To describe the biomedical journal characteristics that are associated with the retraction of papers.
A descriptive cross-sectional study was conducted. All papers retracted and indexed in PubMed ...from January 1st 2013 to December 31st, 2016 were included. We used nine main categories to classify retractions: aspects related with data, authors issues, plagiarism, unethical research, journal issues, review process, conflict of interest, other, and unknown. These categories were further classified as: misconduct, suspicion of misconduct, or no misconduct.
The proportion of retraction was 2.5 per 10,000 publications. Retractions appeared in 611 journals. During the study period, retraction due to misconduct was more frequent among journals with low-impact factor. Within these retracted publications, among low-impact journals the presence of misconduct was higher with a 73% compared to 61% for the high-impact journals (p=0.001). There were differences in the percentage of retractions due to misconduct regarding the journal classification category (p<0.001).
Retraction of publications is present in both high- and low-impact factor biomedical journals, but misconduct is more frequent among the papers retracted from lower impact journals. Measures before and after publication should be taken to limit misconduct.
Describir qué características de las revistas científicas biomédicas se asocian con la retractación de artículos.
Se realizó un estudio transversal en el que se incluyeron todos los artículos retractados e indexados en PubMed del 1 de enero de 2013 al 31 de diciembre de 2016. Las retractaciones también se clasificaron de forma más detallada: problemas con los datos o manejo de datos; aspectos de autoría; plagio; investigación no ética; aspectos relacionados con la revista; problemas con el proceso de revisión; conflicto de intereses o razones desconocidas. Posteriormente se clasificaron como mala conducta, sospecha de mala conducta o sin mala conducta.
La proporción de retractaciones fue de 2,5 por cada 10.000 publicaciones. Hubo retractaciones en 611 revistas. Durante el periodo de estudio, la retractación por mala conducta fue más frecuente en revistas con bajo factor de impacto, y entre los artículos retractados, hubo más mala conducta (73%) entre las revistas de bajo factor de impacto, en comparación con las revistas con alto factor de impacto (61%) (p=0,001). También se observan diferencias en el porcentaje de retractaciones debidas a mala conducta según la categoría de clasificación del Journal Citation Report (p <0,001).
La retractación de publicaciones está presente tanto en revistas de alto como de bajo factor de impacto, pero la retractación por mala conducta es más habitual en revistas biomédicas de bajo impacto. Deben tomarse medidas antes y después de la publicación para limitar la mala conducta científica.
The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular ...neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC), ALS-functional rating scale (ALS-FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant-related adverse event, but there were 43 nonsevere events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were common terminology criteria for adverse events grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris, or MRC scales was observed. Four patients died on days 359, 378, 808, and 1,058 post-transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section mns per sect and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity.
Abstract 4393
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterised by loss of motoneurons (mns), and it has no cure. Cell therapy has neurotrophic effects in animal ...models and has been proposed as a disease-modifying treatment. Our aim was twofold: firstly, to assess the safety of intraspinal infusion of bone marrow mononuclear cells (BMNC) and, ultimately, to look for histopathological signs of cellular neurotrophism.
We conducted an open single arm phase I trial. After six months observation, autologous BMNC were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC) and ALS-FRS, MRC and Norris scales were assessed six and three months prior to the transplant and quarterly afterwards for one year. Pathological studies were performed in case of death.
Eleven patients were included. We did not observe any severe transplant-related adverse event but there were 43 non-severe events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were CTCAE grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris or MRC scales was observed. Four patients died on days 359, 378, 808 and 1058 postransplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of montoneurons in the treated compared to the untreated segments (4.2+/−0.8 mns/section and 0.9+/−0.3 mns/section, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits.
This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence of their neurotrophic activity.
No relevant conflicts of interest to declare.
Stem cells are self‐renewable, pluripotent cells that, in adult life, proliferate by a characteristic asymmetric division in which one daughter cell is committed to differentiation whereas the other ...remains a stem cell. These cells are also characterized by their ability to differentiate into various cell types under heterotopic environmental influences. In the present study, we have explored the potential of adult haematopoietic bone marrow cells to differentiate into cells of oligodendroglial lineage under physiological, active myelinating conditions. We present evidence of generation of cells expressing oligodendroglial specific markers from a bone marrow subpopulation enriched on adult haematopoietic progenitor cells (CD117+) in vivo after intracerebral transplantation into the neonatal mouse brain. Our results suggest that adult bone marrow cells have the capacity to undergo differentiation from haematopoietic to oligodendroglial cells and add support the validity of bone marrow transplants as an alternative treatment for demyelinating diseases of the CNS including Multiple Sclerosis.
Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, and degenerative disease that is up to three times more frequent in young women. MS does not alter fertility and has no impact on ...fetal development, the course of pregnancy, or childbirth. The Pregnancy in Multiple Sclerosis Study in 1998 showed that pregnancy, mostly in untreated women, did not adversely affect MS, as disease activity decreased during pregnancy (although it significantly increased in the first trimester postpartum). These findings, together with the limited information available on the potential risks of fetal exposure to disease modifying treatments (DMTs), meant that women were advised to delay the onset of DMTs, stop them prior to conception, or, in case of unplanned pregnancy, discontinue them when pregnancy was confirmed. Now, many women with MS receive DMTs before pregnancy and, despite being considered a period of MS stability, up to 30% of patients could relapse in the first trimester postpartum. Factors associated with an increased risk of relapse and disability during pregnancy and postpartum include relapses before and during pregnancy, a greater disability at the time of conception, the occurrence of relapses after DMT cessation before conception, and the use of high-efficacy DMTs before conception, especially natalizumab or fingolimod. Strategies to prevent postpartum activity are needed in some patients, but consensus is lacking regarding the therapeutic strategies for women with MS of a fertile age. This, along with the increasing number of DMTs, means that the decision-making processes in aspects related to family planning and therapeutic strategies before, during, and after pregnancy are increasingly more complex. The purpose of this review is to provide an update on pregnancy-related issues in women with MS, including recommendations for counseling, general management, use of DMTs in pre-pregnancy, pregnancy, and postpartum periods, and breastfeeding-related aspects of DMTs.
Objective
Pivotal trial have shown that patients with multiple sclerosis (MS) receiving ocrelizumab had better outcomes. However, data on ocrelizumab in clinical practice are limited. The aim of this ...study was to evaluate the preliminary safety profile and effectiveness of ocrelizumab treatment for multiple sclerosis (MS) in a real‐world clinical setting.
Methods
We conducted a retrospective study including consecutive patients from nine public hospitals in south‐eastern Spain who received ocrelizumab after it was approved.
Results
A total of 228 MS patients were included (144 with relapsing–remitting MS RRMS, 25 secondary progressive MS SPMS, and 59 primary progressive MS PPMS). Median follow‐up period was 12 months (range, 1‐32). No evidence of disease activity (NEDA) status at year 1 was achieved in 91.2% of the relapsing MS (RMS) population, while disability progression was detected in 37.5% of the PPMS patients (median follow‐up period, 19 months). The most common adverse events reported were infusion‐related reactions and infections, with the most common infections being urinary tract infections followed by upper respiratory infections and COVID‐19.
Interpretation
The preliminary results in our real‐world setting show that ocrelizumab presented excellent results in suppressing disease activity with a favorable and consistent safety profile.
Introduction: Patients with Amyothrophyc Lateral Sclerosis (ALS) typically endure a progressive paralysis due to the continued loss of motoneurons that leads them to death in less than 5 years. No ...treatment has changed its natural history. Intraspinal injections of bone marrow mononuclear cells (MNC) have been able to ameliorate the course of ALS in murine models, acting as pumps of trophic factors that keep the motoneurons functional. We have designed a phase I/II clinical trial to check the feasibility of this approach in humans.
Material and Methods: 10 patients were required for this study. Inclusion criteria required a medullar onset of the disease, a forced vital capacity (FVC) >50% and under 90% desaturation time inferior to 2% of the sleeping time. Sixty mL of bone marrow were harvested under sedation. A ficoll procedure was performed in order to obtain the MNC, which were resuspended in 2 mL of saline. After laminectomy, the MNC were infused through a spinal needle in 2 injections 10 and 6 mm deep in the posterior tract of T3–T4 under electrophysiological surveillance. This level was chosen aiming the preservation of the lower intercostals function as a mean to stop the deterioration of the FVC, and thus prolong this patient's survival. Patients are followed for 6 months before the infusion, to establish the individual evolution of the disease, and every three months for 1 year after the procedure.
