Smell loss associated with SARS-CoV-2 is not clinically different from other viruses: a multicenter cohort study.

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.

Aqueous extract OF Moringa oleifera Lam leaves added to freezing extenders damages goat sperm membranes.

BACKGROUND: Semen cryopreservation is a biotechnology used frequently in animal production; however, there are some obstacles, such as those caused by high levels of reactive oxygen species (ROS). Moringa oleifera (MO) is known as a potent source of antioxidants and might be an important adjuvant. OBJECTIVE: The objective of this study was to determine the effect of different concentrations of MO extract supplementation on goat semen cryopreservation efficiency. MATERIALS AND METHODS: Ejaculates (n=6) from four goat breeders were pooled and diluted in skimmed milk (SM) or Tris-egg yolk (TEY)-based extenders and supplemented with different concentrations of MO extract (0, 1, 2 and 5 mg/mL). After the freeze-thaw cycle, sperm kinetics and viability were assessed. RESULTS: With the SM extender, straightness, wobble and plasma membrane integrity were lower than in the control group (P < 0.05). With the TEY extender, wobble was lower in with 5 mg/mL MO extract than in the control group (P < 0.05). As regards sperm ultrastructure, evaluated by SEM, the MO extract, regardless of the diluent used, damaged the membrane of sperm cells in a dose-dependent manner. CONCLUSION: The addition of aqueous extract of MO leaves in both diluents at all concentrations tested affects the parameters of sperm progressivity and damages the plasma membrane in a dose-dependent manner. DOI: 10.54680/fr23310110712.

Tuberculosis infection in HIV vs. non-HIV patients.

OBJECTIVES: Tuberculosis (TB) is the most common opportunistic infection and cause of mortality among people living with HIV, and it is possible that it may also influence the evolution of the HIV infection. We assessed the differences between HIV-positive and -negative people infected with TB. METHODS: The present study is a cross-sectional retrospective study by electronic record revision. We included patients admitted to a tertiary hospital with a diagnosis of TB between 2011 and 2016, comparing those with HIV coinfection with non-HIV patients, according to demographic and clinical characteristics. RESULTS: This study included 591 patients, of whom 32% were HIV-coinfected. HIV-TB patients were younger, with a predominance of male gender. Considering TB risk factors, there was a higher prevalence of homelessness and intravenous drug use in the HIV group. In the non-HIV group, direct contact with other patients with TB and immunosuppression were more prevalent. Relative to TB characteristics, the HIV-coinfected group presents with a higher prevalence of disseminated disease and a higher occurrence of previous TB infection. Cancer was the most frequent cause of immunosuppression in the HIV group and the number testing positive for TB via microbiological culture was lower. Assessment of microbiological resistance and in-hospital mortality showed similar numbers in both groups. CONCLUSIONS: There are few papers comparing clinical course of TB between HIV-infected and non-infected patients. Our study differs from others in the literature as we focused on a country with middling incidence of TB and further characterized the differences between HIV-infected and non-infected patients which can contribute to the management of these patients.

Anti-staphylococcal effects of Myracrodruon urundeuva lectins on nonresistant and multidrug resistant isolates.

AIMS: To evaluate the anti-staphylococcal effects of lectins isolated from bark (MuBL), heartwood (MuHL) and leaves (MuLL) of Myracrodruon urundeuva. METHODS AND RESULTS: The lectins were evaluated for: effects on growth, aggregation, haemolytic activity and biofilm-forming ability of Staphylococcus aureus clinical isolates nonresistant (8325-4) and multidrug resistant (LAC USA300); interference with the expression of virulence genes (hla, rnaIII and spa) of the Agr system of S. aureus; and synergistic effect with the antibiotics cefoxitin and cefotaxime. MuBL, MuHL and MuLL reduced growth (minimal inhibitory concentration (MIC): 12·5-50 µg ml-1 ) and viability (minimal bactericidal concentration (MBC): 100 µg ml-1 ) of 8325-4 and LAC USA300 cells. MuLL (at ½MIC and MIC) reduced LAC USA300 agglutination. The lectins did not interfere with haemolytic activity and expression of hla, rnaIII and spa genes. Only MuHL was able to reduce the biofilm production by 8325-4 (50-400 µg ml-1 ) and LAC USA300 (400 µg ml-1 ). CONCLUSION: The M. urundeuva lectins showed antibacterial activity against nonresistant and resistant clinical isolates of S. aureus and synergistic effects with antibiotics in reducing growth and biofilm formation. SIGNIFICANCE AND IMPACT OF THE STUDY: This work reports bioactive molecules capable of acting as anti-staphylococcal agents, since there are increasing reports of multiresistant isolates of this bacterium.

