Efficacy and safety of dolutegravir/rilpivirine in real-world clinical practice. GeSIDA study 1119.

INTRODUCTION: Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real-world clinical practice. METHODS: Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed. RESULTS: A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/µL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV-RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1-92.6) by intention-to-treat (ITT) and 94.2% (95% CI 91.3-96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low-density lipoprotein-cholesterol, glutamic-pyruvic transaminase (GPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate. CONCLUSIONS: This study confirms the effectiveness, tolerability and safety of DTG/RPV in real-world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one-third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function.

Api m 6 and Api m 10 as Major Allergens in Patients With Honeybee Venom Allergy.

BACKGROUND: Component-resolved diagnosis plays a key role in the diagnosis and treatment of honeybee venom allergy (HVA). Our aim was to study whether any of the allergens not included in the usual diagnostic platforms are relevant in our population. MATERIAL AND METHODS: The allergenic sensitization profile of Spanish patients who experienced a systemic reaction after a honeybee sting and were diagnosed with HVA was studied by immunoblotting based on raw autochthonous Apis mellifera venom characterized using SDS-PAGE and mass spectrometry and a commercial assay (ImmunoCAP). RESULTS: Allergens in the International Union of Immunological Societies database were detected in the raw A mellifera venom extract used, except Api m 12. Sera from 51 patients with a median (IQR) age of 46.2 years (35.6-54.6) were analyzed. ImmunoCAP revealed Api m 1 and Api m 10 to be major allergens (88.2% and 74.5%, respectively). Moreover, Api m 6 (85.4%) was detected by immunoblotting. CONCLUSION: Api m 1, Api m 6, and Api m 10 are major A mellifera venom allergens in our population.

Incidence of recently acquired hepatitis C virus infection among HIV-infected patients in southern Spain.

OBJECTIVES: Spain is close to HCV microelimination, so rates of recently acquired HCV infection (RAHC) should decrease. Nowadays, men who have sex with men (MSM) carry the highest risk of HCV acquisition. Our aim was to estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV. METHODS: Primary RAHC infection was diagnosed when anti-HCV antibody seroconversion was documented. In anti-HCV positive patients, initially without HCV viraemia, a diagnosis of reinfection was established if plasma HCV RNA was detected. RESULTS: All 350 patients tested negative for anti-HCV at baseline and had at least one follow-up visit. Among them, there were 16 RAHC cases from 2016 to 2019. RAHC incidence rates [IR (95% confidence interval, CI)] per 100 person-years were 3.77 (0.5-12.9) in 2016, 1.85 (0.6-4.3) in 2017, 1.49 (0.4-3.8) in 2018 and 1.98 (0.6-4.5) in 2019. Only previous sexually transmitted infections [incidence rate ratio (IRR) = 18.23, 95% CI: 1.93-172.1; P = 0.011], male sex (IRR = 8.33, 95% CI: 1.38-54.15; P = 0.026) and sharing chem-sex drugs (IRR: 4.93, 95% CI: 1.17-20.76; P = 0.030), were independently associated with RAHC. Four out of 42 (9.5%) patients became reinfected. CONCLUSIONS: The incidence of RAHC among HIV-infected patients showed a decrease after 2016, although a lower but steady incidence of residual cases still remains. HCV reinfections showed a similar pattern. New infections were associated with sharing chem-sex drugs among MSM.

Major differences in the larval anatomy of the digestive and excretory systems of three Oestridae species revealed by micro-CT.

Oestrid flies (Diptera: Oestridae) do not feed during the adult stage, so they depend on an efficient assimilation and storage of nutrients during their parasitic larval stage. We describe the general morphology and provide volumetric data for the digestive and excretory organs of the three larval instars of the nasal bot fly Oestrus ovis L., using micro-computed tomography. The size of the digestive and excretory organs greatly increased across larval instars. In all instars, the two salivary glands were remarkably large and formed a 'glandular band' by coming together, but without lumina uniting, at their posterior ends. The distal region of the anterior Malpighian tubules was greatly enlarged and full of highly radio-opaque concretions. Moreover, the anatomy of O. ovis third-instar larva was compared to that of two species of, respectively, similar and different feeding habits: Cephenemyia stimulator (Clark) and Hypoderma actaeon Brauer. Whereas the general morphology and arrangement of the digestive and excretory systems of C. stimulator was similar to that of O. ovis, some differences were observed in H. actaeon: a swollen anterior region of the midgut, salivary glands shorter and not forming a 'band' and anterior Malpighian tubules narrowly uniform throughout their entire length.

