[Impact of the "daily huddle" on the safety of pediatric hospitalized patients]. / Impacto de los «daily huddle¼ en la seguridad del paciente pediátrico hospitalizado.

INTRODUCTION: In 2017, the Joint Commission proposed daily meetings called "huddle" as an indicator of quality of care. They are brief daily meetings of the multidisciplinary team, where security problems of the last 24h are shared and risks are anticipated. The objectives were to describe the most frequent safety events in Pediatric wards, implement improvements in patient safety, improve team communication, implement international safety protocols, and measure the satisfaction of the staff involved. MATERIAL AND METHODS: Prospective, longitudinal and analytical design (June 2020-February 2022), with previous educational intervention. Safety incidents, data related to unequivocal identification, allergy and pain records, data from the Scale for the Early Detection of Deficiencies (SAPI) and the Scale for the Secure Transmission of Information (SBAR) were collected. The degree of satisfaction of the professionals was evaluated. RESULTS: Three hundred forty-eight security incidents were recorded. Medication prescription or administration errors stood out (n=103). Drug prescription or administration errors stood out (n=103), especially those related to high-risk medication: acetaminophen (n=14) (×10 doses of acetaminophen; n=6), insulin (n=6), potassium (n=5) and morphic (n=5). An improvement was observed in the pain record; 5% versus 80% (P<.01), in the SAPI registry 5% versus 70% (P<.01), in SBAER scale 40% vs 100% (P<.01), in unequivocal identification of the patient 80% versus 100%; (P<.01) and in the application of analgesic techniques 60% versus 85% (P=.01). In the survey of professionals, a degree of satisfaction of 8 (7-9.5)/10 was obtained. CONCLUSIONS: Huddles made it possible to learn about security events in our environment and increase the safety of hospitalized patients, and improved communication and the relationship of the multidisciplinary team.

Feasibility of whole genome and transcriptome profiling in pediatric and young adult cancers.

The utility of cancer whole genome and transcriptome sequencing (cWGTS) in oncology is increasingly recognized. However, implementation of cWGTS is challenged by the need to deliver results within clinically relevant timeframes, concerns about assay sensitivity, reporting and prioritization of findings. In a prospective research study we develop a workflow that reports comprehensive cWGTS results in 9 days. Comparison of cWGTS to diagnostic panel assays demonstrates the potential of cWGTS to capture all clinically reported mutations with comparable sensitivity in a single workflow. Benchmarking identifies a minimum of 80× as optimal depth for clinical WGS sequencing. Integration of germline, somatic DNA and RNA-seq data enable data-driven variant prioritization and reporting, with oncogenic findings reported in 54% more patients than standard of care. These results establish key technical considerations for the implementation of cWGTS as an integrated test in clinical oncology.

Declining Use of Corticosteroids for Crohn's Disease Has Implications for Study Recruitment: Results of a Pilot Randomized Controlled Trial.

BACKGROUND: Corticosteroids (CS) have been used extensively to induce remission in Crohn's disease (CD); however, they are associated with severe side effects. We hypothesized that the administration of an exclusive enteral nutrition (EEN) formula to CS would lead to increased CD remission rates and to decreased CS-related adverse events. We proposed to undertake a pilot study comparing EEN and CS therapy to CS alone to assess decrease symptoms and inflammatory markers over 6 weeks. AIM: The overall aim was to assess study feasibility based on recruitment rates and acceptability of treatment in arms involving EEN. METHODS: The pilot study intended to recruit 100 adult patients with active CD who had been prescribed CS to induce remission as part of their care. The patients were randomized to one of three arms: (i) standard-dose CS; (ii) standard-dose CS plus EEN (Modulen 1.5 kcal); or (iii) short-course CS plus EEN. RESULTS: A total of 2009 CD patients attending gastroenterology clinics were screened from October 2018 to November 2019. Prednisone was prescribed to only 6.8% (27/399) of patients with active CD attending outpatient clinics. Of the remaining 372 patients with active CD, 34.8% (139/399) started or escalated immunosuppressant or biologics, 49.6% (198/399) underwent further investigation and 8.8% (35/399) were offered an alternative treatment (e.g., antibiotics, surgery or investigational agents in clinical trials). Only three patients were enrolled in the study (recruitment rate 11%; 3/27), and the study was terminated for poor recruitment. CONCLUSION: The apparent decline in use of CS for treatment of CD has implications for CS use as an entry criterion for clinical trials.