Anaphylaxis: A Decade of a Nationwide Allergy Society Registry.

BACKGROUND AND OBJECTIVES: Anaphylaxis is an acute, life-threatening, multiorgan hypersensitivity reaction. Objective: The aim of this study was to identify the causes of anaphylaxis in Portugal in order to improve our knowledge of epidemiology and management. METHODS: We implemented a nationwide notification system for anaphylaxis over a 10-year period, with voluntary reporting by allergists. Data on 1783 patients with anaphylaxis were included. Etiopathogenesis, manifestations, and clinical management were characterized in detail for both children and adults. RESULTS: The mean age was 32.7 (20.3) years, and 30% were under 18 years of age; 58% were female. The mean age at the first anaphylaxis episode was 27.5 (20.4) years (ranging from 1 month to 88 years). The main culprits of anaphylaxis were foods (48%), drugs (37%) (main trigger in adults, 48%), and hymenoptera venom (7%). The main culprit foods were shellfish (27%), fresh fruit (17%), cow's milk (16%), tree nuts (15%), fish (8%), egg (7%), and peanut (7%). The main drugs were nonsteroidal anti-inflammatory drugs (43%), antibiotics (39%), and anesthetic agents (6%). Other causes included exercise (3%), latex (2%), cold-induced anaphylaxis (2%), and idiopathic anaphylaxis (2%). Most patients (80%) were admitted to the emergency department; only 43% received adrenaline. Anaphylaxis recurred in 41% of patients (21% with ≥3 anaphylactic episodes); 7% used an adrenaline autoinjector device. CONCLUSION: Food is the leading cause of anaphylaxis in Portugal, while drugs were the main elicitors in adults. We emphasize undertreatment with adrenaline and recurrent episodes, highlighting the need to improve diagnostic and therapeutic approaches to anaphylaxis.

Demographic drivers of Norway rat populations from urban slums in Brazil.

The Norway rat is a globally distributed pest, known for its resilience to eradication and control programs. Efficient population control, especially in urban settings, is dependent on knowledge of rat demography and population ecology. We analyzed the relationship between four demographic outcomes, estimated by live-trapping data, and fine-scale environmental features measured at the capture site. Wounds, a proxy for agonistic interactions, were associated with mature individuals. Areas with environmental features favorable to rats, such as open sewers and unpaved earth, were associated with more mature individuals with a better body condition index. The control measures (environmental stressors) are likely to be disrupting the social structure of rat colonies, increasing the frequency and distribution of agonistic interactions, which were common in both sexes and maturity states. The relationship between the favorable environmental conditions and the demographic markers analyzed indicate possible targets for infestation control through environmental manipulation, and could be incorporated into current pest management programs to achieve long-term success. Our study indicate that urban interventions focused on removal of potential resources for rats could be potential long-term solutions by reducing the carrying capacity of the environment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11252-020-01075-2.

Prevalence of Diarrheagenic Escherichia coli (DEC) and Salmonella spp. with zoonotic potential in urban rats in Salvador, Brazil.

Studies evaluating the occurrence of enteropathogenic bacteria in urban rats (Rattus spp.) are scarce worldwide, specifically in the urban environments of tropical countries. This study aims to estimate the prevalence of diarrhoeagenic Escherichia coli (DEC) and Salmonella spp. with zoonotic potential in urban slum environments. We trapped rats between April and June 2018 in Salvador, Brazil. We collected rectal swabs from Rattus spp., and cultured for E. coli and Salmonella spp., and screened E. coli isolates by polymerase chain reaction to identify pathotypes. E. coli were found in 70% of Rattus norvegicus and were found in four Rattus rattus. DEC were isolated in 31.3% of the 67 brown rats (R. norvegicus). The pathotypes detected more frequently were shiga toxin E. coli in 11.9%, followed by atypical enteropathogenic E. coli in 10.4% and enteroinvasive E. coli in 4.5%. From the five black rats (R. rattus), two presented DEC. Salmonella enterica was found in only one (1.4%) of 67 R. norvegicus. Our findings indicate that both R. norvegicus and R. rattus are host of DEC and, at lower prevalence, S. enterica, highlighting the importance of rodents as potential sources of pathogenic agents for humans.

