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.

Experience in neuromuscular diseases in children and adolescents and their comorbidities in a tertiary hospital.

INTRODUCTION: Neuromuscular diseases include a large group of heterogeneous and rare pathologies that affect different components of the motor unit. It is essential to optimize resources to know the prevalence of comorbidities in the most frequent groups to establish an early multidisciplinary approach in a specialized setting. PATIENTS AND METHODS: Retrospective descriptive study of pediatric and adolescent patients with neuromuscular diseases (NMDs). The Inclusion criteria were NMDs patients with motor neuron involvement divided into three groups, depending on the affected component of the motor unit. Group I: involvement of the motor neuron; Group II: peripheral neuropathies; Group III: myopathies. Demographic variables, association with comorbidities, need for respiratory support, and rehabilitative treatment were collected in each group. RESULTS: Ninety-six patients who met the inclusion criteria were studied. In group I, when compared to the other two groups, a higher incidence of scoliosis (68.3%, p = 0.011), deformity of the rib cage (31.3%, p = 0.0001), chronic respiratory insufficiency (62.5%, p = 0.001) and bronchial aspiration (12.5%, p = 0.03) was detected. In this group, 50%of the patients required non-invasive mechanical ventilation (p = 0.0001). The in-hospital requirement for respiratory physiotherapy was higher in group I (75%, p = 0.001). We observed a higher incidence of scoliosis in Group III compared to Group II. CONCLUSIONS: Neuromuscular diseases with motor neuron involvement present more comorbidities and require an early approach after diagnosis to improve prognosis.

Tolerability and outcome of palliative treatment for metastatic pulmonary carcinoma in cats.

OBJECTIVES: Pulmonary carcinoma is uncommon in cats and reporting of outcomes following medical treatment is limited, especially in presence of metastases. The aim of this study was to describe the outcome of cats affected by metastatic primary pulmonary carcinoma and to evaluate the tolerability of palliative treatment in this patient population. MATERIALS AND METHODS: Medical records were searched for cats with a cytological or histopathological diagnosis of primary pulmonary carcinoma and evidence of metastatic disease. Cats were treated with antineoplastic agents, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) or received no systemic treatment. Cases in which thoracic CT was not performed, and those lacking definitive diagnosis by cytology or histopathology or receiving curative-intent surgery were excluded. RESULTS: Thirty-four cats were identified: 18 were treated with antineoplastic agents and 16 received corticosteroids, NSAIDs or no treatment. Presenting clinical signs included coughing (53%), tachypnoea (26%), gastrointestinal signs (35%) and lethargy (18%). CT scan identified metastases to the lung parenchyma in all cases and additional metastatic lesions in 10 of 34 (59%) cases; pleural effusion was detected in 11 cases (32%). The overall median survival time for all cats was 64 days [range 1-1352 days; 95% confidence interval (CI) 48-164]. Presence of respiratory signs at presentation was the only factor influencing survival in the multivariable analysis. CLINICAL SIGNIFICANCE: Medical treatment was well tolerated and appeared to palliate clinical signs in cats with metastatic pulmonary carcinoma, albeit with a modest duration and short overall survival. The role and benefit of chemotherapy/antineoplastic agents versus conventional palliative drugs in this setting remains unclear.

Treatment of advanced-stage canine nasal carcinomas with toceranib phosphate: 23 cases (2015-2020).

