The Severity and Frequency of Systemic Reactions to Hazelnut Are Significantly Higher in Hazelnut Allergic Patients Monosensitized to Cor a 8 than in Patients Polysensitized to Cor a 1, Cor a 8, and Cor a 9.

INTRODUCTION: Hazelnuts are a leading trigger of food allergy. To date, several molecular components of hazelnut are available for component-resolved diagnosis. However, little is known about how simultaneous sensitization to multiple allergens affects the severity of the hazelnut-induced reaction. In a previous study, our group demonstrated a lower risk of systemic reactions to peach in patients sensitized to both Pru p 3 and Pru p 1 than in the patient monosensitized to peach LTP. We aimed to assess whether this was also true in hazelnut allergy in a cohort of adult patients. METHODS: Patients were selected based on a history of symptoms such as urticaria, vomiting, diarrhea, asthma, and anaphylaxis indicative of hazelnut IgE-mediated food allergy and graded according to a clinical severity scale. For all patients, specific IgE was determined for Cor a 1 and Cor a 8 and, for most patients, also Cor a 9. Patients were offered an oral food challenge in open format (OFC) with a cocoa-based roasted hazelnut spread on a voluntary basis in order to prescribe an appropriate diet. RESULTS: A total of two hundred and fourteen patients were recruited. Among these, 43 patients were monosensitized to Cor a 8. One hundred and seventy-one patients were sensitized to Cor a 1 (79.9%), and, among them, 48/171 (28.1%) were also Cor a 8 positive. Cor a 9 was evaluated in 124/214 patients, testing positive in 21/124 (16.9%). Patients monosensitized to Cor a 8 experienced systemic reactions more frequently than those sensitized to Cor a 1 ± Cor a 8 (p < 0.00001), with significantly more severe reactions (p < 0.0005) and testing more frequently positive at OFC (p < 0.0001). Regarding Cor a 9, the sensitized patients were significantly younger (p = 0.0013) and showed reactions of similar severity to patients who tested Cor a 9 negative, and these reactions were milder than in patients monosensitized only to Cor a 8. DISCUSSION/CONCLUSION: Sensitization to Cor a 1 seems to protect from the development of the severe systemic reactions induced by Cor a 8 sensitization, Cor a 9 does not influence the severity of symptoms in adult patients. The OFC with roasted hazelnut may help in dietary guidance.

New stimulation procedures for language mapping in stereo-EEG.

OBJECTIVE: Cortical intracerebral electrical stimulation is an important tool for language mapping in the presurgical work-up of patients with drug-resistant focal epilepsy. Language mapping with stereo-electroencephalography (EEG) is usually performed by high-frequency stimulations (HFS: 50 Hz), whereas low-frequency stimulations (LFS: 1 Hz) are usually considered useful for primary cortices mapping. Little is known in literature about "intermediate" frequencies (IFS: 6-15 Hz). Our objective is to explore the clinical usefulness of IFS in language mapping and identify factors, beyond the electrical parameters, that impact the mapping. METHODS: We studied 23 patients submitted to stereo-EEG for presurgical evaluation. Language mapping was performed in the anterior, posterior and/or basal language region of the dominant hemisphere for language. We included all contact positions within these regions stimulated by HFS (50 Hz, 5 s, 1-3 mA) and IFS (6-15 Hz, 15 s, 5 mA). We compared the capability of both stimulation methods to induce a language deficit without afterdischarges (ADs), and we analyzed factors related to clinical examination, region, and stimulation technique by multivariate analysis. RESULTS: A total of 211 stimulations (98 HFS, 113 IFS) in 70 cortical sites within the anterior (84 stimulations), posterior (137), and basal language region (60) were included. IFS induced more frequently language deficits not associated to AD compared to HFS (37.1% vs 25.7%, p = .0043), whereas HFS provoked more diffuse AD (34.7% vs 15.0%, p = .001). Investigating multiple language functions increased the probability of revealing a deficit (odds ratio [OR] 3.16, p = .0016), independently of the stimulation method. SIGNIFICANCE: IFS are valuable for language mapping, thereby improving the probability of inducing a clinical deficit not accompanied by an AD. The completeness of the clinical examination independently affects the sensitivity of the mapping. IFS are a new tool with potential usefulness for the cortical mapping of other associative cortical regions.

