Percutaneous Gastrostomies: Associated Complications in PUSH vs. PULL Techniques over 12 Years in a Referral Centre.

Objectives: To compare complications associated with percutaneous gastrostomies performed using PUSH and PULL techniques, whether endoscopic (PEG) or radiological (PRG), in a tertiary-level hospital. Methods: This was a prospective observational study. Adult patients who underwent percutaneous PULL or PUSH gastrostomy using PEG or PRG techniques at the Virgen del Rocio University Hospital and subsequently followed up in the Nutrition Unit between 2009-2020 were included. X2 tests or Fisher's test were used for the comparison of proportions when necessary. Univariate analysis was conducted to study risk factors for PRG-associated complications. Results: n = 423 (PULL = 181; PUSH = 242). The PULL technique was associated with a higher percentage of total complications (37.6% vs. 23.8%; p = 0.005), exudate (18.2% vs. 11.2%; p = 0.039), and irritation (3.3% vs. 0%; p = 0.006). In the total sample, there were 5 (1.1%) cases of peritonitis, 3 (0.7%) gastrocolic fistulas, and 1 (0.2%) death due to complications associated with gastrostomy. Gender, age, and different indications were not risk factors for a higher number of complications. The most common indications were neurological diseases (35.9%), head and neck cancer (29%), and amyotrophic lateral sclerosis (17.2%). Conclusions: The PULL technique was associated with more total complications than the PUSH technique, but both were shown to be safe techniques, as the majority of complications were minor.

Gastrostomies: experience and complications with three modalities in a tertiary centre over a 26-year period.

Objectives: To describe the complications associated with the different gastrostomy techniques [endoscopic (PEG), radiologic (PRG), and surgical (SG)] performed in the last 26 years in a terciary hospital. Methods: Retrospective observational study. Patients who underwent gastrostomy at the Virgen del Rocío University Hospital between 1995 and 2021 were included. For PEG, the PULL technique was performed until 2018 and subsequently the PUSH technique predominantly. For PRG, a pigtail catheter was used until 2003, a balloon catheter between 2003 and 2009, and a balloon catheter with gastropexy between 2015 and 2021. For SG, the conventional technique (CSG) was performed until 2009 and since then the laparoscopic assisted percutaneous gastrostomy (PLAG) technique. Descriptive analysis was performed obtaining the median and quartiles of the quantitative variables [P50 (P25-P75)] and the frequency for the qualitative variables [n (%)].The comparison of complications between patients who underwent different techniques was performed with Fisher's test. Results: n = 1,070 (PEG = 608, PRG = 344, SG = 118). The three most frequent indications were head and neck tumors, neurological diseases and gastroesophageal tumors. The percentage of patients who had any complication was 48.9% (PEG-PULL), 23.7% (PEG-PUSH), 38.5% (pigtail PRG), 39.2% (balloon PRG), 29.7% (balloon with gastropexy PRG), 87.3% (CSG), and 41.26% (PLAG). 2 (0.18%) patients died from gastrostomy-related complications. 18(1.68%) presented with peritonitis and 5 (0.4%) presented with gastrocolic fistula. The rest of the complications were minor. Conclusion: Gastrostomy in any of its modalities is currently a safe procedure with a low rate of complications, most of which are minor.

Time-Tested Strategies in Modern Context: A Bibliometric Study of Chemotherapy's Continued Importance in Colorectal Cancer Treatment.

In the landscape of colorectal cancer treatment, classical chemotherapeutic agents such as 5-fluorouracil, capecitabine, irinotecan, oxaliplatin, trifluridine, and tipiracil have historically played a pivotal role. This study presents a comprehensive bibliometric analysis of the top 100 most influential articles focusing on these classic chemotherapy drugs in the management of colorectal cancer. With this, we shed light on their current importance, despite the emergence of new therapeutic targets and treatments in the field of oncology. Systematically evaluating research outputs, this analysis reveals a prevalence of co-authorship among institutions, countries (led by the United States, China, and Europe), and researchers highlighting the global and collaborative nature of efforts in research, utilization, and development of these drugs. Three thematic axes lead the research: pharmacogenetics, the development of new pharmaceutical forms, and the use of adjuvants. This research serves as a foundation for future endeavors, aiding researchers, clinicians, and policymakers in making informed decisions about the direction of research and development in the dynamic field of colorectal cancer therapy.

Ivabradine for controlling heart rate in permanent atrial fibrillation: A translational clinical trial.

BACKGROUND: Pharmacological options for rate control in atrial fibrillation are scarce. Ivabradine was postulated to reduce the ventricular rate in this setting. OBJECTIVES: The objectives of this study were to evaluate the mechanism of inhibition of atrioventricular conduction produced by ivabradine and to determine its efficacy and safety in atrial fibrillation. METHODS: The effects of ivabradine on atrioventricular node and ventricular cells were studied by in vitro whole-cell patch-clamp experiments and mathematical simulation of human action potentials. In parallel, a multicenter, randomized, open-label, phase III clinical trial compared ivabradine with digoxin for uncontrolled permanent atrial fibrillation despite ß-blocker or calcium channel blocker treatment. RESULTS: Ivabradine 1 µM inhibited "funny" current and rapidly activating delayed rectifier potassium channel current by 28.9% and 22.8%, respectively (P < .05). The sodium channel current and L-type calcium channel current were reduced only at 10 µM. Ivabradine slowed the firing frequency of a modeled human atrioventricular node action potential by 10.6% and induced a minimal prolongation of ventricular action potential. Thirty-five (51.5%) patients were randomized to ivabradine and 33 (49.5%) to digoxin. The mean daytime heart rate decreased by 11.6 beats/min (-11.5%) in the ivabradine arm (P = .02) vs 19.6 (-20.6%) in the digoxin arm (P < .001), although the noninferiority margin of efficacy was not met (Z = -1.95; P = .97). The primary safety end point occurred in 3 patients (8.6%) on ivabradine and in 8 (24.2%) on digoxin (P = .10). CONCLUSION: Ivabradine produced a moderate rate reduction in patients with permanent atrial fibrillation. The inhibition of funny current in the atrioventricular node seems to be the main mechanism responsible for this reduction. Compared with digoxin, ivabradine was less effective, was better tolerated, and had a similar rate of serious adverse events.

Endoscopic removal of lumen-apposing metal stents - risk factors for stent embedment, complex removals, and adverse events: analysis from a multicenter prospective case series.

BACKGROUND: Removing lumen-apposing metal stents (LAMSs) may be difficult and even harmful, but these features have seldom been analyzed. We aimed to generate a comprehensive assessment of the feasibility and safety of LAMS retrieval procedures. METHODS: A prospective multicenter case series including all technically successfully deployed LAMSs between January 2019 and January 2020 that underwent endoscopic stent removal. All retrieval-related data were prospectively recorded using standardized telephone questionnaires as part of centralized follow-up that ended after stent removal had been performed. Multivariable logistic regression models assessed the potential risk factors for complex removal. RESULTS: For the 407 LAMSs included, removal was attempted in 158 (38.8 %) after an indwell time of 46.5 days (interquartile range [IQR] 31-70). The median (IQR) removal time was 2 (1-4) minutes. Removal was labelled as complex in 13 procedures (8.2 %), although advanced endoscopic maneuvers were required in only two (1.3 %). Complex removal risk factors were stent embedment (relative risk [RR] 5.84, 95 %CI 2.14-15.89; P = 0.001), over-the-wire deployment (RR 4.66, 95 %CI 1.60-13.56; P = 0.01), and longer indwell times (RR 1.14, 95 %CI 1.03-1.27; P = 0.01). Partial and complete embedment were observed in 14 (8.9 %) and five cases (3.2 %), respectively. The embedment rate during the first 6 weeks was 3.1 % (2/65), reaching 15.9 % (10/63) during the following 6 weeks (P = 0.02). The adverse event rate was 5.1 %, including seven gastrointestinal bleeds (5 mild, 2 moderate). CONCLUSIONS: LAMS removal is a safe procedure, mostly requiring basic endoscopic techniques attainable in conventional endoscopy rooms. Referral to advanced endoscopy units should be considered for stents with known embedment or long indwell times, which may require more technically demanding procedures.

