Perceived surgical difficulty of mandibular third molar extraction. A comparative cross-sectional study of dentists with postgraduate qualification in oral surgery and maxillofacial surgeons in a Spanish subpopulation.

BACKGROUND: Mandibular third molar (MTM) extraction is one of the most frequently performed surgeries in the oral cavity. Establishing the level of surgical difficulty pre-operatively is an essential step to ensure correct treatment planning. In Spain, MTM extraction - especially in cases presenting greater difficulty - is normally performed by doctors specializing in oral and maxillofacial surgery, or by dentists with postgraduate qualifications in oral surgery. The present work set out to analyze the extent to which perceptions of surgical difficulty of the said intervention vary in relation to professional training. MATERIAL AND METHODS: This cross-sectional, descriptive, observational study took the form of a survey. Using a visual analog scale (VAS), participants evaluated both the perceived difficulty of 30 cases of MTM extraction described by means of digital panoramic radiographs and the perceived difficulty deriving from a series of factors conditioning MTM extraction. The results underwent statistical analysis with SPSS Statistics 28.0 software. Non-parametric tests (Mann Whitney test for independent samples and the Kruskal-Wallis test) were applied. RESULTS: A total of 213 surveys were available for analysis. Both groups awarded the greatest importance to clinical experience, followed by anatomical and radiographic factors, root morphology obtaining the highest score among anatomical factors (9.01±1.42), while proximity of the MTM to the inferior alveolar nerve was regarded as the least important anatomical factor (8.11±2.54). Significant differences were only found for patient age, whereby maxillofacial surgeons awarded this factor more importance than dentists. CONCLUSIONS: The different training received by dentists specialized in oral surgery and maxillofacial surgeons did not influence either perceptions of surgical difficulty of MTM extraction, or opinions as to the factors influencing surgical difficulty.

CT scan for early diagnosis of anastomotic leak after colorectal surgery: is rectal contrast useful?

BACKGROUND: Computed tomography (CT) scan with rectal contrast enema (RCE-CT) could increase the detection rate of anastomotic leaks (AL) in the early postoperative period following colorectal surgery, compared to CT scan without RCE. The aim of this study was to assess the benefit of RCE-CT for the early diagnosis of AL following colorectal surgery. METHODS: Patients who had a RCE-CT for suspected AL in the early postoperative period following colorectal surgery with anastomosis between January 2012 and July 2019 at the Dijon University Hospital were retrospectively included. All images were reviewed by two independent observers who were blinded to the original report. The reviewers reported for each patient whether an AL was present or not in each imaging modality (CT scan, then RCE-CT). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were then calculated to determine the diagnostic performance of each modality. RESULTS: One hundred and thirty-nine patients were included. RCE-CT had an increased NPV compared to CT scan (82% vs 77% (p = 0.02) and 84% vs 68% (p < 0.0001) for observers 1 and 2, respectively). RCE-CT had an increased sensitivity compared to CT scan (79% vs 48% (p < 0.0001) for observer 2). RCE-CT had a significant lower false-negative rate for both observers: 18% vs 23% (p = 0.02) and 16% vs 32% (p < 0.0001). CONCLUSIONS: RCE-CT improved the detection rates of AL in the early period following colorectal surgery. RCE-CT should be recommended when a CT scan is negative and AL is still suspected.

Exactly unitary discrete representations of the metaplectic transform for linear-time algorithms.

The metaplectic transform (MT), a generalization of the Fourier transform sometimes called the linear canonical transform, is a tool used ubiquitously in modern optics, for example, when calculating the transformations of light beams in paraxial optical systems. The MT is also an essential ingredient of the geometrical-optics modeling of caustics that we recently proposed. In particular, this application relies on the near-identity MT (NIMT); however, the NIMT approximation used so far is not exactly unitary and leads to numerical instability. Here, we develop a discrete MT that is exactly unitary, and approximate it to obtain a discrete NIMT that is also unitary and can be computed in linear time. We prove that the discrete NIMT converges to the discrete MT when iterated, thereby allowing the NIMT to compute MTs that are not necessarily near-identity. We then demonstrate the new algorithms with a series of examples.

Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Quinolones.

The consumption of quinolones as first-line treatment has increased in recent years, leading to an increase in the incidence of hypersensitivity reactions (HSRs) to this antibiotic group. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for effective clinical practice. The recommendations were drafted by an expert panel that reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to quinolones are immediate and severe. The risk for HSRs is higher in patients who report allergy to ß-lactams, moxifloxacininduced anaphylaxis, and immediate reactions than in patients who report reactions to quinolones inducing other symptoms. The usefulness of skin tests in diagnosing HSRs to quinolones is controversial, with sensitivity and specificity varying between studies. Most in vitro tests are produced in-house, with no validated commercial options. The basophil activation test has proven useful for diagnosing immediate reactions, albeit with diverse results regarding sensitivity. Drug provocation testing is currently the gold standard for confirming or excluding the diagnosis and for finding safe alternatives, although it is contraindicated in patients with severe reactions. Cross-reactivity between quinolones has proven controversial in several studies, with the lowest cross-reactivity reported for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternatives are available.

Spanish Society of Allergology and Clinical Immunology (SEAIC) Vision of Drug Provocation Tests.

The controlled drug provocation test (DPT) is currently considered the gold standard for the diagnosis of drug allergy. Adverse drug reactions (ADRs) are an increasingly common presenting complaint in both primary and specialized care. In Spain, ADRs are usually assessed via the allergology department, which rules out immunological mechanisms in up to 90% of cases. An adequate approach to ADRs clearly impacts the costs and efficacy of the treatments prescribed by other specialists. Consequently, if we did not use DPTs, patients would require more expensive, more toxic, and less effective treatments in many cases. In recent years, many new drugs have been developed. This document is intended to be a practical guideline for the management of DPTs according to the vision of the Spanish Allergology Society. The diagnostic work-up begins with a detailed clinical history. Skin tests are only useful for some medications, and in most cases the diagnosis can only be confirmed by DPT. Although cross-reactivity is common, DPTs can confirm the diagnosis and help to find an alternative drug. Programmed individualized patient management based on the type of drug to be studied and the patient´s comorbidities usually enables a solution to be found in most cases.

Bactericidal and fungicidal capacity of Ag2O/Ag nanoparticles synthesized with Aloe vera extract.

This research aims to provide an alternative eco-friendly way to obtain silver species and assess their bactericidal activity. This study reports the synthesis of Ag2O nanoparticles and Ag nanoparticles reduced with a green synthesis method, using a low-cost and commercial Aloe vera extract. The crystalline phases of Ag and Ag2O nanoparticles were analyzed by X-ray diffraction. The oxidation states for both species were determined by X-ray photoelectron spectroscopy. The optical properties of the material were studied through optical absorption, which resulted in well-defined band centered at 545 nm. This result is attributed to the morphology and size of the silver nanoparticles. In addition, antibacterial tests were performed on AgNPs biosynthesized with A. vera with the Kirby-Bauer protocol on Gram-negative and Gram-positive bacteria Escherichia coli and Staphylococcus aureaus, respectively. Moreover, antifungal tests were performed with various species from Candida.

The effects of advanced maternal age on T-cell subsets at the maternal-fetal interface prior to term labor and in the offspring: a mouse study.

Women who conceive at 35 years of age or older, commonly known as advanced maternal age, have a higher risk of facing parturition complications and their children have an increased risk of developing diseases later in life. However, the immunological mechanisms underlying these pathological processes have yet to be established. To fill this gap in knowledge, using a murine model and immunophenotyping, we determined the effect of advanced maternal age on the main cellular branch of adaptive immunity, T cells, at the maternal-fetal interface and in the offspring. We report that advanced maternal age impaired the process of labor at term, inducing dystocia and delaying the timing of delivery. Advanced maternal age diminished the number of specific proinflammatory T-cell subsets [T helper type 1 (Th1): CD4+ IFN-γ+ , CD8+ IFN-γ+ and Th9: CD4+ IL-9+ ], as well as CD4+ regulatory T cells (CD4+ CD25+ FoxP3+ T cells), at the maternal-fetal interface prior to term labor. Advanced maternal age also altered fetal growth and survival of the offspring in early life. In addition, infants born to advanced-age mothers had alterations in the T-cell repertoire but not in CD71+ erythroid cells (CD3- CD71+ TER119+ cells). This study provides insight into the immune alterations observed at the maternal-fetal interface of advanced-age mothers and their offspring.

