Chitosan for the treatment of inflammation of the oral mucosa: A systematic review.

BACKGROUND: Chitosan is a cheap, accessible, nontoxic, biocompatible, and biodegradable compound. Also, this polysaccharide possesses antibacterial and anti-inflammatory properties. Consequently, a wide range of chitosan applications in the dentistry field has been explored. This work aimed to conduct a systematic review to address the clinical efficacy of chitosan for the treatment of oral mucositis. MATERIAL AND METHODS: The design of the included studies were observational studies, randomized clinical trials (RCT), and non-randomized clinical trials (non-RCT), whereas, a series of cases, in vivo, and in vitro studies were excluded. The search was performed in PubMed, Web of Science, Scopus, Dentistry and Oral Sciences Source, and ClinicalTrials. Gray literature was searched at Google Scholar. Relevant data from all included studies were recorded. The risk of bias (using RoB 2) and the quality (using Grading of Recommendations Assessment, Development, and Evaluation, GRADE) assessments were carried out. RESULTS: From the 8413 records screened, 5 clinical trials fully met the eligibility criteria, which comprised a total of 192 participants suffering oral lesions and pain related to oral mucositis. 100% of the included studies exhibited a high risk of bias. The quality of the studies was between low and very low. CONCLUSIONS: The results of the included studies suggest that chitosan can diminish pain and improve the healing of ulcers in oral mucositis. However, there is no conclusive evidence of chitosan as a superior treatment for oral mucositis compared with other current therapies.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part II)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la Reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado entre el 26 y el 28 de octubre en Ámsterdam. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta segunda parte, se presentan las novedades sobre las estrategias terapéuticas de escalado y desescalado de los tratamientos modificadores de la enfermedad (TME), cuándo y a quién iniciar o cambiar a TME de alta eficacia, la definición de fracaso terapéutico, la posibilidad de tratar el síndrome radiológico asilado, el futuro del tratamiento personalizado y la medicina de precisión, la eficacia y seguridad del autotrasplante de células madre hematopoyéticas, diferentes aproximaciones en el diseño de ensayos clínicos y en las medidas de resultados para evaluar TME en fases progresivas, retos en el diagnóstico y tratamiento del deterioro cognitivo, y tratamiento en situaciones especiales (embarazo, comorbilidad y personas mayores). Además, se muestran los resultados de algunos de los últimos estudios realizados con cladribina oral y evobrutinib presentados en el ECTRIMS 2022.

A multidisciplinary consensus statement on the optimal pharmacological treatment for metastatic hormone-sensitive prostate cancer.

Androgen deprivation therapy (ADT) is the mainstay treatment for metastatic hormone-sensitive prostate cancer (mHSPC). The addition of docetaxel or new hormone therapies (abiraterone, apalutamide, or enzalutamide) improves overall survival and is currently the standard of care. However, the decision on the specific regimen to accompany ADT should be discussed with the patient, considering factors such as possible associated toxicities, duration of treatment, comorbidities, patient preferences, as there is no sufficient evidence to recommend one regimen over the other in most cases. This paper summarizes the evidence on the management of mHSPC and provides consensus recommendations on the optimal treatment in combination with ADT in mHSPC patients, with special attention to the patient's clinical profile.

[Lambert-Eaton myasthenic syndrome]. / Síndrome miasteniforme de Lambert-Eaton.

INTRODUCTION: Early diagnosis based on clinical findings, neurophysiological studies and serum antibody titres allows early initiation of symptomatic treatment and oncological screening. Reports of patients with LEMS in Latin America are scarce. AIM: This article aims to describe the characteristics of patients with LEMS from a private centre in Buenos Aires, Argentina, and to compare them with those of other series that have been published. PATIENTS AND METHODS: The medical records of 13 patients with LEMS with clinical findings, compatible electromyogram and/or positive antibodies were reviewed. Follow-up was performed until associated neoplasia was ruled out or confirmed according to the recommended algorithms. RESULTS: Four patients were diagnosed with T-LEMS, two of them with small-cell lung carcinoma. Of the nine patients with NT-LEMS, five had a DELTA-P score of 3 and 4. Nine patients presented with the classic clinical triad from the onset of the disease. All patients had electromyogram findings compatible with presynaptic neuromuscular plaque defect. Of the total, 70% improved symptomatically with pyridostigmine. CONCLUSIONS: The clinical findings, together with compatible neurophysiological studies, are sufficient for the diagnosis of LEMS. The relationship between the DELTA-P score and the risk of small-cell lung carcinoma could not be replicated. Symptomatic treatment with pyridostigmine represents an effective therapeutic alternative.

