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Importance: BRAF/MEK inhibitors revolutionized the treatment of BRAF V600E-variant anaplastic thyroid carcinoma (BRAFv-ATC), offering improved outcomes for patients with this previously incurable disease. Observations: Anaplastic thyroid carcinoma (ATC) accounts for approximately half of thyroid cancer-related deaths. It presents as a rapidly growing tumor that often invades locoregional structures and spreads to distant sites early; therefore, prompt diagnosis, staging, and treatment initiation are of the essence in the treatment of ATC. Although most oncologists will encounter a patient with ATC in their practice, the rarity of this disease makes treatment challenging, particularly because those with BRAFv-ATC no longer have a dismal prognosis. BRAF/MEK kinase inhibitors have transformed the outlook and treatment of BRAFv-ATC. Therefore, molecular profiling to identify these patients is critical. More recently, the addition of immunotherapy to BRAF/MEK inhibitors as well as the use of the neoadjuvant approach were shown to further improve survival outcomes in BRAFv-ATC. Many of these recent advances have not yet been incorporated in the currently available guidelines, allowing for disparities in the treatment of patients with BRAFv-ATC across the US. With the increasing complexity in the management of BRAFv-ATC, this Consensus Statement aims to formulate guiding recommendations from a group of experts to facilitate therapeutic decision-making. Conclusions and Relevance: This Consensus Statement from the FAST (Facilitating Anaplastic Thyroid Cancer Specialized Treatment) group at MD Anderson Cancer Center emphasizes that rapid identification of a BRAF V600E pathogenic variant and timely initiation of sequential therapy are critical to avoid excess morbidity and mortality in patients with BRAFv-ATC. In the past decade, remarkable progress has been made in the treatment of patients with BRAFv-ATC, justifying these new evidence-based recommendations reached through a consensus of experts from a high-volume center.
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To develop an inhalable drug delivery system, we synthesized poly (lactic-co-glycolic acid) nanoparticles with Remdesivir (RDV NPs) as an antiviral agent against SARS-CoV-2 replication and formulated Remdesivir-loaded nanocomposites (RDV NCs) via coating of RDV NPs with novel supramolecular cell-penetrating peptide nanofibers (NFs) to enhance cellular uptake and intracellular drug delivery. RDV NPs and RDV NCs were characterized using variou techniques, including Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), and fluorescent microscopy. The cytotoxicity of RDV NCs was assessed in Vero E6 cells and primary human lung epithelial cells, with no significant cytotoxicity observed up to 1000 µg mL-1 and 48 h. RDV NCs were spherically shaped with a size range of 200-300 nm and a zeta potential of â¼+31 mV as well as indicating the presence of coated nanofibers. Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR), immunofluorescence and plaque assays of SARS-CoV-2 infected Vero E6 treated with RDV NCs showed significantly higher antiviral activities compared to those of free drug and uncoated RDV NPs. RDV NCs exhibited high antiviral activity against SARS-CoV-2, and the nanocomposite platform has the potential to be developed into an inhalable drug delivery system for other viral infections in the lungs.
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Objectives: International guidelines recommend resection of suspected localised renal cell carcinoma (RCC), with surgical series showing benign pathology in 30%. Non-invasive diagnostic tests to differentiate benign from malignant tumours are an unmet need. Our objective was to determine diagnostic accuracy of imaging modalities for detecting cancer in T1 renal tumours. Methods: A systematic review was performed for reports of diagnostic accuracy of any imaging test compared to a reference standard of histopathology for T1 renal masses, from inception until January 2023. Twenty-seven publications (including 2277 tumours in 2044 participants) were included in the systematic review, and nine in the meta-analysis. Results: Forest plots of sensitivity and specificity were produced for CT (seven records, 1118 participants), contrast-enhanced ultrasound (seven records, 197 participants), [99mTc]Tc-sestamibi SPECT/CT (five records, 263 participants), MRI (three records, 220 participants), [18F]FDG PET (four records, 43 participants), [68Ga]Ga-PSMA-11 PET (one record, 27 participants) and [111In]In-girentuximab SPECT/CT (one record, eight participants). Meta-analysis returned summary estimates of sensitivity and specificity for [99mTc]Tc-sestamibi SPECT/CT of 88.6% (95% CI 82.7%-92.6%) and 77.0% (95% CI 63.0%-86.9%) and for [18F]FDG PET 53.5% (95% CI 1.6%-98.8%) and 62.5% (95% CI 14.0%-94.5%), respectively. A comparison hierarchical summary receiver operating characteristic (HSROC) model did not converge. Meta-analysis was not performed for other imaging due to different thresholds for test positivity. Conclusion: The optimal imaging strategy for T1 renal masses is not clear. [99mTc]Tc-sestamibi SPECT/CT is an emerging tool, but further studies are required to inform its role in clinical practice. The field would benefit from standardisation of diagnostic thresholds for CT, MRI and contrast-enhanced ultrasound to facilitate future meta-analyses.
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Distance control in many-particle systems is a fundamental problem in nature. This becomes particularly relevant in systems of active agents, which can sense their environment and react by adjusting their direction of motion. We employ agent-based simulations to investigate the complex interplay between agent activity, characterized by Péclet number Pe , reorientation maneuverability Ω , vision angle θ and vision range R 0 , and agent density, which determines agent distancing and dynamics. We focus on semi-dense crowds, where the vision range is much larger than the particle size. The minimal distance to the nearest neighbors, exposure time, and persistence of orientation direction are analyzed to characterize the behavior. With increasing particle speed at fixed maneuverability, particles approach each other more closely, and exhibit shorter exposure times. The temporal persistence of motion decreases with increasing Pe , reflecting the impact of activity and maneuverability on direction changes. For a vision angle θ = π / 4 , we observe the emergence of flocking aggregates with a band-like structure, somewhat reminiscent of the bands in the Vicsek model. Additionally, for vision angles θ ≥ π / 2 , several quantities are found to display a universal scaling behavior with scaling variable Pe 3 / 2 / Ω . Our results are in good agreement with recent experiments of pedestrians in confined spaces.
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CONTEXT: Telomerase reverse transcriptase (TERT) promoter-mutated thyroid cancers are associated with a decreased rate of disease-free and disease-specific survival. High-quality analytical validation of a diagnostic test promotes confidence in the results that inform clinical decision-making. OBJECTIVE: This work aimed to demonstrate the analytical validation of the Afirma TERT promoter mutation assay. METHODS: TERT promoter C228T and C250T variant detection in genomic DNA (gDNA) was analyzed by assessing variable DNA input and the limit of detection (LOD) of variant allele frequency (VAF). The negative and positive percentage agreement (NPA and PPA) of the Afirma TERT test was examined against a reference primer pair as was the analytical specificity from potential interfering substances (RNA and blood gDNA). Further, the intrarun, interrun, and interlaboratory reproducibility of the assay were tested. RESULTS: The Afirma TERT test is tolerant to variation in DNA input amount (7-13â ng) and can detect expected positive TERT promoter variants down to 5% VAF LOD at 7â ng DNA input with greater than 95% sensitivity. Both NPA and PPA were 100% against the reference primer pair. The test remains accurate in the presence of 20% RNA or 80% blood gDNA for an average patient sample that typically has 30% VAF. The test also demonstrated a 100% confirmation rate when compared with an external next-generation sequencing-based reference assay executed in a non-Veracyte laboratory. CONCLUSION: The analytical robustness and reproducibility of the Afirma TERT test support its routine clinical use among thyroid nodules with indeterminate cytology that are Afirma Genomic Sequencing Classifier suspicious or among Bethesda V/VI nodules.
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Mutación , Regiones Promotoras Genéticas , Telomerasa , Neoplasias de la Tiroides , Telomerasa/genética , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/sangre , Reproducibilidad de los Resultados , Análisis Mutacional de ADN/métodos , Análisis Mutacional de ADN/normas , Frecuencia de los Genes , Sensibilidad y EspecificidadRESUMEN
Background and Aims: The coronavirus disease 2019 (COVID-19) pandemic stimulated a paradigm shift in medical and surgical education from in-person teaching to online teaching. It is unclear whether an in-person or online approach to surgical teaching for medical students is superior. We aim to compare the outcomes of in-person versus online surgical teaching in generating interest in and improving knowledge of surgery in medical students. We also aim the quantify the impact of a peer-run surgical teaching course. Methods: A six-session course was developed by medical students and covered various introductory surgical topics. The first iteration was offered online to 70 UK medical students in March 2021, and the second iteration was in-person for 20 students in November 2021. Objective and subjective knowledge was assessed through questionnaires before and after each session, and also for the entire course. Data were analyzed from this mixed-methods study to compare the impact of online versus in-person teaching on surgical knowledge and engagement. Results: Students in both iterations showed significant improvement of 33%-282% across the six sessions in knowledge and confidence after completing the course (p < 0.001). There was no significant difference in the level of objective knowledge, enjoyment, or organization of the course between online and in-person groups, although the in-person course was rated as more engaging (mean Likert score 9.1 vs. 9.7, p = 0.033). Discussion: Similar objective and subjective surgical teaching outcomes were achieved in both iterations, including in "hands-on" topics such as suturing, gowning, and gloving. Students who completed the online course did not have any lower knowledge or confidence in their surgical skills; however, the in-person course was reported to be more engaging. Surgical teaching online and in-person may be similarly effective and can be delivered according to what is most convenient for the circumstances, such as in COVID-19.
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Neutrophilic dermatoses (NDs) refer to a group of cutaneous conditions histologically characterized by the dense accumulation of neutrophils in the skin in the absence of infection. NDs have been associated with underlying autoimmune connective tissue disorders (CTDs) such as systemic lupus erythematosus (SLE), Sjogren's syndrome, and dermatomyositis. We describe a case of neutrophilic dermatoses as a manifestation of a SLE flare.
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Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Síndrome de Sjögren , Enfermedades de la Piel , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Enfermedades de la Piel/patología , Enfermedades Autoinmunes/complicaciones , Piel/patología , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnósticoRESUMEN
Background: The dabrafenib plus trametinib combination (DT) has revolutionized the treatment of BRAFV600E-mutated anaplastic thyroid carcinoma (BRAFm-ATC). However, patients eventually develop resistance and progress. Single-agent anti-PD-1 inhibitor spartalizumab has shown a median overall survival (mOS) of 5.9 months. Combination of immunotherapy with BRAF/MEK inhibitors (BRAF/MEKi) seems to improve outcomes compared with BRAF/MEKi alone, although no direct comparison is available. BRAF-targeted therapy before surgery (neoadjuvant approach) has also shown improvement in survival. We studied the efficacy and safety of DT plus pembrolizumab (DTP) compared with current standard-of-care DT alone as an initial treatment, as well as in the neoadjuvant setting. Methods: Retrospective single-center study of patients with BRAFm-ATC treated with first-line BRAF-directed therapy between January 2014 and March 2023. Three groups were evaluated: DT, DTP (pembrolizumab added upfront or at progression), and neoadjuvant (DT before surgery, and pembrolizumab added before or after surgery). The primary endpoint was mOS between DT and DTP. Secondary endpoints included median progression-free survival (mPFS) and response rate with DT versus DTP as initial treatments, and the exploratory endpoint was mOS in the neoadjuvant group. Results: Seventy-one patients were included in the primary analysis: n = 23 in DT and n = 48 in DTP. Baseline demographics were similar between groups, including the presence of metastatic disease at start of treatment (p = 0.427) and prior treatments with surgery (p = 0.864) and radiation (p = 0.678). mOS was significantly longer with DTP (17.0 months [confidence interval CI, 11.9-22.1]) compared with DT alone (9.0 months [CI, 4.5-13.5]), p = 0.037. mPFS was also significantly improved with DTP as the initial treatment (11.0 months [CI, 7.0-15.0]) compared with DT alone (4.0 months [CI, 0.7-7.3]), p = 0.049. Twenty-three patients were in the exploratory neoadjuvant group, where mOS was the longest (63.0 months [CI, 15.5-110.5]). No grade 5 adverse events (AEs) occurred in all three cohorts, and 32.4% had immune-related AEs, most frequently hepatitis and colitis. Conclusions: Our results show that in BRAFm-ATC, addition of pembrolizumab to dabrafenib/trametinib may significantly prolong survival. Surgical resection of the primary tumor after initial BRAF-targeted therapy in selected patients may provide further survival benefit. However, conclusions are limited by the retrospective nature of the study. Additional prospective data are needed to confirm this observation.
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Imidazoles , Piridonas , Pirimidinonas , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/genética , Estudios Retrospectivos , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica , Oximas , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , MutaciónRESUMEN
Cell membrane-derived nanoparticles (NPs) have recently gained popularity due to their desirable features in drug delivery such as mimicking properties of native cells, impeding systemic clearance, and altering foreign body responses. Besides NP technology, adoptive immunotherapy has emerged due to its promise in cancer specificity and therapeutic efficacy. In this research, we developed a biomimetic drug carrier based on chimeric antigen receptor (CAR) transduced T-cell membranes. For that purpose, anti-HER2 CAR-T cells were engineered via lentiviral transduction of anti-HER2 CAR coding lentiviral plasmids. Anti-HER2 CAR-T cells were characterized by their specific activities against the HER2 antigen and used for cell membrane extraction. Anti-cancer drug Cisplatin-loaded poly (D, l-lactide-co-glycolic acid) (PLGA) NPs were coated with anti-human epidermal growth factor receptor 2 (HER2)-specific CAR engineered T-cell membranes. Anti-HER2 CAR-T-cell membrane-coated PLGA NPs (CAR-T-MNPs) were characterized and confirmed via fluorescent microscopy and flow cytometry. Membrane-coated NPs showed a sustained drug release over the course of 21 days in physiological conditions. Cisplatin-loaded CAR-T-MNPs also inhibited the growth of multiple HER2+ cancer cells in vitro. In addition, in vitro uptake studies revealed that CAR-T-MNPs showed an increased uptake by A549 cells. These results were also confirmed via in vivo biodistribution and therapeutic studies using a subcutaneous lung cancer model in nude mice. CAR-T-MNPs localized preferentially at tumor areas compared to those of other studied groups and consisted of a significant reduction in tumor growth in tumor-bearing mice. In Conclusion, the new CAR modified cell membrane-coated NP drug-delivery platform has demonstrated its efficacy both in vitro and in vivo. Therefore, CAR engineered membrane-coated NP system could be a promising cell-mimicking drug carrier that could improve therapeutic outcomes of lung cancer treatments.
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BACKGROUND: There is little robust data about the cardiovascular safety of hydroxychloroquine in patients with rheumatoid arthritis (RA), who often have cardiovascular comorbidities. We examined the association between use of hydroxychloroquine (HCQ) in patients with RA and major adverse cardiovascular events (MACE). METHODS: In a retrospective cohort of Medicare beneficiaries aged ≥ 65 years with RA, we identified patients who initiated HCQ (users) and who did not initiate HCQ (non-users) between January 2015-June 2017. Each HCQ user was matched to 2 non-users of HCQ using propensity score derived from patient baseline characteristics. The primary outcome was the occurrence of MACE, defined as acute admissions for stroke, myocardial infarction, or heart failure. Secondary outcomes included all-cause mortality and the composite of MACE and all-cause mortality. Cox proportional hazards model was used to compare outcomes between HCQ users to non-users. RESULTS: The study included 2380 RA patients with incident HCQ use and matched 4633 HCQ non-users over the study period. The mean follow-up duration was 1.67 and 1.63 years in HCQ non-users and users, respectively. In multivariable models, use of HCQ was not associated with the risk of MACE (hazard ratio 1.1; 95% CI: 0.832-1.33). However, use of HCQ was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.45-0.64) and the composite of all-cause mortality and MACE (HR 0.67; 95% CI: 0.58-0.78). CONCLUSION: HCQ use was independently associated with a lower risk of mortality in older adults with RA but not with incidence of MACE events. Key Points ⢠Using an incident user design (to avoid the biases of a prevalent user design) and a population-based approach, we examined the effect of hydroxychloroquine (HCQ) on the risk of major cardiovascular events (MACE) in older patients with RA. ⢠We did not find an association between HCQ use and incident MACE. We did, however, find a significant association with the composite outcome (MACE and all-cause mortality) driven by a significant reduction in all-cause mortality with HCQ use.
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Antirreumáticos , Artritis Reumatoide , Infarto del Miocardio , Humanos , Anciano , Estados Unidos/epidemiología , Hidroxicloroquina/efectos adversos , Antirreumáticos/efectos adversos , Estudios Retrospectivos , Medicare , Artritis Reumatoide/complicaciones , Infarto del Miocardio/complicacionesRESUMEN
Pregnancy complicated by incisional hernia is rare but can become an obstetric challenge if the gravid uterus becomes displaced or incarcerated into the hernial sac or if there is ulceration of the overlying dermis as a result of increased intra-abdominal pressure being transmitted to the skin. We report a case of a pregnant woman presenting with a large incisional hernia at 19 weeks of gestation and discuss how problems encountered with progressing pregnancy were managed conservatively by adopting a multidisciplinary team approach (which included surgeons and radiologists). She underwent a caesarean section at 35 weeks of gestation due to active bleeding from the ulcerated skin and foetal growth restriction with subsequent staged secondary hernia repair at a tertiary centre. Close surveillance is mandatory, and a decision on the mode and timing of delivery as well as when to perform the surgical repair of the fascial defect should be team based.
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Cavidad Abdominal , Hernia Incisional , Complicaciones del Embarazo , Femenino , Humanos , Embarazo , Cesárea/efectos adversos , Hernia Incisional/cirugía , Hernia Incisional/complicaciones , Complicaciones del Embarazo/cirugía , Útero/cirugíaRESUMEN
Increasing evidence suggests that there is a pivotal role for physical force (mechanotransduction) in the initiation and/or the perpetuation of spondyloarthritis; the review contained herein examines that evidence. Furthermore, we know that damage and inflammation can limit spinal mobility, but is there a cycle created by altered spinal mobility leading to additional damage and inflammation?Over the past several years, mechanotransduction, the mechanism by which mechanical perturbation influences gene expression and cellular behaviour, has recently gained popularity because of emerging data from both animal models and human studies of the pathogenesis of ankylosing spondylitis (AS). In this review, we provide evidence towards an appreciation of the unsolved paradigm of how biomechanical forces may play a role in the initiation and propagation of AS.
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Espondiloartritis , Espondilitis Anquilosante , Humanos , Fenómenos Biomecánicos , Mecanotransducción Celular , Índice de Severidad de la Enfermedad , Espondiloartritis/etiología , Espondilitis Anquilosante/etiología , InflamaciónRESUMEN
The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for BRAF-mutated solid tumors and are routinely used in RR-DTCs in many centers. However, none of the currently available treatments are curative, and most patients will ultimately show progression. Current research efforts are therefore focused on identifying resistance mechanisms to tyrosine kinase inhibitors and ways to overcome them. Various novel treatment strategies are under investigation, including immunotherapy, redifferentiation therapy, and second-generation kinase inhibitors. In this review, we will discuss currently available drugs for advanced RR-DTCs, potential mechanisms of drug resistance and future therapeutic avenues.
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Adenocarcinoma , Neoplasias de la Tiroides , Estados Unidos , Humanos , Radioisótopos de Yodo , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Inmunoterapia , Inhibidores de Proteínas Quinasas/uso terapéutico , Resistencia a MedicamentosRESUMEN
Recent advances in micro- and nano-technologies allow the construction of complex active systems from biological and synthetic materials. An interesting example is active vesicles, which consist of a membrane enclosing self-propelled particles, and exhibit several features resembling biological cells. We investigate numerically the behavior of active vesicles, where the enclosed self-propelled particles can adhere to the membrane. A vesicle is represented by a dynamically triangulated membrane, while the adhesive active particles are modelled as active Brownian particles (ABPs) that interact with the membrane via the Lennard-Jones potential. Phase diagrams of dynamic vesicle shapes as a function of ABP activity and particle volume fraction inside the vesicle are constructed for different strengths of adhesive interactions. At low ABP activity, adhesive interactions dominate over the propulsion forces, such that the vesicle attains near static configurations, with protrusions of membrane-wrapped ABPs having ring-like and sheet-like structures. At moderate particle densities and strong enough activities, active vesicles show dynamic highly-branched tethers filled with string-like arrangements of ABPs, which do not occur in the absence of particle adhesion to the membrane. At large volume fractions of ABPs, vesicles fluctuate for moderate particle activities, and elongate and finally split into two vesicles for large ABP propulsion strengths. We also analyze membrane tension, active fluctuations, and ABP characteristics (e.g., mobility, clustering), and compare them to the case of active vesicles with non-adhesive ABPs. The adhesion of ABPs to the membrane significantly alters the behavior of active vesicles, and provides an additional parameter for controlling their behavior.
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Introduction: Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a rare adverse event. In this study, we characterize clinical outcomes of patients with ICI-DM and evaluate survival impact of this complication on melanoma patients. Research design & methods: We conducted a retrospective review of 76 patients diagnosed with ICI-DM from April 2014 to December 2020. Results: 68% of patients presented in diabetic ketoacidosis, 16% had readmissions for hyperglycemia, and hypoglycemia occurred in 70% of patients after diagnosis. Development of ICI-DM did not impact overall survival or progression-free survival in melanoma patients. Conclusion: Development of ICI-DM is associated with long-term insulin dependence and pancreatic atrophy; the use of diabetes technology in this patient population can help improve glycemic control.
Cancer treatment with immune checkpoint inhibitors can cause irreversible side effects. In this study, we describe the clinical presentations of 76 patients who developed immune checkpoint inhibitor diabetes mellitus, a rare complication of checkpoint inhibitor therapy that requires lifelong treatment with insulin therapy. Most patients presented with a life-threatening hyperglycemic emergency and had experienced weight loss and hyperglycemia several weeks prior to diagnosis. After diagnosis, these patients are at risk for high and low blood sugars, but the use of glucose monitoring devices and insulin pumps can help improve blood sugar control. In our study, the development of this complication did not affect survival for melanoma patients. We need to improve awareness of this rare complication to ensure timely treatment for patients.
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Diabetes Mellitus , Melanoma , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Melanoma/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
BACKGROUND: Multiple sclerosis (MS) is frequently diagnosed in people of reproductive age, many of whom will become pregnant following diagnosis. Although many women report an improvement in symptoms and relapses during pregnancy, symptoms such as fatigue and spasticity are commonly reported and can worsen. Prescribing medications during pregnancy and breastfeeding presents unique challenges and guidance on the use of symptomatic therapies is limited. OBJECTIVES: This paper aims to provide a consensus on the current evidence base to facilitate informed decision-making and optimise pre-conception counselling. METHODS: A list of most commonly prescribed medications for symptom management in MS was created using pregnancy and MS-related READ codes in the Welsh GP Dataset, followed by a review by MS neurologists. RESULTS: A final list of 24 medications was generated for review. Searches were performed on each medication, and evidence graded using standardised criteria. Evidence-based recommendations were developed and distributed to experts in the field and revised according to feedback using modified Delphi criteria. CONCLUSIONS: Our guidelines provide evidence-based recommendations on the safety of symptomatic therapies during pregnancy and breastfeeding for general practitioners and specialist teams working with people with MS who are hoping to embark on pregnancy or are currently pregnant. Individual risk-benefit ratios should be considered during pre-conception counselling to optimise symptom burden and minimise harm to both parent and child.
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Esclerosis Múltiple , Embarazo , Niño , Humanos , Femenino , Esclerosis Múltiple/terapia , Lactancia Materna , Consenso , Técnica Delphi , Espasticidad MuscularRESUMEN
OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS: This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION: Application of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.
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Antirreumáticos , Enfermedades Musculoesqueléticas , Reumatología , Niño , Humanos , Estados Unidos , Antirreumáticos/uso terapéutico , Enfermedades Musculoesqueléticas/tratamiento farmacológico , VacunaciónRESUMEN
OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS: This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION: Application of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.
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Antirreumáticos , Enfermedades Musculoesqueléticas , Enfermedades Reumáticas , Reumatología , Niño , Humanos , Estados Unidos , Antirreumáticos/uso terapéutico , Enfermedades Musculoesqueléticas/tratamiento farmacológico , Vacunación , Enfermedades Reumáticas/tratamiento farmacológicoRESUMEN
Multiple sclerosis (MS) frequently affects women of childbearing age, and an increasing number of disease-modifying therapies are available. However, a consequence of this is that women and clinicians face complex shared decisions surrounding disease-modifying therapy use in pregnancy and postpartum. It has been suggested that there are both knowledge and communication gaps that need to be addressed in order to improve outcomes for women with MS desiring a pregnancy. Existing pregnancy studies are subject to limitations including selection bias and missing data; however, when these are combined with clinical expertise, consensus guidelines can be developed and used as a framework to support this complex decision-making process. This commentary paper aims to provide a practical and evidence-based overview of the safety of disease-modifying therapies and symptomatic drug therapies during pregnancy and breastfeeding, along with highlighting where insufficient data exist to guide practice.
Multiple sclerosis is more common in women than men, and many women with multiple sclerosis have not completed their families when they are diagnosed. This means that they face complicated decisions around using disease-modifying therapies, many of which have limited evidence for use in pregnancy. Conversations between clinicians and women with multiple sclerosis around pregnancy do not always address all of the issues that women face, partly because not all of the needed information is available. Consensus guidelines have recently been developed, and both experience and opinion have been used to inform these. This paper provides a practical overview of the use of treatments for MS and its symptoms.