Differential Impact of ALK Mutations in Neuroblastoma.

PURPOSE: The tyrosine kinase receptor anaplastic lymphoma kinase (ALK) can be abnormally activated in neuroblastoma, and somatic ALK mutations occur in 6%-10% of patients. The differential clinical impact of these mutations has not been clearly elucidated. METHODS: Data on patients with neuroblastoma harboring ALK mutations were retrospectively analyzed. ALK sequencing was performed by whole-genome sequencing, hybrid-based capture of targeted exomes, or hotspot ALK mutation profiling. The differential impact of ALK mutation site on clinical characteristics, response to treatment, and survival was analyzed. In a subgroup of patients with locoregional neuroblastoma diagnosed after 2014, the impact of all ALK mutations was compared with wild-type ALK. RESULTS: Of 641 patients with neuroblastoma with ALK status analyzed on at least one tumor sample, 103 (16%) had tumors harboring ALK mutations. Mutations existed across all ages (birth to 67.8 years), stages (30% locoregional and 70% metastatic), and risk groups (20%, 11%, and 69% with low-, intermediate-, and high-risk disease, respectively). Mutation sites included F1174 (51%), R1275 (29%), R1245 (10%), and others (10%). Mutation site was not prognostic for progression-free survival or overall survival in the entire cohort, high-risk subgroup, or locoregional subgroup. Locoregional tumors with any ALK mutation were generally invasive: L2 by International Neuroblastoma Research Group staging in 30/31 patients with a 2-year progression-free survival (59%, 95% CI, 37.4 to 80.5) that was inferior to historical controls. This observation was corroborated in the post-2014 subgroup in which gross total resection was less likely for ALK-mutated tumors. CONCLUSION: Somatic ALK mutations are present across all stages and risk groups of neuroblastoma. No specific mutation carries differential prognostic significance. Locoregional neuroblastoma has an invasive phenotype when harboring somatic ALK mutations in this population.

Differences in the response in the dermis of the tails of young and old SD rats to treatment with bipolar RF.

BACKGROUND: The passing of the years is marked by intrinsic (chronological) and extrinsic aging, caused by photoaging, which is characterized by a decrease in collagen and the deposition of abnormal elastic fibers in the dermis. The use of bipolar radiofrequency (RF) increases fibroblast proliferation and differentiation, accompanied by collagen synthesis and a subsequent increase in connective tissue, and it is not known whether the biological effects of this type of radiofrequency on the dermis are similar regardless of the age of the individual or whether such effects are altered by the aging process itself. AIMS: The objective was to perform a histological study of the changes in the tail dermis of young and old rats after submitting them to bipolar RF, to determine cell proliferation and volume of connective tissue. METHODS: One part of the rat tail was fixed in formol and processed for light microscopy and another part processed for electron microscopy. RESULTS: The number of fibroblasts/unit area and cells positive to nuclear proliferation antigen was higher in young animals. Significant differences were observed regarding expression of HSP-47 protein, and the value was always lower in old rats. No significant differences were observed in the percentage of connective tissue. No histological alterations were observed in any rats. CONCLUSION: Treatment with RF increased the number of fibroblasts located in the connective tissue of the young rats. In addition, the effect of a single treatment on the population of fibroblasts in young animals was sufficient to activate the synthesis of new collagen.

Cyclosporine A plus low-dose steroid treatment in COVID-19 improves clinical outcomes in patients with moderate to severe disease: A pilot study.

