Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

[Translated article] Descriptive study of spinal instrumentation-related infections in a tertiary hospital.

INTRODUCTION: Spinal instrumentation-related infections (SIRI) are one of the main causes of post-surgical complication and comorbidity. Our objective was to describe the clinical and microbiological characteristics, treatment and prognosis of these infections. MATERIAL AND METHODS: We conducted a retrospective study in our institution (2011-2018) including adult patients undergoing spinal instrumentation who met the diagnostic criteria for confirmed infection. Superficial surgical wound and deep intraoperative samples were processed for microbiological culture. The medical and orthopaedic team was always the same. RESULTS: Forty-one cases were diagnosed of which 39 patients (95.1%) presented early infection (<3 months after initial surgery) with symptoms in the first two weeks, mean CRP at diagnosis was 133mg/dl and 23% associated bacteremia. The remaining two patients (4.8%) were chronic infections (symptoms >3 months after surgery). The treatment of choice in early infections was the Debridement, Antibiotics and Implant Retention (DAIR) strategy without removal of the bone graft, which successfully resolved 84.2% of the infections. The main aetiology was gram-positive (Staphylococcus aureus: 31.7%), followed by gram-negative and polymicrobial flora. Antibiotics were optimised according to cultures with a mean duration of 12 weeks. CONCLUSIONS: In early infections, early diagnosis and DAIR strategy (with bone graft retention) demonstrated a healing rate higher than 80%.

Four-year Epidemiological Surveillance of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy: Current Situation and Trends. / Vigilancia epidemiológica en los últimos 4 años del Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea: situación actual y tendencias.

BACKGROUND: The epidemiological surveillance of contact dermatitis is one of the objectives of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. Knowing whether the prevalence of positive tests to the different allergens changes over time is important for this monitoring process. OBJECTIVES: To describe the various temporary trends in allergen positivity in the GEIDAC standard series from 2018 through December 31, 2022. METHODS: This was a multicenter, observational trial of consecutive patients analyzed via patch tests as part of the study of possible allergic contact dermatitises collected prospectively within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. The data was analyzed using 2 statistical tests: one homogeneity test (to describe the changes seen over time) and one trend test (to see whether the changes described followed a linear trend). RESULTS: A total of 11327 patients were included in the study. Overall, the allergens associated with a highest sensitization were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix i. A statistically significant decrease was found in the percentage of methylisothiazolinone positive tests across the study years with an orderly trend. CONCLUSIONS: Although various changes were seen in the sensitizations trends to several allergens of the standard testing, it became obvious that a high sensitization to nickel, methylchloroisothiazolinone/methylisothiazolinone and fragrances mix i remained. Only a significant downward trend was seen for methylisothiazolinone.

Descriptive study of spinal instrumentation-related infections in a tertiary hospital. / Estudio descriptivo de las infecciones asociadas con instrumentación de columna en un hospital terciario.

INTRODUCTION: Spinal instrumentation-related infections (SIRI) are one of the main causes of post-surgical complication and comorbidity. Our objective was to describe the clinical and microbiological characteristics, treatment and prognosis of these infections. MATERIAL AND METHODS: We conducted a retrospective study in our institution (2011-2018) including adult patients undergoing spinal instrumentation who met the diagnostic criteria for confirmed infection. Superficial surgical wound and deep intraoperative samples were processed for microbiological culture. The medical and orthopaedic team was always the same. RESULTS: Forty-one cases were diagnosed of which 39 patients (95.1%) presented early infection (<3 months after initial surgery) with symptoms in the first two weeks, mean CRP at diagnosis was 133mg/dl and 23% associated bacteremia. The remaining two patients (4.8%) were chronic infections (symptoms >3 months after surgery). The treatment of choice in early infections was the Debridement, Antibiotics and Implant Retention (DAIR) strategy without removal of the bone graft, which successfully resolved 84.2% of the infections. The main etiology was gram-positive (Staphylococcus aureus: 31.7%), followed by gram-negative and polymicrobial flora. Antibiotics were optimized according to cultures with a mean duration of 12 weeks. CONCLUSIONS: In early infections, early diagnosis and DAIR strategy (with bone graft retention) demonstrated a healing rate higher than 80%.