Clinical utility of urinary gluten immunogenic peptides in the follow-up of patients with coeliac disease.

BACKGROUND: Gluten-free diet (GFD) is the only treatment for patients with coeliac disease (CD) and its compliance should be monitored to avoid cumulative damage. AIMS: To analyse gluten exposures of coeliac patients on GFD for at least 24 months using different monitoring tools and its impact on duodenal histology at 12-month follow-up and evaluate the interval of determination of urinary gluten immunogenic peptides (u-GIP) for the monitoring of GFD adherence. METHODS: Ninety-four patients with CD on a GFD for at least 24 months were prospectively included. Symptoms, serology, CDAT questionnaire, and u-GIP (three samples/visit) were analysed at inclusion, 3, 6, and 12 months. Duodenal biopsy was performed at inclusion and 12 months. RESULTS: At inclusion, 25.8% presented duodenal mucosal damage; at 12 months, this percentage reduced by half. This histological improvement was indicated by a reduction in u-GIP but did not correlate with the remaining tools. The determination of u-GIP detected a higher number of transgressions than serology, regardless of histological evolution type. The presence of >4 u-GIP-positive samples out of 12 collected during 12 months predicted histological lesion with a specificity of 93%. Most patients (94%) with negative u-GIP in ≥2 follow-up visits showed the absence of histological lesions (p < 0.05). CONCLUSION: This study suggests that the frequency of recurrent gluten exposures, according to serial determination of u-GIP, could be related to the persistence of villous atrophy and that a more regular follow-up every 6 months, instead of annually, provides more useful data about the adequate adherence to GFD and mucosal healing.

Efficacy of gel containing organic extra virgin olive oil for peristomal skin hygiene: A pilot randomised controlled trial.

AIM: To assess the efficacy and safety of the application, during stoma hygiene, of a pH-neutral gel containing organic EVOO (oEVOO) for the maintenance of peristomal skin integrity. METHOD: Patients with a colostomy or ileostomy were enrolled in a pilot randomized controlled trial and assigned treatment with a pH-neutral gel made from natural products including oEVOO or usual stoma hygiene gel. The primary outcome was three domains of abnormal peristomal skin: Discolouration, Erosion and Tissue overgrowth. Secondary outcomes that were evaluated included skin moisture; oiliness; skin elasticity; water-oil balance; patients' perceptions; difficulty inserting and removing the pouching system; pain, any other chemical, infectious, mechanical, or immunological complications of concern. The intervention lasted 8 weeks. RESULTS: Twenty-one patients were recruited for the trial and randomly assigned to either the experimental group (n = 12) or the control group (n = 9). The groups did not differ significantly in terms of patient characteristics. No significant differences between groups were identified either at baseline (p = 0.203) or at the end of the intervention (p = 0.397). In the experimental group, domains of abnormal peristomal skin improved after the intervention. The difference observed before and after the intervention was statistically significant (p = 0.031). CONCLUSION: The use of a gel containing oEVOO has shown similar levels of efficacy and safety to other gels commonly used for peristomal skin hygiene. It is also relevant to highlight that a significant improvement in skin condition was observed in the experimental group before and after the intervention.

Multitraction with rubber bands and surgical silk as a method to facilitate endoscopic submucosal dissection.

We propose this variant of the clip technique as a method that assist traction during endoscopic submucosal dissection (ESD): traction on the mucosa plane using an hemoclip carrying a surgical silk and three rubber bands, before the incision, to allow easier access to the submucosa space. We propose this variant with the intention of facilitating access to ESD quickly and safely for beginners.

Differences in the prognostic value of the electrocardiographic pattern after cardiac resynchronization therapy according to age.