The alarmin interleukin-1α causes preterm birth through the NLRP3 inflammasome.

Sterile intra-amniotic inflammation is a clinical condition frequently observed in women with preterm labor and birth, the leading cause of neonatal morbidity and mortality worldwide. Growing evidence suggests that alarmins found in amniotic fluid, such as interleukin (IL)-1α, are central initiators of sterile intra-amniotic inflammation. However, the causal link between elevated intra-amniotic concentrations of IL-1α and preterm birth has yet to be established. Herein, using an animal model of ultrasound-guided intra-amniotic injection of IL-1α, we show that elevated concentrations of IL-1α cause preterm birth and neonatal mortality. Additionally, using immunoblotting techniques and a specific immunoassay, we report that the intra-amniotic administration of IL-1α induces activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in the fetal membranes, but not in the decidua, as evidenced by a concomitant increase in the protein levels of NLRP3, active caspase-1, and IL-1ß. Lastly, using Nlrp3-/- mice, we demonstrate that the deficiency of this inflammasome sensor molecule reduces the rates of preterm birth and neonatal mortality caused by the intra-amniotic injection of IL-1α. Collectively, these results demonstrate a causal link between elevated IL-1α concentrations in the amniotic cavity and preterm birth as well as adverse neonatal outcomes, a pathological process that is mediated by the NLRP3 inflammasome. These findings shed light on the mechanisms underlying sterile intra-amniotic inflammation and provide further evidence that this clinical condition can potentially be treated by targeting the NLRP3 inflammasome.

Contraindications to intravenous thrombolysis in prehospital triage of thrombectomy candidates.

BACKGROUND AND PURPOSE: The existence of contraindications to intravenous thrombolysis (IVT) is considered a criterion for direct transfer of patients with suspected acute stroke to thrombectomy-capable centers in the prehospital setting. Our aim was to assess the utility of this criterion in a setting where routing protocols are defined by the Madrid - Direct Referral to Endovascular Center (M-DIRECT) prehospital scale. METHODS: This was a post hoc analysis of the M-DIRECT study. Reported contraindications to IVT were retrospectively collected from emergency medical services reports and categorized into late window, anticoagulant treatment and other contraindications. Final diagnosis and treatment rates were compared between patients with and without reported IVT contraindications and according to anticoagulant treatment or late window categories. RESULTS: The M-DIRECT study included 541 patients. Reported IVT contraindications were present in 227 (42.0%) patients. Regarding final diagnosis no significant differences were found between patients with or without reported IVT contraindications: ischaemic stroke (any) 65.6% vs. 62.1%, ischaemic stroke with large vessel occlusion (LVO) 32.2% vs. 28.3%, hemorrhagic stroke 15.4% vs. 15.6%, stroke mimic 18.9% vs. 22.3% respectively. Amongst patients with LVO, endovascular thrombectomy (EVT) was performed less often in the presence of IVT contraindications (56.2% vs. 74.2%). M-DIRECT-positive patients had higher rates of LVO and EVT compared with M-DIRECT-negative patients independent of reported IVT contraindications. CONCLUSIONS: Reported IVT contraindications alone do not increase EVT likelihood and should not be considered to determine routing in urban stroke networks.

Spanish Guidelines for Diagnosis, Management, Treatment, and Prevention of DRESS Syndrome.

BACKGROUND AND OBJECTIVE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. Objective: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided.

Technology at the service of surgery in a new technique of autotransplantation by guided surgery: a case report.

