High-resolution diffusion tensor imaging of the fornix predicts memory function in multiple sclerosis.

Background: Cognitive dysfunction is a known symptom of multiple sclerosis (MS), with memory recognized as a frequently impacted domain. Here, we used high-resolution MRI at 7 tesla to build on cross-sectional work by evaluating the longitudinal relationship of diffusion tensor imaging (DTI) measures of the fornix to episodic memory performance. Methods: A sample of 80 people with multiple sclerosis (mean age 51.9 ± 8.1 years; 24% male) underwent baseline clinical evaluation, neuropsychological assessment, and MRI. Sixty-four participants had follow-up neuropsychological testing after 1-2 years. Linear regression was used to assess the relationship of baseline imaging measures to follow-up episodic memory performance, measured using the Selective Reminding Test and Brief Visuospatial Memory Test. A reduced prediction model included cognitive function at baseline, age, sex, and disease course. Results: Radial (ß = -0.222, p < 0.026; likelihood ratio test (LRT) p < 0.018), axial (ß = -0.270, p < 0.005; LRT p < 0.003), and mean (ß = -0.242, p < 0.0139; LRT p < 0.009) diffusivity of the fornix significantly added to the model, with follow-up analysis indicating that a longer prediction interval may increase accuracy. Conclusion: These results suggest that fornix DTI has predictive value specific to memory function in MS and warrants additional investigation in the drive to develop predictors of disease progression.

n-3 PUFAs Show Promise as Adjuvants in Chemotherapy, Enhancing their Efficacy while Safeguarding Hematopoiesis and Promoting Bone Generation.

Cancer ranks as the second leading cause of mortality in high-income countries, underscoring the critical need for effective therapeutic strategies. One prominent approach, chemotherapy, is widely employed for treating solid tumors. However, the significant adverse effects associated with chemotherapy, notably myeloablation and osteonecrosis, impart considerable challenges by compromising immune function and diminishing patients' quality of life. Furthermore, the emergence of chemotherapy resistance poses a formidable hurdle in achieving successful cancer treatment outcomes. In this context, the focus is on exploring alternative approaches to enhance the efficacy of cancer treatment and mitigate its adverse consequences. Among these approaches, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), two n-3 polyunsaturated fatty acids (PUFAs), have garnered substantial interest. These PUFAs exhibit the potential to influence membrane lipid composition and modulate critical gene expressions associated with cancer, such as Bcl-2, PI3K, NF-κB, and phosphorylated Akt, thereby potentially reducing cancer risk. Moreover, emerging evidence highlights their ability to augment chemotherapy efficacy, particularly in drug-resistant cancer cells. Importantly, both preclinical and clinical investigations have provided compelling evidence supporting the protective effects of n-3 PUFAs on healthy cells. Leveraging these findings, there has been growing attention on the exploration of n-3 PUFAs as adjuvants to chemotherapy. This strategic approach holds promise in mitigating the adverse effects linked to chemotherapy, notably myeloablation and osteonecrosis, while simultaneously enhancing its effectiveness in combating cancer. This comprehensive review delves into the multifaceted attributes of n-3 PUFAs, encompassing their cytotoxic properties, potential as chemopreventive agents, and their prospective role in ameliorating the adverse effects commonly associated with chemotherapy, with a particular emphasis on myeloablation and osteonecrosis. By elucidating the intricate interplay between n-3 PUFAs and cancer treatment paradigms, this review contributes to the expanding body of knowledge aimed at refining cancer therapeutic strategies and enhancing patient outcomes.

n-3 PUFAs synergistically enhance the efficacy of doxorubicin by inhibiting the proliferation and invasion of breast cancer cells.

Breast cancer stands as a prominent contributor to cancer-related fatalities among women globally, characterized by an unfavorable prognosis, low survival rates, and its conventional treatment approach involving chemotherapy. Doxorubicin (DOXO) represents a potent anti-tumor agent widely employed in combating breast cancer. Regrettably, a substantial proportion of patients eventually develop resistance to DOXO treatment, elevating the risk of relapse and adverse clinical outcomes. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), recognized as essential components of the human diet, have exhibited considerable promise in targeting malignant cells, initiating apoptosis, and impeding tumor proliferation and metastatic dissemination. Combining these nutritional supplements, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with DOXO presents a compelling strategy to augment treatment efficacy. The present study was conducted employing a breast cancer cell line, MCF-7, to assess the synergistic potential of DHA, EPA, and DOXO. Remarkably, the combination treatment yielded a substantial increase in cytotoxicity compared to the administration of DOXO alone. Furthermore, an enhancement in the suppression of metastasis was evident in the combination treatment relative to the exclusive use of DOXO. Cell cycle analysis unveiled that cells subjected to the combination treatment exhibited a more pronounced arrest in the G1 phase, signifying the combination's heightened effectiveness in impeding cell progression into the doubling phase. Collectively, the amalgamation of n-3 polyunsaturated fatty acids (n-3 PUFAs) emerges as a potent strategy for enhancing the therapeutic potential of DOXO, effectively restraining the growth and dissemination of breast cancer cells.