Liver Stiffness at the Time of Sustained Virological Response Predicts the Clinical Outcome in People Living With Human Immunodeficiency Virus and Hepatitis C Virus With Advanced Fibrosis Treated With Direct-acting Antivirals.

BACKGROUND: Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). METHODS: In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication-hepatic decompensation or hepatocellular carcinoma (HCC)-or requiring liver transplant after SVR. RESULTS: During a median (Q1-Q3) follow-up of 31.6 (22.7-36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28-9.12]), pretreatment CPT class B or C (62.5 [3.08-1246.42]) and MELD scores (1.37 [1.03-1.82]), CPT class B or C at SVR (10.71 [1.32-87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49-13.15]), FIB-4 index at SVR (1.39 [1.13-1.70]), and LS at SVR (1.05 [1.02-1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant. CONCLUSIONS: LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.

Simplification to dual therapy (atazanavir/ritonavir + lamivudine) versus standard triple therapy [atazanavir/ritonavir + two nucleos(t)ides] in virologically stable patients on antiretroviral therapy: 96 week results from an open-label, non-inferiority, randomized clinical trial (SALT study).

OBJECTIVES: We evaluated whether maintenance therapy with atazanavir/ritonavir plus lamivudine (ATV/r + 3TC) was non-inferior to ATV/r plus two nucleosides (ATV/r + 2NUCs) at 96 weeks of follow-up. METHODS: SALT is a multicentre, open-label, non-inferiority clinical trial in HIV-1-infected virologically suppressed patients. Hepatitis B virus surface antigen-negative subjects with no previous treatment failure/resistance mutations and HIV-1-RNA <50 copies/mL for ≥6 months were randomized (1 : 1) to ATV/r + 3TC or ATV/r + 2NUCs. The primary endpoint was HIV-1-RNA <50 copies/mL in the PP population. Non-inferiority was demonstrated if the lower bound of the 95% CI for the difference was not below -12%. RESULTS: Some 286 patients were analysed. At week 96, 74.4% had HIV-1-RNA <50 copies/mL in the ATV/r + 3TC arm versus 73.9% in the ATV/r + 2NUCs arm (95% CI for the difference, -9.9%-11.0%). In both groups, similar values were observed for patients with confirmed virological failure in ATV/r + 3TC versus ATV/r + 2NUCs (9 versus 5), death (1 versus 0), discontinuation due to ART-related toxicity (7 versus 11), withdrawal from the study (7 versus 9) and loss to follow-up (6 versus 6). One patient taking ATV/r + 2NUCs developed resistance mutations (M184V and L63P). Similar values were obtained for change in mean CD4 count [19 versus 18 cells/mm3 (95% CI for the difference, -49.3-50.7), grade 3-4 adverse events (70.7% versus 70.2%) and changes in the global deficit score, -0.3 (95% CI, -0.5 to -0.1) for ATV/r + 3TC, versus -0.2 (95% CI, -0.4 to -0.1) for ATV/r + 2NUCs]. CONCLUSIONS: The long-term results of switching to ATV/r + 3TC show that this strategy is effective, safe and non-inferior to ATV + 2NUCs in virologically suppressed HIV-infected patients.

Molecular diagnosis of allergy to Anisakis simplex and Gymnorhynchus gigas fish parasites.

BACKGROUND: There has been an increase in the prevalence of hypersensitivity to Anisakis simplex. There are fish parasites other than Anisakis simplex whose allergenicity has not yet been studied. OBJECTIVE: To assess IgE hypersensitivity caused by fish parasite allergens in patients with gastro-allergic symptoms after consumption of fish, shellfish or cephalopods, compared with healthy subjects, pollen allergic individuals and children with digestive symptoms after eating marine food. METHODS: We carried out in vivo tests (skin prick) and in vitro tests (specific IgE determination, Western blot) and component resolved diagnostics (CRD) using microarray analysis in all patients. RESULTS: CRD better detected sensitisation to allergens from marine parasites than skin prick tests and determination of specific IgE by CAP. Sensitisation to Gymnorhynchus gigas was detected in 26% of patients measured by skin prick tests and 36% measured by IgE. CONCLUSIONS: The prevalence of hypersensitivity to marine parasite allergens other than Anisakis simplex should be studied, and the most appropriate technique for this is CRD.

Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination.

Although MRI is the gold standard for the diagnosis and monitoring of multiple sclerosis (MS), current conventional MRI techniques often fail to detect cortical alterations and provide little information about gliosis, axonal damage and myelin status of lesioned areas. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) provide sensitive and complementary measures of the neural tissue microstructure. Additionally, specific white matter tract integrity (WMTI) metrics modelling the diffusion in white matter were recently derived. In the current study we used the well-characterized cuprizone mouse model of central nervous system demyelination to assess the temporal evolution of diffusion tensor (DT), diffusion kurtosis tensor (DK) and WMTI-derived metrics following acute inflammatory demyelination and spontaneous remyelination. While DT-derived metrics were unable to detect cuprizone induced cortical alterations, the mean kurtosis (MK) and radial kurtosis (RK) were found decreased under cuprizone administration, as compared to age-matched controls, in both the motor and somatosensory cortices. The MK remained decreased in the motor cortices at the end of the recovery period, reflecting long lasting impairment of myelination. In white matter, DT, DK and WMTI-derived metrics enabled the detection of cuprizone induced changes differentially according to the stage and the severity of the lesion. More specifically, the MK, the RK and the axonal water fraction (AWF) were the most sensitive for the detection of cuprizone induced changes in the genu of the corpus callosum, a region less affected by cuprizone administration. Additionally, microgliosis was associated with an increase of MK and RK during the acute inflammatory demyelination phase. In regions undergoing severe demyelination, namely the body and splenium of the corpus callosum, DT-derived metrics, notably the mean diffusion (MD) and radial diffusion (RD), were among the best discriminators between cuprizone and control groups, hence highlighting their ability to detect both acute and long lasting changes. Interestingly, WMTI-derived metrics showed the aptitude to distinguish between the different stages of the disease. Both the intra-axonal diffusivity (Da) and the AWF were found to be decreased in the cuprizone treated group, Da specifically decreased during the acute inflammatory demyelinating phase whereas the AWF decrease was associated to the spontaneous remyelination and the recovery period. Altogether our results demonstrate that DKI is sensitive to alterations of cortical areas and provides, along with WMTI metrics, information that is complementary to DT-derived metrics for the characterization of demyelination in both white and grey matter and subsequent inflammatory processes associated with a demyelinating event.

Clinical, virological and phylogenetic characterization of a multiresistant HIV-1 strain outbreak in naive patients in southern Spain.

BACKGROUND: We describe the characteristics of an HIV-1 strain with six viral reverse transcriptase mutations (D67N, T69N/D, V118I, V179D, T215S and K219Q), which we have called the Malaga strain. This strain was detected in treatment-naive patients from southern Spain. METHODS: The study was undertaken at the Virgen de la Victoria Hospital, Malaga, a reference centre for the study of HIV-1 genotype resistance in Andalusia (the 'Costa del Sol'), Spain. Genotypic resistance testing was done in an automated sequencer. Phylogenetic analysis was performed using a 630 bp region of the reverse transcriptase with the mutations mentioned. RESULTS: Between 2007 and 2014, we detected the Malaga strain in 30 treatment-naive patients. All were MSM, seen at five hospitals on the Costa del Sol. In all cases, the HIV-1 was subtype B with viral tropism R5. Phylogenetic analysis based on the reverse transcriptase sequence showed consistent grouping (with a bootstrap value of the common node of 100%) of the isolates that shared the mutation pattern mentioned. This strain has not been detected elsewhere or in previously treated patients. All of the patients treated with first-line combination ART responded. CONCLUSIONS: We report a cluster of an HIV-1 strain with multiple resistance mutations that was transmitted over a period of >8 years, affecting 30 naive patients from the same geographical area. The strain was susceptible to first-line combination ART.

Efficacy and safety of switching to abacavir/lamivudine (ABC/3TC) plus rilpivirine (RPV) in virologically suppressed HIV-infected patients on HAART.