BACKGROUND: COVID-19 pandemic causes high global morbidity and mortality and better medical treatments to reduce mortality are needed. OBJECTIVE: To determine the added benefit of cyclosporine A (CsA), to low-dose steroid treatment, in patients with COVID-19. METHODS: Open-label, non randomized pilot study of patients with confirmed infection of SARS-CoV-2 hospitalized from April to May 2020 at a single centre in Puebla, Mexico. Patients were assigned to receive either steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days. RESULTS: A total of 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ± 13.3; 69% men), and 104 steroids alone (age 54.06 ± 13.8; 61% men). All patients received clarithromycin, enoxaparin and methylprednisolone or prednisone up to 10 days. Patient's death was associated with hypertension (RR = 3.5) and diabetes (RR = 2.3). Mortality was 22 and 35% for CsA and control groups (P = 0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (P = 0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, P = 0.001, log-rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39-3.34, 95%CI, P = 0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35-2.83, 95%CI, P = 0.0003) for all patients. CONCLUSION: CsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.

Effect of Bifidobacterium infantis NLS super strain in symptomatic coeliac disease patients on long-term gluten-free diet - an exploratory study.

Bifidobacterium infantis NLS super strain (B. infantis NLS-SS) was previously shown to alleviate gastrointestinal symptoms in newly diagnosed coeliac disease (CD) patients consuming gluten. A high proportion of patients following a gluten-free diet experiences symptoms despite dietary compliance. The role of B. infantis in persistently symptomatic CD patients has not been explored. The aim of the study was to evaluate the effect of B. infantis NLS-SS on persistent gastrointestinal symptoms in patients with CD following a long-term GFD. We conducted a randomised, cross-over, double-blind, placebo-controlled trial in symptomatic adult CD patients on a GFD for at least two years. After one-week run-in, patients were randomised to B. infantis NLS-SS or placebo for 3 weeks with cross-over after a 2-week wash-out period. We estimated changes (Δ) in celiac symptom index (CSI) before and after treatment. Stool samples were collected for faecal microbiota analysis (16S rRNA sequencing). Gluten immunogenic peptide (GIP) excretion in stool and urine samples was measured at each study period. Eighteen patients were enrolled; six patients were excluded due violations in protocol. For patients with the highest clinical burden, CD symptoms were lower in probiotic than in placebo treatment (P=0.046). B. infantis and placebo treated groups had different microbiota profiles as assessed by beta diversity clustering. In probiotic treated groups, we observed an increase in abundance of B. infantis. Treatment with B. infantis was associated with decreased abundance of Ruminococcus sp. and Bifidobacterium adolescentis. GIP excretion in stools and urine was similar at each treatment period. There were no differences in adverse effects between the two groups. B. infantis NLS-SS improves specific CD symptoms in a subset of highly symptomatic treated patients (GFD). This is associated with a shift in stool microbiota profile. Larger studies are needed to confirm these findings. ClinicalTrials.gov: NCT03271138.

Host immune interactions in chronic inflammatory gastrointestinal conditions.

PURPOSE OF REVIEW: We performed a literature review of the latest studies on the interactions between the host immune system and microbes in chronic intestinal inflammatory conditions. RECENT FINDINGS: The mechanisms leading to celiac disease (CeD) and inflammatory bowel disease (IBD), the most common chronic inflammatory gastrointestinal conditions, are complex. The intestinal homeostasis depends on the interactions between the microbiota, the intestinal mucosa and the host immune system. Failure to achieve or maintain equilibrium between a host and its microbiota has the potential to induce chronic conditions with an underlying inflammatory component. Mechanisms by which intestinal microbes trigger inflammation include the alteration of intestinal permeability, activation of the host immune system and digestion of dietary antigens with a consequent repercussion on tolerance to food. Therefore, therapies modulating gut microbiota, including diet, antibiotics, probiotics and faecal transplantation have a potential in CeD and IBD. Probiotics are effective to treat pouchitis and faecal transplant for ulcerative colitis, but the evidence is less clear in Crohn's disease or CeD. SUMMARY: Diverse regulatory mechanisms cooperate to maintain intestinal homeostasis, and a breakdown in these pathways may precipitate inflammation. The role of microbiota inducing immune dysfunction and inflammation supports the therapeutic rationale of manipulating microbiota to treat chronic inflammatory conditions.

[Visual recovery as the target for glaucoma]. / Visuelle Regeneration als Ziel für das Glaukom.