Effect of ibudilast on thalamic magnetization transfer ratio and volume in progressive multiple sclerosis.

BACKGROUND: Thalamic volume (TV) is a sensitive biomarker of disease burden of injury in multiple sclerosis (MS) and appears to reflect overall lesion loads. Ibudilast showed significant treatment effect on brain atrophy and magnetization transfer ratio (MTR) of normal-appearing brain tissue but not in new/enlarging T2 lesion in the SPRINT-MS randomized clinical trial. OBJECTIVE: To evaluate the effect of ibudilast on thalamic tissue integrity and volume in the SPRINT-MS. METHODS: A total of 255 participants with progressive MS were randomized to oral ibudilast or placebo, and thalamic MTR and normalized TV over 96 weeks were quantified. Mixed-effect modeling assessed treatment effects on the thalamic MTR and TV, separately. Similarly, the measures were compared between the participants with confirmed disability progression (CDP). RESULTS: Ibudilast's treatment effect was observed compared to placebo for thalamic MTR (p = 0.03) but not for TV (p = 0.68) while TV correlated with T2 lesion volume (p < 0.001). CDP associated with thalamic MTR (p = 0.04) but not with TV (p = 0.7). CONCLUSION: Ibudilast showed an effect on thalamic MTR, which was associated with CDP, suggesting a clinically relevant effect on thalamic tissue integrity. However, the treatment effect was not observed in TV, suggesting that thalamic atrophy is more closely associated with global inflammatory activity than local tissue integrity. CLINICALTRIALS.GOV: NCT01982942.

Neurodegeneration in multiple sclerosis.

Axonal loss in multiple sclerosis (MS) is a key component of disease progression and permanent neurologic disability. MS is a heterogeneous demyelinating and neurodegenerative disease of the central nervous system (CNS) with varying presentation, disease courses, and prognosis. Immunomodulatory therapies reduce the frequency and severity of inflammatory demyelinating events that are a hallmark of MS, but there is minimal therapy to treat progressive disease and there is no cure. Data from patients with MS, post-mortem histological analysis, and animal models of demyelinating disease have elucidated patterns of MS pathogenesis and underlying mechanisms of neurodegeneration. MRI and molecular biomarkers have been proposed to identify predictors of neurodegeneration and risk factors for disease progression. Early signs of axonal dysfunction have come to light including impaired mitochondrial trafficking, structural axonal changes, and synaptic alterations. With sustained inflammation as well as impaired remyelination, axons succumb to degeneration contributing to CNS atrophy and worsening of disease. These studies highlight the role of chronic demyelination in the CNS in perpetuating axonal loss, and the difficulty in promoting remyelination and repair amidst persistent inflammatory insult. Regenerative and neuroprotective strategies are essential to overcome this barrier, with early intervention being critical to rescue axonal integrity and function. The clinical and basic research studies discussed in this review have set the stage for identifying key propagators of neurodegeneration in MS, leading the way for neuroprotective therapeutic development. This article is categorized under: Immune System Diseases > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology.

Visual imaging as a predictor of neurodegeneration in experimental autoimmune demyelination and multiple sclerosis.

Thalamic volume is associated with clinical disability in multiple sclerosis (MS) and is vulnerable to secondary neurodegeneration due to its extensive connectivity throughout the central nervous system (CNS). Using a model of autoimmune demyelination that exhibits CNS-infiltrating immune cells in both spinal cord white matter and optic nerve, we sought to evaluate neurodegenerative changes due to lesions affecting the spino- and retino-thalamic pathways. We found comparable axonal loss in spinal cord white matter and optic nerve during the acute phase of disease consistent with synaptic loss, but not neuronal cell body loss in the thalamic nuclei that receive input from these discrete pathways. Loss of spinal cord neurons or retinal ganglion cells retrograde to their respective axons was not observed until the chronic phase of disease, where optical coherence tomography (OCT) documented reduced inner retinal thickness. In patients with relapsing-remitting MS without a history of optic neuritis, OCT measures of inner retinal volume correlated with retino-thalamic (lateral geniculate nucleus) and spino-thalamic (ventral posterior nucleus) volume as well as neuroperformance measures. These data suggest retinal imaging may serve as an important noninvasive predictor of neurodegeneration in MS.