TITLE: Síndrome miasteniforme de Lambert-Eaton.Introducción. El síndrome miasteniforme de Lambert-Eaton (LEMS) es una patología paraneoplásica (T-LEMS) o idiopática autoinmunitaria (NT-LEMS) ocasionada por autoanticuerpos contra los canales de calcio dependientes del voltaje presinápticos de la unión neuromuscular. El 60% de los T-LEMS se asocia a carcinoma de pulmón de células pequeñas. Una puntuación Dutch-English LEMS Tumor Association Prediction (DELTA-P) mayor de 3 denota un riesgo elevado de dicha asociación. El diagnóstico precoz fundado en los hallazgos clínicos, estudios neurofisiológicos y dosificación de títulos de anticuerpos en el suero permite iniciar tempranamente el tratamiento sintomático y la búsqueda oncológica. Son escasos los informes de pacientes con LEMS en Latinoamérica. Objetivo. Describir las características de pacientes con LEMS de un centro privado de Buenos Aires, Argentina, y compararlas con las de otras series publicadas. Pacientes y métodos. Se revisaron historias clínicas de 13 pacientes con LEMS con hallazgos clínicos, electromiograma compatible y/o anticuerpos positivos. Se realizó seguimiento hasta descartar o confirmar una neoplasia asociada de acuerdo con los algoritmos recomendados. Resultados. Cuatro pacientes presentaron diagnóstico de T-LEMS, dos de ellos con carcinoma de pulmón de células pequeñas. De los nueve pacientes con NT-LEMS, cinco presentaron una puntuación DELTA-P de 3 y 4. Nueve pacientes presentaron la tríada clínica clásica desde el inicio. Todos los pacientes presentaron en el electromiograma hallazgos compatibles con defecto de placa neuromuscular presináptico. El 70% mejoró sintomáticamente con piridostigmina. Conclusiones. Los hallazgos clínicos, junto con los estudios neurofisiológicos compatibles, resultan suficientes para el diagnóstico de LEMS. No pudo replicarse la relación entre puntuación DELTA-P y riesgo de carcinoma de pulmón de células pequeñas. El tratamiento sintomático con piridostigmina representa una alternativa terapéutica eficaz.

Differential diagnosis in acute inflammatory myelitis.

INTRODUCTION: Establishing differential diagnosis between different inflammatory causes of acute transverse myelitis (ATM) can be difficult. The objective of this study was to see which clinical, imaging or laboratory findings best contribute to confirm ATM etiology. METHODS: We reviewed clinical history, MRI images, CSF and serum laboratory tests in a retrospective study of patients presenting ATM. Univariate and multivariate multinomial logistic regression analysis was performed for each of the items listed above. RESULTS: One hundred and seventy-two patients were analyzed in the study: 68 with multiple sclerosis (MS), 67 presenting idiopathic myelitis (IM; 23 of which were recurrent), 21 who developed positive systemic-antibodies associated myelitis (SAb-M) and 16 with neuromyelitis optica spectrum disorders (NMOSD). The following factors were associated with increased risk of developing MS: lower values in the modified Rankin scale at admission; positive oligoclonal bands (OCB); higher spinal cord lesion load; presence of brain demyelinating lesions; and disease recurrence. Longitudinally extended (LE) lesions, brain demyelinating lesions, and recurrences also contributed to final diagnosis of NMOSD. Multivariate multinomial logistic regression analysis showed presence of LE lesions increased risk of NMOSD and recurrence of ATM. Whereas, brain demyelinating lesions, and presence of OCB increased risk of MS. CONCLUSIONS: ATM etiology may be clarified on the basis of spinal cord and brain MRI findings, together with CSF biochemistry and serum laboratory test results, allowing more timely and exact diagnosis as well as specific therapy for cases of uncertain origin.

The rs2234694 and 50 bp Insertion/Deletion polymorphisms of the SOD1 gene are associated with breast cancer risk in a Mexican population.

OBJECTIVE: The rs2234694 and 50 bp insertion/deletion (Ins/Del) polymorphisms of the SOD1 gene have been shown to be associated with many diseases, but in breast cancer (BC) their association has not been detected. The purpose of this study was to determine the frequency and association of SOD1 gene polymorphisms (rs2234694 and 50 bp Ins/Del) in BC patients in the Mexican population. MATERIALS AND METHODS: The SOD1 polymorphisms were determined by Polymerase Chain Reaction (PCR) in Mexican healthy subjects and BC patients. RESULTS: The rs2234694 polymorphism was associated with BC susceptibility when BC patients and the control group were compared for the AC genotype (p<0.0001), the AC/CC genotype (dominant model: p<0.0001), and the C allele (p<0.0001). The 50 bp Ins/Del polymorphism was associated with BC susceptibility for the Del allele (p=0.048), although the association between the dominant model AC/CC (rs2234694) and BC patients was evident for menopause [adjusted odds ratio (OR) 1.65 (95% CI 1.05-2.7); p=0.048], Ki-67 (≥15%) (OR1.9, 95% CI 1.14- 3.16, p=0.016), and the presence of DM2 (OR 2.4, 95% CI 1.35- 4.31, p=0.003). A protective association for BC of the rs2234694 polymorphism was observed in patients younger than 50 years positive for estrogen receptor (ER) and progesterone receptor (PR), carrying the AC genotypes (OR 0.47, 95% CI 0.23-0.94, p= 0.033) and CC (OR 0.11, 95% CI 0.013-1.07, p=0.047). The association between the InsDel/DelDel (dominant model; 50 bp Ins/Del) genotype and BC with metastatic lymph nodes (OR 1.5, 95% CI 1.1-2.25, p=0.019), hematologic toxicity (OR 1.5, 95%CI 1.1-2.23, p=0.015), gastric toxicity (OR 1.5, 95%CI 1.1-2.07, p=0.030), and Ki-67 (≥15%) (OR1.6, 95%CI 1.2-2.26, p=0.002) was evident, indicating that these factors may contribute significantly to BC risk. The C/Ins haplotype was also associated with BC susceptibility (OR3.47, 95% CI 1.62-7.74, p=0.001). CONCLUSIONS: rs2234694 and 50 bp Ins/Del polymorphisms in the SOD1 gene were associated with BC susceptibility in a Mexican population. A protective association for BC of the rs2234694 polymorphism was observed in patients younger than 50 years positive for ER and PR, carrying the AC genotypes. The haplogenotypes AA/InsIns and AC/InsDel could contribute significantly to BC risk in gastric and hematologic toxicities, metastatic lymph nodes, and the presence of DM2 in the Mexican population analyzed.

Effect of cadmium on the concentration of essential metals in a human chondrocyte micromass culture.

BACKGROUND: An essential element imbalance in the joint might favor gradual degeneration of the articular cartilage. It has been reported that cadmium (Cd) plays an antagonistic role with regards to the presence of essential elements, such as zinc (Zn), iron (Fe), and manganese (Mn), which may favor the development of disabling diseases, like osteoarthritis (OA) and osteoporosis. METHODS: 3D cultures of human chondrocytes were phenotyped with the Western blot technique and structurally evaluated with histological staining. The samples were exposed to 1, 5, and 10 µM of CdCl2 for 12 h, with a non-exposed culture as control. The concentration of Cd, Fe, Mn, Zn, chromium (Cr), and nickel (Ni) was quantified through plasma mass spectrometry (ICP-MS). The data were analyzed with a Kruskal Wallis test, a Kendall's Tau test and Spearman's correlation coefficient with the Stata program, version 14. RESULTS: Our results suggest that Cd exposure affects the structure of micromass cultures and plays an antagonistic role on the concentration of essential metals, such as Zn, Ni, Fe, Mn, and Cr. CONCLUSION: Cd exposure may be a risk factor for developing joint diseases like OA, as it can interfere with cartilage absorption of other essential elements that maintain cartilage homeostasis.