Clinical Features of Wheat Allergy Are Significantly Different between Tri a 14 Sensitized Patients and Tri a 19 Sensitized Ones.

INTRODUCTION: Wheat is the most important cereal for human nutrition but its high consumption is associated to an increasing complaint of wheat-related disorders, many of which are allergic in nature and different in respect to the involved allergens. In this study, we compared the clinical aspects of wheat allergy presented by patients sensitized to Tri a 19 in respect to those presented by patients sensitized to Tri a 14. METHODS: With this aim, we selected patients sensitized to 1 or both of the 2 allergens, and among these we identified those who were really wheat allergic and reactive on the basis of a standardized methodology. We evaluated the clinical features such as the kind and severity of symptoms, the coexistence of triggering factors such as physical exercise and NSAIDs and alcohol consumption, and the association with other allergens and with various immunologic parameters. Wheat allergy in Tri a 19 sensitized patients was confirmed through a questionnaire while the patients sensitized to Tri a 14 underwent wheat challenge with 100 g of pasta followed by exercise on a treadmill. RESULTS: Seventy-nine patients sensitized to Tri a 14 and 40 patients sensitized to Tri a 19 were recruited. The 2 sensitizations were independent with a significant inverse relation (p < 0.00001). The Tri a 19 sensitized patients presented, in respect to the Tri a 14 sensitized ones, an older age (p = 0.0017), a higher risk to be wheat allergic (p < 0.0001), a higher severity of the reactions (p < 0.00001) and a higher association with some cofactors, namely alcohol (p < 0.0005) and physical exercise (p = 0.003). On the contrary, Tri a 14 sensitization was associated with atopy (p < 0.0001), with a higher probability of patients being asymptomatic (p < 0.0001) and being sensitized to other foods, in particular to nuts and cereals (p < 0.00001). CONCLUSIONS: Sensitization to Tri a 19 or Tri a 14 determines different clinical pictures. In particular, sensitization to Tri a 19 implies a higher probability of severe reactions, even dependent on daily triggers, while that to Tri a 14 implies a higher cross-reactivity with other foods but it's more frequently asymptomatic, making a food challenge necessary to prevent useless food avoidance.

Basal Tryptase High Levels Associated with a History of Arterial Hypertension and Hypercholesterolemia Represent Risk Factors for Severe Anaphylaxis in Hymenoptera Venom-Allergic Subjects over 50 Years Old.

INTRODUCTION: Allergy to Hymenoptera venom (HV) may lead to life-threatening anaphylaxis. Some of the factors influencing the symptom's severity are still undetermined. The aim of this study was to identify the clinical aspects associated with the most severe reactions in a population with HV allergy, by comparing clinical and immunochemical biomarkers between patients with previous local large reactions (LLRs) and systemic reactions (SRs). METHODS: We selected adult patients with a history of HV allergy, with positive diagnostic tests and a correlation with one single Hymenoptera species. Age, gender, atopy, serum basal tryptase (sBT) value, total IgE, venom-specific IgE, history of hypertension, cardiovascular diseases, and hypercholesterolemia were compared between patients with previous LLRs and SRs. RESULTS: 460 adult patients (381 SRs, 79 LLRs) were included. Age (p = 0.0097), male gender (p < 0.0001), arterial hypertension (p = 0.046), hypercholesterolemia (p = 0.009), and higher sBT levels (p = 0.0004) were significantly associated with severe reactions as independent variables. Moreover, considering the previous variables as risk factors, there was a significant and progressive increase in the odds of being Mueller III + IV as the number of positive variables increased. Patients with sBT ≥6.4 ng/mL adjusted for any of the positive variables had increased the risk of Mueller grade IV reaction (p < 0.0001). CONCLUSION: According to our results, older age, male gender, arterial hypertension, hypercholesterolemia, and increased levels of sBT ≥6.4 ng/mL are risk factors for severe anaphylaxis to HV in adults. Atopy and allergic asthma do not increase the risk of HV-induced SRs.