Association between early initiation of breastfeeding and reduced risk of respiratory infection: Implications for nonseparation of infant and mother in the COVID-19 context.

Early initiation of breastfeeding, within 1 h of birth, is vital for the health of newborns and reduces morbidity and mortality. Secondary analysis of the 2016 Nepal Demographic and Health Survey (DHS) showed that early initiation of breastfeeding significantly reduced the risk of acute respiratory infection (ARI) in children under 2 years. Early initiation of breastfeeding requires maternal proximity. Separation of infant and mother inhibits early initiation of breastfeeding and increases the risk that infants will suffer from ARIs. However, during the COVID-19 pandemic, guidance varied, with some recommending that infants and mothers with SARS-CoV-2 be isolated from one another. Nepal's Ministry of Health and Population recommended nonseparation, but the adherence to this guidance was inconsistent. Maternal proximity, nonseparation and early initiation of breastfeeding should be promoted in all birthing facilities.

Sensitivity of T1/T2-weighted ratio in detection of cortical demyelination is similar to magnetization transfer ratio using post-mortem MRI.

BACKGROUND: Detecting cortical demyelination using magnetic resonance imaging (MRI) in multiple sclerosis (MS) remains a challenge. Magnetization transfer ratio (MTR), T1-weighted/T2-weighted ratio (T1T2R), and T2-weighted (T2w) signal are sensitive to cortical demyelination, but their accuracy is unknown. OBJECTIVES: To quantify the sensitivity, specificity, and accuracy of postmortem T1T2R, MTR, and T2w in detecting cortical demyelination. METHODS: In situ postmortem MRIs from 9 patients were used to measure T1T2R, MTR, and T2w along the midline of cortical gray matter and classified as normal or abnormal. MRIs were co-registered and compared to hemispheric myelin staining. The sensitivity, specificity, and accuracy of T1T2R, MTR, and T2w in detecting cortical demyelination were measured. RESULTS: The mean age (standard deviation) at death was 64.7 (+/-13.7) years with a disease duration of 23.8 (+/-10.5) years. The sensitivity was 78% for MTR, 75% for T1T2R, and 63% for T2w. The specificity was 46% (T2w), 13% (T1T2R), and 29% (MTR). The accuracy was 71% (T2w), 39% (MTR), and 42% (T1T2R). There were no significant differences between different MRI measures in cortical demyelination or intracortical/subpial lesion detection. CONCLUSIONS: Although somewhat sensitive, the modest specificity of conventional MRI modalities for cortical demyelination indicates that they are influenced by cortical changes other than demyelination. Improved acquisition and post-processing are needed to reliably measure cortical lesion load.

The VitMin Lab Sandwich-ELISA Assays for Iron and Inflammation Markers Compared Well with Clinical Analyzer Reference-Type Assays in Subsamples of the Nepal National Micronutrient Status Survey.

BACKGROUND: The low cost and small specimen volume of the VitMin Lab ELISA assays for serum ferritin (Fer), soluble transferrin receptor (sTfR), C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) have allowed their application to micronutrient surveys conducted in low-resource countries for ∼2 decades. OBJECTIVES: We conducted a comparison between the ELISA and reference-type assays used in the US NHANES. METHODS: Using the Roche clinical analyzer as a reference, we measured random subsets of the 2016 Nepal National Micronutrient Status Survey (200 serum samples from children aged 6-59 mo; 100 serum samples from nonpregnant women) for Fer, sTfR, CRP, and AGP. We compared the combined data sets with the ELISA survey results using descriptive analyses. RESULTS: The Lin's concordance coefficients between the 2 assays were ≥0.89 except for sTfR (Lin's ρ = 0.58). The median relative difference to the reference was as follows: Fer, -8.5%; sTfR, 71.2%; CRP, -19.5%; and AGP, -8.2%. The percentage of VitMin samples agreeing within ±30% of the reference was as follows: Fer, 88.5%; sTfR, 1.70%; CRP, 74.9%; and AGP, 92.9%. The prevalence of abnormal results was comparable between the 2 assays for Fer, CRP, and AGP, and for sTfR after adjusting to the Roche assay. Continued biannual performance (2007-2019) of the VitMin assays in CDC's external quality assessment program (6 samples/y) demonstrated generally acceptable performance. CONCLUSIONS: Using samples from the Nepal survey, the VitMin ELISA assays produced mostly comparable results to the Roche reference-type assays for Fer, CRP, and AGP. The lack of sTfR assay standardization to a common reference material explains the large systematic difference observed for sTfR, which could be corrected by an adjustment equation pending further validation. This snapshot comparison together with the long-term external quality assessment links the survey data generated by the VitMin Lab to the Roche assays used in NHANES.