High fructose-containing drinking water-induced steatohepatitis in rats is prevented by the nicotinamide-mediated modulation of redox homeostasis and NADPH-producing enzymes.

An imbalance in the redox state, increased levels of lipid precursors and overactivation of de novo lipogenesis determine the development of fibrosis during nonalcoholic steatohepatitis (NASH). We evaluated the modulation of NADPH-producing enzymes associated with the antifibrotic, antioxidant and antilipemic effects of nicotinamide (NAM) in a model of NASH induced by excess fructose consumption. Male rats were provided drinking water containing 40% fructose for 16 weeks. During the last 12 weeks of fructose administration, water containing NAM was provided to some of the rats for 5 h/day. The biochemical profiles and the ghrelin, leptin, lipoperoxidation and TNF-α levels in serum and the glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME) and NADP+-dependent isocitric dehydrogenase (IDP) levels, the reduced/oxidized glutathione (GSH/GSSG) and reduced/oxidized nicotinamide adenine dinucleotide (phosphate) (NAD(P)H/NAD(P)+) ratios, and the levels of various lipogenic and fibrotic markers in the liver were evaluated. The results showed that hepatic fibrosis induced by fructose consumption was associated with weight gain, hunger-satiety system dysregulation, hyperinsulinemia, dyslipidemia, lipoperoxidation and inflammation. Moreover, increased levels of hepatic G6PD and ME activity and expression, the NAD(P)H/NAD(P)+ ratios, and GSSG concentration and increased expression of lipogenic and fibrotic markers were detected, and these alterations were attenuated by NAM administration. Specifically, NAM diminished the activity and expression of G6PD and ME, and this effect was associated with a decrease in the NADPH/NADP+ ratios, increased GSH levels and decreased lipoperoxidation and inflammation, ameliorating fibrosis and NASH development. NAM reduces liver steatosis and fibrosis by regulating redox homeostasis through a G6PD- and ME-dependent mechanism.

Renal Doppler ultrasound resistive index vs. renal scintigraphy with 99mTc-DTPA as diagnostic test for ureteropelvic junction obstruction in children. / Ecografía Doppler renal con medición de índices de resistencia vs. gammagrafía renal con 99mTc-DTPA para el diagnóstico de estenosis ureteropiélica en niños.

OBJECTIVE: A cross-sectional study was carried out with the objective of evaluating the usefulness of Doppler ultrasound with resistive index (RI) measure compared with renal scintigraphy with 99mTc-DTPA in children with unilateral ureteropelvic junction obstruction. METHODS: The study included children under 15 years with a diagnosis of unilateral ureteropelvic junction obstruction, healthy contralateral kidney with or without an antecedent of ureteropyeloplasty. The selected patients were sent to the Nuclear Medicine Department to carry out a renal scintigraphy with 99mTc-DTPA and days later were sent to the Radiology Department for the performance of Renal Doppler Ultrasound with RI. RESULTS: A total of 21 patients were included in the study, 15 males and 6 females, representing 71.4% and 28.6%, respectively. Mean age was 5.3 years. Only 3 had an antecedent of ureteropyeloplasty in the affected kidney. The scintigraphy reported data of unilateral obstruction in 18 patients, including the 3 patients with previous surgery. The average glomerular filtration rate (GFR) obtained with the scintigraphy was 100.28ml/min. The average GFR in affected kidneys was 43.03ml/min and 57.24ml/min in healthy kidneys (p<.001). Doppler ultrasound with RI reported ectasia in 100% of the affected kidneys and one normal contralateral kidney. The average RI in affected kidneys was 0.69mm/s and 0.50mm/s in healthy kidneys (p<.001). CONCLUSIONS: With the results obtained, we can suggest that ultrasound Doppler with measurement of RI can be an alternative tool to renal scintigraphy with 99mTc-DTPA in some cases.