OBJECTIVES: In this cohort study, we analyzed if a specific pattern in three leads of the electrocardiogram (Rs in V1, Qr in aVL, or rS in I) was associated with outcomes after cardiac resynchronization therapy (CRT) depending on age. METHODS: Patients with CRT devices were included from January 2012 to April 2019. We divided the sample into 2 groups, those with age ≥ 75 years old and those younger. The primary endpoint was a composite of all-cause death and heart failure (HF) hospitalization at 1 year. RESULTS: We included 111 patients. Patients older than 75 years (26.1%, n = 29) had a significantly higher rate of hypertension and atrial fibrillation and received less frequently optimal medical therapy. The patterns were observed in 32 (39.0%) younger patients and 11 (37.9%) older patients. Patients who presented any of them had a lower incidence of the primary endpoint in the younger group (0 vs. 14%, p = 0.029), but not in the older group (9.1 vs. 27.8%, p = 0.24). The presence of a basal QRS duration greater than 160 ms was associated with a higher rate of the primary endpoint in the elderly (50 vs. 13%, p = 0.015), but not in the younger group (16.7 vs. 7.1%, p = 0.254). CONCLUSIONS: The presence of the selected patterns after CRT is associated with a lower incidence of all-cause death and hospitalization for HF in patients younger than 75 years, but not in those older than 75 years. Conversely, baseline QRS duration was associated with worse outcomes in older patients, but not in the younger group.

Undergraduate nursing students' knowledge of Alzheimer's disease and related dementias care.

BACKGROUND: The increase in the number of people with Alzheimer's disease and Related Dementias (ADRD) will results in an increased need for nurses with up-to-date knowledge of ADRD and who are well-educated in ADRD care. Therefore, it is important to be sure that this topic is covered in the undergraduate nursing curriculum. PURPOSE: To assess undergraduate nursing students' knowledge of Alzheimer's disease and related dementias care. METHOD: Cross-sectional study carried out among nursing students at two universities in southern Spain. The University of Jaen (UJA)-Alzheimer's Care scale was used to measure their knowledge. RESULTS: The mean age of the students was 21.39 years, and 83.2% of the 678 students were women. For students, the UJA-Alzheimer's Care scale has a good fit and reliability of 0.99 for the items and 0.74 for the persons, according to the Rasch model. The mean knowledge score of nursing students was 15.33 (SD 3.69) out of 23; (95%CI: 15.06-15.61). The value of the latent variable (theta) was 1.16 (SD 1.21); (95%CI: 1.06-1.25). The factors positively associated with students' knowledge were the number of years in the program, experience in caring for a patient with ADRD during their placements, and the education on ADRD received in the nursing program as self-rated by the students. CONCLUSION: The UJA-Alzheimer's Care scale is a useful tool for measuring knowledge of ADRD care among nursing students in Spain and other Spanish-speaking countries. Nursing students at the two universities reached moderate scores in the knowledge of ADRD care. More years in the nursing program, practical experience in clinical placements, and higher self-rated level of education on ADRD received during the program were associated with higher scores on knowledge.

Nurses and ward managers' perceptions of leadership in the evidence-based practice: A qualitative study.

AIM: To describe nurses and ward managers' experiences with nursing leadership in the implementation of evidence-based practice. BACKGROUND: The implementation of evidence-based practice requires to identify the most suitable styles of nursing leadership for the successful application. DESIGN: A qualitative descriptive study. METHODS: The study was carried out with 57 nurses (clinical nurses and ward managers) in eight focus groups from five public hospitals. Template analysis, using the Promoting Action on Research Implementation in Health Services framework, was used. The Consolidated Criteria for Reporting Qualitative Research guide was followed in planning and reporting this research. RESULTS: Three types of nursing leadership were identified: traditional leadership, medium leadership and transformational leadership. Traditional leadership was the most frequent, with a predominance of bureaucratic tasks for ward managers, so implementation of evidence-based practice is difficult. CONCLUSION: Nurses do not feel empowered and they perceive the changes as an imposition. In the absence of strong leadership for evidence-based practice, a natural leader emerges. IMPLICATIONS FOR NURSING MANAGEMENT: Clinical nurses demand more empowerment for decision-making, and ward managers need clarity of roles. To create an environment favourable to evidence-based practice, it is necessary consider the role of the transformational leader.