Composition of fatty acids, tocopherols, tocotrienols and ß-carotene content in oils of seeds of Brazilian Sapindaceae and Meliaceae species.

This study analyzes the lipid composition and the oxidative stability of oils of Sapindaceae and Meliaceae seeds. The oil content ranged from 14.7% (Guarea guidonia) to 30.1% (Allophylus puberulus and Paullinia elegans). Ten fatty acids were identified in seed oils. Guarea guidonia seeds accumulated mainly oleic (44.9%) and linoleic (24.1%) acid, whereas the unusual gondoic and paullinic acids were identified in A. puberulus (15.8%; 8.9%) and P. elegans (14.4%; 44.2%), respectively. The oil of P. elegans had the highest oxidative stability (16.2 h.). Tocopherol predominated in A. puberulus (10.4 mg/100 g) and tocotrienol predominated in G. guidonea and P. elegans (2.6 mg/100 g). The vitamers α-tocopherol, γ-tocopherol, and γ-tocotrienol were found in the studied oils. ß-carotene was predominantly detected in the oil of A. puberulus seeds (22.4 µg/g). Guarea guidonia seed oil has a high potential in food due to richness in essential fatty acids. In turn, A. puberulus and P. elegans oils could be suggested for other industrial purposes (e.g., biodiesel, varnishes, paints, soaps, or oleochemicals) due to their content of long-chain fatty acids.

Chlorinated metronidazole as a promising alternative for treating trichomoniasis.

Trichomoniasis is the most common non-viral, sexually transmitted infection affecting humans worldwide. The main treatment for trichomoniasis is metronidazole (MTZ). However, adverse effects and reports of resistance have stimulated the development of therapeutic alternatives. The ease of manipulation of the side chains of MTZ coupled with its safety makes this molecule attractive for the development of new drugs. In this context, we evaluated the activity of the chlorinated MTZ derivative, MTZ-Cl, on sensitive and resistant strains of Trichomonas vaginalis. MTZ-Cl presented a remarkable activity against both sensitive and resistant strains. In vitro and in vivo toxicity assays indicated that the new molecule is safe for future clinical trials. Furthermore, we noticed different rates of free radical production between the sensitive and resistant strains. MTZ-Cl induced a higher release of nitric oxide (NO, ~ 9000 a.u.) by both sensitive and resistant strains. However, the sensitive strain produced a greater amount of H2O2 (~ 1,800,000 a.u.) and superoxide radicals (~ 350,000 a.u.) in the presence of MTZ. In the resistant strain, production of these radicals was more prominent when MTZ-Cl was used. Collectively, these results suggest that NO is an important molecule in the trichomonacidal activity against resistant and sensitive strains, suggesting an alternative pathway for MTZ-Cl activation. We highlight the high trichomonacidal potential of MTZ-Cl, improving the effectiveness of treatment and reducing side effects. In addition, MTZ-Cl is derived from a well-established drug on the world market that presents low toxicity to human cells, suggesting its safety to proceed with future clinical trials.

Methods for quantifying eggs and oviposition rate of Dawestrema cycloancistrium (Monogenea: Dactylogyridae), monogenean parasite of Arapaima gigas (Teleostei: Osteoglossidae).

Dawestrema cycloancistrium is the main ectoparasite causing mortality in fingerlings of pirarucu (Arapaima gigas) in Amazonian aquaculture. Very little is known about the D. cycloancistrium reproductive index and appropriate methods of collecting eggs for investigation. This study aimed to determine the oviposition rate of D. cycloancistrium. To achieve this aim, two egg quantification methods were tested: the estimative method (ME) and the total counting method (MT). Compared with the MT, the ME overestimated the number of eggs counted, which were 2943.5 ± 2840.6 and 1041.5 ± 533 eggs, and the oviposition rate, which was 80.1 ± 58.7 and 31.4 ± 16.4 eggs/parasite/day, for ME and MT, respectively. These results show that for studies quantifying D. cycloancistrium eggs, the total eggs in the sample must be counted, as the estimates made using subsamples are not representative. Using the MT, the oviposition rate for D. cycloancistrium was determined to be 31.4 ± 16.4 eggs per adult parasite per day. The present study demonstrates the egg production capacity of a monogenean species parasite of A. gigas, providing basic biological data for D. cycloancistrium.

