST 2000 enzyme-linked immunosorbent assay is a potentially useful assay for measuring sulfidoleukotrienes released in vitro by allergen-challenged basophils. However, we observed that the positive-control reagent yielded positive signals in cell-free systems. These false-positive results depended on using a mouse anti-FcepsilonRI monoclonal antibody and were prevented by degranulation-inducing reagents other than mouse monoclonal antibodies.

Possible relationship between systemic side effects and sensitization to rPar j 2 in allergic patients submitted to an ultra-rush (20 min) sublingual immunotherapy and selected by component resolved diagnosis.

BACKGROUND: The pollen of Parietaria spp., a weed of the Urticaceae family, is a major cause of respiratory allergy in the Mediterranean area, where the most common species are Parietaria judaica and Parietaria officinalis. In this study, we evaluated the specific serum IgE-binding profiles to individual P. judaica pollen recombinant major allergen, and Phleum pratense cytoskeletal profilin and a 2-EF-hand calcium-binding allergen homologous to cross-reactive Parietaria pollen allergens, in patients allergic to pollen with positive skin test towards Parietaria spp. extract. METHODS: The present observation included 220 patients from the province of Cuneo, north-west Italy, all suffering from rhino-conjunctivitis and/or asthma selected on the basis of skin test positive to P. judaica extract. The sera were evaluated for specific IgE reactivity to P. judaica pollen major recombinant(r) allergen Par j 2, Phleum pratense pollen allergens rPhl p 7 (2-EF-hand calcium binding protein) and rPhl p 12 (profilin), both identified as cross-reactive Parietaria spp. allergens, using Pharmacia CAP System. Out of 220 patients, 37 patients with IgE reactivity to rPar j 2 and 105 patients sensitized to at least one timothy pollen major allergen (i. e. rPhl p 1, rPhl p 2, natural Phl p 4 and rPhl p 6) were submitted to an ultra-rush protocol of sublingual immunotherapy (SLIT). The occurrence of adverse reactions were evaluated in both groups. RESULTS: All 220 patients with pollinosis and positive in vivo skin prick tests had in vitro positive CAP results to P. judaica natural extract. On the contrary, in these patients the prevalence of Par j 2-specific IgE was only 33.2% (73/220). In fact, 116/220 (52.7%) patients with serum specific IgE to crude Parietaria pollen extract had specific IgE to Phl p 12, 18/220 (8.1%) subjects with specific IgE to rPhl p 12 also exhibited specific IgE to Phl p 7 and 26/220 (11.8%) subjects had specific IgE against rPhl p 7. Particularly, geometric mean (25th-75th percentile) of specific IgE to rPar j 2 were as follows: 2.87 kUA/l (1.005-7.465). Out of 73 patients with specific IgE to rPar j 2, 7 subjects (9.6%) had also specific IgE to rPhl p 7, 12 (16.4%) had specific IgE to rPhl p 12 and 4 (4.1%) patients had specific IgE to both recombinant allergens. Of 37 patients under an ultra-rush protocol of SLIT, 3 subjects (8.1%) experienced generalized urticaria, and 1 of them also had diarrhea 3 h after the last dose of Parietaria judaica extract oral-vaccine administration. On the contrary, no systemic reactions were observed in 105 patients after Phleum pratense extract oral intake after a similar ultra-rush SLIT protocol (p = 0.0046). CONCLUSIONS: In the light of present findings, allergen extract-based diagnosis, in vivo and in vitro, cannot discriminate allergic patients that are genuinely sensitized to Parietaria spp. major allergens or to other major allergens to which current immunotherapeutic allergy extracts are standardized. Therefore, in vitro component resolved diagnosis is the unique tool to define the disease eliciting molecule(s). Finally, during sublingual immunotherapy, not only the dose of allergen, but also the biochemical characteristic of the major allergen administered may be an important factor in determining possible systemic reactions.

A pilot study of feasibility of ultra-rush (20-25 minutes) sublingual-swallow immunotherapy in 679 patients (699 sessions) with allergic rhinitis and/or asthma.

Few studies have evaluated the occurrence of immediate adverse reactions in allergic patients after an ultra-rush regimen of different commercial allergen extracts for sublingual immunotherapy (SLIT) Methods: 679 patients took part in trials of specific ultra-rush SLIT for the treatment of IgE-mediated rhinitis and/or IgE-mediated asthma. 14 patients received two different sublingual allergen vaccines during two distinct SLIT sessions. On the whole, 699 SLIT sessions were performed. The build up ultrarush phase involved the administration every five minutes of increasing doses of either different allergen extracts. The cumulative allergen extract solution after half an hour was several times the dose administered at the start of subcutaneous immunotherapy (range 4.7-525 microg of major allergens). All patients tolerated the treatment very well. 122 (17.96%) had mild local symptoms (pruritus of the buccal cavity) that spontaneously disappeared with increasing dose. Two patients allergic to Parietaria had urticaria about three hours after the last sublingual Parietaria-extract intake. A subject allergic to Artemisia vulgaris pollen had urticaria and rhinitis two hours later than the last dose of vaccine. As reported in our previous study, no immediate severe adverse reactions were observed after that rapidly increasing doses of allergen extract were administered in a very short period to a large number of patients, showing the excellent safety profile of ultra-rush SLIT.