Skin injuries associated with severe life-threatening situations: A new conceptual framework.

PURPOSE: To create a conceptual framework for skin injuries developing in patients whose lives are severely compromised or who are expected to die within a short period of time. To name and classify these types of skin injuries. To describe the clinical features of the different types of skin injuries that may occur in terminally ill and/or dying patients. DESIGN: A sequential design with several different phases (a literature review, a nominal group, and a consensus conference) was used. METHODS: Six experts with extensive knowledge of these types of injuries were selected for the nominal group. The traditional eight-phase nominal group technique was followed. The consensus conference consisted of participants voting on different options based on the statements elaborated with the expert panel summarizing the best scientific evidence available. FINDINGS: Using all these elements, a conceptual framework was constructed to identify skin injuries associated with severe life-threatening situations (SI-SLTSs), defined as unpredictable and therefore unpreventable injuries indicating a serious threat to life or even imminent death. These injuries can occur in two forms: (a) as skin injuries associated with multiple organ dysfunction syndrome (SI-MODSs) or (b) as skin injuries associated with severe vasoconstriction (SI-ESVs). SI-MODSs develop very quickly and suddenly. They progress from superficial to deep stages abruptly, even within hours. The severity of the injuries does not reflect the care provided to the patient. Individuals suffering from these injuries have an irreversible clinical condition. SI-ESVs also appear in individuals who are in a very critical, even terminal, clinical condition. They are frequently treated in the ICU and may exhibit severe vasoconstriction due to their disease process (e.g., shock), sometimes exacerbated by vasoconstriction caused by various drugs (e.g., noradrenaline). CONCLUSIONS: We have developed a conceptual framework for skin injuries developing in patients whose lives are severely compromised or who are expected to die within a short period of time and have named them SI-SLTSs, distinguishing between SI-MODSs and SI-ESVs. CLINICAL RELEVANCE: This new conceptual framework may help clinicians understand the mechanisms and the pathophysiology of skin injuries that develop in terminally ill and/or dying patients associated with multi-organ failure. Through this new framework these injuries can be identified and differentiated from pressure injuries or other dependence-related skin lesions.

Circulating Tumor Cells Enumeration from the Portal Vein for Risk Stratification in Early Pancreatic Cancer Patients.

BACKGROUND: Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). METHODS: In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy. RESULTS: CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months; p = 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months; p = 0.004). These significant correlations were not observed in CVC analyses. CONCLUSIONS: CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.

Conceptual Framework for Incontinence-Associated Dermatitis Based on Scoping Review and Expert Consensus Process.

Incontinence-associated dermatitis (IAD) has been studied over the last decades, but gaps in the knowledge related to its identification, etiological agents, and risk factors remain. We carried out a scoping review about IAD that included systematic reviews, experimental, and observational studies about IAD and its potential risk factors. We retrieved 24 articles that described 100 potential risk factors and which were synthesized by the authors and proposed to a panel of experts. Panelists used a structured process of consensus development to create a conceptual framework of factors associated with IAD. This framework proposes that liquid fecal material, when combined with exposure to urine and stool, and bacterial contaminated urine are etiological factors for development of IAD. The framework also proposes 2 pathophysiological mechanisms and 8 main risk factors for IAD development. The proposed model could improve the quality of care for patients with or at risk of IAD, assisting healthcare professionals to identify at-risk patients, diagnose the type of lesion, and establish adequate and effective prevention and treatment measures.

Kennedy terminal ulcer and other skin wounds at the end of life: An integrative review.