BACKGROUND: Visual recovery is an established but poorly studied phenomenon in glaucoma. OBJECTIVE: To provide insights into functional recovery of retinal ganglion cells (RGCs) with a view to providing information on the development of forms of treatment that improve RGC function after injury. METHOD: A model of recoverable RGC function in the mouse eye, induced by short-term elevation of intraocular pressure (IOP). RESULTS: The RGCs manifest near complete functional recovery after a prolonged period of dysfunction following acute IOP elevation. Increasing age and a high fat diet were subsequently found to impair recovery, whereas exercise substantially improved recovery such that older mice recovered in a similar way to young mice. CONCLUSION: Injured RGCs have the capacity to restore function after periods of functional impairment. Therapies that specifically target injured RGCs and enhance their capacity to recover function may provide a new approach for treating glaucoma.

No evidence of increased ocular involvement in candidemic patients initially treated with echinocandins.

Candins are commonly used as initial therapy in patients with candidemia and are known to diffuse poorly into ocular tissue. The aim of our multicenter study was to assess whether eye involvement was more common in patients initially treated with echinocandins. We performed a post hoc analysis of a prospective, multicenter, population-based candidemic surveillance program implemented in Spain during 2010-2011 (CANDIPOP project). Eye involvement was detected in 13 of 168 patients with candidemia (7.7%) who underwent ophthalmoscopy. Two patients had endophthalmitis, while the remaining patients had chorioretinitis. The frequency of ocular candidiasis was similar in patients receiving initial therapy with candins (3/56; 5.4%) or with other regimens (10/112; 8.9%). At multivariate analysis, risk conditions for eye involvement were dialysis after candidemia (OR, 19.4; 95% CI, 1.7-218.4) and involvement of organs other than the eye (OR, 5.4; 95% CI, 1.1-25.7). In conclusion, eye involvement was not found to be more frequent in patients receiving initial therapy with echinocandins than in patients receiving other drugs.

Derivation and validation of a diagnostic test for irritable bowel syndrome using latent class analysis.

BACKGROUND: The accuracy of symptom-based diagnostic criteria for irritable bowel syndrome (IBS) is modest. AIMS: To derive and validate a new test that utilises latent class analysis. METHODS: Symptom, colonoscopy, and histology data were collected from 1981 patients and 360 patients in two cohorts referred to secondary care for investigation of their gastrointestinal symptoms in Canada and the UK, respectively. Latent class analysis was used to identify naturally occurring clusters in patient-reported symptoms in the Canadian dataset, and the latent class model derived from this was then applied to the UK dataset in order to validate it. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated for the latent class models. RESULTS: In the Canadian cohort, the model had a sensitivity of 44.7% (95% CI 40.0-50.0) and a specificity of 85.3% (95% CI 83.4-87.0). Positive and negative LRs were 3.03 (95% CI 2.57-3.56) and 0.65 (95% CI 0.59-0.71) respectively. A maximum positive LR of 3.93 was achieved following construction of a receiver operating characteristic curve. The performance in the UK cohort was similar, with a sensitivity and specificity of 52.5% (95% CI 42.2-62.7) and 84.3% (95% CI 79.3-88.6), respectively. Positive and negative LRs were 3.35 (95% CI 2.38-4.70) and 0.56 (95% CI 0.45-0.68), respectively, with a maximum positive LR of 4.15. CONCLUSIONS: A diagnostic test for IBS, utilising patient-reported symptoms incorporated into a latent class model, performs as accurately as symptom-based criteria. It has potential for improvement via addition of clinical markers, such as coeliac serology and faecal calprotectin.

Poor predictive value of lower gastrointestinal alarm features in the diagnosis of colorectal cancer in 1981 patients in secondary care.