Nilotinib-induced bone marrow CD34+/lin-Ph+ cells early clearance in newly diagnosed CP-Chronic Myeloid Leukemia: Final report of the PhilosoPhi34 study.

Chronic Myeloid Leukemia is a clonal disorder characterized by the presence of the Ph-chromosome and the BCR-ABL tyrosine-kinase (TK). Target-therapy with Imatinib has greatly improved its outcome. Deeper and faster responses are reported with the second-generation TKI Nilotinib. Sustained responses may enable TKI discontinuation. However, even in a complete molecular response, some patients experience disease recurrence possibly due to persistence of quiescent leukemic CD34+/lin-Ph+ stem cells (LSCs). Degree and mechanisms of LSCs clearance during TKI treatment are not clearly established. The PhilosoPhi34 study was designed to verify the in-vivo activity and timecourse of first-line Nilotinib therapy on BM CD34+/lin-Ph+ cells clearance. Eighty-seven CP-CML patients were enrolled. BM cells were collected and tested for Ph+ residual cells, at diagnosis, 3, 6 and 12 months of treatment. FISH analysis of unstimulated CD34+/lin- cells in CCyR patients were positive in 8/65 (12.3%), 5/71 (7%), 0/69 (0%) evaluable tests, respectively. Per-Protocol analysis response rates were as follows: CCyR 95% at 12 months, MR4.5 31% and 46% at 12 and 36 months, respectively. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin- cells was performed on 30 patients at diagnosis and after, on 79 patients at diagnosis vs 12 months of nilotinib treatment vs 10 healthy subjects. Data demonstrated some genes significantly different expressed: NFKBIA, many cell cycle genes, ABC transporters, JAK-STAT signaling pathway (JAK2). In addition, a correlation between different expression of some genes (JAK2, OLFM4, ICAM1, NFKBIA) among patients at diagnosis and their achievement of an early and deeper MR was observed.

Role of Multiple Comorbidities and Therapies in Conditioning the Clinical Severity of DRESS: A Mono-Center Retrospective Study of 25 Cases.

DRESS/DiHS is a complex and potentially fatal drug reaction. Little is known about risk factors and elements that can help to identify patients with a severe reaction early. The aim of the study was to investigate those factors favoring the disease and its severity by analyzing the clinical conditions and therapies preceding the reaction. We conducted a retrospective analysis on patients admitted to our center between 2010 and 2020 who were discharged with a diagnosis of DRESS. We used the RegiSCAR diagnostic criteria. We defined the severity of DRESS using the criteria of Mizukawa et al. We included 25 patients (15 females) with a median age of 66 years. Skin involvement, eosinophilia, and liver injury were the most important aspects. Allopurinol was found to be the most involved drug. Reaction severity was significantly associated with the number of daily medications (p=0.0067) and an age of at least 68 years (p=0.013). In addition, 75% of severe cases had at least three comorbidities in history, and most of the severe cases were female. In our study the advanced age, the high number of comorbidities and home therapies, and the inflammatory state were found to be predisposing elements to the development of the disease and its severity.

Bacillus Calmette-Guerin vaccination Policy and Consumption of Ammonium Chloride-Enriched Confectioneries May Be Factors Reducing COVID-19 Death Rates in Europe.

BACKGROUND: The 2019 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continued into 2020, and the coronavirus disease-2019 (COVID-19) associated death toll increased. OBJECTIVES: To analyze COVID-19 death rates in European countries or regions to determine whether there was a significant association between bacillus Calmette-Guérin (BCG) vaccination policy and lower rates of COVID-19 related deaths. METHODS: Certain Northern European countries or regions had low death rates regardless of BCG policy. The authors assumed the consumption of foods containing salmiak (NH4Cl) was a common and peculiar cause of the reduced COVID-19 related death rates in these countries, because NH4Cl is a known lysosomotropic agent, which has been indicated to inhibit or prevent SARS-CoV infection. To check the possible effectiveness of salmiak consumption against COVID-19 related death, the authors used a linear regression model with the death rate as the dependent variable and BCG-policy and salmiak consumption score as independent variables. RESULTS: Using least squares regression and a robust standard error algorithm, the authors found a significant effect exerted by the independent variables (P < 0.0005 for BCG and P = 0.001 for salmiak). Salmiak score alone was significant (P = 0.016) when using least squares regression with robust error algorithm. CONCLUSIONS: The results seem to confirm an association between BCG-positive vaccination policy and salmiak consumption, and lower death rates from COVID-19. Implementing BCG vaccination policy and fortification of foods with salmiak (NH4Cl) may have a significant impact on the control of SARS-CoV epidemic.