Biological and physicochemical properties of biosurfactants produced by Lactobacillus jensenii P6A and Lactobacillus gasseri P65.

BACKGROUND: Lactobacillus species produce biosurfactants that can contribute to the bacteria's ability to prevent microbial infections associated with urogenital and gastrointestinal tracts and the skin. Here, we described the biological and physicochemical properties of biosurfactants produced by Lactobacillus jensenii P6A and Lactobacillus gasseri P65. RESULTS: The biosurfactants produced by L. jensenii P6A and L. gasseri P65 reduced the water surface tension from 72 to 43.2 mN m-1 and 42.5 mN m-1 as their concentration increased up to the critical micelle concentration (CMC) values of 7.1 and 8.58 mg mL-1, respectively. Maximum emulsifying activity was obtained at concentrations of 1 and 5 mg mL-1 for the P6A and P65 strains, respectively. The Fourier transform infrared spectroscopy data revealed that the biomolecules consist of a mixture of carbohydrates, lipids and proteins. The gas chromatography-mass spectrum analysis of L. jensenii P6A biosurfactant showed a major peak for 14-methypentadecanoic acid, which was the main fatty acid present in the biomolecule; conversely, eicosanoic acid dominated the biosurfactant produced by L. gasseri P65. Although both biosurfactants contain different percentages of the sugars galactose, glucose and ribose; rhamnose was only detected in the biomolecule produced by L. jensenii P6A. Emulsifying activities were stable after a 60-min incubation at 100 °C, at pH 2-10, and after the addition of potassium chloride and sodium bicarbonate, but not in the presence of sodium chloride. The biomolecules showed antimicrobial activity against clinical isolates of Escherichia coli and Candida albicans, with MIC values of 16 µg mL-1, and against Staphylococcus saprophyticus, Enterobacter aerogenes and Klebsiella pneumoniae at 128 µg mL-1. The biosurfactants also disrupted preformed biofilms of microorganisms at varying concentrations, being more efficient against E. aerogenes (64%) (P6A biosurfactant), and E. coli (46.4%) and S. saprophyticus (39%) (P65 biosurfactant). Both strains of lactobacilli could also co-aggregate pathogens. CONCLUSIONS: This report presents the first characterization of biosurfactants produced by L. jensenii P6A and L. gasseri P65. The antimicrobial properties and stability of these biomolecules indicate their potential use as alternative antimicrobial agents in the medical field for applications against pathogens that are responsible for infections in the gastrointestinal and urogenital tracts and the skin.

Restless legs syndrome in Wilson's disease: frequency, characteristics, and mimics.

OBJECTIVE: To determine characteristics, clinical significance, frequency, and mimics of restless legs syndrome (RLS) in a cohort of Wilson's disease (WD, n = 42/f = 18), compared to healthy, matched controls. MATERIALS AND METHODS: Structured clinical interviews (patients and caregiving family members), repeated neurological examinations (afternoon and presleep), comprehensive laboratory tests, WD-, RLS-, and sleep-specific rating scales, and video-polysomnography. RESULTS: Thirteen patients with WD (13/42 = 31.0%) clearly fulfilled the five diagnostic criteria of RLS; in eight patients (19.1%), the burden of RLS was clinically significant. The RLS was of moderate severity, equally distributed among sexes, manifested mainly in the evening and before falling asleep, and had developed mostly after clinical manifestation of WD (time elapsed 10.2 ± 14.5 years), still at a young mean age (27.5 ± 11.5 years). The known RLS-associated features were absent (normal iron and kidney parameters) or rare (positive family history, polyneuropathy). Compared to WD patients without RLS, patients with RLS were significantly elder and had suffered longer from WD. WD-specific RLS mimics as well as RLS confounding motor comorbidities (dystonia, tremor, chorea) were frequent and a diagnostic challenge; in difficult cases, the differentiation was reached by clinical observation of the motor behavior in the evening or at nighttime. CONCLUSION: RLS was frequent in this cohort of WD and might be causally related to WD. RLS should be included in the diagnostic work-up of WD. In complex motor disorders, differential diagnosis of RLS might require evening/nighttime examination and video-polysomnography. In WD patients with a clinically significant RLS, treatment with dopaminergic substances may be considered.