We analysed the efficacy and safety of switching from a regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTI) or integrase inhibitors (INI) to ABC/3TC + RPV in virologically suppressed HIV-infected patients. This multicentre, retrospective study comprised asymptomatic HIV-infected patients who switched from 2 NRTI + NNRTI or 2 NRTI + INI to ABC/3TC + RPV between February 2013 and December 2013; all had undetectable HIV viral load prior to switching. Efficacy and safety, and changes in lipids and cardiovascular risk (CVR) were analysed at 48 weeks. Of 85 patients (74.1 % men, mean age 49.5 years), 83 (97.6 %) switched from a regimen based on NNRTI (EFV 74, RPV 5, ETV 2, NVP 2), and 45 (53 %) switched from TDF/FTC to ABC/3TC. The main reasons for switching were toxicity (58.8 %) and convenience (29.4 %). At 48 weeks, 78 (91.8 %) patients continued taking the same regimen; efficacy was 88 % by intention to treat, and 96 % by per protocol. Two patients were lost to follow-up and five ceased the new regimen (4 due to adverse effects and 1 virologic failure). Mean CD4 cell counts increased (744 vs. 885 cells/µL; p = 0.0001), and there were mean decreases in fasting total cholesterol (-15.9 mg/dL; p < 0.0001) and LDL-cholesterol (-11.0 mg/dL; p < 0.004), with no changes in HDL-cholesterol, triglycerides, total cholesterol:HDL-cholesterol ratio, and CVR. ABC/3TC + RPV is effective and safe in virologically-suppressed patients on antiretroviral therapy (ART). Forty-eight weeks after switching the lipid profile improved with decreases in total and LDL cholesterol.

Endophthalmitis related to lemon allergy in a heroin addict.

BACKGROUND: Heroin and its contaminants may be an important source of allergens in young people. We present a case of severe endophthalmitis in a patient that also suffered from anaphylactoid symptoms (hypotension, urticaria, glottic oedema) whenever he ingested lemon. METHODS: Prick tests with a battery of 42 aeroallergens including fruits and citrus fruits (orange, mandarin, grapefruit and lemon) and specific IgE to these allergens were carried out. Immunodetection was performed using the patient's serum and the following allergens: lemon, Candida, Aspergillus, Penicillium and Alternaria recombinant Alt 1 (Laboratories Diater). RESULTS: Skin tests were negative for Candida, Penicillium, Aspergillus and Cladosporium (ALK-Spain) as were specific IgE antibodies for CAP (Thermofisher, Sweden) and positive only for lemon and, doubtfully, to Candida. Specific IgE tests to pollen, arthropods, fungi, dander and foods were positive only for lemon (0.49kU/L). Serological study of fungi ruled out fungal infection at that time. The immunodetection showed that the patient's serum recognised a protein of approximately 25kDa of lemon peel, one of approximately 12-13kDa of Penicillium, and perfectly recognised Alt a 1. CONCLUSIONS: Lemon surface can be contaminated by Candida and other fungi. In heroin addicts with positive skin tests for lemon, the possibility of these serious complications should be taken into account.

Expression of endogenous retroviruses is negatively regulated by the pluripotency marker Rex1/Zfp42.

Rex1/Zfp42 is a Yy1-related zinc-finger protein whose expression is frequently used to identify pluripotent stem cells. We show that depletion of Rex1 levels notably affected self-renewal of mouse embryonic stem (ES) cells in clonal assays, in the absence of evident differences in expression of marker genes for pluripotency or differentiation. By contrast, marked differences in expression of several endogenous retroviral elements (ERVs) were evident upon Rex1 depletion. We demonstrate association of REX1 to specific elements in chromatin-immunoprecipitation assays, most strongly to muERV-L and to a lower extent to IAP and musD elements. Rex1 regulates muERV-L expression in vivo, as we show altered levels upon transient gain-and-loss of Rex1 function in pre-implantation embryos. We also find REX1 can associate with the lysine-demethylase LSD1/KDM1A, suggesting they act in concert. Similar to REX1 binding to retrotransposable elements (REs) in ES cells, we also detected binding of the REX1 related proteins YY1 and YY2 to REs, although the binding preferences of the two proteins were slightly different. Altogether, we show that Rex1 regulates ERV expression in mouse ES cells and during pre-implantation development and suggest that Rex1 and its relatives have evolved as regulators of endogenous retroviral transcription.

Utility of opium seed extract tests in preventing hypersensitivity reactions during surgery.

BACKGROUND: Anaphylaxis during anaesthesia is fatal in 3-9% of patients and analgesics, including opioids, and is the second most common medicament-related cause, although the prevalence is underestimated. We recently found that patients may generate IgE antibodies to opium seeds. OBJECTIVES: To determine the diagnostic accuracy of specific antibodies to morphine, codeine, rocuronium and oil body and aqueous fractions of Papaver somniferum seeds in the diagnosis and prevention of allergy to opioids. METHODS: Patients with hypersensitivity reactions during surgery, and severe clinical allergy (pollen, tobacco), and illicit heroin users were selected. The sensitivity, specificity and predictive values of in vivo and in vitro diagnostic techniques including oil body and aqueous fractions of P. somniferum seeds were measured. RESULTS: We studied 203 patients, with mean age 35.1±17.1 and 200 healthy controls. Patients sensitised to heroin or with hypersensitivity reactions during surgery responded to P. somniferum seed tests. Of patients not known to be sensitised to opioids, the highest positivity was in patients sensitised to tobacco (p<0.001). Opium seed skin tests and IgE, especially the oil body fraction, were more sensitive (64.2%) and specific (98.4%) than morphine, codeine and rocuronium tests for opioid sensitivity. Pollen allergy was not a risk factor for sensitisation to morphine. CONCLUSIONS: Sensitivity to opioids and intraoperative anaphylaxis can be diagnosed by routine tests. IgE and skin tests for the oil body fraction of P. somniferum had the highest sensitivity for sensitisation to opioids.

Atraumatic restorative treatment and Carisolv use for root caries in the elderly: 2-year follow-up randomized clinical trial.

OBJECTIVES: New preventive and treatment strategies are required to address the high prevalence of caries among the elderly. The main objective of this study was to analyze the effectiveness of Carisolv® gel to improve the clinical behavior of restorations obtained by atraumatic restorative treatment (ART) in root caries of elderly patients. A secondary objective was to determine the factors associated with the failure of ART restorations after a 2-year follow up. MATERIAL AND METHODS: A randomized controlled trial with 2-year follow-up was designed for this purpose. Candidate caries lesions were randomly assigned to an ART group for root caries treatment with the conventional ART technique, filling with glass ionomer, or an ART + Carisolv® gel for the same ART plus the application of a caries solvent (Carisolv®). Evaluations were conducted at 6, 12, and 24 months. RESULTS: A total of 81 restorations were performed, 37 in the ART group and 44 in the ART + Carisolv® gel group, with 22 and 26 restorations, respectively, surviving at the end of the 24-month follow-up. Survival rates at 24 months did not significantly differ between ART (63 %) and ART + Carisolv® gel (62 %) restorations. The best model for predicting the failure of the restorations included the number of tooth-brushings/day, the presence or not of prosthesis, the anterior or posterior location of the tooth, and the baseline plaque level. CONCLUSION: The application of Carisolv does not modify the survival rate of ART restorations in elderly patients. CLINICAL RELEVANCE: The use of Carisolv gel does not improve the outcomes of atraumatic restorative treatment.

Ex vivo UV-vis and FTIR photoacoustic spectroscopy of natural nanoemulsions from cellulose nanocrystals and saponins topically applied into the skin: Diffusion rates and physicochemical evaluation.

Nanoemulsions are increasingly gaining importance in the development of topically applied medicine and cosmetic products because their small droplets favor the penetration rates of active compounds into the body. In this scenario, the measurements of their diffusion rates as well as eventual physicochemical changes in the target tissues are of utmost importance. It is also recognized that the use of natural surfactants can avoid allergic reactions as frequently observed for synthetic products. The natural saponins extracted from Sapindus Saponaria have the property of forming foam and are exploited as biocompatible and biodegradable, while cellulose nanocrystals are known to increase the stability of a formulation avoiding the coalescence of drops at the interface. Therefore, nanoemulsions combining natural saponins and cellulose nanocrystals are promising systems that may facilitate greater diffusion rates of molecules into the skin, being candidates to substitute synthetic formulations. This study applied the Photoacoustic Spectroscopy technique to measure the diffusion rates and the physicochemical properties of nanoemulsified formulations containing saponins and cellulose nanocrystals topically applied to the skin. The ex vivo study combined the first-time photoacoustic measurements performed in both ultraviolet-visible and mid-infrared spectral regions. The toxicity of these formulations in L929 cells was also evaluated. The results showed that the formulations were able to propagate throughout the skin to a depth of approximately 756 µm, reaching the dermal side. The non-observation of absorbing band shifting or new bands in the FTIR spectra suggests that there were no structural changes in the skin as well as in the formulations after the nanoemulsions administration. The cytotoxicity results showed that the increase of cellulose nanocrystals concentration decreased cellular toxicity. In conclusion, the results demonstrated the advantage of combining photoacoustic methods in the ultraviolet-visible and mid-infrared spectral regions to analyze drug diffusion and interaction with the skin tissues. Both methods complement each other, allowing the confirmation of the nanoemulsion diffusion through the skin and also suggesting there were no detectable physicochemical changes in the tissues. Formulations stabilized with saponins and cellulose nanocrystals showed great potential for the development of topically administered cosmetics and drugs.

Sheep and goat immune responses to nose bot infestation: a review.

Oestrus ovis L. (Diptera: Oestridae) is a cosmopolitan agent of myiasis in sheep and goats. The parasitic phase begins after adult females deposit first-stage larvae (L1) into the nostrils of hosts; these larvae develop into L2 and L3 in the nasal and sinus horn cavities. Sneezing and nasal discharges are the major clinical signs in infected animals. The pathogenesis of O. ovis infection is caused by: (a) the trauma resulting from the mechanical action of spines and hooks during larval movement on mucosal membranes, and, more importantly, (b) an allergenic reaction provoked by molecules excreted/secreted by larvae, of which salivary antigens are those mainly recognized by the host's immune system. The recruitment of immune reactive cells increases gradually from the nasal to sinus cavities in infected hosts. Mast cells, eosinophils, macrophages and lymphocytes are always more numerous in infected than non-infected animals. Humoral (antibody) systemic response of immunoglobulin G (IgG) usually reaches seroconversion 2-4 weeks post-first infection and the highest levels are observed during the development of L2 and L3 larvae. Local antibody responses include specific IgG, which has been found to negatively correlate with larval survival and development. Hypersensitivity reaction, immunomodulation, immunization trials and mixed infections of O. ovis and helminths are discussed.

Food anaphylaxis in antiphospholipid syndrome and thrombosis.

BACKGROUND: We have observed that some cases of food anaphylaxis were followed by severe thrombosis associated to anticardiolipin antibodies. Food anaphylaxis associated with antiphospholipid syndrome has seldom been published. OBJECTIVE: The aims were: 1) to test anticardiolipin antibodies in an important number of patients with anaphylaxis due to vegetal foods and their relationship with possible thrombosis; and 2) to study seed and fruit hypersensitivity in patients with previous thrombotic events associated with antiphospholipid antibodies (aCL). METHODS: We included 30 patients diagnosed of thrombosis associated with aCL, 52 patients who suffered from anaphylaxis due to seeds or fruits, and 120 control patients. Haematological, cardiopulmonary vascular and rheumatologic studies had been performed as needed. In vivo and in vitro allergy tests with a large battery of vegetal allergens were carried out in all the patients. Measurement of IgG aCL antibodies and specific IgE to vegetal food was done by ELISA and CAP-FEIA (Phadia). Immunodetection and inhibitions with lipoproteins belonging to seeds were performed. RESULTS: Seventy-five percent of the patients diagnosed as having antiphospholipid primary syndrome had specific IgE against different proteins from different vegetable allergens, most of them seeds, and clearly against lipoproteins that were also recognised by the patients with food anaphylaxis but not by the control cases. Among the patients with anaphylaxis, 28% had anticardiolipin antibodies and 17.3% thrombosis. CONCLUSION: Our study suggests that seed lipoproteins which cause severe food anaphylaxis might have a potential role in the antiphospholipid syndrome and related thrombosis.

Functional, Clinical, and Sociodemographic Variables Associated with Risk of In-Hospital Mortality by COVID-19 in People over 80 Years Old.

OBJECTIVES: The objective is to assess the role of functional, clinical, and analytic parameters in predicting mortality in older patients hospitalized due to COVID-19. DESIGN: Cohort study with a mean follow-up of 12.8 days. SETTING: Public university hospital (Madrid, Spain). PARTICIPANTS: 499 patients 80 and above consecutively admitted to a Spanish public university hospital between 4 March 2020 and 16 May 2020. MEASUREMENTS: Mortality was the main outcome. Data of sociodemographic variables (age, sex, living), comorbidities, polypharmacy, functional status, date of hospital admission and length of stay was recorded. Clinical symptoms, laboratory and X-ray findings were collected at time of admission. For multivariant analysis, logistic regressions were performed to identify risk factors for death. RESULTS: Mean age was 86.7±4.4 with 37% of death. Mortality was associated with male gender [odds ratio (OR) 1.50; 95% confidence interval (CI) 1.01-2.24], with a 5-points increase on Barthel Index [OR 1.01 (95%CI 1.00-1.02)], higher Charlson Index score [OR 1.13 (95%CI 1.02-1.26)] and comorbidities [OR 1.28 (95%CI 1.06-1.53)], hyperpolipharmacy [OR 2.00 (95%CI 1.04-3.82)], unilateral pneumonia [OR 1.83 (95%CI 1.01-3.30)], higher levels of C-reactive protein [OR 1.09 (95%CI 1.06-1.12)] and creatine [OR 1.48 (95%CI 1.15-1.89)]. Higher oxygen levels were a protective factor [OR 0.92 (95%CI 0.89-0.95)]. CONCLUSIONS: Functional status, being male, a higher burden of comorbidities, hyperpolipharmacy, unilateral pneumonia and some laboratory parameters predict in-hospital mortality in this older population. The knowledge of these mortality risk factors should be used to improve the survival of older hospitalized patients.

Fetal liver and bone marrow JORO 75+ lymphocyte progenitors are precursors of CD4+8- TCR/CD3- early thymocytes.

We show here that cell sorter purified JORO 75+ lymphocyte progenitors from fetal liver or bone marrow of adult mice give rise in vitro to CD4+8- T cell receptor (TCR)/CD3- early thymocytes and CD4+8- TCR/CD3+ thymocyte subsets after coculture with the EH6 subcapsular thymic epithelial cell line, recombinant interleukin 7 (rIL-7) and F (supernatants from the FLS4.1 fetal liver stromal cell line). We find that in cultures that had additionally received rIL-2, CD4-8+ TCR/CD3+ cells were also generated. The results strongly suggest that fetal liver and marrow JORO 75+ lymphocyte progenitors are precursors to the early CD4+8- TCR/CD3- intrathymic population previously identified in the adult mouse. The EH6 subcapsular thymic epithelial cell line should facilitate the study of the molecular events responsible for very early stages of T cell development including T lymphocyte-lineage commitment.

T cell growth factor abrogates concanavalin A-induced suppressor cell function.

Concanavalin A (Con-A)-induced suppressor T cells were found to respond to T cell growth factor (TCGF) by proliferation. TCGF abrogated the suppressor activity exerted by these cells on phytohemagglutinin (PHA)- and alloantigen- induced lymphocyte proliferation and on pokeweed mitogen (PWM)-driven immunoglobulin secretion. The Con-A-activated suppressor T cells absorbed the TCGF activity, preincubation of these active suppressor cells with TCGF abolished their suppressor activity and addition of increasing numbers of Con-A-activated T cells reverted the abrogator,/ effect of TCGF. Altogether, these findings suggest that Con-A-induced suppressor T cells exert their function by decreasing the available levels of TCGF. Cyclosporin-A (CYA), which is known to inhibit the expression of receptors for TCGF on T cells, also inhibited the suppressor activity as determined in both indicator systems, namely PHA- or alloantigen-induced DNA synthesis and PWM-induced immunoglobulin synthesis. CYA made Con-A-treated T cells unresponsive to TCGF and unable to absorb the growth factor, supporting the notion that CYA inhibits the expression of TCGF receptors on T cells, a mechanism by which this drug seems to abrogate Con-A-induced suppressor T cell function.