[Divertículo de Meckel con tejido pancreático ectópico en un niño de 12 años con invaginación intestinal. Reporte de caso y revisión de la literatura]. / Meckel diverticulum with ectopic pancreatic tissue in a 12-year-old boy with intestinal invagination. Case report and review of the literature.

INTRODUCCIÓN: El divertículo de Meckel es un remanente del conducto onfalomesentérico y su prevalencia es del 2%. CASO CLÍNICO: Niño de 12 años con dolor abdominal, acompañado de evacuaciones mucosanguinolentas y hematemesis, con masa en cuadrante inferior derecho. En la laparotomía quirúrgica se encontró invaginación, y se realizó desinvaginación y resección del divertículo de Meckel. CONCLUSIÓN: La asociación de divertículo de Meckel con tejido pancreático heterotópico en niños es poco frecuente. Clínicamente, su principal manifestación es la invaginación intestinal en la literatura revisada, y el ultrasonido constituye el mejor estudio para el diagnóstico de invaginación intestinal, no así para el divertículo de Meckel o el tejido pancreático heterotópico, en los que la tomografía sería una opción. INTRODUCTION: Meckel's diverticulum is a remnant of the omphalomesenteric duct and its prevalence is 2%. CLINICAL CASE: A 12-year-old male with abdominal pain, accompanied by muco-sanguineous evacuations and hematemesis, with right lower quadrant mass. In the laparotomy, invasion was found; intussusception reduction and resection of the Meckel's diverticulum was performed. CONCLUSION: The association of Meckel's diverticulum with heterotopic pancreatic tissue in children is rare, its main manifestation is intussusception and ultrasound is an option for diagnosis.

Pharmacogenetic biomarkers of response in Crohn's disease.

Crohn's disease (CD) is a chronic condition, which affects the immune system. It can also affect any part of the digestive tract and be associated with external manifestations. The causes of the disease remain unknown, although it seems to be the result of a combination of factors, such as genetic predisposition, environment, lifestyle and the composition of the microbiota, among others. The treatment protocol begins with a change in eating and smoking habits, and is continued with different lines of treatment, including corticosteroids, immunomodulators and biologic therapy (infliximab and adalimumab), which have shown differences in response among patients, especially with biologic treatment. Several studies have considered the possibility that these differences in response are caused by the genetic variability of patients. Many genes have been investigated as potential predictors of response to biological drugs, such as ADAM17, ATG16L1, EMSY, CASP9, CCNY, CNTN5, FASLG, FCGR, NOD2, PTGER4, IL13, IL1B, IL27, IL11, IL17F, TNF and TNFR genes. In this review, we will gather the information on influence of gene polymorphisms investigated to date on response to biological drugs in CD patients.

Photosynthetically active radiation and carbon gain drives the southern orientation of Myrtillocactus geometrizans fruits.

The equatorial orientation of reproductive structures is known in some columnar cacti from extratropical deserts. It has been hypothesised that photosynthetically active radiation (PAR) interception is the main reason for this orientation, because of its key effect on nocturnal CO2 uptake. However, there are no studies addressing both the effect of PAR and its consequence, carbon gain, on fruit orientation. Accordingly, we tested whether PAR and carbon gain could explain the southern fruit orientation of Myrtillocactus geometrizans, an inter-tropical columnar cactus. We studied three populations of M. geometrizans in Mexico. For each population, azimuth of fruits, total daily PAR, nocturnal acid accumulation (NAA) and fruit production were measured. The relationships between rib orientation and number of fruits, as well as total daily PAR, were evaluated using periodic regressions. The effect of total daily PAR and NAA on number of fruits was assessed using generalised linear models. During spring, mean fruit orientation had a south azimuth for three populations. Likewise, rib orientation had a significant effect on fruit production, with the south-facing ribs having the maximum number of fruits. Total daily PAR was highest in the south-facing ribs, at least for those in the northern and central populations. Furthermore, during spring, there was a significant positive effect of total daily PAR and NAA on fruit production. Our results provide strong evidence that the higher carbon gain in equatorial ribs, through a highest interception of PAR, would be the responsible factor for equatorial orientation of fruits in an inter-tropical columnar cactus.

A Scheduled Program of Molecular Screening for Epstein-Barr Virus Decreases the Incidence of Post-transplantation Lymphoproliferative Disease in Pediatric Liver Transplantation.

This is a cohort, retrospective, comparative study of all liver transplant recipients from a single center, from May 1998 to July 2015. Patients were divided into two groups according to the type of Epstein-Barr viral load monitoring. For group I (1998-2007), polymerase chain reaction (PCR) was not available or it was only qualitative with limited access. For group II (2008-2015), we used periodically scheduled quantitative PCR in plasma and leukocytes, with aggressive tapering of immunosuppression as soon as viral replication was detected. Ninety-eight recipients were included, 41 (41.8%) were Epstein-Barr virus (EBV) - seronegative before liver transplantation (LT). EBV replication was confirmed in 74 patients (75.5%), being more frequent in seronegative (87.8%) than seropositive patients (66.6%). Eight recipients (8.1%) developed post-transplantation lymphoproliferative disorder (PTLD) on average at 14.3 months post-LT, seven of eight were <3 years at LT, four of eight were D+/R- for EBV, and all had post-LT EBV replication confirmed by PCR. PTLD was classified as lymphoma (n = 4), polymorphic polyclonal (n = 3), and lymphoid hyperplasia (n = 1). Five patients died, and three cleared PTLD after immunosuppression tapering or interruption. There were no significant differences in the etiology, age at LT (5.6 vs. 7.3 years, P = .069), patients <4 years (53.2% vs. 35.3%, P = .103), or EBV seronegative recipients (44.7% vs. 37.3%, P = .54); however, the incidence of PTLD decreased from 14.9% to 1.9% (P = .026), and graft rejection from 51.1% to 29.4% (P = .039). One- and 5-year patient survival rates were 94.7% and 85%, respectively, with no differences between groups. This strategy dramatically decreased the incidence of PTLD (14.9% vs. 1.9%), without increasing the incidence of rejection; therefore, we recommend that it should be used in the follow-up of all pediatric LT recipients.

Spanish consensus on the use of natalizumab (Tysabri®)-2013.

INTRODUCTION: Natalizumab treatment has been shown to be very efficacious in clinical trials and very effective in clinical practice in patients with relapsing-remitting multiple sclerosis, by reducing relapses, slowing disease progression, and improving magnetic resonance imaging patterns. However, the drug has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The first consensus statement on natalizumab use, published in 2011, has been updated to include new data on diagnostic procedures, monitoring for patients undergoing treatment, PML management, and other topics of interest including the management of patients discontinuing natalizumab. MATERIAL AND METHODS: This updated version followed the method used in the first consensus. A group of Spanish experts in multiple sclerosis (the authors of the present document) reviewed all currently available literature on natalizumab and identified the relevant topics would need updating based on their clinical experience. The initial draft passed through review cycles until the final version was completed. RESULTS AND CONCLUSIONS: Studies in clinical practice have demonstrated that changing to natalizumab is more effective than switching between immunomodulators. They favour early treatment with natalizumab rather than using natalizumab in a later stage as a rescue therapy. Although the drug is very effective, its potential adverse effects need to be considered, with particular attention to the patient's likelihood of developing PML. The neurologist should carefully explain the risks and benefits of the treatment, comparing them to the risks of multiple sclerosis in terms the patient can understand. Before treatment is started, laboratory tests and magnetic resonance images should be available to permit proper follow-up. The risk of PML should be stratified as high, medium, or low according to presence or absence of anti-JC virus antibodies, history of immunosuppressive therapy, and treatment duration. Although the presence of anti-JC virus antibodies is a significant finding, it should not be considered an absolute contraindication for natalizumab. This update provides general recommendations, but neurologists must use their clinical expertise to provide personalised follow-up for each patient.

Pharmacogenetics of pemetrexed combination therapy in lung cancer: pathway analysis reveals novel toxicity associations.

Identification of polymorphisms that influence pemetrexed tolerability could lead to individualised treatment regimens and improve quality of life. Twenty-eight polymorphisms within eleven candidate genes were genotyped using the Illumina Human Exome v1.1 BeadChip and tested for their association with the clinical outcomes of non-small cell lung cancer and mesothelioma patients receiving pemetrexed/platinum doublet chemotherapy (n=136). GGH rs11545078 was associated with a reduced incidence of grade ⩾3 toxicity within the first four cycles of therapy (odds ratio (OR) 0.25, P=0.018), as well as reduced grade ⩾3 haematological toxicity (OR 0.13, P=0.048). DHFR rs1650697 conferred an increased risk of grade ⩾3 toxicity (OR 2.14, P=0.034). Furthermore, FOLR3 rs61734430 was associated with an increased likelihood of disease progression at mid-treatment radiological evaluation (OR 4.05, P=0.023). Polymorphisms within SLC19A1 (rs3788189, rs1051298 and rs914232) were associated with overall survival. This study confirms previous pharmacogenetic associations and identifies novel markers of pemetrexed toxicity.

Congenital proptosis secondary to orbital teratoma. Clinicopathological study.

CASE REPORT: A newborn male with right proptosis secondary to a retroocular mass. Ophthalmological examination also showed corneal ulcer and perforation, iris hernia, total ophthalmoplegia, chemosis and eyelid retraction. The histopathology diagnosis was mature teratoma. DISCUSSION: Teratomas are tumors composed of a mixture of mature tissues consisting of 3 germ layers. Congenital teratomas of the orbit are very rare and should be included as a possibility in cases with a primary tumor in the orbit.

[Pilot study of intravenous fluid therapy management in adult patients at a tertiary care hospital]. / Estudio piloto sobre el manejo de la fluidoterapia intravenosa en pacientes adultos de un hospital de tercer nivel.

UNLABELLED: The purpose of intravenous fluid therapy (IFT) is to maintain or restore internal equilibrium by administering fluids and/or different electrolyte components. Its correct use and the prevention of complications arising from their misuse depend on the knowledge of the medical team on this subject. We analyzed this issue in different clinical areas of a tertiary hospital. MATERIAL AND METHODS: We performed a descriptive cross-sectional pilot study via a questionnaire given to physicians specializing in internal medicine (IM) and digestive system surgery (SDS) who perform clinical practice in hospital units with unit dose drug dispensing system. We designed an anonymous questionnaire with 25 questions relative to knowledge of theory and practices, as well as the opinion of physicians regarding IFT. We evaluated the association between nominal qualitative variables with the Chi-square or Fisher's exact test. The behavior of the quantitative variables was assessed using the t-student test. The analysis of the data was generated using SAS/STAT, Version 9. RESULTS: 28 questionnaires were collected from 13 surgeons and 15 digestive interns. Over 40% of specialists considered further education in IFT a necessity , especially regarding its prescription (SDS: 61.54%, IM: 71.43%). No statistically significant differences were found between the specialties in terms of perceived frequency of complications associated with IFT or in the frequency indication with the exception of hypovolemic shock, which is considered to be more prevalent in gastrointestinal surgery (p = 0.046). 90% of professionals prefer an individualized prescription. Statistically significant differences in terms of scores in the area of knowledge, with IM physicians achieving the highest scores (p = 0.014). There were also differences in attitude but they are not significant (p = 0.162). Knowledge of intravenous fluid increases with years of clinical experience (Spearman correlation coefficient = 0.386, p = 0.047). CONCLUSIONS: The professionals who prescribe IFT perceive the need to design IFT training programs, together with the production of guides and consensus protocols.