The Strategic Alliance between Clinical and Molecular Science in the War against SARS-CoV-2, with the Rapid-Diagnostics Test as an Indispensable Weapon for Front Line Doctors.

Our work concerns the actual problem of spread of SARS- CoV-2 outbreak which requires fast and correct as possible answer. In current scenario, the need of rapid answer put away the imperative of proper methodology. We focus on the serogical immunoassay for diagnosis of Covid-19 as an important weapon not only for diagnostic purpose, but also for epidemiologic one. The right equilibrium between high speed, low cost and accuracy is obtained with easy-to-use decentralized point-of-care test as the colloidal gold-based immunochromatographic strip assay which detects IgM and IgG antibodies directed against SARS-CoV-2. As our aim is to evaluate the efficacy of Covid-19 rapid tests and of serological assays in real-life settings, we designed a research protocol aimed to establish how to use correctly these diagnostics, taking into account the different possible clinical and epidemiological scenarios.

Surgery in patients with childhood-onset epilepsy: analysis of complications and predictive risk factors for a severely complicated course.

OBJECT: To compare the occurrence of surgery-related complications in patients with childhood-onset focal epilepsy operated on in the paediatric or in the adult age. To investigate risk factors for surgery-related complications in the whole cohort, with special attention to age at surgery and severe morbidity. METHODS: A cohort of 1282 patients operated on for childhood-onset focal epilepsy was retrospectively analysed. Occurrence of surgery-related complications, including a severely complicated course (SCC: surgical complication requiring reoperation and/or permanent neurological deficit and/or death), was compared between patients operated on in the paediatric age (<16 year-old; 452 cases) and, respectively, in adulthood (≥16 year-old; 830 cases). The whole cohort of patients was also evaluated for risk factors for a SCC. RESULTS: At last contact (median follow-up 98 months), 74.5% of patients were in Engel's class I (78.0% of children and 73.0% of adults). One hundred patients (7.8%) presented a SCC (6.4% for children and 8.6% for adult patients). Postoperative intracranial haemorrhages occurred more frequently in adult cases. At multivariate analysis, increasing age at operation, multilobar surgery, resections in the rolandic/perirolandic and in insulo-opercular regions were independent risk factors for a SCC. CONCLUSIONS: Surgery for childhood-onset focal epilepsy provides excellent results on seizures and an acceptable safety profile at any age. Nevertheless, our results suggest that increasing age at surgery is associated with an increase in odds of developing severe surgery-related complications. These findings support the recommendation that children with drug-resistant, symptomatic (or presumed symptomatic) focal epilepsy should be referred for a surgical evaluation as early as possible after seizure onset.

Anti-Neutrophil Cytoplasmic Antibodies Positivity and Anti-Leukotrienes in Eosinophilic Granulomatosis with Polyangiitis: A Retrospective Monocentric Study on 134 Italian Patients.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis associated with asthma, anti-neutrophil cytoplasmic antibodies (ANCA) positivity, and tissue eosinophilia. OBJECTIVE: To describe the presenting clinical features, significant biochemical alterations, and also potential pathogenic factors in adult patients diagnosed in our Center over a period of >20 years. METHOD: A retrospective study of EGPA patients diagnosed from 1994 to 2019 at ASST Grande Ospedale Metropolitano Niguarda Ca' Granda, Milan (Italy), which was performed according to the 1990 American College of Rheumatology criteria and Chapel Hill Consensus Conference definition. A dataset was compiled, registering demographic and clinical features, biochemical analysis at onset, and also the therapies received 3 months prior to EGPA diagnose. Statistical analyses were subsequently conducted dividing patients in 2 groups based on ANCA positivity and comparing them. RESULTS: Two groups were clearly identified by ANCA serology and specific organ involvement in accordance with literature reports; however, our data underline for the first time the association between anti-leukotriene receptor antagonists (LTRAs) and ANCA positivity. The group of previously treated patients presents an OR of 6.42 to be ANCA positive. This finding could be attributed to an imbalanced stimulation of leukotriene receptors, inducing both mast cells activation and an increased neutrophil extracellular traps release from neutrophils. CONCLUSION: Despite the limitations of this retrospective study, the association between LTRAs and ANCA antibodies elucidates the mechanism by which innate immunity is directly involved in tolerance breakdown and autoantibodies production. Validation of our results with targeted studies could clarify the differences between ANCA-positive and ANCA-negative patients with important consequences on the use of some drug classes in the treatment of EGPA and asthmatic subjects.

