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.

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.

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 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.

[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.

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.

Usefulness of procalcitonin clearance as a prognostic biomarker in septic shock. A prospective pilot study.

OBJECTIVE: To evaluate procalcitonin clearance as a prognostic biomarker in septic shock. DESIGN: Prospective, observational pilot study. SETTING: Intensive care unit. PATIENTS: Patients admitted to the ICU due to septic shock and multiorgan dysfunction. INTERVENTIONS: Serum concentrations of procalcitonin were determined within 12h of onset of septic shock and multiorgan dysfunction (coinciding with admission to the ICU), and the following extractions were obtained after 24, 48 and 72h in patients who survived. DATA COLLECTED: Demographic data, Acute Physiology and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment score, data on the primary focus of infection, and patient outcome (ICU mortality). RESULTS: Procalcitonin clearance was higher in survivors than in non-survivors, with significant differences at 24h (73.9 [56.4-83.8]% vs 22.7 [-331-58.4], p<0.05) and 48h (81.6 [71.6-91.3]% vs -7.29 [-108.2-82.3], p<0.05). The area under the ROC curve was 0.74 (95%CI, 0.54-0.95, p<0.05) for procalcitonin clearance at 24h, and 0.86 (95%CI, 0.69-1.0, p<0.05) at 48h. CONCLUSIONS: ICU mortality was associated to sustained high procalcitonin levels, suggesting that procalcitonin clearance at 48h may be a valuable prognostic biomarker.

Occular complications following dental local anesthesia.

OBJECTIVE: To determine the frequency of appearance and the factors most commonly associated with ocular complications following dental local anesthesia, also establishing the location and type of anesthesia used. STUDY DESIGN: An indexed search in the Pubmed and Compludoc databases was carried out with the keywords "oral anesthesia", "ocular", "ophthalmologic", "damage", "complications", "injection". We established a limitation that the literature had to have been published after the year 1970. A total of 19 articles were obtained, forming a total sample of 37 patients. The patient's sex, age, nerve anesthetized, type of anesthetic used, ophthalmological complication present, recovery time, treatment and side effects were analyzed. RESULTS: There is a higher involvement of females (77%). The average age was 34.2 years. There was no preference for an anesthetic technique. Diplopia was the most common complication (65%), which coincides with the data from other authors. Almost all of the complications were of a temporary nature, with an average recovery time of 68 minutes. CONCLUSIONS: This is one of the few studies of its kind in dental literature, it thus being difficult to make precise conclusions. Ophthalmological complications are seldom a problem, diplopia being the most common among them. The authors appear to indicate an intravascular injection of the anesthetic as the cause of the problem, and therefore, it should be avoided in order to prevent accidents at the ocular level.

Prognostic value of lung ultrasound and its link with inflammatory biomarkers in patients with SARS-CoV-2 infection.

BACKGROUND: Lung ultrasound (LUS) has shown to correlate well with the findings obtained by chest computed tomography (CT) in acute-phase COVID-19. Although there is a significant correlation between blood biomarkers and CT radiological findings, a potential correlation between biochemical parameters and LUS images is still unknown. Our purpose was to evaluate whether mortality can be predicted from either of two lung ultrasound scoring systems (LUSS) as well as the potential association between lung lesions visualised by LUS and blood biomarkers. METHODS: We performed a retrospective observational study on 45 patients aged>70 years with SARS-CoV-2 infection who required hospitalisation. LUS was carried out at admission and on day 7, when the clinical course was favourable or earlier in case of worsening. Disease severity was scored by means of LUSS in 8 (LUSS8) and in 12 (LUSS12) quadrants. LUS and blood draw for inflammatory marker analysis were performed at the same time. RESULTS: LUSS8 vs LUSS12 predicted mortality in 93.3% vs 91.1% of the cases; their associated odds ratios (OR) were 1.67 (95% CI 1.20-2.31) and 1.57 (95% CI 1.10-2.23), respectively. The association between biochemical parameters and LUSS scores was significant for ferritin; the OR for LUSS12 was 1.005 (95% CI 1.001-1.009) and for LUSS8 1.005 (95% CI 1.0-1.1), using thresholds for both of them. CONCLUSIONS: The prognostic capacity of LUSS12 does not surpass that of LUSS8. There is a correlation between ferritin levels and LUSS.

Impact of Sepsis Flow Chip, a novelty fast microbiology method, in the treatment of bacteremia caused by Gram-negative bacilli.

OBJECTIVE: The aim of this study was to assess the impact of the information provided by the new Sepsis Chip Flow system (SFC) and other fast microbiological techniques on the selection of the appropriate antimicrobial treatment by the clinical researchers of an antimicrobial stewardship team. METHODS: Two experienced clinical researchers performed the theoretical exercise of independently selecting the treatment for patients diagnosed by bacteremia due to bacilli gram negative (BGN). At first, the clinicians had only available the clinical characteristics of 74 real patients. Sequentially, information regarding the Gram stain, MALDI-TOF, and SFC from Vitro were provided. Initially, the researchers prescribed an antimicrobial therapy based on the clinical data, later these data were complementing with information from microbiological techniques, and the clinicians made their decisions again. RESULTS: The data provided by the Gram stain reduced the number of patients prescribed with combined treatments (for clinician 1, from 23 to 7, and for clinician 2, from 28 to 12), but the use of carbapenems remained constant. In line with this, the data obtained by the MALDI-TOF also decreased the combined treatment, and the use of carbapenems remained unchanged. By contrast, the data on antimicrobial resistance provided by the SFC reduced the carbapenems treatment. CONCLUSIONS: From the theoretical model the Gram stain and the MALDI-TOF results achieved a reduction in the combined treatment. However, the new system tested (SFC), due to the resistance mechanism data provided, not only reduced the combined treatment, it also decreased the prescription of the carbapenems.