AIMS: To undertake an integrative literature review to identify, analyse and synthesize current literature on the Kennedy terminal ulcer (KTU) and other unavoidable skin injuries that appear at the end of life regardless of the healthcare context in which they occur. METHODS: Integrative review following the Whittemore and Knafl methodology. The search was carried out in PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus. It was limited to articles in English, French, Portuguese and Spanish. As there is little scientific production on the subject, no restrictions were applied regarding publication date. RESULTS: Only 17 articles met the inclusion criteria. These articles were reviewed and analysed. Four relevant issues emerged: Skin failure, SCALE, Kennedy Terminal Ulcer, Trombley-Brennan: different names for the same problem; the defining characteristics and physiopathology of KTU; the differences between KTU and other injuries; and the care approach for KTU and other unavoidable injuries at the end of life. CONCLUSIONS: We identified gaps regarding the physiopathology of KTU since the current knowledge is based only on hypotheses. There is also a large gap in the knowledge about care approaches, perhaps because care plans are not recorded. Despite this, it is clear that the main objective in this situation at the end of life would be to prioritize patient comfort and quality of life.

A Bibliometric Evaluation of the Top 100 Cited Dimethyl Fumarate Articles.

Dimethyl fumarate is a cytoprotective and immunomodulatory drug used in the treatment of multiple sclerosis. We performed a bibliometric study examining the characteristics and trends of the top 100 cited articles that include dimethyl fumarate in the title. On 21 September 2020 we carried out an electronic search in the Web of Science (WOS), seeking articles that include the following terms within the title: dimethyl fumarate, BG-12, or Tecfidera. To focus our investigation on original research, we refined the search to include only articles, early access, others, case report, and clinical trials. We obtained a total of 1115 items, which were cited 7169 times, had a citation density of 6.43 citations/item, and an h-index of 40. Around 2010, there was a jump in the number of published articles per year, rising from 5 articles/year up to 12 articles/year. We sorted all the items by the number of citations and selected the top 100 most cited (T100). The T100 had 4164 citations, with a density of 37 citations/year and contained 16 classic research articles. They were published between 1961 and 2018; the years 2010-2018 amassed nearly 80% of the T100. We noted 17 research areas with articles in the T100. Of these, the number one ranking went to neurosciences/neurology with 39 articles, and chemistry ranked second on the T100 list with 14 items. We noticed that the percentage of articles belonging to different journals changed depending on the time period. Chemistry held the highest number of papers during 1961-2000, while pharmacology andneurosciences/neurology led the 2001-2018 interval. A total of 478 authors from 145 institutions and 25 countries were included in the T100 ranking. The paper by Gold R et al. was the most successful with 14 articles, 1.823 citations and a density of 140.23 citations/year. The biotechnological company Biogen led the T100 list with 20 articles. With 59 published articles, the USA was the leading country in publications. We concluded that this study analyzed the use of and research on dimethyl fumarate from a different perspective, which will allow the readership (expert or not) to understand the relevance of classic and recent literature on this topic.

Hospitalised patients with palliative care needs: Spain and Sweden compared.

OBJECTIVES: This study aimed to describe and compare symptoms, care needs and types of diagnoses in hospitalised patients with palliative care needs in Spain and Sweden. METHODS: A cross-sectional, population-based study was carried out at two hospitals in both Spain and Sweden. Using a questionnaire, we performed 154 one-day inventories (n=4213) in Spain and 139 in Sweden (n=3356) to register symptoms, care needs and diagnoses. Descriptive analyses were used. RESULTS: The proportion of patients with care needs in the two countries differed (Spain 7.7% vs Sweden 12.4%, p<0.001); however, the percentage of patients with cancer and non-cancer patients was similar. The most prevalent symptoms in cancer and non-cancer patients in both countries were deterioration, pain, fatigue and infection. The most common cancer diagnosis in both countries was lung cancer, although it was more common in Spain (p<0.01), whereas prostate cancer was more common among Swedish men (p<0.001). Congestive heart failure (p<0.001) was a predominant non-cancer diagnosis in Sweden, whereas in Spain, the most frequent diagnosis was dementia (p<0.001). Chronic obstructive pulmonary disease was common in both countries, although its frequency was higher in Spain (p<0.05). In total, patients with cancer had higher frequencies of pain (p<0.001) and nausea (p<0.001), whereas non-cancer patients had higher frequencies of deterioration (p<0.001) and infections (p<0.01). CONCLUSIONS: The similarities in symptoms among the patients indicate that the main focus in care should be on patient care needs rather than diagnoses. Integrating palliative care in hospitals and increasing healthcare professional competency can result in providing optimal palliative care.