BACKGROUND: The aim of this case report was to use a surgical technique for autotransplantation of tooth using virtually planned 3D printed surgical templates for guided osteotomy preparation of the recipient of donor tooth. CASE PRESENTATION: An 18-year-old male patient received autotransplantation of the right mandibular third molar to replace an included right second molar. This procedure was based on guided implant surgery methods by superimposition of DICOM files and 3D data sets of the jaws. In order to design a 3D-printed template with the aid of a fully digital workflow; the third molar was conserved in PRGF during the surgical procedure and the tooth socket was prepared with a template and the help of a 3D-printed donor tooth copy in order to prevent iatrogenic damage to the donor tooth. This template and replica were manufactured using 3D-printing techniques. The transplanted tooth was placed in infra-occlusion and fixed with a suture splint and root canal therapy was performed 15 days later. The intervention was be accomplished by performing preplanned virtual transplantations with guided osteotomies to ensure accurate donor tooth placement in the new recipient site. The 24 months follow-up showed physiological clinical and radiologic results compatible with healing periradicular tissues. CONCLUSIONS: This approach enables the planning and production of a 3D printed surgical template using the latest diagnostic methods and techniques of guided implant surgery. These accurate virtually predesigned surgical templates and printed analogues of the donor tooth could facilitate autotransplantation, ensuring an atraumatic surgical protocol.

Fungal Planet description sheets: 1042-1111.

Novel species of fungi described in this study include those from various countries as follows: Antarctica, Cladosporium arenosum from marine sediment sand. Argentina, Kosmimatamyces alatophylus (incl. Kosmimatamyces gen. nov.) from soil. Australia, Aspergillus banksianus, Aspergillus kumbius, Aspergillus luteorubrus, Aspergillus malvicolor and Aspergillus nanangensis from soil, Erysiphe medicaginis from leaves of Medicago polymorpha, Hymenotorrendiella communis on leaf litter of Eucalyptus bicostata, Lactifluus albopicri and Lactifluus austropiperatus on soil, Macalpinomyces collinsiae on Eriachne benthamii, Marasmius vagus on soil, Microdochium dawsoniorum from leaves of Sporobolus natalensis, Neopestalotiopsis nebuloides from leaves of Sporobolus elongatus, Pestalotiopsis etonensis from leaves of Sporobolus jacquemontii, Phytophthora personensis from soil associated with dying Grevillea mccutcheonii. Brazil, Aspergillus oxumiae from soil, Calvatia baixaverdensis on soil, Geastrum calycicoriaceum on leaf litter, Greeneria kielmeyerae on leaf spots of Kielmeyera coriacea. Chile, Phytophthora aysenensis on collar rot and stem of Aristotelia chilensis. Croatia, Mollisia gibbospora on fallen branch of Fagus sylvatica. Czech Republic, Neosetophoma hnaniceana from Buxus sempervirens. Ecuador, Exophiala frigidotolerans from soil. Estonia, Elaphomyces bucholtzii in soil. France, Venturia paralias from leaves of Euphorbia paralias. India, Cortinarius balteatoindicus and Cortinarius ulkhagarhiensis on leaf litter. Indonesia, Hymenotorrendiella indonesiana on Eucalyptus urophylla leaf litter. Italy, Penicillium taurinense from indoor chestnut mill. Malaysia, Hemileucoglossum kelabitense on soil, Satchmopsis pini on dead needles of Pinus tecunumanii. Poland, Lecanicillium praecognitum on insects' frass. Portugal, Neodevriesia aestuarina from saline water. Republic of Korea, Gongronella namwonensis from freshwater. Russia, Candida pellucida from Exomias pellucidus, Heterocephalacria septentrionalis as endophyte from Cladonia rangiferina, Vishniacozyma phoenicis from dates fruit, Volvariella paludosa from swamp. Slovenia, Mallocybe crassivelata on soil. South Africa, Beltraniella podocarpi, Hamatocanthoscypha podocarpi, Coleophoma podocarpi and Nothoseiridium podocarpi (incl. Nothoseiridium gen. nov.) from leaves of Podocarpus latifolius, Gyrothrix encephalarti from leaves of Encephalartos sp., Paraphyton cutaneum from skin of human patient, Phacidiella alsophilae from leaves of Alsophila capensis, and Satchmopsis metrosideri on leaf litter of Metrosideros excelsa. Spain, Cladophialophora cabanerensis from soil, Cortinarius paezii on soil, Cylindrium magnoliae from leaves of Magnolia grandiflora, Trichophoma cylindrospora (incl. Trichophoma gen. nov.) from plant debris, Tuber alcaracense in calcareus soil, Tuber buendiae in calcareus soil. Thailand, Annulohypoxylon spougei on corticated wood, Poaceascoma filiforme from leaves of unknown Poaceae. UK, Dendrostoma luteum on branch lesions of Castanea sativa, Ypsilina buttingtonensis from heartwood of Quercus sp. Ukraine, Myrmecridium phragmiticola from leaves of Phragmites australis. USA, Absidia pararepens from air, Juncomyces californiensis (incl. Juncomyces gen. nov.) from leaves of Juncus effusus, Montagnula cylindrospora from a human skin sample, Muriphila oklahomaensis (incl. Muriphila gen. nov.) on outside wall of alcohol distillery, Neofabraea eucalyptorum from leaves of Eucalyptus macrandra, Diabolocovidia claustri (incl. Diabolocovidia gen. nov.) from leaves of Serenoa repens, Paecilomyces penicilliformis from air, Pseudopezicula betulae from leaves of leaf spots of Populus tremuloides. Vietnam, Diaporthe durionigena on branches of Durio zibethinus and Roridomyces pseudoirritans on rotten wood. Morphological and culture characteristics are supported by DNA barcodes.

BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases.

BACKGROUND: BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF-mutated CRLMs. METHODS: The study included patients who underwent resection for BRAF-mutated CRLMs in 24 centres between 2012 and 2016. A case-matched comparison was made with 183 patients who underwent resection of CRLMs with wild-type BRAF during the same interval. RESULTS: Sixty-six patients who underwent resection for BRAF-mutated CRLMs in 24 centres were compared with 183 patients with wild-type BRAF. The 1- and 3-year disease-free survival (DFS) rates were 46 and 19 per cent for the BRAF-mutated group, and 55·4 and 27·8 per cent for the group with wild-type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1- and 3-year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild-type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild-type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF-mutated group (48 versus 29·8 per cent; P = 0·034). CONCLUSION: These results support surgical treatment for resectable BRAF-mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non-metastatic colorectal cancer.

Nutritional and non-nutritional agents that stimulate white adipose tissue browning.

Obesity is a public health problem present in both developed and developing countries. The white adipose tissue (WAT) is the main deposit of lipids when there is an excess of energy. Its pathological growth is directly linked to the development of obesity and to a wide number of comorbidities, such as insulin-resistance, cardiovascular disease, among others. In this scenario, it becomes imperative to develop new approaches to the treatment and prevention of obesity and its comorbidities. It has been documented that the browning of WAT could be a suitable strategy to tackle the obesity epidemic that is developing worldwide. Currently there is an intense search for bioactive compounds with anti-obesity properties, which present the particular ability to generate thermogenesis in the brown adipose tissue (BAT) or beige. The present study provide recent information of the bioactive nutritional compounds capable of inducing thermogenesis and therefore capable of generate positive effects on health.

Pseudo-differential representation of the metaplectic transform and its application to fast algorithms.

The metaplectic transform (MT), also known as the linear canonical transform, is a unitary integral mapping that is widely used in signal processing and can be viewed as a generalization of the Fourier transform. For a given function $ \psi $ψ on an $ {N} $N-dimensional continuous space $ {\textbf q} $q, the MT of $ \psi $ψ is parameterized by a rotation (or more generally, a linear symplectic transformation) of the $ 2{N} $2N-dimensional phase space $ ({\textbf q},{\textbf p}) $(q,p), where $ {\textbf p} $p is the wavevector space dual to $ {\textbf q} $q. Here, we derive a pseudo-differential form of the MT. For small-angle rotations, or near-identity transformations of the phase space, it readily yields asymptotic differential representations of the MT, which are easy to compute numerically. Rotations by larger angles are implemented as successive applications of $ {K} \gg 1 $K≫1 small-angle MTs. The algorithm complexity scales as $ {O}({K}{{N}^3}{{N}_p}) $O(KN3Np), where $ {{N}_p} $Np is the number of grid points. Here, we present a numerical implementation of this algorithm and discuss how to mitigate the associated numerical instabilities.

Elevation of isoprostanes in polycystic ovary syndrome and its relationship with cardiovascular risk factors.