OBJECTIVE: To determine the median survival time (MST) of dogs with nasal carcinoma treated with toceranib phosphate. MATERIAL AND METHODS: The databases of four Spanish referral hospitals were retrospectively searched for dogs with a diagnosis of nasal tumours presented between January 2015 and October 2020. Dogs treated with radiotherapy or other chemotherapies prior toceranib were excluded. RESULTS: Twenty-three dogs with a confirmed nasal carcinoma treated with toceranib phosphate and with a CT scan for initial staging according to Adams Modified Staging System were included. Nine dogs had a stage III nasal carcinoma whereas 14 dogs had a stage IV nasal carcinoma. No dog had stages I and II nasal carcinoma. The median overall survival time was 139 days. The difference between the MST between dogs with stages III and IV was not statistically significant [P = 0.6, 140 days for stage III (range 46-401) vs 120 days for stage IV (range 23-600)]. Overall, dogs with epistaxis achieved a longer median survival (166 days) than dogs without epistaxis (83 days). Toceranib phosphate was generally well tolerated. Most dogs had an initial clinical benefit followed by progressive disease. SIGNIFICANCE: This is the first study to report the MST in dogs with stages III and IV nasal carcinoma treated with toceranib phosphate. This retrospective study showed that toceranib phosphate decreases the clinical signs associated with nasal carcinomas.

Outcomes of an enhanced recovery after radical cystectomy program in a prospective multicenter study: compliance and key components for success.

OBJECTIVE: To investigate the effect of an Enhanced Recovery After Surgery (ERAS) program on complications and length of stay (LOS) after radical cystectomy (RC) and to assess if the number and type of components of ERAS play a key role on the decrease of surgical morbidity. MATERIALS AND METHODS: We analyzed the data of 277 patients prospectively recruited in 11 hospitals undergoing RC initially managed according to local practice (Group I) and later within an ERAS program (Group II). Two main outcomes were defined: 90-day complications rate and LOS. As secondary variables we studied 90-day mortality, 30-day readmission and transfusion rate. RESULTS: Patients in Group II had a higher use of ERAS measures (98.6%) than those in Group I (78.2%) (p < 0.05). Patients in Groups I and II experienced similar complications (70.5% vs. 66%, p = 0.42). LOS was not different between Groups I and II (12.5 and 14 days, respectively, p = 0.59). The risk of having any complication decreases for patients having more than 15 ERAS measures adopted [RR = 0.815; 95% confidence interval (CI) 0.667-0.996; p = 0.045]. Avoidance of transfusion and nasogastric tube, prevention of ileus, early ambulation and a fast uptake of a regular diet are independently associated with the absence of complications. CONCLUSIONS: Complications and LOS after RC were not modified by the introduction of an ERAS program. We hypothesize that at least 15 measures should be applied to maximize the benefit of ERAS.

Virulence properties of three new Photobacterium species affecting cultured fish.

AIMS: Several virulence factors of three new Photobacterium species: Photobacterium toruni, Photobacterium malacitanum and Photobacterium andalusiense associated with diseases of cultured redbanded seabream (Pagrus auriga) were studied. The exoenzymatic activities, adherence and cytotoxic capabilities, and iron-uptake mechanisms were determined both in bacterial extracellular products (ECP) and whole bacterial cells. The histopathology damages provoked on redbanded seabream by the ECP was also studied. METHODS AND RESULTS: The highest exoenzymatic activities of the ECP were alkaline- and acid-phosphatase, phosphohydrolase and lipase. The ECP were strongly lethal for fish at 4-96 h post-inoculation (p.i). Histological changes were evident at 96 hpi of ECP, affecting head kidney, splenic parenchyma and heart. Cytotoxicity assays, on three fish lines and one human cell line, were conducted using whole bacterial cells and their ECP. The new species tested were cytotoxic only for fish cell lines using whole bacterial cells. Bacterial adherence showed an adherence index moderate on CHSE-214 cell line. All strains showed variable haemolytic activity, and were able to grow under iron-limiting conditions, although the CAS reactivitiy was very low. However, all strains produced high amounts of extracelullar citrate that could be used as iron carrier, and use haem as iron source, except the P. toruni strains because a deletion in the genomic region encoding this ability in all Vibrionaceae members. CONCLUSIONS: The toxic activity of the bacterial ECPs was thermolabile, and not associated with their thermoresistant lipopolysaccharide content. The virulence of the strains tested could not be related to the haemolytic activity. Iron uptake could be based on the use of endogenous citrate as iron carrier and P. toruni lacks the ability to use haem as iron source. SIGNIFICANCE AND IMPACT OF THE STUDY: The study analyses for the first time the virulence properties of three new species of Photobacterium pathogenic for fish.