A bibliometric evaluation of the top 100 cited natalizumab articles.

Natalizumab is being used in recurrent multiple sclerosis despite its history of market withdrawal due to lethal cases. We have carried out a bibliometric analysis of this drug from 1999 to February 2020 in order to assess the real impact of the use natalizumab with the goal to identify the key articles that sustain the current knowledge on the therapeutic possibilities of this compound. We have extracted from the Web of Science the top 100 most cited records (T100) and tabulated data on the journal, authors, publication year, number of citations, countries and institutions of publication, T100-records, citation density and citations per record of the works. The 100 most cited articles were selected from a total of 32,507 citations out of 2817 publications with an h-number of 74, 11.54 citations/publication, and a density of 1544.79 citations/year. Citations ranged from 63 of the paper placed in the 100th position (T100) to 1940 of the paper in the first position (T1). T2 was cited 888 times, and the difference in the number of citations between T1 and T2 was higher than that between T2 and T10. T1, T2 and T3 are clinical trials. When articles are arranged by institution and nationality having more than 10 T100 articles, biotechnology company Biogen and the USA, respectively, lead the ranking, but we also find that 8 out of 10 are academic European institutions. A co-authorship analysis reveals an intense collaborative activity between countries and institutions. We conclude that the clinical and academic communities have shown a sustained interest in natalizumab for the therapy of recurrent multiple sclerosis over the last 20 years.

Negative predictive value of the repeated absence of gluten immunogenic peptides in the urine of treated celiac patients in predicting mucosal healing: new proposals for follow-up in celiac disease.

BACKGROUND: The treatment of celiac disease (CD) is a lifelong gluten-free diet (GFD). The current methods for monitoring GFD conformance, such as a dietary questionnaire or serology tests, may be inaccurate in detecting dietary transgressions, and duodenal biopsies are invasive, expensive, and not a routine monitoring technique. OBJECTIVES: Our aim was to determine the clinical usefulness of urine gluten immunogenic peptides (GIP) as a biomarker monitoring GFD adherence in celiac patients and to evaluate the concordance of the results with the degree of mucosal damage. METHODS: A prospective observational study was conducted involving 22 de novo CD patients, 77 celiac patients consuming a GFD, and 13 nonceliac subjects. On 3 d of the week, urine samples were collected and the GIP concentrations were tested. Simultaneously, anti-tissue transglutaminase antibodies, questionnaire results, clinical manifestations, and histological findings were analyzed. RESULTS: Approximately 24% (18 of 76) of the celiac patients consuming a GFD exhibited Marsh II-III mucosal damage. Among this population, 94% (17 of 18) had detectable urine GIP; however, between 60% and 80% were asymptomatic and exhibited negative serology and appropriate GFD adherence based on the questionnaire. In contrast, 97% (31 of 32) of the celiac patients without duodenal damage had no detectable GIP. These results demonstrated the high sensitivity (94%) and negative predictive value (97%) of GIP measurements in relation to duodenal biopsy findings. In the de novo CD-diagnosed cohort, 82% (18 of 22) of patients had measurable amounts of GIP in the urine. CONCLUSIONS: Determining GIP concentrations in several urine samples may be an especially convenient approach to assess recent gluten exposure in celiac patients and appears to accurately predict the absence of histological lesions. The introduction of GIP testing as an assessment technique for GFD adherence may help in ascertaining dietary compliance and to target the most suitable intervention during follow-up.