Duplication of Dio3 genes in teleost fish and their divergent expression in skin during flatfish metamorphosis.

Deiodinase 3 (Dio3) plays an essential role during early development in vertebrates by controlling tissue thyroid hormone (TH) availability. The Atlantic halibut (Hippoglossus hippoglossus) possesses duplicate dio3 genes (dio3a and dio3b). Expression analysis indicates that dio3b levels change in abocular skin during metamorphosis and this suggests that this enzyme is associated with the divergent development of larval skin to the juvenile phenotype. In larvae exposed to MMI, a chemical that inhibits TH production, expression of dio3b in ocular skin is significantly up-regulated suggesting that THs normally modulate this genes expression during this developmental event. The molecular basis for divergent dio3a and dio3b expression and responsiveness to MMI treatment is explained by the multiple conserved TREs in the proximal promoter region of teleost dio3b and their absence from the promoter of dio3a. We propose that the divergent expression of dio3 in ocular and abocular skin during halibut metamorphosis contributes to the asymmetric pigment development in response to THs.

Evaluation of genotype x environment interactions in cotton using the method proposed by Eberhart and Russell and reaction norm models.

Cotton produces one of the most important textile fibers of the world and has great relevance in the world economy. It is an economically important crop in Brazil, which is the world's fifth largest producer. However, studies evaluating the genotype x environment (G x E) interactions in cotton are scarce in this country. Therefore, the goal of this study was to evaluate the G x E interactions in two important traits in cotton (fiber yield and fiber length) using the method proposed by Eberhart and Russell (simple linear regression) and reaction norm models (random regression). Eight trials with sixteen upland cotton genotypes, conducted in a randomized block design, were used. It was possible to identify a genotype with wide adaptability and stability for both traits. Reaction norm models have excellent theoretical and practical properties and led to more informative and accurate results than the method proposed by Eberhart and Russell and should, therefore, be preferred. Curves of genotypic values as a function of the environmental gradient, which predict the behavior of the genotypes along the environmental gradient, were generated. These curves make possible the recommendation to untested environmental levels.

Estimates of repeatability coefficients and the number of the optimum measure to select superior genotypes in Annona muricata L.

The aim of this study was to evaluate repeated measures over the years to estimate repeatability coefficient and the number of the optimum measure to select superior genotypes in Annona muricata L. The fruit production was evaluated over 16 years in 71 genotypes without an experimental design. The estimation of variance components and the prediction of the permanent phenotypic value were performed using REML/BLUP proceedings. The coefficient of determination, accuracy, and selective efficiency increased when measures increased. The coefficient of determination of 80% was reached beyond 8 crop seasons with high accuracy and selective efficiency. Thus, the evaluation of 8 crop seasons can be suitable to select superior genotypes in the A. muricata L. breeding program. Predicted selection gain had a high magnitude for fruit production indicating that it is possible to take a progressive genetic advance for this trait over cycle breeding.

Genetic diversity of native populations of Croton tetradenius Baill. using ISSR markers.

Brazil has about 300 Croton species in different types of vegetation. Croton tetradenius Baill., which is endemic to the Northeast region and predominant in the Caatinga vegetation, stands out among the several species of this genus. Considering the importance of knowing the genetic variability of a species, the objective of this study was to analyze the genetic diversity of the genotypes of natural populations of C. tetradenius in the State of Sergipe, using ISSR molecular markers. Forty individuals were sampled in four natural populations of the State of Sergipe, Brazil. Thirteen primers were used for DNA amplification using ISSR-PCR, totaling 77 amplified fragments, of which 94.8% were polymorphic. Results of the cluster analysis obtained by the Jaccard's similarity index, using the UPGMA method, resulted in the formation of six distinct clusters. Analysis of molecular variance (AMOVA), used to estimate the genetic variability among populations, revealed significant genetic variance (P < 0.01) between and within the studied populations, and most of the genetic diversity was found (87%) within populations. According to the Jaccard's similarity index, none of the studied plants was genetically identical. CTE210 and CTE305 presented high similarity index (0.76), while CTE105 presented low similarity index (<0.16) with all related individuals. ISSR markers were efficient and allowed the formation of a molecular profile, and had sufficient polymorphism to estimate the genetic variability between the accessions of the studied populations.