Alternate use of thrombopoietin receptor agonists in adult primary immune thrombocytopenia patients: A retrospective collaborative survey from Italian hematology centers.

Sequential use of the TPO-RAs romiplostim and eltrombopag in ITP patients failing either agent was retrospectively evaluated to assess efficacy and impact of clinical characteristics on outcome. Patients were grouped into 5 categories: efficacy issues: 1st TPO-RA failure; loss of response; non-efficacy issues: platelet fluctuations; patient's preference; adverse event development. Either one TPO-RA sequence was analyzed at 3 month and at last follow-up. 106/546 patients on TPO-RA underwent switch and 65% achieved, regained or maintained a short- term response independent of switch sequence, gender or age; lower response rates were associated with lines of previous therapy; disease duration lowers probability to respond. Clinically, patients switched for efficacy issue did not differ from those switched for non-efficacy issues. Response was achieved/regained in 57.8% of patients switched for efficacy issues, the lowest response rates were observed in non-responders to 1st TPO-RA; 80% of patients switched for non-efficacy issues maintained a response. Platelet fluctuation resolved in 44.4%. Of the 49 patients evaluable for long-term outcome, 27 were in response on therapy; 16 discontinued the TPO-RA for reasons other than efficacy, while only 6 were non responders. We confirm the efficacy of TPO-RA switch; once achieved, response to the 2nd TPO-RA seems durable.

Mite-Induced Asthma and IgE Levels to Shrimp, Mite, Tropomyosin, Arginine Kinase, and Der p 10 Are the Most Relevant Risk Factors for Challenge-Proven Shrimp Allergy.

BACKGROUND: Shrimp sensitization is common in the general population, but the presence of symptoms is only moderately related to sensitization. A point still at issue is which in vivo and/or in vitro tests (food challenge, component-resolved diagnosis, house dust mite [HDM] sensitization) can help in distinguishing shrimp-allergic subjects from subjects that are sensitized but tolerant. METHODS: The aim of this study was to evaluate the role of IgE to the different shrimp and mite allergens in distinguishing shrimp challenge-positive from challenge-negative patients. Subjects with suspected hypersensitivity reactions to shrimp, positive skin prick tests (SPTs), and/or anti-shrimp IgE were submitted to open and double-blind placebo-controlled food challenges (DBPCFC). Specific IgE to shrimp, mites, and the recombinants rPen a 1, rDer p 1, 2, and 10 were tested using ImmunoCAP-FEIA. IgE immunoblotting was performed to identify the patients' allergenic profiles. RESULTS: In total, 13 out of 51 (25.5%) patients with reported reactions to shrimp were truly shrimp allergic (7 DBPCFC positive and 6 with documented severe reactions). These patients had significantly higher skin test wheal diameters than nonallergic patients, as well as higher levels of IgE to rPen a 1 and rDer p 10. HDM-induced asthma and the simultaneous presence of anti-nDer p 1, 2, and 10 IgE levels increased the risk of true shrimp allergy. CONCLUSION: Food challenge tests are mandatory for the diagnosis of shrimp allergy. Tropomyosin is associated with clinical reactivity. HDM-induced asthma and anti-mite IgE are risk factors for shrimp allergy.

A new tool for touch-free patient registration for robot-assisted intracranial surgery: application accuracy from a phantom study and a retrospective surgical series.

OBJECTIVE The purpose of this study was to compare the accuracy of Neurolocate frameless registration system and frame-based registration for robotic stereoelectroencephalography (SEEG). METHODS The authors performed a 40-trajectory phantom laboratory study and a 127-trajectory retrospective analysis of a surgical series. The laboratory study was aimed at testing the noninferiority of the Neurolocate system. The analysis of the surgical series compared Neurolocate-based SEEG implantations with a frame-based historical control group. RESULTS The mean localization errors (LE) ± standard deviations (SD) for Neurolocate-based and frame-based trajectories were 0.67 ± 0.29 mm and 0.76 ± 0.34 mm, respectively, in the phantom study (p = 0.35). The median entry point LE was 0.59 mm (interquartile range [IQR] 0.25-0.88 mm) for Neurolocate-registration-based trajectories and 0.78 mm (IQR 0.49-1.08 mm) for frame-registration-based trajectories (p = 0.00002) in the clinical study. The median target point LE was 1.49 mm (IQR 1.06-2.4 mm) for Neurolocate-registration-based trajectories and 1.77 mm (IQR 1.25-2.5 mm) for frame-registration-based trajectories in the clinical study. All the surgical procedures were successful and uneventful. CONCLUSIONS The results of the phantom study demonstrate the noninferiority of Neurolocate frameless registration. The results of the retrospective surgical series analysis suggest that Neurolocate-based procedures can be more accurate than the frame-based ones. The safety profile of Neurolocate-based registration should be similar to that of frame-based registration. The Neurolocate system is comfortable, noninvasive, easy to use, and potentially faster than other registration devices.

Femtograms of Interferon-γ Suffice to Modulate the Behavior of Jurkat Cells: A New Light in Immunomodulation.

Since interferon-γ (IFN-γ) tunes both innate and adaptive immune systems, it was expected to enter clinical practice as an immunomodulatory drug. However, the use of IFN-γ has been limited by its dose-dependent side effects. Low-dose medicine, which is emerging as a novel strategy to treat diseases, might circumvent this restriction. Several clinical studies have proved the efficacy of therapies with a low dose of cytokines subjected to kinetic activation, while no in vitro data are available. To fill this gap, we investigated whether low concentrations, in the femtogram range, of kinetically activated IFN-γ modulate the behavior of Jurkat cells, a widely used experimental model that has importantly contributed to the present knowledge about T cell signaling. In parallel, IFN-γ in the nanogram range was used and shown to activate Signal transducer and activator of transcription (STAT)-1 and then to induce suppressor of cytokine signaling-1 (SOCS-1), which inhibits downstream signaling. When added together, femtograms of IFN-γ interfere with the transduction cascade activated by nanograms of IFN-γ by prolonging the activation of STAT-1 through the downregulation of SOCS-1. We conclude that femtograms of IFN-γ exert an immunomodulatory action in Jurkat cells.

Endovascular treatment for acute ischemic stroke.

BACKGROUND: In patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed. METHODS: We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours after onset, to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Treatments were to be given as soon as possible after randomization. The primary outcome was survival free of disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death) at 3 months. RESULTS: A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate. CONCLUSIONS: The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-PA. (Funded by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367.).

Risk of Adverse Pregnancy Outcomes in Women with CKD.

CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; "general" combined outcome (preterm delivery, NICU, SGA); and "severe" combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4-5: "general" combined outcome, 34.1% versus 90.0%; "severe" combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a "baseline risk" for adverse pregnancy-related outcomes linked to CKD.

Anti-Amoxicillin Immunoglobulin E, Histamine-2 Receptor Antagonist Therapy and Mast Cell Activation Syndrome Are Risk Factors for Amoxicillin Anaphylaxis.

