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.

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.

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

La diabetes mellitus tipo 3c (DM3c) es una diabetes (DM) del páncreas exocrino que habrá que sospechar siempre que existan antecedentes de pancreatitis crónica (PC), pancreatitis aguda (PA) o recidivante (PAR) (80% de los casos) o una DM de nueva aparición en individuos a partir de los 50 años sin otra justificación (pruebas de autoinmunidad negativas, anticuerpos contra la descarboxilasa del ácido glutámico). Se trata de una entidad mal diagnosticada como diabetes tipo 2 (DM2) (90%) y, por ello, de no sospecharla puede pasar inadvertida. Para su diagnóstico son de utilidad la ecografía abdominal, la determinación del antígeno tumoral carbohydrate antigen 19-9 (CA 19.9), la resonancia magnética nuclear (RMN) o la tomografía axial computarizada (TAC). El tratamiento es el mismo de la DM2, aunque con ciertas especificaciones según el tipo de fármacos y con la particularidad de que al tratarse de una «diabetes frágil» habrá que tener mayor precaución con las hipoglucemias (monitorización). Asimismo, al ser una enfermedad del páncreas exocrino habrá que tratar específicamente esta para evitar las alteraciones metabólicas, malabsortivas y/o nutricionales (AU)

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 diabetes» 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 (AU)

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

Antecedentes y objetivos Estudios previos que cuantifican el coste de la diabetes tipo 2 (DM2) muestran resultados muy dispares. Nos planteamos definir el perfil del paciente con DM2 en Andalucía, analizar el uso de recursos sanitarios y, cuantificar su coste económico en el año 2022. Pacientes y métodos Estudio multicéntrico, transversal y descriptivo; 385 pacientes con DM2 de toda Andalucía (IC 95%; error: 5%). Datos analizados: edad, sexo, asistencia a consultas de Atención Primaria (AP), de enfermería, de urgencias y de especialidades hospitalarias; consumo de fármacos en general y antidiabéticos en particular, tiras de glucemia, pruebas complementarias y días de ingreso hospitalario. Resultados Edad media: 70,7 ± 12,44 años; 53,6% hombres. Contactos asistenciales: médico de AP: 8,36 ± 4,69; enfermería: 7,17 ± 12; consultas hospitalarias: 2,31 ± 2,38; urgencias: 1,71 ± 2,89. Días de ingreso hospitalario: 2,26 ± 6,46. Analíticas: 3,79 ± 5,45 y 2,17 ± 3,47 Rx. Fármacos consumidos: 9,20 ± 3,94 (1,76 ± 0,90 antidiabéticos). Tiras glucemia: 184 ± 488. Coste anual: 5.171,05 €/paciente/año (2.228,36 € por ingresos hospitalarios, 1.702,87 € por fármacos y 1.239,82 € por asistencias y pruebas complementarias). Conclusiones El andaluz con DM2 tiene 71 años de edad, consume 10 fármacos diferentes y trata su DM2 con doble terapia. Tiene 20 asistencias/año (75% en AP), cuatro análisis, dos Rx y precisa dos días de ingreso hospitalario. Los costes sanitarios directos superan los 5.000 €/año. Lo que supone 41,66% del presupuesto de la Consejería de Salud y triplica el gasto medio por habitante (AU)

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 (AU)

[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.

[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.

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.

Pharmacologic Treatment of Anti-MDA5 Rapidly Progressive Interstitial Lung Disease.

Purpose of the Review: Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders. The presence of different autoantibodies allows clinicians to define distinct phenotypes. Antibodies against the melanoma differentiation-associated protein 5 gene, also called anti-MDA5 antibodies, are associated with a characteristic phenotype, the clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease. This review aims to analyze the different pharmacological options for the treatment of rapidly progressive interstitial lung disease in patients with anti-MDA5 antibodies. Recent Findings: Evidence-based therapeutic recommendations suggest that the best initial approach to treat these patients is an early combination of immunosuppressive drugs including either glucocorticoids and calcineurin inhibitors or a triple therapy adding intravenous cyclophosphamide. Tofacitinib, a Janus kinase inhibitor, could be useful according to recent reports. High ferritin plasma levels, generalized worsening of pulmonary infiltrates, and ground-glass opacities should be considered predictive factors of a bad outcome. In this scenario, clinicians should consider rescue therapies such as therapeutic plasma exchange, polymyxin-B hemoperfusion, veno-venous extracorporeal membrane oxygenation, or even lung transplantation. Summary: Combined immunosuppressive treatment should be considered the first-line therapy for patients with anti-MDA5 rapidly progressive interstitial lung disease. Aggressive rescue therapies may be useful in refractory patients.

[Evaluation of the validity of Ag PANBIO-COVID19 in the diagnosis of SARS-CoV-2 infection in asymptomatic or mildly infected patients]. / Evaluación de la validez del Ag PANBIO-COVID19 de Abbott en el diagnóstico de la infección por SARS-CoV-2 en pacientes asintomáticos o con infección leve.

OBJECTIVE: To assess the validity of SARS-CoV-2 Antigen (Ag) detection for the diagnosis of SARS-CoV-2 infection in mildly infected or asymptomatic patients. METHODS: Observational study to evaluate diagnostic tests. Non-hospitalized patients with indication for diagnostic testing for SARS-CoV-2 infection were included. The diagnostic test to be evaluated was the determination of Ag and as a reference standard to determine the presence of viral RNA the RT-PCR was used. RESULTS: A total of 494 patients were included. Of these 71.5% (353/494) had symptoms and 28.5% (141/494) were asymptomatic (presurgery screening (35/494) and confirmed case-contact (106/494). The overall sensitivity of the Ag test was 61.1% and the specificity was 99.7%. The sensitivity and specificity in the asymptomatic group were 40% and 100% respectively, and in the symptomatic group 63.5% and 99.6% respectively. In turn, the sensitivity and specificity in the group of symptomatic patients varied according to the time of symptom evolution: in patients with recent symptoms, they were 71.4% and 99.6% respectively, while in patients with symptoms of more than 5 days of evolution, they were 26.7% and 100% respectively. In all groups studied, the presence of antigen is associated with a high viral load (Ct<30 cycles). CONCLUSIONS: The use of Ag detection test is not indicated for the diagnosis of SARS-CoV-2 infection in asymptomatic patients or with symptoms of more than 5 days of evolution, but it could be useful in patients with symptoms of 1-5 days of evolution.

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.

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.

Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours: results from the COPPADIS cohort.

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose.