Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023.

The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring. In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants. The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term "lines of therapy" no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.

PURPOSE: A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population. METHODS: We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies. RESULTS: TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls. CONCLUSION: Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.

Chondrosarcoma secondary to hereditary multiple osteochondromas with spinal cord compression: A case report and systematic review.

Background: Hereditary multiple osteochondromas (HMOs) are a rare genetic disorder characterized by the formation of multiple benign osteochondromas that can undergo malignant transformation into chondrosarcoma. Case Description: A 24-year-old male with a history of HMO and osteochondroma surgery 4 years ago, presented with back pain and paresthesias. The magnetic resonance showed a right paravertebral infiltrating mass at the T12-L1 level causing spinal cord compression. Following en bloc resection of the tumor, the patient's symptoms/ signs resolved. The final pathological diagnosis was consistent with a chondrosarcoma. Conclusion: Chondrosarcomas secondary to HMO with spinal cord compression are rare. These patients often presenting with significant myelopathy/cord compression should undergo gross total resection where feasible to achieve the best outcomes.

Reduction in cervical length after vaginal progesterone in women with short cervix is significantly associated with preterm delivery at ≤ 34 weeks and < 37 weeks of gestation.

OBJECTIVE: To evaluate the association between changes in cervical length (CL) after vaginal progesterone treatment and preterm delivery (PTD). METHODS: This was a retrospective cohort study that included 197 singleton pregnancies without (n = 178) and with (n = 19) a history of PTD which were found to have a short cervix (≤ 25 mm) between 18 + 0 and 23 + 6 weeks' gestation with a follow-up transvaginal CL measurement taken at least 1 week after vaginal progesterone treatment started. Receiver-operating-characteristics (ROC)-curve analysis was performed and three CL shortening patterns were evaluated: (1) ≥ 10% reduction; (2) ≥ 20% reduction; and (3) ≥ 5 mm reduction relative to the first CL measurement. The predictive performance of each CL reduction cut-off and its association with PTD ≤ 34 weeks and PTD < 37 weeks were evaluated. RESULTS: Overall, the rate of PTD ≤ 34 weeks was 16.8% (33/197) and that of PTD < 37 weeks was 36.5% (72/197). The area under the ROC curve of cervical shortening expressed in % for predicting PTD ≤ 34 weeks and PTD < 37 weeks was 0.703 and 0.608, respectively. Cervical shortening was observed in 60/197 (30.5%) patients, with 49/60 (81.7%) women showing ≥ 10% reduction, 32/60 (53.3%) ≥ 20% reduction and 27/60 (45.0%) ≥ 5 mm reduction in CL. Sensitivity and specificity for PTD ≤ 34 weeks were, respectively, 48.5% and 79.9% for ≥ 10% reduction; 36.4% and 87.8% for ≥ 20% reduction; and 27.3% and 89.0% for ≥ 5 mm reduction in CL. For PTD < 37 weeks, sensitivity and specificity were, respectively, 36.1% and 81.6% for ≥ 10% reduction; 27.8% and 90.4% for ≥ 20% reduction; and 20.8% and 90.4% for ≥ 5 mm reduction in CL. The highest positive likelihood ratios for PTD ≤ 34 and < 37 weeks were for ≥ 20% CL reduction (2.98 (95% CI, 1.62-5.49) and 2.89 (95% CI, 1.52-5.57), respectively). Despite significant differences in sensitivity among the different cut-offs for cervical shortening, favoring the ≥ 10% reduction cut-off, a reduction of ≥ 20% in CL showed the strongest association with PTD ≤ 34 weeks (odds ratio (OR), 4.11 (95% CI, 1.75-9.62)) and < 37 weeks (OR, 3.62 (95% CI, 1.65-7.96)), as compared with a less pronounced reduction in CL. CONCLUSIONS: In women with a short cervix treated with vaginal progesterone, a reduction in CL on a subsequent ultrasound scan can predict PTD ≤ 34 and < 37 weeks. A ≥ 20% reduction in CL had the highest positive likelihood ratio and association with PTD ≤ 34 and < 37 weeks compared with ≥ 10% or ≥ 5 mm reduction. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.

Background: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide. Methods/Findings: In our ongoing USA feasibility/efficacy clinical trial, data collated with other ongoing and earlier published results proved high performance of an Immunochromatographic-test(ICT) that enables accurate, rapid diagnosis/treatment, establishing new paradigms for care. Overall results from patient blood and/or serum samples tested with ICT compared with gold-standard-predicate-test results found ICT performance for 4606 sera/1876 blood, 99.3%/97.5% sensitive and 98.9%/99.7% specific. However, in the clinical trial the FDA-cleared-predicate test initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon's Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO ASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening. Conclusions/Significance: This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories. Author's Summary: Toxoplasmosis is a major health burden for developed and developing countries, causing damage to eyes and brain, loss of life and substantial societal costs. Prompt diagnosis in gestational screening programs enables treatment, thereby relieving suffering, and leading to > 14-fold cost savings for care. Herein, we demonstrate that using an ICT that meets WHO ASSURED-criteria identifying persons with/without antibody to Toxoplasma gondii in sera and whole blood with high sensitivity and specificity, is feasible to use in USA clinical practice. We find this new approach can help to obviate the problem of detection of false positive anti- T.gondii IgM results for those without IgG antibodies to T.gondii when this occurs in present, standard of care, predicate USA FDA cleared available assays. Thus, this accurate test facilitates gestational screening programs and a global initiative to diagnose and thereby prevent and treat T.gondii infection. This minimizes likelihood of false positives (IgG and/or IgM) while maintaining maximum sensitivity. When isolated IgM antibodies are detected, it is necessary to confirm and when indicated continue follow up testing in ∼2 weeks to establish seroconversion. Presence of a positive ICT makes it likely that IgM is truly positive and a negative ICT makes it likely that IgM will be a false positive without infection. These results create a new, enthusiastically-accepted, precise paradigm for rapid diagnosis and validation of results with a second-line test. This helps eliminate alarm and anxiety about false-positive results, while expediting needed treatment for true positive results and providing back up distinguishing false positive tests.

Predictors of complex PTSD: the role of trauma characteristics, dissociation, and comorbid psychopathology.

BACKGROUND: Complex Posttraumatic Stress Disorder (CPTSD) has previously been associated with earlier trauma onset, repeated interpersonal traumatization, more dissociation, and more comorbid psychopathology. However, it is still debated if the afore-mentioned risk factors are related to CPTSD diagnosis or rather indicative of a more severe form of post-traumatic distress. The aim of this study was to compare patients with a CPTSD diagnosis to those with PTSD in trauma characteristics (onset, chronicity, interpersonal nature, familiarity with perpetrator), dissociation, and psychiatric comorbidities, while accounting for symptom severity. METHODS: In total, N = 81 patients with a trauma history (n = 43 with CPTSD; n = 37 with PTSD) underwent diagnostic interviews by trained clinicians and completed measures on CPTSD symptom severity, trauma characteristics, and dissociation (Screening for Complex PTSD; Dissociative Experience Scale Taxon). RESULTS: Patients with CPTSD reported earlier onset of trauma, more trauma perpetrated by acquaintances or family members, and more comorbidities than those with PTSD, also when accounting for symptom severity. No group differences in chronicity and dissociation were found. Severity of CPTSD was associated with earlier onset, familiarity with perpetrator, more comorbid (affective) disorders, and dissociation in both diagnostic groups. CONCLUSION: Findings largely confirm earlier research, suggesting that CPTSD is associated with traumatic events that start earlier in life and are perpetrated by acquaintances. Focusing on transdiagnostic symptoms, such as dissociation, may help to detain symptom deterioration. Due to the small sample size, findings need to be interpreted with caution and further research is needed to replicate findings in larger samples. Future research should also elucidate possible working mechanisms besides dissociation, such as emotion dysregulation or negative self-image.