Immune gene expression in gilthead seabream (Sparus aurata) after Lymphocystis disease virus (LCDV-Sa) challenge resulting in asymptomatic infection.

AIMS: To determine the immune gene expression response of gilthead seabream (Sparus aurata) that is experimentally infected with the lymphocystivirus LCDV-Sa. METHODS AND RESULTS: Viral DNA and transcripts were detected by qPCR in all samples from fish injected with LCDV-Sa, demonstrating that the virus establish a systemic and asymptomatic infection. The expression of 23 immune-related genes was also analysed by RT-qPCR in the head kidney (HK) and intestine at several times post-infection (dpi). In HK, the expression of five type I interferon (IFN)-related genes (ifn, irf3, mx2, mx3 and isg15), il10 and ck10 was upregulated at 1-3 dpi, while genes related to the inflammation process (tnfα, il1ß, il6, casp1) were not differentially expressed or even downregulated. The expression profile in the intestine was different regarding type I INF-related genes. An upregulated c3 and ighm expression was observed in both HK and intestine at 3-8 dpi. Finally, the transcription of nccrp1 and mhcIIα was induced in HK, whereas tcrß expression was downregulated in both organs. CONCLUSIONS: LCDV-Sa seems to trigger an immune response in gilthead seabream characterized by a partial activation of type I IFN system and a lack of systemic inflammatory response which may be related to viral persistence. SIGNIFICANCE AND IMPACT OF THE STUDY: The immune response observed in gilthead seabream infected by LCDV-Sa could be implicated in the establishment of an asymptomatic persistent infection.

Asthma diagnosis in infants and preschool children: a systematic review of clinical guidelines.

BACKGROUND AND AIM: The definition and diagnosis of asthma are the subject of controversy that is particularly intense in the case of individuals in the first years of life, due to reasons such as the difficulty of performing objective pulmonary function tests or the high frequency with which the symptoms subside in the course of childhood. Since there is no consensus regarding the diagnosis of asthma in preschool children, a systematic review has been carried out. MATERIALS AND METHODS: A systematic search was made of the clinical guidelines published in the last 10 years and containing information referred to the concept or diagnosis of asthma in childhood - including the first years of life (infants and preschool children). A series of key questions were established, and each selected guide was analyzed in search of answers to those questions. The review protocol was registered in the international prospective register of systematic reviews (PROSPERO), with registration number CRD42017074872. RESULTS: Twenty-one clinical guidelines were selected: 10 general guides (children and adults), eight pediatric guides and three guides focusing on preschool children. The immense majority accepted that asthma can be diagnosed from the first years of life, without requiring pulmonary function tests or other complementary techniques. The response to treatment and the exclusion of other alternative diagnoses are key elements for establishing the diagnosis. Only one of the guides denied the possibility of diagnosing asthma in preschool children. CONCLUSIONS: There is generalized although not unanimous agreement that asthma can be diagnosed in preschool children.

The theoretical reliability of PCR-based fish viral diagnostic methods is critically affected when they are applied to fish populations with low prevalence and virus loads.