Ultramorphological changes in gill rakers of Astyanax altiparanae (Characidae) kept in contaminated environments.

Most water bodies in Brazil, and in the world, are contaminated by some types of pollutants, ranging from sewage to metal/chemicals, carcinogenic products, and biodegradable detergents. Despite the extensive knowledge on their effects on fish biology and especially on gill morphology, research that concerns their impacts on gill rakers and implications in parameters such as food consumption cannot be found in the literature. Gill rakers are vital because, together with gills, they are responsible for the defense and protection of the organism and for selecting appropriate food for survival. When detergents, which can act as toxic chemical agents, get in contact with the body of the fish, they can cause severe effects that must be understood. Therefore, our study investigated ultramorphological changes in gill rakers of Astyanax altiparanae (Lambeth) caused by the exposure to biodegradable detergents. Fish were exposed to a 1 mg/L dilution of a mixture of detergents and pure water from an artesian well for 5 months. Results revealed that the first month of exposure to detergent caused dilation of chemical receptors in taste buds and the rise of a large number of orifices for mucus release among pavement cells in gill rakers, although only a small amount of mucus was found in fish exposed both to pure water and the detergent dilution. After 5 months, there was an increase in the dilation of these chemoreceptors, excess mucus on gill rakers of detergent groups, and the emergence of microbridges between microridges in pavement cells.

Self-medication of anaphylactic reactions due to Hymenoptera stings-an EAACI Task Force Consensus Statement.

An anaphylactic reaction due to a Hymenoptera sting is a clinical emergency, and patients, their caregivers as well as all healthcare professionals should be familiar with its recognition and acute management. This consensus report has been prepared by a European expert panel of the EAACI Interest Group of Insect Venom Hypersensitivity. It is targeted at allergists, clinical immunologists, internal medicine specialists, pediatricians, general practitioners, emergency department doctors, and any other healthcare professional involved. The aim was to report the scientific evidence on self-medication of anaphylactic reactions due to Hymenoptera stings, to inform healthcare staff about appropriate patient self-management of sting reactions, to propose indications for the prescription of an adrenaline auto-injector (AAI), and to discuss other forms of medication. First-line treatment for Hymenoptera sting anaphylaxis is intramuscular adrenaline. Prescription of AAIs is mandatory in the case of venom-allergic patients who suffer from mast cell diseases or with an elevated baseline serum tryptase level and in untreated patients with a history of a systemic reaction involving at least two different organ systems. AAI prescription should also be considered in other specific situations before, during, and after stopping venom immunotherapy.

Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sézary syndrome.

BACKGROUND: Quisinostat is a hydroxamate, second-generation, orally available pan-histone deacetylase inhibitor. OBJECTIVES: To evaluate the efficacy and safety of oral quisinostat in patients with previously treated cutaneous T-cell lymphoma (CTCL). METHODS: Patients received quisinostat 8 mg or 12 mg on days 1, 3 and 5 of each week in 21-day treatment cycles. Primary efficacy end point was cutaneous response rate (RR) based on the modified Severity Weighted Assessment Tool (mSWAT). Secondary end points included global RR, duration of response (DOR) in skin, progression-free survival (PFS), pruritus relief, safety and pharmacodynamic markers. RESULTS: Eight of 26 (25 evaluable) patients achieved ≥ 50% reduction in mSWAT score at least once, with confirmed cutaneous response in six (RR 24%). There was a low global RR of 8%. DOR in skin ranged from 2·8 to 6·9 months. Median PFS was 5·1 months. Pruritus relief was more frequent in cutaneous responders (67%) than nonresponders (32%). Serial tumour biopsies revealed an increase in acetylated tubulin, indicating a target effect of histone deacetylase 6. Twenty-one of 26 (81%) patients were withdrawn from the study before or at clinical cut-off; five (19%) continued to receive treatment with quisinostat. The most common drug-related adverse events were nausea, diarrhoea, asthenia, hypertension, thrombocytopenia and vomiting. Grade 3 drug-related adverse events included hypertension, lethargy, pruritus, chills, hyperkalaemia and pyrexia. CONCLUSIONS: Quisinostat 12 mg three times weekly is active in the treatment of patients with relapsed or refractory CTCL, with an acceptable safety profile. Combination therapy with other drugs active in CTCL may be appropriate.