Evaluation of recombinant and native timothy pollen (rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4)- specific IgG4 antibodies induced by subcutaneous immunotherapy with timothy pollen extract in allergic patients.

BACKGROUND: Allergen immunotherapy is a widely accepted treatment for IgE-mediated allergies. The evaluation of immunotherapy-induced IgG4 antibodies based on allergen extract is questionable because the amount of allergen-extract-specific IgG4 to individual disease-eliciting allergens cannot be determined using crude allergen extracts. In this study, we examined the specific IgE and IgG4 serum binding profiles to individual Phleum pratense allergens in grass-pollen-sensitive patients who had received grass-pollen-specific immunotherapy (SIT). METHODS: The study included 33 patients from North-West Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. A modified "cluster" regimen of injections of a standardized aluminium-adsorbed P.pratense extract, with once-weekly visits and 10 injections for 5 weeks followed by 3 weeks of maintenance injections was instituted. Patients' sera were analyzed for specific IgE and IgG4 reactivity to individual P. pratense allergens (recombinant Phl p 1, Phl p 2, Phl p 5, Phl p 6, Phl p 7, Phl p 11, Phl p12 and native Phl p 4) and natural P. pratense extract using the Pharmacia CAP system. RESULTS: IgE reactivities to new allergen components were not detected by CAP in treated patients after 15 weeks and a cumulative dose of approximately 65 microg of the major allergen Phl p 5. Patients lacking specific IgE reactivity towards individual allergens at the start of SIT did not produce significant levels of specific serum IgG4 to serum IgE-negative allergens. On the other hand, an increase in specific IgG4 only to allergens to which patients were previously sensitized was observed. Significant increases in specific IgG4 levels to rPhl p 1 (p < 0.05), 2 (p < (0.01), 5 (p < 0.0001), 6 (p < 0.0001), 7 (p < 0.05), 11 (p < 0.05) and nPhl p 4 (p < 0.01) were observed after P. pratense extract immunotherapy. No significant rPhl p 12-specific IgG4 antibody increase was documented after treatment. CONCLUSION: These findings suggest that Phl p 12 was underrepresented in the extract used, as indicated by the low specific IgG4 response induced by this grass-pollen-specific vaccine. Thus, the simple detection of specific serum IgG4 antibodies a few weeks after the start of SIT could represent a valuable tool to estimate the presence of relevant allergens in a given immunotherapeutic allergen extract.

Detection of specific IgE antibodies in the sera of patients allergic to birch pollen using recombinant allergens Bet v 1, Bet v 2, Bet v 4: evaluation of different IgE reactivity profiles.

BACKGROUND: Birch pollen is a significant cause of immediate hypersensitivity among susceptible subjects in temperate climates, affecting 5-54% of the population in western Europe. We examined the specific serum IgE antibodies towards recombinant allergens Bet v 1, Bet v 2 and Bet v 4 in birch-sensitive patients from the province of Cuneo, north-west Italy. METHODS: Sera were obtained from 372 patients with symptomatic birch pollen-induced allergic rhinitis and/or asthma. A subgroup of these patients suffered from oral allergy syndrome after eating apple. Their sera were evaluated for specific IgE against natural birch pollen and apple extract, as well as Bet v 1, Bet v 2 and Bet v 4 using Pharmacia CAP system (Pharmacia, Uppsala, Sweden). RESULTS: Of 372 patients 215 (57.80%) had serum-specific IgE towards Bet v 1. A total of 166 sera (44.62%) contained serum-specific IgE to Bet v 2, while Bet v 4 IgE reactivity was documented in 35 subjects (9.41%). Moreover, 146 (39.25%) patients were monosensitized to Bet v 1; 96 (25.81%) patients were monosensitized to Bet v 2; only four sera (1.08%) contained specific IgE towards Bet v 4. Thirty-nine sera (11.02%) did not contain specific IgE to these individual birch pollen allergens. Of course, all 372 sera (100%) had specific IgE against natural birch pollen extract, of which 162 (43.55%) contained specific IgE to apple extract (75.35% of Bet v 1 positive sera). CONCLUSION: In this study we observed that three birch pollen recombinant allergens alone, could sufficiently identify 90% of birch pollen-sensitive patients. Therefore, for a more precise IgE profile of patients allergic to birch, further purified birch pollen allergens (i.e. Bet v 6, Bet v 7, Bet v 8) will be required.