Transition of Adolescents With Severe Asthma From Pediatric to Adult Care in Spain: The STAR Consensus.

OBJECTIVES: To assess the degree of consensus among a multidisciplinary expert panel on the transition of adolescents with severe asthma from pediatric to adult care. METHODS: A 61-item survey was developed based on guidelines for other chronic diseases, covering transition planning, preparation, effective transfer, and follow-up. A 2-round Delphi process assessed the degree of consensus among 98 experts (49 pediatricians, 24 allergists, and 25 pulmonologists). Consensus was established with ≥70% agreement. RESULTS: Consensus was reached for 42 items (70%). Panelists were unable to agree on an age range for initiation of transition. The main goal during the transition identified by the experts is for adolescents to gain autonomy in managing severe asthma and prescribed treatments. The panelists agreed on the importance of developing an individualized plan, promoting patient autonomy, and identifying factors associated with the home environment. They agreed that the adult health care team should have expertise in severe asthma, biologics, and management of adolescent patients. Pediatric and adult health care teams should share clinical information, agree on the criteria for maintaining biological therapy, and have an on-site joint visit with the patient before the effective transfer. Adult health care professionals should closely follow the patient after the effective transfer to ensure correct inhaler technique, adherence, and attendance at health care appointments. CONCLUSION: This consensus document provides the first roadmap for Spanish pediatric and adult teams to ensure that key aspects of the transition process in severe asthma are covered. The implementation of these recommendations will improve the quality of care offered to the patient.

GABAB Receptor Chemistry and Pharmacology: Agonists, Antagonists, and Allosteric Modulators.

The GABAB receptors are metabotropic G protein-coupled receptors (GPCRs) that mediate the actions of the primary inhibitory neurotransmitter, γ-aminobutyric acid (GABA). In the CNS, GABA plays an important role in behavior, learning and memory, cognition, and stress. GABA is also located throughout the gastrointestinal (GI) tract and is involved in the autonomic control of the intestine and esophageal reflex. Consequently, dysregulated GABAB receptor signaling is associated with neurological, mental health, and gastrointestinal disorders; hence, these receptors have been identified as key therapeutic targets and are the focus of multiple drug discovery efforts for indications such as muscle spasticity disorders, schizophrenia, pain, addiction, and gastroesophageal reflex disease (GERD). Numerous agonists, antagonists, and allosteric modulators of the GABAB receptor have been described; however, Lioresal® (Baclofen; ß-(4-chlorophenyl)-γ-aminobutyric acid) is the only FDA-approved drug that selectively targets GABAB receptors in clinical use; undesirable side effects, such as sedation, muscle weakness, fatigue, cognitive deficits, seizures, tolerance and potential for abuse, limit their therapeutic use. Here, we review GABAB receptor chemistry and pharmacology, presenting orthosteric agonists, antagonists, and positive and negative allosteric modulators, and highlight the therapeutic potential of targeting GABAB receptor modulation for the treatment of various CNS and peripheral disorders.

Incidence of Fatal Anaphylaxis: A Systematic Review of Observational Studies.

BACKGROUND: Fatal anaphylaxis is very rare, with an incidence ranging from 0.5 to 1 deaths per million person-years. OBJECTIVE: Based on a systematic review, we aimed to explain differences in the reported incidence of fatal anaphylaxis based on the methodological and demographic factors addressed in the various studies. METHODS: We searched PubMed/MEDLINE, EMBASE, and the Web of Science for relevant retrospective and prospective cohort studies and registry studies that had assessed the anaphylaxis mortality rate for the population of a country or for an administrative region. The research strategy was based on combining the term "anaphylaxis" with "death", "study design", and "main outcomes" (incidence). RESULTS: A total of 46 studies met the study criteria and included 16,541 deaths. The range of the anaphylaxis mortality rate for all causes of anaphylaxis was 0.002-2.51 deaths per million person-years. Fatal anaphylaxis due to food (range 0.002-0.29) was rarer than deaths due to drugs (range 0.004-0.56) or Hymenoptera venom (range 0.02-0.61). The frequency of deaths due to anaphylaxis by drugs increased during the study period (IRR per year, 1.02; 95%CI, 1.00-1.04). We detected considerable heterogeneity in almost all of the meta-analyses carried out. CONCLUSION: The incidence of fatal anaphylaxis is very low and differs according to the various subgroups analyzed. The studies were very heterogeneous. Fatal anaphylaxis due to food seems to be less common than fatal anaphylaxis due to drugs or Hymenoptera venom.