AIMS: The reliability of polymerase chain reaction (PCR) techniques is an important issue in viral diagnosis, and it is even crucial when they must be applied for detection of viruses in asymptomatic carriers. The problems will arise when the aim is to study wild fish populations, where the viral loads and prevalence values are extremely low. We have evaluated several PCR procedures employed by two laboratories for monitoring fish captured in several oceanographic campaigns performed in the Gulf of Cádiz. METHODS AND RESULTS: To evaluate the reliability of different diagnostics test used, we have re-analysed fish samples that had been previously subjected to diagnosis for a surveillance of viruses performed in 2010-2011 in wild fish populations. The following parameters were employed: the clinical sensitivity (Ss), the clinical specificity (Sp), the predictive positive value, the predictive negative value, and the positive and negative likelihood ratio (LR+ and LR- ). For viral nervous necrosis virus, a RT-PCR procedure supplemented by nested PCR showed the highest values (100%) for all the parameters. For viral haemorrhagic septicaemia virus, the highest values were provided by RT-PCR supplemented by dot-blot hybridization. In the case of infectious pancreatic necrosis virus, none of the procedures yielded 100% for any parameter. CONCLUSIONS: The results obtained for viral prevalence indicate: (i) that the conservation of the samples at -80°C did not affect to the capacity of detection of the virus in the tissues, and (ii) that the reproducibility of the diagnosis can be affected by factors including the staff experience and/or the materials employed. Finally, the use of a combination of procedures in advised to ensure the maximum reliability of the diagnosis when it is applied to asymptomatic fish populations. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper describes a strategy of combining diagnostic tests for the surveillance and monitoring of wild fish populations to reduce underestimation of the prevalence of viruses this type of populations.

Mortality hospital of nonagenarian patients in Internal Medicine. / Mortalidad hospitalaria de pacientes nonagenarios en Medicina Interna.

OBJECTIVES: To describe the predictors of hospital mortality in nonagenarian patients. PATIENTS AND METHOD: We retrospectively studied 421 patients aged 90 years or older hospitalised in a department of internal medicine. Using logistic regression, we analysed the association between demographic, clinical and functional parameters and hospital mortality. RESULTS: The mean age was 92.5 years (SD±2.5), and 265 (62.9%) of the patients were women. The main diagnoses were infectious diseases (257 patients, 61%) and heart failure (183, 43.5%), and the mean stay was 11.9 days (SD±8.6). During the hospitalisation, 96 patients died (22.8%). The predictors of mortality were age (P=.002), functional state (P=.006), comorbidity (P=.018) and diagnoses of pneumonia (P=.001), sepsis (P=.012) and respiratory failure (P<.001). CONCLUSION: The hospital mortality of nonagenarian patients treated in internal medicine exceeds 20% and is associated with pneumonia, comorbidity burden and functional impairment.

Rare earth elements mobility processes in an AMD-affected estuary: Huelva Estuary (SW Spain).

Huelva Estuary is a transition zone where REE-rich acidic waters interact with saline-alkaline seawater. This mixing process influences the geochemical and mineralogical characteristics of particulate and dissolved fractions. The Tinto River has >11,000µgL-1 dissolved REE (pH=1.66), whereas seawater only reaches 8.75·10-2µgL-1 dissolved REE (pH=7.87). REE-normalized patterns in "pH<6 solutions" are parallel and show similarities, diminishing their concentration as pH increases. Sequential extraction performed on the generated precipitates of mixed solutions indicates that most REE are associated to the residual phase. In a second order, REE are associated with soluble salts at pH3 and 3.5 whereas in sediments generated at pH4 and 5, they are distributed in salts (1° extraction), poorly crystallized Fe-bearing minerals (schwertmannite, 3° extraction) and well crystallized Fe-bearing minerals (goethite - hematite, 4° extraction). Finally, precipitated REE are highest at pH6 newly formed minerals with a release to solution in higher pH.

Clinical presentation, treatment and outcome in 31 dogs with presumed primary colorectal lymphoma (2001-2013).

The objective of this multicentre retrospective study was to describe clinical presentation, treatment and outcome and to determine prognostic factors for dogs with presumed primary colorectal lymphoma (PCRL). A total of 31 dogs were included. The predominant features of PCRL were high grade (n = 18) and immunophenotype B (n = 24). Most dogs were substage b (n = 25) with higher prevalence of haematochezia (n = 20). One dog had surgery only. Thirty dogs received chemotherapy; amongst them 13 had surgery or radiotherapy. Progression free survival (PFS) was 1318 days and disease-related median survival time (MST) was 1845 days. Fourteen dogs were alive at the end of the study with a median follow-up time of 684 days (3-4678 days). Younger dogs had longer PFS (P = 0.031) and disease-related MST (P = 0.01). Presence of haematochezia corresponded with longer PFS (P = 0.02). Addition of local treatment to chemotherapy did not significantly improve the outcome (P = 0.584). Canine PCRL has considerably longer PFS and MST than other forms of non-Hodgkin's lymphoma.