BACKGROUND: Clinicians are advised to refer patients with lower gastrointestinal (GI) alarm features for urgent colonoscopy to exclude colorectal cancer (CRC). However, the utility of alarm features is debated. AIM: To assess whether performance of alarm features is improved by using a symptom frequency threshold to trigger referral, or by combining them into composite variables, including minimum age thresholds, as recommended by the National Institute for Health and Care Excellence (NICE). METHODS: We collected data prospectively from 1981 consecutive adults with lower GI symptoms. Assessors were blinded to symptom status. The reference standard to define CRC was histopathological confirmation of adenocarcinoma in biopsy specimens from a malignant-looking colorectal lesion. Controls were patients without CRC. Sensitivity, specificity, positive predictive values (PPVs) and negative predictive values were calculated for individual alarm features, as well as combinations of these. RESULTS: In identifying 47 (2.4%) patients with CRC, individual alarm features had sensitivities ranging from 11.1% (family history of CRC) to 66.0% (loose stools), and specificities from 30.5% (loose stools) to 75.6% (family history of CRC). Using higher symptom frequency thresholds improved specificity, but to the detriment of sensitivity. NICE referral criteria also had higher specificities and lower sensitivity, with PPVs above 4.8%. More than 80% of those with CRC met at least one of the NICE referral criteria. CONCLUSIONS: Using higher symptom frequency thresholds for alarm features improved specificity, but sensitivity was low. NICE referral criteria had PPVs above 4.8%, but sensitivities ranged from 2.2% to 32.6%, meaning many cancers would be missed.

Duodenal membranes: a late diagnosis evidenced by foreign bodies.

One of the causes of congenital incomplete duodenal obstruction is the presence of duodenal membranes. This condition requires a high index of suspicion for an early and accurate diagnosis. We present two cases of duodenal obstruction with initial diagnosis of foreign bodies that were surgically intervened and where incomplete duodenal membranes were an incidental finding. The clinical course of these patients had a different pattern than expected and thus, it is imperative to use a multidisciplinary approach in this group of patients and separate them from other subtypes of duodenal obstruction.

Emerging Mitochondrial Therapeutic Targets in Optic Neuropathies.

Optic neuropathies are an important cause of blindness worldwide. The study of the most common inherited mitochondrial optic neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) has highlighted a fundamental role for mitochondrial function in the survival of the affected neuron-the retinal ganglion cell. A picture is now emerging that links mitochondrial dysfunction to optic nerve disease and other neurodegenerative processes. Insights gained from the peculiar susceptibility of retinal ganglion cells to mitochondrial dysfunction are likely to inform therapeutic development for glaucoma and other common neurodegenerative diseases of aging. Despite it being a fast-evolving field of research, a lack of access to human ocular tissues and limited animal models of mitochondrial disease have prevented direct retinal ganglion cell experimentation and delayed the development of efficient therapeutic strategies to prevent vision loss. Currently, there are no approved treatments for mitochondrial disease, including optic neuropathies caused by primary or secondary mitochondrial dysfunction. Recent advances in eye research have provided important insights into the molecular mechanisms that mediate pathogenesis, and new therapeutic strategies including gene correction approaches are currently being investigated. Here, we review the general principles of mitochondrial biology relevant to retinal ganglion cell function and provide an overview of the major optic neuropathies with mitochondrial involvement, LHON and ADOA, whilst highlighting the emerging link between mitochondrial dysfunction and glaucoma. The pharmacological strategies currently being trialed to improve mitochondrial dysfunction in these optic neuropathies are discussed in addition to emerging therapeutic approaches to preserve retinal ganglion cell function.

Impact of an influenza vaccine educational programme on healthcare personnel.

Influenza vaccination has been shown to be the most effective preventive strategy to reduce influenza-related morbidity and mortality in high-risk groups. Despite healthcare personnel (HCP) being considered part of such high-risk groups, their vaccination coverage is low in Europe. In January 2012, we distributed an 18-question survey regarding influenza vaccination to HCP at Gregorio Marañon Paediatric Hospital, in Madrid, Spain. After we documented that only ~30% of HCP were vaccinated an educational programme was implemented in October 2012 before the next influenza season. In January 2013, the same survey delivered again to all HCP documented a significant increase in vaccination rates (from 30% to 40%, P = 0·007) mainly among physicians and for patients' protection. In summary we found that a simple and inexpensive educational programme significantly improved the uptake of influenza vaccination in HCP in our centre. Nevertheless, vaccination rates remained low, and broader and updated campaigns are needed to overcome perception barriers.