Results: 26 of 116 clinical histories submitted for revision to enter the trial initially met the inclusion criteria. Out of 26, 15 patients had to be excluded because they didn't meet the inclusion criteria either in the first or subsequent visits prior to the procedure. Seven patients, 3 males and 4 females (median age 46 years, range 32 – 61) have been infused so far. All patients had received multiple prior medical treatments. Median time from diagnosis to cellular infusion was 20 months (range 15 – 47). We infused a total of 402 ×106 (240–602.8) MNC, including 3.16 ×106 (0.96–10.25) CD34+ cells. After ≥6 months of follow-up, assessment of the FVC's evolution and the score points of the international ALS-FRS, Norris and MRC scales, revealed that of two rapidly evolving patients, one achieved stabilization of the progression and one was unaffected by the intervention. Five patients whose disease evolved more slowly also achieved stabilization of the functional scales or maintained basal FVC values (Fig. 1). Serial magnetic resonance image studies did not show any spinal cord damage. There were two severe adverse reactions (AE): 1 syncope secondary to constipation, and 1 admission due to a high tract respiratory infection with transient respiratory insufficiency in the patient in which the transplant was ineffective. Other AEs of WHO grade 1 or 2 and less than 2 months of duration were: constipation (7), intercostal pain (3), CSF hypotension (2) and lower limbs paresthesias (5, 1 of them persistent). After 6 months of follow-up, all patients had asymptomatic abolition of the somato-sensorial potentials of the posterior tract.
Conclusions: The procedure was safe and feasible. No major complications or significant morbility was observed. Stabilization of the disease was achieved in 6 of the first 7 patients included in the protocol. The only unresponsive patient had developed bulbar involvement at the time of the infusion, an already known adverse prognostic factor for response to this type of cellular therapy.
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OBJECTIVE:To (1) determine the value of the recently proposed criteria of neuromyelitis optica (NMO) spectrum disorder (NMOSD) that unify patients with NMO and those with limited forms (NMO/LF) with ...aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies; and (2) investigate the clinical significance of the serologic status in patients with NMO.
METHODS:This was a retrospective, multicenter study of 181 patients fulfilling the 2006 NMO criteria (n = 127) or NMO/LF criteria with AQP4-IgG (n = 54). AQP4-IgG and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies were tested using cell-based assays.
RESULTS:Patients were mainly white (86%) and female (ratio 6.5:1) with median age at onset 39 years (range 10–77). Compared to patients with NMO and AQP4-IgG (n = 94), those with NMO/LF presented more often with longitudinally extensive transverse myelitis (LETM) (p < 0.001), and had lower relapse rates (p = 0.015), but similar disability outcomes. Nonwhite ethnicity and optic neuritis presentation doubled the risk for developing NMO compared with white race (p = 0.008) or LETM presentation (p = 0.008). Nonwhite race (hazard ratio HR 4.3, 95% confidence interval CI 1.4–13.6) and older age at onset were associated with worse outcome (for every 10-year increase, HR 1.7, 95% CI 1.3–2.2). Patients with NMO and MOG-IgG (n = 9) had lower female:male ratio (0.8:1) and better disability outcome than AQP4-IgG-seropositive or double-seronegative patients (p < 0.001).
CONCLUSIONS:In patients with AQP4-IgG, the similar outcomes regardless of the clinical phenotype support the unified term NMOSD; nonwhite ethnicity and older age at onset are associated with worse outcome. Double-seronegative and AQP4-IgG-seropositive NMO have a similar clinical outcome. The better prognosis of patients with MOG-IgG and NMO suggests that phenotypic and serologic classification is useful.
Wells syndrome, also known as eosinophilic cellulitis, is a rare dermatosis with approximately 200 cases previously described in the literature. Here, we present a case of a patient with multiple ...sclerosis with Wells syndrome induced by dimethyl fumarate (DMF).
A 41-year-old Caucasian woman was treated with DMF in July 2021. One week later, she experienced itching on her upper and lower right arm, followed by the appearance of erythematous plaques covered with vesicles. The complete blood count showed an increased eosinophil count of up to 2,000 µL. The histological images demonstrated dermal eosinophil infiltration concordant with Wells syndrome. The clinical course was benign, with complete resolution of the lesions and normalization of the eosinophil count within four weeks. Administration of corticosteroids was not necessary.
Eosinophilia is rare in patients with multiple sclerosis treated with DMF and usually does not require dosage adjustments. Although clinical manifestations of eosinophilia in these patients are very rare, it is important for practitioners to recognize the symptoms. Many neuroleptic drugs can induce eosinophilia and systemic symptoms; therefore, physicians must be aware of the risks associated with DMF and neuroleptic drugs, particularly for quetiapine, which contains fumarate.
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