Spanish translation and validation of the Scale for Contraversive Pushing to measure pusher behaviour.

INTRODUCTION: The aim of this study was to develop and validate a Spanish-language version of the Scale for Contraversive Pushing, used to diagnose and measure pusher behaviour in stroke patients. METHODS: Translation-back translation was used to create the Spanish-language Scale for Contraversive Pushing; we subsequently evaluated its validity and reliability by administering it to a sample of patients. We also analysed its sensitivity to change in patients identified as pushers who received neurological physiotherapy. RESULTS: Experts indicated that the content of the scale was valid. Internal consistency was very good (Cronbach's alpha of 0.94). The intraclass correlation coefficient showed high intra- and interobserver reliability (0.999 and 0.994, respectively). The Kappa and weighted Kappa coefficients were used to measure the reliability of each item; the majority obtained values above 0.9. Lastly, the differences between baseline and final evaluations of pushers were significant (paired sample t test), showing that the scale is sensitive to changes obtained through physical therapy. CONCLUSIONS: The Spanish-language version of the Scale for Contraversive Pushing is valid and reliable for measuring pusher behaviour in stroke patients. In addition, it is able to evaluate the ongoing changes in patients who have received physical therapy.

[Effectiveness of respiratory physiotherapy combined with postural education in children with chronic neurological diseases].

BACKGROUND: Children with chronic neurological diseases present motor disability and increased respiratory morbidity and mortality. The aim of this study was to assess whether children with chronic neurological impairment benefit from respiratory physiotherapy and postural hygiene. METHODS: Quasi-experimental study in which six fortnightly respiratory physiotherapy sessions and workshops on postural hygiene were carried out on children aged 0 to 6 years with chronic neurological disease and respiratory impairment. A PedsQL questionnaire assessed respiratory clinical variables, expectorated secretions, respiratory exacerbations and quality of life. Assessments were performed at baseline, post-intervention, and at a 3-month follow-up. RESULTS: After physiotherapy sessions, all participants (n=30) experienced a significant (p<0.001) improvement in average oxygen saturation (94.37 to 98.3%), heart rate (126.03 to 103.6 beats/minute) and respiratory rate (42.13 to 34.27 breaths/minute), as well as a decrease in secretions (from 45.33 to 28.17 mL). This improvement was maintained after a 3-month follow-up. The average respiratory exacerbations decreased (p<0.001) compared to the previous six months: hospitalizations (from 1.6 to 0.5), visits to the emergency department (from 2.59 to 1.53) and to primary care Pediatric consultations (from 7 to 5.03). The mean score on the PedsQL questionnaire demonstrated a significant increase (p<0.001) in the quality of life after the intervention for physical (27%, to 73.4) and mental health (12%, to 70.09%). CONCLUSION: Respiratory physiotherapy combined with postural hygiene is effective for the clinical status and quality of life in children with chronic neurological diseases, and therefore could be introduced in habitual clinical practice.

Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)☆.

BACKGROUND: We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274). PATIENTS AND METHODS: The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D. RESULTS: In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m2, three dose-limiting toxicities (hypertension, n = 2; increased alanine aminotransferase, n = 1) were reported, establishing 14 mg/m2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n = 31], PFS-4 by Kaplan-Meier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade ≥3. CONCLUSIONS: The lenvatinib RP2D was 14 mg/m2. Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherapy as part of a randomized, controlled trial (NCT04154189), in pediatric solid tumors in combination with everolimus (NCT03245151), and as a single agent in a basket study with enrollment ongoing (NCT04447755).

Medical and Legal Aspects of the Practice of Teledermatology in Spain. / Aspectos medicolegales de la práctica de la teledermatología en España.

Teledermatology is now fully incorporated into our clinical practice. However, after reviewing current legislation on the ethical aspects of teledermatology (data confidentiality, quality of care, patient autonomy, and privacy) as well as insurance and professional responsibility, we observed that a specific regulatory framework is still lacking and related legal aspects are still at a preliminary stage of development. Safeguarding confidentiality and patient autonomy and ensuring secure storage and transfer of data are essential aspects of telemedicine. One of the main topics of debate has been the responsibilities of the physicians involved in the process, with the concept of designating a single responsible clinician emerging as a determining factor in the allocation of responsibility in this setting. A specific legal and regulatory framework must be put in place to ensure the safe practice of teledermatology for medical professionals and their patients.

Patient characteristics, clinical course and factors associated to ICU mortality in critically ill patients infected with SARS-CoV-2 in Spain: A prospective, cohort, multicentre study. / Características, evolución clínica y factores asociados a la mortalidad en UCI de los pacientes críticos infectados por SARS-CoV-2 en España: estudio prospectivo, de cohorte y multicéntrico.

BACKGROUND: The clinical course of COVID-19 critically ill patients, during their admission in the intensive care unit (UCI), including medical and infectious complications and support therapies, as well as their association with in-ICU mortality has not been fully reported. OBJECTIVE: This study aimed to describe clinical characteristics and clinical course of ICU COVID-19 patients, and to determine risk factors for ICU mortality of COVID-19 patients. METHODS: Prospective, multicentre, cohort study that enrolled critically ill COVID-19 patients admitted into 30 ICUs from Spain and Andorra. Consecutive patients from March 12th to May 26th, 2020 were enrolled if they had died or were discharged from ICU during the study period. Demographics, symptoms, vital signs, laboratory markers, supportive therapies, pharmacological treatments, medical and infectious complications were reported and compared between deceased and discharged patients. RESULTS: A total of 663 patients were included. Overall ICU mortality was 31% (203 patients). At ICU admission non-survivors were more hypoxemic [SpO2 with non-rebreather mask, 90 (IQR 83 to 93) vs. 91 (IQR 87 to 94); P<.001] and with higher sequential organ failure assessment score [SOFA, 7 (IQR 5 to 9) vs. 4 (IQR 3 to 7); P<.001]. Complications were more frequent in non-survivors: acute respiratory distress syndrome (ARDS) (95% vs. 89%; P=.009), acute kidney injury (AKI) (58% vs. 24%; P<10-16), shock (42% vs. 14%; P<10-13), and arrhythmias (24% vs. 11%; P<10-4). Respiratory super-infection, bloodstream infection and septic shock were higher in non-survivors (33% vs. 25%; P=.03, 33% vs. 23%; P=.01 and 15% vs. 3%, P=10-7), respectively. The multivariable regression model showed that age was associated with mortality, with every year increasing risk-of-death by 1% (95%CI: 1 to 10, P=.014). Each 5-point increase in APACHE II independently predicted mortality [OR: 1.508 (1.081, 2.104), P=.015]. Patients with AKI [OR: 2.468 (1.628, 3.741), P<10-4)], cardiac arrest [OR: 11.099 (3.389, 36.353), P=.0001], and septic shock [OR: 3.224 (1.486, 6.994), P=.002] had an increased risk-of-death. CONCLUSIONS: Older COVID-19 patients with higher APACHE II scores on admission, those who developed AKI grades ii or iii and/or septic shock during ICU stay had an increased risk-of-death. ICU mortality was 31%.

Is India on the right pathway to reduce CO2 emissions? Decomposing an enlarged Kaya identity using the LMDI method for the period 1990-2016.

Nowadays, India is the third-largest CO2 emitter and energy consumer in the world, and, it is soon expected to surpass China as the most populated country. Therefore, it is of great interest to analyse how India is developing its energy transition to a lower-carbon economy. This work analyses the evolution of the main driving forces of CO2 emissions in India during the period 1990-2016 through the use of an enlarged version of the Kaya identity, which establishes a link between CO2 emissions, types of energy sources (16), size of the economic sectors (3) and value of the Gross Domestic Product. India's CO2 emissions increased by 276% in the period under study, due to the rapid economic growth of India, which has been the dominating driving force contributing to the increase in CO2 emissions by 241%, while the energy intensity has been the main one reducing them by approximately -47%. So far, the use of coal has supported the rapid economic growth and the contribution of renewable energy, although significant, is still short compared to the total amount of energy employed. Remarkably, the estimated value of the emission intensity for 2020 supposes a 26% reduction concerning the value in 2005. According to this result, India is on the right pathway to fulfil its Nationally Determined Contribution but not to reduce its net CO2 emissions.

Risk factors and management of incisional hernia after cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal surface malignancies.

BACKGROUND: The incidence of incisional hernia in patients with peritoneal surface malignancies treated by cytoreduction plus hyperthermic intraperitoneal chemotherapy (HIPEC) remains unclear, and the criteria commonly used to indicate their repair cannot be applied in these patients. The objective of this work was to analyze the incidence of incisional hernias in these patients, identify the risk factors associated with their appearance, and propose an algorithm for their management. METHODS: We analyzed a series of patients with malignant pathologies of the peritoneal surface treated by cytoreduction with peritonectomy and HIPEC procedures between January 2008 and June 2017. Only patients with a minimum postoperative follow-up period of 12 months were included. RESULTS: Our series included 282 patients, 28 (10%) of whom developed an incisional hernia during the follow-up period. Fifty-one patients, all with ovarian cancer with peritoneal dissemination, did not receive HIPEC after cytoreduction as they were part of the control arm of the CARCINOHIPEC clinical trial (NCT02328716) or because they did not provide specific informed consent. In the multivariate analysis, treatment with HIPEC (OR 2.56, 95% CI [1.57, 4.31], p = 0.032) and the administration of preoperative systemic chemotherapy (OR = 1.59, 95% CI [1.26, 3.58], p = 0.041) were found to be independent factors related to the appearance of an incisional hernia. CONCLUSIONS: The incidence of incisional hernia after cytoreduction and HIPEC is within the ranges described in the literature for other abdominal surgery procedures. The use of systemic chemotherapy and treatment with HIPEC, in particular, were identified as factors related to their occurrence.

Altered materno-fetal transfer of 13C-polyunsaturated fatty acids in obese pregnant women.

BACKGROUND & AIMS: Maternal obesity at conception is considered a major predictor of offspring obesity. This could by driven at least in part by an altered placental fat transfer. However, the pathophysiological mechanisms involved are not fully understood. We investigated the in vivo materno-fetal transfer of fatty acids (FAs) in obese pregnant women using stable isotopes. METHODS: Ten obese and ten normo-weight pregnant women (control) received orally a bolus of 13C-labeled FAs 12 h before elective caesarean section: oleic acid (13C-OA), linoleic acid (13C-LA) and docosahexaenoic acid (13C-DHA). Maternal blood samples were collected at -12 (basal), -8, -4, -2, 0 h relative to the time of cesarean section. At the time of birth, arterial and venous cord bloods as well as placental tissue were collected. FAs composition was determined by gas-liquid chromatography and isotopic enrichment by gas chromatography-combustion-isotope ratio mass spectrometry. RESULTS: Maternal plasma insulin and placental weight tended to higher values in obese pregnant women although they did not present serum hyperlipidemia. Higher concentrations of 13C-LA and 13C-DHA were found in non-esterified FAs fraction in maternal plasma of obese mothers. The ratio of placental uptake for 13C-LA and 13C-DHA was lower in obese women compared to normal weight pointing toward a limited capacity of FA placental transfer, especially of essential FAs. Maternal insulin was associated to this lower placenta/maternal plasma ratio for both 13C-LA (R = -0.563, P = 0.012) and 13C-DHA (R = -0.478, P = 0.033). In addition, the ratio cord/maternal plasma of 13C-LA was significantly lower in obese women compared to controls. CONCLUSIONS: In conclusion, obese mothers without hyperlipidemia showed a reduced materno-fetal transfer of polyunsaturated FAs which could affect fetal development. This affect dietary recommendation for obese pregnant women. TRIAL REGISTRY NUMBER: ISRCTN69794527.