Evaluation of adjuvant carboplatin chemotherapy in the management of surgically excised anal sac apocrine gland adenocarcinoma in dogs.

There is no widely accepted standard of care for canine anal sac apocrine gland adenocarcinoma (ASAGAC). Surgery alone is inadequate in many cases, but the benefit of adjuvant chemotherapy is not well established. The primary objective of this retrospective study was to evaluate the role of carboplatin chemotherapy in the post-operative management of ASAGAC. Seventy-four dogs with naturally occurring ASAGAC underwent surgery. Forty-four dogs received adjuvant carboplatin and 30 did not. Median overall survival (OS) was 703 days. Median time to progression (TTP) was 384 days. Only primary tumour size and lymph node metastasis at diagnosis significantly impacted the outcome. Differences in OS and TTP, between the dogs that received adjuvant carboplatin and those that did not, failed to reach statistical significance. Treatment of progressive disease, whilst not limited to chemotherapy, significantly prolonged the survival. This study shows that adjuvant carboplatin chemotherapy is well tolerated and may have a role in the management of dogs with ASAGAC.

[Consensus-based approach for severe paediatric asthma in routine clinical practice]. / Consenso para el abordaje del asma grave pediátrica en la práctica clínica habitual.

INTRODUCTION: Accurate identification of paediatric patients with severe asthma is essential for an adequate management of the disease. However, criteria for defining severe asthma and recommendations for control vary among different guidelines. MATERIAL AND METHODS: An online survey was conducted to explore expert opinions about the definition and management of severe paediatric asthma. To reach a consensus agreement, a modified Delphi technique was used, and practice guidelines were prepared after the analysis of the results. RESULTS: Eleven paediatric chest disease physicians and allergy specialists with wide expertise in severe asthma responded to the survey. Consensus was reached in 50 out of 65 questions (76.92%). It was considered that a patient has severe asthma if during the previous year they have required 2 or more cycles of oral steroids, required daily treatment with medium doses of inhaled corticosteroids (with other controller medication) or high doses (with or without other controller medication), did not respond to optimised conventional treatment, or if the disease threatened the life of the patient or seriously impairs their quality of life. The definition of severe asthma may also include patients who justifiably use health resources on a regular basis, or have psychosocial or environmental factors impeding control. For monitoring, the use of questionnaires designed specifically for paediatric population, such as CAN or ACT, is recommended. As regards treatment, the use of omalizumab should be considered prior to the use of oral corticosteroids. CONCLUSIONS: This paper provides consensus recommendations that may be useful in the management of severe paediatric asthma.

Neurokinin-1 receptor expression and antagonism by the NK-1R antagonist maropitant in canine melanoma cell lines and primary tumour tissues.

We interrogated the neurokinin-1 receptor (NK-1R)/substance P (SP) pathway in canine melanoma tumour tissues and cell lines. NK-1R messenger RNA (mRNA) and protein expression were observed in the majority of tumour tissues. Immunohistochemical assessment of archived tissue sections revealed NK-1R immunoreactivity in 11 of 15 tumours, which may have diagnostic, prognostic and therapeutic utility. However, we were unable to identify a preclinical in vitro cell line or in vivo xenograft model that recapitulates NK-1R mRNA and protein expression documented in primary tumours. While maropitant inhibited proliferation and enhanced apoptosis in cell lines, in the absence of documented NK-1R expression, this may represent off-target effects. Furthermore, maropitant failed to suppress tumour growth in a canine mouse xenograft model derived from a cell line expressing mRNA but not protein. While NK-1R represents a novel target, in the absence of preclinical models, in-species clinical trials will be necessary to investigate the therapeutic potential for antagonists such as maropitant.