Anatomy of the mastoid triangle and morphometric sex differences.

OBJECTIVE OF THE STUDY: This study aimed to quantify the area of the mastoid triangle (MT) and assess potential morphometric differences between males and females. PATIENTS: The sample consisted of 244 dry human skulls, with biological sex known based on genetic analysis, collected from a medicolegal osteological database from Central-Western Brazil. MATERIALS AND METHODS: The study was observational, analytical, and cross-sectional. The skulls were analyzed using Heron's equation to calculate the area of the MT. The landmarks connecting each of the sides of the triangle were: Porion (Po)>Mastoidale (Ma)>Asterion (Ast). Morphometric references were calculated and compared based on sex. RESULTS: The area of the MT was nearly 14% larger in males compared to females (p<0.05). The mean MT area for the right and left sides of males were 684.11±93.25mm2 and 668.94±111.95mm2, respectively. In females, the mean MT for the right and left sides were 588.93±91.09mm2 and 582.88±102.98mm2, respectively. Right and left side measurements were significantly different (p<0.05), except for Po-Ast (p=0.232). CONCLUSION: Morphometric features regarding the MT were slightly different between males and females. Application of the MT as a dimorphic tool should be adjuvant. Moreover, this tool should be considered carefully, especially because the sex-based differences were statistically significant, but discrete between males and females.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Influence of the Flowable Resin Layer on Bond Strength Between Resin Cement and a Universal Adhesive Applied in the Immediate Dentin-sealing Technique.

OBJECTIVES: The present study evaluated the influence of a flowable resin layer on bond strength between resin cement and a universal adhesive applied using an immediate dentin sealing (IDS) technique. METHODS AND MATERIALS: Coronary portions of bovine teeth were randomly divided into six groups (n=15). In the IDS.U group, the exposed dentin was immediately sealed with the Single Bond Universal adhesive (3M ESPE) following the self-etching protocol. In the IDS.UF group, a layer of Filtek Z350 (3M ESPE) flow resin was applied over the universal adhesive. In the DDS (control) group, the dentin was kept "fresh" and delayed dentin sealing was performed. After 24 hours in distilled water at 37°C, dentin surfaces were treated with pumice, phosphoric acid, and the application of the universal adhesive in the IDS.U and IDS. UF groups. The DDS group was treated with pumice and the universal adhesive was applied. The samples received cylinders of resin cement Rely X Ultimate (3M ESPE) made with the aid of starch tubes of 0.96 mm in diameter and 2 mm in length. They were submitted to the microshear bond strength test (µSBS) at 0.5 mm/min, after 24 hours (T1) and 3 months (T2). The fracture areas were evaluated qualitatively using a DSM 300 microscope (KOZO) with 45× magnification and classified as: adhesive, cohesive in cement, cohesive in dentin, or mixed. Samples were analyzed by scanning electron microscopy (SEM). The data were compared statistically between groups using the Kruskal-Wallis test, and intra-groups using the Mann-Whitney test (α=0.05). RESULTS: There were no significant differences between groups for the bond strength values (p>0.05). The IDS.UF group showed higher values at 3 months, when compared to the values of 24 hours (p<0.001). All groups showed a predominance of adhesive fracture (86.7% to 100%). SEM showed dentinal tubules exposed in the IDS.U and DDS groups; in the IDS.UF group, the tubules were completely sealed. CONCLUSIONS: The flow resin can be used on the adhesive when using the IDS technique because it increased the bond strength values after 3 months and promoted effective sealing of the dentinal tubules.

Update of the PANCCO clinical practice guidelines for the treatment of ulcerative colitis in the adult population.

Ulcerative colitis (US) is a chronic disease of unknown etiology. It is incurable and its clinical course is intermittent, characterized by periods of remission and relapse. The prevalence and incidence of the disease has been increasing worldwide. The update presented herein includes the participation of healthcare professionals, decision-makers, and a representative of the patients, all of whom declared their conflicts of interest. Answerable clinical questions were formulated, and the outcomes were graded. The information search was conducted on the Medline/PubMed, Embase, Epistemonikos, and LILACS databases, and covered grey literature sources, as well. The search was updated on November 30, 2020, with no restrictions regarding date or language. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification system was implemented to establish the strength of the recommendation and quality of evidence. A formal consensus was developed, based on the RAND/UCLA methodology and the document was peer reviewed. The short version of the Clinical Practice Guidelines for the Treatment of Ulcerative Colitis in the Adult Population is presented herein, together with the supporting evidence and respective recommendations. In mild-to-moderate UC, budesonide MMX is an option when treatment with 5-ASA fails, and before using systemic steroids. In moderate-to-severe UC, infliximab, adalimumab, vedolizumab, ustekinumab, and tofacitinib can be used as first-line therapy. If there is anti-TNF therapy failure, ustekinumab and tofacitinib provide the best results. In patients with antibiotic-refractory pouchitis, anti-TNFs are the treatment of choice.

Clinical utility of comprehensive circulating tumor DNA genotyping compared with standard of care tissue testing in patients with newly diagnosed metastatic colorectal cancer.

BACKGROUND: Comprehensive biomarker testing is essential in selecting optimal treatment for patients with metastatic colorectal cancer (mCRC); however, incomplete genotyping is widespread, with most patients not receiving testing for all guideline-recommended biomarkers, in part due to reliance on burdensome sequential tissue-based single-biomarker tests with long waiting times or availability of only archival tissue samples. We aimed to demonstrate that liquid biopsy, associated with rapid turnaround time (TAT) and lower patient burden, effectively identifies guideline-recommended biomarkers in mCRC relative to standard of care (SOC) tissue testing. PATIENTS AND METHODS: Prospectively enrolled patients with previously untreated mCRC undergoing physician discretion SOC tissue genotyping submitted pretreatment blood samples for comprehensive circulating tumor DNA (ctDNA) analysis with Guardant360 and targeted RAS and BRAF analysis with OncoBEAM. RESULTS: Among 155 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 82 patients, versus 88 identified with comprehensive ctDNA (52.9% versus 56.8%, noninferiority demonstrated down to α = 0.005) and 69 identified with targeted PCR ctDNA analysis (52.9% versus 44.5%, noninferiority rejected at α = 0.05). Utilizing ctDNA in addition to tissue increased patient identification for a guideline-recommended biomarker by 19.5% by rescuing those without tissue results either due to tissue insufficiency, test failure, or false negatives. ctDNA median TAT was significantly faster than tissue testing when the complete process from sample acquisition to results was considered (median 10 versus 27 days, P < 0.0001), resulting in accelerated biomarker discovery, with 52.0% biomarker-positive patients identified by ctDNA versus 10.2% by SOC tissue 10 days after sample collection (P < 0.0001). CONCLUSIONS: Comprehensive ctDNA genotyping accurately identifies guideline-recommended biomarkers in patients with mCRC at a rate at least as high as SOC tissue genotyping, in a much shorter time. Based on these findings, the addition of ctDNA genotyping to clinical practice has significant potential to improve the care of patients with mCRC.

Airborne ultrasonic application on hot air-drying of pork liver. Intensification of moisture transport and impact on protein solubility.

Nowadays, there is increasing interest in developing strategies for the efficient and sustainable use of animal by-products, such as pork liver. In order to stabilize the product, a prior dehydration stage may be required due to its high perishability. The water removal process of pork liver is energy costly and time consuming, which justifies its intensification using novel technologies. In this sense, the aim of this study was to assess the effect of the airborne application of power ultrasound on the hot air-drying of pork liver. For that purpose, drying experiments were carried out at 30, 40, 50, 60 and 70 °C on pork liver cylinders at 2 m·s-1 with (US) and without ultrasonic application (AIR). The drying process was modeled from the diffusion theory and, in the dried pork liver, the protein solubility was analyzed in order to determine the effect of drying on the protein quality. The ultrasound application increased the drying rate, shortening the drying time by up to 40% at 30 °C. The effect of power ultrasound at high temperatures (60 and 70 °C) was of lesser magnitude. Drying at 70 °C involved a noticeable reduction in the protein solubility for dried liver, while the impact of ultrasound application on the solubility was not significant (p > 0.05).