BACKGROUND: ß-Lactam antibiotics (mainly amoxicillin, AX) are the drugs that most frequently induce systemic drug allergy reactions. OBJECTIVE: We attempted to identify the risk factors associated with systemic reactions to AX. METHODS: All patients who were referred to our department for suspected hypersensitivity reactions to AX over a 6-month period were evaluated for anti-AX immunoglobulin E (IgE) levels and skin-test positivity for ß-lactams. Age, sex, concomitant diseases, therapies, total IgE, serum tryptase levels and signs and symptoms suggesting mast cell activation syndrome (MCAS) were analyzed in relation to the severity of the reaction in accordance with the Mueller classification. RESULTS: Sixty-seven patients were selected: 39 with mild reactions such as cutaneous or gastrointestinal symptoms (grades I and II) and 28 with severe systemic reactions (grades III and IV). Anti-AX IgE levels and total IgE were significantly higher in severe reactions than in mild ones (p < 0.00005, p = 0.0037). Treatment with histamine-2 receptor antagonists (anti-H2) was significantly related to severe reactions (p = 0.007). No significant correlations were found between the severity of the reactions and dyslipidemia or levels of angiotensin-converting enzyme and tryptase. CONCLUSION: Anti-AX IgE levels were the most significant immunological parameter distinguishing patients who presented with severe reactions to AX and those with mild reactions. Higher values of total IgE, the use of gastroprotective drugs and signs and symptoms suggesting an MCAS significantly increased the odds ratio of having a severe reaction. The risk of serious adverse reactions to AX increased in older patients and in males, but this trend was not significant.

Prognostic relevance of the flow cytometric count of medullar blasts in myelodysplastic syndromes.

OBJECTIVE: The medullar blast count is a milestone in the prognostic assessment in myelodysplastic syndromes (MDS). The optical microscopy (OM) may sometimes be inaccurate in this disease. The aim of this work is to test the flow immunocytometric (FCM) determinations of medullar immature cells (CD45(±) ) and the expression, among them, of CD33, CD34, and CD117 markers, for their prognostic relevance. METHODS: In a retrospective analysis of 98 patients affected by MDS, the IPSS was re-calculated by means of the FCM determination of blasts. Survival of patients at low or intermediate-1 IPSS risk was compared with the survival of patients at intermediate-2 or high IPSS risk. In the 64 cases with OM blast count lower than 5%, the survival of patients with the FCM count of medullar blasts ≤2% was compared with that of patients with FCM count >2%. RESULTS: Each single marker had a prognostic weight comparable to the optical blast count. The FCM blast count was particularly efficient in distinguishing the risk of having up to 2% or more than 2% of blasts in patients without OM excess of blasts. CONCLUSION: This method is interesting as prognostic tool, especially in patients without excess of blast.

Serum tryptase detected during acute coronary syndrome is significantly related to the development of major adverse cardiovascular events after 2 years.

BACKGROUND: One of the greatest challenges in cardiovascular medicine is to define the best tools for performing an accurate risk stratification for the recurrence of ischemic events in acute coronary syndrome (ACS) patients. METHODS: We followed 65 ACS patients enrolled in a previous pilot study for 2 years after being discharged, focusing on the occurrence of major adverse cardiovascular events (MACE). The relationship between serum tryptase levels on admission, SYNergy between percutaneous coronary intervention with the TAXUS drug-eluting stent and the cardiac surgery score (SX-score), cardiovascular complexity and MACE at 2 years follow-up were analyzed. RESULTS: The ACS population was divided in two groups: patients with MACE (n = 23) and patients without MACE (n = 42). The tryptase measurement at admission (T0) and at discharge (T3) and SX-score were higher in patients who experienced MACE than in those without (p = 0.0001, p < 0.0001 and p = 0.006, respectively). Conversely, we found no significant association between MACE and C-reactive protein (CRP), and between MACE and maximum level of high-sensitivity troponin (hs-Tn) values. Among all patients with MACE, 96% belonged to the group that presented with cardiovascular complexity at the beginning of ACS index admission (p < 0.0001). The predictive accuracy of serum tryptase for MACE at follow up set at the cut-off point of 4.95 ng/ml at T0 and of 5.2 ng/ml at T3. Interestingly, patients with both the above cut-off tryptase values at T0 and at T3 presented a 1320% increase in the odds of developing MACE (p < 0.0001). CONCLUSION: In ACS patients, serum tryptase measured during index admission is significantly correlated to the development of MACE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker.