Severe Allergy as a Chronic Inflammatory Condition From a Systems Biology Perspective.

Persistent and unresolved inflammation is a common underlying factor observed in several and seemingly unrelated human diseases, including cardiovascular and neurodegenerative diseases. Particularly, in atopic conditions, acute inflammatory responses such as those triggered by insect venom, food or drug allergies possess also a life-threatening potential. However, respiratory allergies predominantly exhibit late immune responses associated with chronic inflammation, that can eventually progress into a severe phenotype displaying similar features as those observed in other chronic inflammatory diseases, as is the case of uncontrolled severe asthma. This review aims to explore the different facets and systems involved in chronic allergic inflammation, including processes such as tissue remodelling and immune cell dysregulation, as well as genetic, metabolic and microbiota alterations, which are common to other inflammatory conditions. Our goal here was to deepen on the understanding of an entangled disease as is chronic allergic inflammation and expose potential avenues for the development of better diagnostic and intervention strategies.

Effects of Age, Period, and Cohort on the Incidence of Psoriasis in Spain: A 30-year Review (1990-2019).

AIM: This study aimed to investigate the effects of age, period, and cohort on the incidence of psoriasis in Spain from 1990 through 2019 using the Global Burden of Disease (GBD) database and age-period-cohort (A-P-C) analysis. METHODS: We conducted an ecological trend study to analyze the incidence rates of psoriasis in Spain from 1990 through 2019. Joinpoint Regression Program, Version 5.0.2 - May 2023; Surveillance Research Program, National Cancer Institute and National Cancer Institute A-P-C tools were used to identify trends and assess the effects of age, period, and cohort. RESULTS: From 1990 through 2019, an estimated 2.99 million cases of psoriasis were diagnosed in Spain, with a mean annual increase of 0.49%. Significant decreases in age-standardized incidence rates (ASIR) were reported for both sexes, with women consistently maintaining a slightly higher ASIR. Joinpoint analysis revealed multiple turning points in the downward trend, indicating periods of stabilization. A-P-C analysis demonstrated significant declines in both net (overall trend) and local drift (age-specific trends), indicating a broad decrease in the incidence of psoriasis across most age groups. While the risk of psoriasis increased with age, peaking in the 50-54 age group, it declined thereafter. Furthermore, the analysis revealed a continuous decline in risk from 1990 through 2019 for both sexes, with individuals born in the early 21st century exhibiting a significantly lower risk vs those born in the early 20th century. CONCLUSION: This study observed a slight decline in the reported psoriasis ASIR in Spain, potentially due to reduced exposure to risk factors. However, limitations in data and the complexity of factors influencing the incidence of psoriasis require further research.

Effects of Age, Period, and Cohort on the Incidence of Psoriasis in Spain: A 30-year Review (1990­2019).

AIM: This study aimed to investigate the effects of age, period, and cohort on the incidence of psoriasis in Spain from 1990 through 2019 using the Global Burden of Disease (GBD) database and age-period-cohort (A-P-C) analysis. METHODS: We conducted an ecological trend study to analyze the incidence rates of psoriasis in Spain from 1990 through 2019. Joinpoint software and National Cancer Institute A-P-C tools were used to identify trends and assess the effects of age, period, and cohort. RESULTS: From 1990 through 2019, an estimated 2.99 million cases of psoriasis were diagnosed in Spain, with a mean annual increase of 0.49%. Significant decreases in age-standardized incidence rates (ASIR) were reported for both sexes, with women consistently maintaining a slightly higher ASIR. Joinpoint analysis revealed multiple turning points in the downward trend, indicating periods of stabilization. A-P-C analysis demonstrated significant declines in both net (overall trend) and local drift (age-specific trends), indicating a broad decrease in the incidence of psoriasis across most age groups. While the risk of psoriasis increased with age, peaking in the 50-54 age group, it declined thereafter. Furthermore, the analysis revealed a continuous decline in risk from 1990 through 2019 for both sexes, with individuals born in the early 21st century exhibiting a significantly lower risk vs those born in the early 20th century. CONCLUSION: This study observed a slight decline in the reported psoriasis ASIR in Spain, potentially due to reduced exposure to risk factors. However, limitations in data and the complexity of factors influencing the incidence of psoriasis require further research.

Efficacy and safety of oral sirolimus for high-flow vascular malformations in real clinical practice.

BACKGROUND: Vascular malformations are a complex pathology with few treatment options. In previously published studies, oral sirolimus (rapamycin) has shown promising results in the treatment of low-flow vascular malformations, but its usefulness in high-flow vascular malformations is controversial. AIM: To evaluate the efficacy and safety of sirolimus for the treatment of high-flow vascular malformations in real-life practice. METHODS: In a unit specializing in vascular anomalies, patients treated with oral sirolimus for high-flow vascular malformations were located by consulting the drug dispensations. Reviewing the electronic medical records, data on patient demographics, vascular malformation characteristics, treatments, toxicity and clinical course were collected and statistically analysed. RESULTS: Nine patients with vascular malformations were included: eight had arteriovenous malformation and one had arteriovenous fistula. Six of these malformations were isolated while three were part of a syndrome. Sirolimus was initiated at a dosage of 1-4 mg/day to be taken as a single dose. Partial response was observed in eight of the nine patients (88.9%) with high-flow vascular malformation, while worsening was observed in the remaining patient. The treatment was well tolerated and at the most recent follow-up, five patients remained on treatment with oral sirolimus. CONCLUSION: Our results show that oral sirolimus is a well-tolerated therapeutic option, with an excellent safety profile, which can be useful in the long-term stabilization of patients with high-flow vascular malformations. Single-daily dosage may improve long-term adherence to treatment without worsening its effectiveness.

Effect of antibiotics on biofilm inhibition and induction measured by real-time cell analysis.

AIMS: The purpose of the current work was to study the pattern and dynamics of biofilm formation in clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis in the presence of 10 antibiotics with different action mechanisms. METHODS AND RESULTS: By using impedance measurements in microtitre plates with gold electrodes we have assessed the antibiotic effect on bacterial biofilm growth in real time. The impedance measurements appear to combine both cellular growth and matrix production, representing a measurement of total biofilm mass. Several clinical and reference strains were tested, showing different slopes and cell index values which correlated with their capacity to form biofilms as assessed by attachment to standard microtitre well plates and safranin staining. Biofilms were heavily reduced in biofilm mutants or by protease treatment in protein-based biofilm matrixes. Antibiotic resistance patterns of biofilms, which were very different to those obtained by traditional methods like epsilon-tests on solid media, revealed features that would pass unnoticed by end-point methods. CONCLUSIONS: Once the biofilm is formed, antibiotic efficacy dramatically reduced and sub-inhibitory concentrations of some antibiotics, such as linezolid and clarithromycin, stimulated biofilm growth, stressing the importance of studying antibiotic resistance under biofilm growth conditions in real time. SIGNIFICANCE AND IMPACT OF THE STUDY: Real-time biofilm analysis provides a promising tool to evaluate antibiotic therapy in clinical biofilm-mediated infections.

Acaricidal activity of Metarhizium anisopliae isolated from paddocks in the Mexican tropics against two populations of the cattle tick Rhipicephalus microplus.

The acaricidal effects of 55 strains of Metarhizium anisopliae (Metschnikoff) Sorokin, 1883 (Hypocreales: Clavicipitaceae) isolated from paddocks of cattle farms were evaluated in two Rhipicephalus microplus (Canestrini 1887) (Ixodida: Ixodidae) populations, of which one was multi-resistant and one was susceptible to chemical acaricides. Percentage mortality and reproductive efficiency indices in R. microplus were evaluated by adult immersion tests at a dose of 1 × 108 conidia/mL for each fungal strain. Some strains were selected to calculate lethal concentrations to kill 50% (LC50 ) and 99% (LC99 ) of engorged ticks. Strains MaV22, MaV26 and MaV55 induced 100% mortality in R. microplus on day 14. Strains MaV05, MaV09 and MaV22 caused mortality of >90% from day 12 onward in both tick populations. The most effective acaricidal fungal strain, MaV55, inhibited egg laying by 54.86 and 55.86% in acaricide-resistant and -susceptible R. microplus populations, respectively. None of the fungal strains had statistically significant effects on larval hatching. In conclusion, nine strains of M. anisopliae demonstrated high acaricidal effects against R. microplus and reduced its egg laying. No differences in acaricidal effects were observed between the two populations of ticks tested.

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy.

Airway epithelium is the cellular structure with the greatest surface exposed to a plethora of environmental airborne substances, including microorganisms, respiratory viruses, air pollutants, and allergens. In addition to being a protective physical barrier at the air-liquid interface, the airway epithelium acts as an effective chemical and immunological barrier that plays a crucial role in orchestrating the immune response in the lungs, by supporting the activation, recruitment, and mobilization of immune cells. Airway epithelium dysfunction has been clearly associated with various airway inflammatory diseases, such as allergic asthma. Although it is not fully understood why a person develops respiratory allergy, a growing body of evidence shows that the nature of the host's immune response is strongly determined by the state of the airway epithelium at the time of contact with the inhaled allergen. Our review highlights the physiological state of airway epithelium as a key element in the development of allergy and, particularly, in exacerbation of asthma. We review the role of physiological oxidants as signaling molecules in lung biology and allergic diseases and examine how high exposure to air pollutants (eg, cigarette smoke and diesel particles) can contribute to the increased incidence of respiratory allergy and exacerbation of the disease.

Empirical monotherapy with meropenem or combination therapy: the microbiological point of view.

The increase in the number of clinical isolates of multiresistant Enterobacteriaceae and Pseudomonas aeruginosa raises problems in decision-making on empirical treatments for severe Gram-negative bacilli-associated infections. The aim of our study is to determine the resistance of meropenem in our setting and the co-resistance of a combination of this compound with two antibiotics from different families: amikacin and ciprofloxacin. Between 2009 and 2013, a total of 81,310 clinical isolates belonging to the main species of Enterobacteriaceae and 39,191 clinical isolates of P. aeruginosa isolated in 28 hospitals in the Valencian Community on the South East Mediterranean Coast of Spain were analyzed using data provided by RedMiva (microbiological surveillance network of the Valencian Community). Meropenem resistance in Enterobacteriaceae increased from 0.16 % in 2009 to 1.25 % in 2013. Very few Enterobacteriaceae strains resistant to meropenem were sensitive to ciprofloxacin; in contrast, the combination of meropenem and amikacin led to a marked decrease in the risk of the microorganisms being resistant to both drugs (RR = 34 in 2013). In the case of P. aeruginosa, meropenem resistance also increased (from 14.32 % in 2009 to 24.52 % in 2013). Most meropenem-resistant P. aeruginosa isolates were also resistant to fluoroquinolones. However, the addition of amikacin led to a more than three-fold decrease in the risk of resistance. In our setting, empirical treatment with meropenem is adequate in enterobacterial infections, but poses difficulties when infection due to P. aeruginosa is suspected, in which case a combination of meropenem and amikacin has been shown to have a higher microbiological success rate.

Immunologic responses to the major allergen of Olea europaea in local and systemic allergic rhinitis subjects.

OBJECTIVE: To evaluate the in vivo and in vitro responses to nOle e 1 in allergic rhinitis (AR) and local allergic rhinitis (LAR) patients sensitized to olive tree pollen (OL) confirmed by nasal allergen provocation test (NAPT). METHODS: Twelve subjects with AR, 12 with LAR and 12 subjects as control group (CG) were selected. Skin testing and NAPT with nOle e 1 were performed. Eosinophilic cationic protein (ECP) and tryptase were measured in nasal lavages before and after NAPT. Serum IgE to OL allergens was measured by ELISA. Basophil activation tests (BAT) with OL and nOle e 1 and dendritic cell maturation/proliferation studies were carried out. RESULTS: All AR (12/12) and 10/12 (83%) of LAR had a +NAPT to nOle e 1. ECP levels in nasal lavages were significantly increased after NAPT in both AR and LAR compared with CG at 15 min (P < 0.05). Serum IgE was positive only in AR. All AR had +BAT responses to OL and 10/12 to nOle e 1 (83%); 8/12 LAR (66.6%) had a +BAT to OL and 4/12 (33%) to nOle e 1, with only one subject of the CG with a +BAT to both OL and nOle e 1 (8%). Dendritic cell proliferation to nOle e 1 was increased in AR compared to LAR and CG (P = 0.019 and P = 0.001, respectively). CONCLUSION: Both AR and LAR had a similar in vivo response to nOle e 1 with release of inflammatory mediators. Specific basophil activation with OL and nOle e 1 was observed in LAR confirming previous data obtained with dust mites.

Mucosal associated invariant T cells: Powerhouses of the lung.

The lungs face constant environmental challenges from harmless molecules, airborne pathogens and harmful agents that can damage the tissue. The lungs' immune system includes numerous tissue-resident lymphocytes that contribute to maintain tissue homeostasis and to the early initiation of immune responses. Amongst tissue-resident lymphocytes, Mucosal Associated Invariant T (MAIT) cells are present in human and murine lungs and emerging evidence supports their contribution to immune responses during infections, chronic inflammatory disorders and cancer. This review explores the mechanisms underpinning MAIT cell functions in the airways, their impact on lung immunity and the potential for targeting pulmonary MAIT cells in a therapeutic context.

[Antihypertensive prescription in type 2 diabetes patients in Andalusia and SEH-LELHA 2022 guidelines: An economic cost evaluation]. / Prescripción de antihipertensivos en personas con diabetes tipo 2 en Andalucía y recomendaciones SEH-LELHA 2022: evaluación del coste y uso.

OBJECTIVE: This study aims to analyze the prescription of antihypertensive drugs in patients with type 2 diabetes (T2D) in Andalusia, comparing it with the SEH-LELHA 2022 guidelines, and to assess the direct cost of these treatments. MATERIALS AND METHODS: A multicentric, cross-sectional, and descriptive study was conducted with 385 T2D patients. Participants were randomly selected from the patient lists of 120 primary care physicians from Andalusia. Inclusion criteria included a diagnosis of T2D and complete clinical records for the year 2022. Demographic data and drug prescription information were collected, with the average cost per patient being calculated. RESULTS: The mean age of the subjects was 70.72 years, with 53.51% being male. A total of 70.9% of the patients were taking antihypertensive drugs, the most common being ACE inhibitors/ARBs (70.9%), diuretics (70.1%), beta-blockers (40.0%), and calcium channel blockers (20.0%). Each patient took an average of 2.46±1.06 antihypertendsive, and fixed association of 2 or more antihypertensive drugs were used by 40.9% of the studied patients. The annual cost per patient was 141.45€/year. CONCLUSIONS: The study reveals strong adherence to the SEH-LELHA 2022 guidelines among physicians in Andalusia regarding the of antihypertensives for T2D patients, with a significant preference for Renin-Angiotensin System blockers, diuretics, and beta-blockers. However, a notable deviation in prescription practices was observed with the frequent choice of doxazosin over spironolactone, despite the latter being the recommended option for resistant hypertension. Although the overall expenditure on antihypertensives is moderate, their cost-effectiveness is enhanced by the efficacy of these treatments in preventing cardiovascular complications.

Rising testicular cancer incidence in Spain despite declining mortality: an age-period-cohort analysis.

BACKGROUND: Testicular cancer, primarily affecting young men, has seen an alarming rise globally. This study delves into incidence and mortality trends in Spain from 1990 to 2019 using the Global Burden of Disease (GBD) database and the Age-Period-Cohort (A-P-C) model. METHODS: We analyzed GBD data on testicular cancer cases and deaths in Spain, calculating age-standardized rates (ASIR and ASMR) and employing Joinpoint regression to identify significant shifts. The A-P-C model further dissected the effects of age, period, and birth cohort on these trends. RESULTS: A striking doubling in testicular cancer incidence was observed, from 3.09 to 5.40 per 100,000 men (1.9% annual increase), while mortality rates remained stable and even decreased in younger age groups (0.34 to 0.26 per 100,000, 0.8% annual decrease). Joinpoint analysis revealed four distinct periods of increasing incidence, with a recent slowdown. The A-P-C model highlighted a consistent rise in incidence risk with each successive generation born after 1935, contrasting with a progressive decline in mortality risk across cohorts, particularly marked for those born since the 1960s. CONCLUSION: While mortality rates are encouraging, Spain reflects the global trend of escalating testicular cancer incidence. The A-P-C analysis suggests a generational influence, but the underlying causes remain elusive. Further research is crucial to understand these trends and implement effective prevention strategies to combat this growing health concern.

[Type 2 diabetes in Andalusia: Resources use and economic cost]. / Diabetes tipo 2 en Andalucía: uso de recursos y coste económico.

BACKGROUND AND OBJECTIVES: Previous studies that quantify the cost of type 2 diabetes (DM2) show very different results. We set out to define the profile of the patient with DM2 in Andalusia, analyze the use of health resources and quantify their economic cost during 2022. PATIENTS AND METHODS: Multicenter, cross-sectional and descriptive study. Three hundred and eighty-five patients with DM2 from Andalusia (confidence level: 95%; error: 5%). DATA ANALYZED: age, sex, attendance at primary care (PC), nursing, emergency and hospital specialty consultations; consumption of drugs in general and antidiabetics in particular, blood glucose strips, complementary tests and hospitalization days. RESULTS: Mean age: 70.7 ± 12.44 years; 53.6% men. Care contacts: PC physician: 8.36 ± 4.69; nursing: 7.17 ± 12; hospital visits: 2.31 ± 2.38; emergencies: 1.71 ± 2.89; hospitalization days: 2.26 ± 6.46. LABORATORY TESTS: 3.79 ± 5.45 and 2.17 ± 3.47 Rx. Drugs consumed: 9.20 ± 3.94 (1.76 ± 0.90 antidiabetics). Blood glucose strips: 184 ± 488. Annual cost: 5171.05 €/patient/year (2228.36 € for hospital admissions, 1702.87 € for drugs and 1239.82 € for assistance and complementary tests). CONCLUSIONS: The DM2 Andalusian is 71 years old, consumes 10 different drugs and treats DM2 with double therapy. He has been 20 attendances/year (75% in PC), 4 analyses, 2 X-rays and requires 2 days of hospitalization. Direct healthcare costs goes over 5000 €/year. This represents 41.66% of the budget of the Andalusian Ministry of Health and triples the average cost per habitant.

[Type 3 c diabetes: Approach from the first level doctor]. / La diabetes tipo 3c. Abordaje desde el médico del primer nivel.

DM3c is diabetes (DM) of the exocrine pancreas that must be suspected whenever there is a history of chronic pancreatitis (CP), acute pancreatitis (AP) or recurrence (80% of cases) or new-onset DM in individuals from over 50 years of age without any other justification (negative autoimmunity tests, Glutamic Acid Decarboxylase antibodies). It is an entity misdiagnosed as type 2 diabetes (DM2) (90%) and therefore, if it is not suspected, it can go unnoticed. For its diagnosis, abdominal ultrasound, determination of the CA 19.9 tumor antigen (carbohydrate antigen 19-9), nuclear magnetic resonance (NMR) or computerized axial tomography (CT) are useful. The treatment is the same as DM2, although certain specifications depend on the type of drugs and with the particularity that in dealing with «fragile diabetes¼ greater caution must be taken with hypoglycemia (monitoring). Likewise, as it is a disease of the exocrine pancreas, it will have to be specifically treated to avoid metabolic, malabsorptive and/or nutritional alterations.

Mortality rates for Parkinson's disease are increasing in Spain. An age-period-cohort and joinpoint analysis of mortality rates from 1981 to 2020.

BACKGROUND: Mortality in Parkinson's disease is increasing worldwide, but Spanish data need further study. OBJECTIVE: To analyse the mortality trends of Parkinson's disease in Spain between 1981 and 2020. METHODS: This observational retrospective study assessed the Parkinson's disease mortality data from 1981 to 2020 collected from the National Statistics Institute of Spain. Age-standardised mortality rates were analysed by age and sex groups, detecting significant mortality trends through a joinpoint analysis. Age-period-cohort effect and potential years of life lost analyses were conducted. The European standard population of 2013 was considered for the analyses. RESULTS: A total of 88 034 deaths were assessed. The overall age-standardised mortality rate rose throughout the period from 3.67 to 8.57 per 100 000 inhabitants. Mortality rates in men were higher than in women, 11.63 versus 6.57 deaths per 100 000 inhabitants. The sex ratio showed an increase in premature mortality in men during 2020. The overall joinpoint analysis recorded a rise in mortality, primarily since the 20th century, mainly in male and older groups, that matched with a period effect. The age effect was detected, confirming higher mortality at an older age. The analysis of potential years of life lost detected a growth in this rate, changing from 0.66 in 1981 to 1.06 in 2020. CONCLUSIONS: Mortality data for Parkinson's disease in Spain rose significantly in forty years. Mortality rate was higher in the male and age group above 75 years of age. The sex ratio showed premature mortality in men in 2020, which will need further study.

Rubella immune status among immigrant and nonimmigrant women in Spain.

A cross-sectional study of seroprevalence of rubella antibodies was carried out in all immigrant pregnant women (1,627) from February 2006 to June 2010. For each immigrant woman one Spanish pregnant woman was recruited. The seroprevalence of IgG antibodies against rubella in immigrant women was 92% (95% confidence interval [CI]: 90.4-93.3), and in native women was 97.7% (95%CI: 96.7-98.4) (P < 0.001). Immunity against was lowest among women from Latin America (odds ratio [OR]: 0.17), followed by women from Asia (OR: 0.20), Sub-Saharan Africa (OR: 0.27) and Northern Africa (OR: 0.37). Female immigrants from developing countries should be targeted for immunization to reduce the risk of congenital rubella.

Impaired fasting glucose, ancestry and waist-to-height ratio: main predictors of incident diagnosed diabetes in the Canary Islands.

AIMS: To estimate the incidence rate and risk factors for diabetes in the Canary Islands. METHODS: A total of 5521 adults without diabetes were followed for a median of 3.5 years. Incident cases of diabetes were self-declared and validated in medical records. The following factors were assessed by Cox regression to estimate the hazard ratios for diabetes: impaired fasting glucose (5.6 mmol/l ≤ fasting glucose ≤ 6.9 mmol/l), BMI, waist-to-height ratio (≥ 0.55), insulin resistance (defined as triglycerides/HDL cholesterol ≥ 3), familial antecedents of diabetes, Canarian ancestry, smoking, alcohol intake, sedentary lifestyle, Mediterranean diet, social class and the metabolic syndrome. RESULTS: The incidence rate was 7.5/10(3) person-years (95% CI 6.4-8.8). The greatest risks were obtained for impaired fasting glucose (hazard ratio 2.6; 95% CI 1.8-3.8), Canarian ancestry (hazard ratio 1.9; 95% CI 1.0-3.4), waist-to-height ratio (hazard ratio 1.7; 95% CI 1.1-2.5), insulin resistance (hazard ratio 1.5; 95% CI 1.0-2.2) and paternal history of diabetes (hazard ratio 1.5; 95% CI 1.0-2.3). The metabolic syndrome (hazard ratio 1.9; 95% CI 1.3-2.8) and BMI ≥ 30 kg/m(2) (hazard ratio 1.7; 95% CI 1.0-2.7) were significant only when their effects were not adjusted for impaired fasting glucose and waist-to-height ratio, respectively. CONCLUSIONS: The incidence of diabetes in the Canary Islands is 1.5-fold higher than that in continental Spain and 1.7-fold higher than in the UK. The main predictors of diabetes were impaired fasting glucose, Canarian ancestry, waist-to-height ratio and insulin resistance. The metabolic syndrome predicted diabetes only when its effect was not adjusted for impaired fasting glucose. In individuals with Canarian ancestry, genetic susceptibility studies may be advisable. In order to propose preventive strategies, impaired fasting glucose, waist-to-height ratio and triglyceride/HDL cholesterol should be used to identify subjects with an increased risk of developing diabetes.