Vertebroplasty in the treatment of vertebral tumors: postprocedural outcome and quality of life.

The results of percutaneous vertebroplasty with polymethylmethacrylate (PMMA) of vertebral metastases were evaluated by a retrospective review of a consecutive series of 21 patients, with special reference to functional outcome. Patients complained of vertebral pain in all cases. Walking was impossible for 13 patients. Ten patients presented neurological deficit. Treatment included percutaneous vertebroplasty in all patients, radiotherapy in 15 patients and neural decompression surgery in 3 patients. Mean duration of hospitalization was 14.1 days (range 2-60 days) and the mean follow-up was 5.6 months (range 1-18 months). Preprocedural pain, measured by the visual analog scale (VAS), was 9.1, decreasing to 3.2 after the procedure and 2.8 at the last follow-up visit. Morphinics were discontinued in 7 of 14 patients following discharge from hospital. Ten out of 13 (77%) patients recovered walking capacity. Neurological status improved in three out of five patients. No further vertebral compression occurred in the vertebrae treated. Overall, 81% of the patients in this study were satisfied or very satisfied with the procedure. One patient (5%) had transitory radicular neuritis after the procedure. No major complications were observed. In conclusion, percutaneous vertebroplasty with PMMA proved to be safe and beneficial, providing significant and early improvement in the functional status of patients with spinal metastasis.

Percutaneous vertebroplasty: long-term clinical and radiological outcome.

We assessed radiographic and functional outcome in 13 patients with a minimum of 5 years follow-up from a prospectively monitored series of 17 patients who underwent percutaneous vertebroplasty (PPV). A visual analogue scale (VAS) and the short McGill questionnaire (MPQ) were used to assess average symptoms. The VAS showed significant improvement after treatment: the initial score was 9.07+/-0.6 (mean+/-SD), falling to 2.07 (1.14) on the third day, 1.07 (1.07) by the third month and 2.15 (2.6) at 5 years. Pain reduction was statistically significant ( P<0.001). The MPQ showed a significant improvement after treatment ( P<0.001), but had worsened by the last follow-up. All patients were "very" or "somewhat satisfied" with the procedure. We saw no further collapse of the vertebrae injected or migration or changes in the shape of the cement. A new fracture was seen in three patients, affecting four vertebrae, only two of which were adjacent to the treated level. On CT following the procedure, there was cement in the epidural veins adjacent to the vertebra in 48% of cases, but only patient developed a transitory neuritis.

Measurement of IgE antibodies against purified grass-pollen allergens (Phl p 1, 2, 3, 4, 5, 6, 7, 11, and 12) in sera of patients allergic to grass pollen.

BACKGROUND: Current allergy diagnosis is performed with allergen extracts which contain a variety of allergenic and nonallergenic components. The availability of highly purified and well-characterized allergen molecules seems to be an advantage of component-based diagnosis. METHODS: With the immunoenzymatic CAP FEIA System, we measured specific IgE levels to the recombinant allergens rPhl p 1, rPhl p 2, rPhl p 5, rPhl p 6, rPhl p 7, rPhl p 11, rPhl p 12, and native Phl p 4 in 77 sera of patients allergic to grass pollen, in order to evaluate the IgE-binding frequency to these purified grass-pollen allergens and their relationship to rBet v 4, rBet v 2, and other allergens. RESULTS: The frequency of sensitization was as follows: rPhl p 1=93.5%; rPhl p 2=67.5%; rPhl p 5=72.7%; rPhl p 6=68.8%; rPhl p 7=7.8%; rPhl p 11=53.2%; rPhl p 12=35.1%; and native Phl p 4=88.3%. As expected, rPhl p 7 and rPhl p 12 had a very good correlation (Spearman's r) with Bet v 4 (r=0.95%, P<0.05) and rBet v 2 (r=0.99, P<0.05), respectively. Good correlations of rPhl p 12 with papain (r=0.93, P<0.05), latex (r=0.92, P<0.05), and bromelain (r=0.86, P<0.05) were found. Highly variable individual sensitization patterns were observed. CONCLUSIONS: A new clinical approach has allowed the determination of specific allergograms for the different patients and may therefore be of great importance for more specific diagnosis. The use of component-resolved diagnostics may be useful to evaluate the allergen content of an extract for immunotherapy by monitoring patient's IgE and IgG directed to relevant allergens.

Evaluation of IgE antibodies to recombinant pollen allergens (Phl p 1, Phl p 2, and Phl p 5) in a random sample of patients with specific IgE to Phleum pratense.

BACKGROUND: We measured specific IgE levels against the recombinant allergens (RAs) rPhl p 1, rPhl p 2, and rPhl p 5 in patients allergic to grass pollen, and examined the existence of different patterns of IgE production to RAs. The seasonal variations of IgE levels to rPhl p 1, rPhl p 2, and rPhl p 5 were considered, too. METHODS: Blood was taken from 276 consecutive patients with allergy to grass pollen diagnosed by patient history and skin prick testing. Total and specific serum IgE was measured by the immunoenzymatic CAP FEIA System. Eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were assessed by radioimmunoassay according to the instructions of the manufacturers. RESULTS: We observed eight different patterns of IgE production to rPhl p 1, rPhl p 2, and rPhl p 5 in patients with specific IgE to timothy grass. A significant difference between the values of IgE levels to timothy and the sum of each level of specific IgE to individual RAs was found (P = 0.039, Wilcoxon matched pairs test) in the whole population (n = 276 subjects). In four subgroups of patients, the sum of each level of specific IgE to individual RAs was equal to the levels of specific IgE to timothy grass extract. In one subgroup, the sum of IgE to RAs was lower than the levels of IgE to the natural counterpart (P = 0.013). A lack of subjects in two subgroups did not permit comparison at all. Finally, three subjects with specific IgE to timothy did not show specific IgE to RAs. Out of 276 patients, blood was taken from two different groups of subjects at different time points: November-January and May-July, respectively. The median values were as follows: total IgE = 139 kU/l, IgE to timothy = 10.2 kUA/l; IgE to rPhl p 1 = 3.6 kUA/l, to rPhl p 2 = <0.35 kUA/l, and to rPhl p 5 = 1.1 kUA/l; ECP = 8.25 microg/l; MPO = 303.08 microg/l (before exposure to grass pollen); total IgE = 159 kU/l, IgE to timothy = 57.2 kUA/l; IgE to rPhl p 1 = 22.1 kUA/l, to rPhl p 2 = 5.9 kUA/l, and to rPhl p 5 = 3.9 kUA/l; ECP = 16.21 microg/l; MPO = 413.09 microg/l (during the pollen season). There were significant variations of specific IgE levels between the patients exposed to pollen and the unexposed patients. Moreover, there were statistical differences in the IgE, ECP, and MPO levels in sera before and during the pollen season P<0.035, P<0.017, and P<0.0062, respectively. CONCLUSIONS: The results suggest that RAs allow establishment of the patient's IgE-reactivity profile, encourage future research, and encourage manufacturers to produce further RAs for precise diagnosis and substantially improved immunotherapy injection of only those allergens against which significant amounts of specific IgE are produced.

A comparative study of the tryptase release test and the cellular allergen stimulation test (CAST) in mite sensitive patients.

BACKGROUND: The stimulation of blood basophils to release mediators in vitro is widely used for diagnosis of allergic diseases. Tryptase release and sulphidopeptideleukotriene production are both triggered by cross-bridging of adjacent IgE molecules on the surface of IgE-bearing basophils. OBJECTIVE: We have compared the sensitivity of tryptase release test (TRT) and cellular allergen stimulation test (CAST) which, respectively, measure tryptase and sulphidopeptideleukotrienes that are produced upon cell stimulation by mite extracts. METHODS: Blood was taken from 247 patients with allergy to mites and 137 non-allergic control subjects. We measured tryptase release from basophils after allergen challenge in vitro by sandwich radioimmunoassay. The sulphidopeptideleukotrienes production was quantified by an ELISA test based on a monoclonal antibody which recognized leukotriene T4 (LTC4) and its metabolites LTD4 and LTE4. RESULTS: Our data show that both methods are equally effective to distinguish allergic patients from normal controls (P > 0.0001). There was a significant correlation between mite-specific serum IgE and CAST results (r = 0.69 for Dermatophagoides pteronyssinus; r = 0.73 for Dermatophagoides farinae). Correlations between IgE against mites and tryptase values appeared rather poor (r = 0.47 for Dermatophagoides pteronyssinus; 0.49 for Dermatophagoides farinae). Moreover, the data were used for the calculation of sensitivity, specificity, prevalence, and overall efficiency (Roc/Galen & Gambino analysis). The results were as follows: 71%, 87%, 64%, 76% (CAST results for Dermatophagoides farinae); 64%, 78%, 53%, 70% (TRT results for Dermatophagoides farinae). CONCLUSION: The partial discrepancies observed could be interpreted as a consequence of conditions that were technically not optimal. False-positive results may be due to the action of some non-specific cytotoxic agent, false-negative results may be due to hyporesponsive basophils or the low number of cells participating in the reaction and finally, in the case of TRT, to G4 monoclonal antibody to tryptase employed.