PURPOSE: To evaluate the plasma level of 8-isoprostanes in women with polycystic ovary syndrome. To also investigate whether there is a relationship between 8-isoprostanes and several cardiovascular risk factors. METHODS: A total of 125 women with polycystic ovary syndrome and 169 healthy women were enrolled in this case-control study. 8-Isoprostanes and different parameters were measured in all subjects. Patients were evaluated for the presence of polycystic ovary syndrome according to the Rotterdam Consensus Conference criteria. RESULTS: 8-Isoprostanes levels were significantly higher in patients with polycystic ovary syndrome (138.4 ± 104.1 pg/mL) compared with control group (68.6 ± 34.3 pg/mL) (p < 0.001). The mean of triglycerides, lipid accumulation product, C-reactive protein, homocysteine, insulin, and homeostatic model assessment for insulin resistance were significantly higher in polycystic ovary syndrome patients with high 8-isoprostanes than those with normal 8-isoprostanes (p < 0.05). The Pearson correlation analyses showed that 8-isoprostanes levels in polycystic ovary syndrome group had a positive correlation with waist circumference, triglycerides, low-density lipoprotein cholesterol, apolipoprotein B, homocysteine, insulin, homeostatic model assessment for insulin resistance. CONCLUSIONS: Patients with polycystic ovary syndrome have higher 8-isoprostanes levels and it is associated with several cardiovascular risk factors.

Specific immunotherapy in local allergic rhinitis: A randomized, double-blind placebo-controlled trial with Phleum pratense subcutaneous allergen immunotherapy.

BACKGROUND: Allergen immunotherapy has been shown to be an effective treatment for local allergic rhinitis (LAR) to house dust mites. Studies with pollen allergen immunotherapy are limited to observational studies. The aim of this study was to evaluate the clinical efficacy and safety of Phleum pratense subcutaneous immunotherapy (Phl-SCIT) in LAR. METHODS: In a randomized double-blind placebo-controlled study, 56 patients with moderate-severe LAR to grass pollen received Phl-SCIT with a depigmented polymerized pollen vaccine or placebo for the first year, and Phl-SCIT the second one. The blind was maintained throughout the study. Primary outcome was combined symptom medication score (CSMS) during grass pollen season (GPS). Secondary clinical outcomes included organ-specific symptoms, medication-free days, rhinitis severity and asthma control. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), nasal allergen provocation test (NAPT), skin testing, serum levels of specific IgG4 and specific IgE and safety were also evaluated. RESULTS: Subcutaneous immunotherapy (SCIT) had a short-term and sustained effect with significant improvements of all primary and secondary clinical outcomes and RQLQ score. SCIT significantly increased serum sIgG4 levels and allergen tolerance, from the 6th to 24th months of treatment. At the end of the study, 83% of patients treated with ≥6 months of SCIT tolerated a concentration of P. pratense over 50 times higher than baseline, and 56% gave a negative NAPT. SCIT was well tolerated; six mild local reactions occurred, and there were no serious adverse events related to the study medication. CONCLUSIONS: Subcutaneous immunotherapy with depigmented polymerized allergen extracts is a safe and clinically effective treatment for LAR to P. pratense.

Coelomycetous Dothideomycetes with emphasis on the families Cucurbitariaceae and Didymellaceae.

The taxonomy of the coelomycetes has undergone dramatic changes in recent years, but remains controversial due to the high number of taxa involved, their poor morphological differentiation, the rare occurrence of the sexual morphs, and rapid loss of fertility in vitro. In the present study, we revisited the families Cucurbitariaceae and Didymellaceae (Pleosporales, Dothideomycetes), which include numerous plant pathogens, endophytic species associated with a wide host range, and saprobes. The taxonomy of two of the most relevant genera, i.e. Phoma and Pyrenochaeta, remains ambiguous after several phylogenetic studies, and needs further revision. We have studied a total of 143 strains of coelomycetes from clinical or environmental origin, by combining the LSU, ITS, tub2 and rpb2 sequences for a multi-locus analysis and a detailed morphological comparison. The resulting phylogenetic tree revealed that some fungi previously considered as members of Cucurbitariaceae represented five different families, and four of them, Neopyrenochaetaceae, Parapyrenochaetaceae, Pseudopyrenochaetaceae and Pyrenochaetopsidaceae, are proposed here as new. Furthermore, 13 new genera, 28 new species, and 20 new combinations are proposed within the Pleosporineae. Moreover, four new typifications are introduced to stabilise the taxonomy of these fungi.