[Prognostic power of soluble urokinase plasminogen activator receptor (suPAR) for short-term mortality in patients seen in Emergency Departments due to infections]. / Poder pronóstico de mortalidad a corto plazo del receptor soluble activador del plasminógeno tipo uroquinasa (suPAR) en los pacientes atendidos en urgencias por infección.

OBJECTIVE: To analyse and compare 30-day mortality prognostic power of several biomarkers (C-reactive protein, procalcitonin, lactate and suPAR) in patients seen in emergency departments (ED) due to infections. Secondly, if these could improve the accuracy of systemic inflammatory response syndrome (SIRS) and quick Sepsis-related Organ Failure Assessment (qSOFA). METHODS: A prospective, observational and analytical study was carried out on patients who were treated in an ED of one of the eight participating hospitals. An assessment was made of 32 independent variables that could influence mortality at 30 days. They covered epidemiological, comorbidity, functional, clinical and analytical factors. RESULTS: The study included 347 consecutive patients, 54 (15.6%) of whom died within 30 days of visiting the ED. SUPAR has got the best biomarker area under the curve (AUC)-ROC to predict mortality at 30 days of 0.836 (95% CI: 0.765-0.907; P <.001) with a cut-off > 10 ng/mL who had a sensitivity of 70% and a specificity of 86%. The score qSOFA ≥ 2 had AUC-ROC of 0.707 (95% CI: 0.621-0.793; P < .001) with sensitivity of 53% and a specificity of 89%. The mixed model (suPAR > 10 ng/mL plus qSOFA ≥ 2) has improved the AUC-ROC to 0.853 [95% CI: 0.790-0.916; P < .001] with the best prognostic performance: sensitivity of 39% and a specificity of 97% with a negative predictive value of 90%. CONCLUSIONS: suPAR showed better performance for 30-day mortality prognostic power from several biomarkers in the patients seen in ED due to infections. Score qSOFA has better performance that SRIS and the mixed model (qSOFA ≥ 2 plus suPAR > 10 ng/mL) increased the ability of qSOFA.

Latin American consensus on the quality indicators for comprehensive care clinics for patients with inflammatory bowel disease: PANCCO-GETECCU.

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic and incurable entity. The aim of the Pan American Crohn's and Colitis Organisation (PANCCO) is to create awareness of IBD, with special emphasis on Latin America, and the primary objective of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU, the Spanish acronym) is to obtain the accreditation of the clinical and therapeutic criteria for the diagnosis and treatment of IBD. AIM: To carry out a consensus for evaluating the approval criteria that a Comprehensive Care Clinic for Latin American IBD patients must meet, to be considered a center of excellence. MATERIALS AND METHODS: Fourteen clinical experts participated in the consensus. They were made up of specialists in gastroenterology, with broad clinical experience, spanning several years, in managing the care of a large number of patients with IBD, as well as advanced specialists in IBD. Thirteen of the participants came from 11 Latin American countries (Argentina, Brazil, Colombia, Dominican Republic, Ecuador, Guatemala, Mexico, Peru, Puerto Rico, Uruguay, and Venezuela) that have IBD clinics. An expert from Spain, representing the GETECCU, provided the methodologic support. The consensus consisted of 52 statements divided into three sections: 1) Structure indicators, 2) Process indicators, and 3) Result indicators. The Delphi panel method was applied. RESULTS: The present Latin American consensus describes the quality indicators that a Comprehensive Care Clinic for IBD patients must meet, to be considered a center of excellence, taking into account the needs of our region. CONCLUSIONS: This is the first Latin American consensus, jointly carried out by the PANCCO and GETECCU, to present accreditation standards for centers of excellence in the care of patients with IBD.