Consensus Definitions and Interpretation Templates for Magnetic Resonance Imaging of Defecatory Pelvic Floor Disorders: Proceedings of the Consensus Meeting of the Pelvic Floor Disorders Consortium of the American Society of Colon and Rectal Surgeons, the Society of Abdominal Radiology, the International Continence Society, the American Urogynecologic Society, the International Urogynecological Association, and the Society of Gynecologic Surgeons.

The Pelvic Floor Disorders Consortium (PFDC) is a multidisciplinary organization of colorectal surgeons, urogynecologists, urologists, gynecologists, gastroenterologists, radiologists, physiotherapists, and other advanced care practitioners. Specialists from these fields are all dedicated to the diagnosis and management of patients with pelvic floor conditions, but they approach, evaluate, and treat such patients with their own unique perspectives given the differences in their respective training. The PFDC was formed to bridge gaps and enable collaboration between these specialties. The goal of the PFDC is to develop and evaluate educational programs, create clinical guidelines and algorithms, and promote high quality of care in this unique patient population. The recommendations included in this article represent the work of the PFDC Working Group on Magnetic Resonance Imaging of Pelvic Floor Disorders (members listed alphabetically in Table 1). The objective was to generate inclusive, rather than prescriptive, guidance for all practitioners, irrespective of discipline, involved in the evaluation and treatment of patients with pelvic floor disorders.

Timing of Invasive Mechanical Ventilation and Mortality among Patients with Severe COVID-19-associated Acute Respiratory Distress Syndrome.

BACKGROUND: Severe acute respiratory distress syndrome associated with coronavirus disease-2019 (COVID-19) (CARDS) pneumonitis presents a clinical challenge as regards to the timing of intubation and ambiguity of outcome. There is a lack of clear consensus on when to switch patients from trials of noninvasive therapies to invasive mechanical ventilation. We investigated the effect of the timing of intubation from the time of admission on the clinical outcome of CARDS. AIM AND OBJECTIVE: The aim and objective was to analyze the effect of timing of intubation early (within 48 hours of admission to critical care unit) versus delayed (after 48 hours of admission to critical care unit) on mortality in severe CARDS patients. MATERIALS AND METHODS: A retrospective observational study performed in a 28-bedded COVID-19 intensive care unit of a tertiary care hospital in Pune, India. All patients admitted between April 1, 2020, and October 15, 2020, with confirmed COVID-19 (RT-PCR positive) requiring mechanical ventilation were included in the study. RESULTS: The primary outcome was in-hospital mortality. Among 2,230 patients that were admitted to the hospital, 525 required critical care (23.5%), invasive mechanical ventilation was needed in 162 patients and 147 (28%) of critical care admission were included in the study cohort after exclusion. Seventy-five patients (51%) were intubated within 48 hours of critical care admission (early group) and 72 (48.9%) were intubated after 48 hours of critical care admission (delayed group). With regards to the total of 147 included patients; male patients were 74.1% with a median age of 59 years (interquartile range, 51-68 years). Diabetes (44.9%) and hypertension (43.5%) were the most common comorbidities. Higher admission acute physiology and chronic health evaluation II scores and lower absolute lymphocyte count were observed in patients intubated within 48 hours. The early intubated group had a mortality of 60% whereas the same was observed as 77.7% in delayed intubation group, and this difference was statistically significant (p = 0.02). CONCLUSION: Current study concludes that early intubation is associated with improved survival rates in severe CARDS patients. HOW TO CITE THIS ARTICLE: Zirpe KG, Tiwari AM, Gurav SK, Deshmukh AM, Suryawanshi PB, Wankhede PP, et al. Timing of Invasive Mechanical Ventilation and Mortality among Patients with Severe COVID-19-associated Acute Respiratory Distress Syndrome. Indian J Crit Care Med 2021;25(5):493-498.

Deep grey matter injury in multiple sclerosis: a NAIMS consensus statement.

Although multiple sclerosis has traditionally been considered a white matter disease, extensive research documents the presence and importance of grey matter injury including cortical and deep regions. The deep grey matter exhibits a broad range of pathology and is uniquely suited to study the mechanisms and clinical relevance of tissue injury in multiple sclerosis using magnetic resonance techniques. Deep grey matter injury has been associated with clinical and cognitive disability. Recently, MRI characterization of deep grey matter properties, such as thalamic volume, have been tested as potential clinical trial end points associated with neurodegenerative aspects of multiple sclerosis. Given this emerging area of interest and its potential clinical trial relevance, the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative held a workshop and reached consensus on imaging topics related to deep grey matter. Herein, we review current knowledge regarding deep grey matter injury in multiple sclerosis from an imaging perspective, including insights from histopathology, image acquisition and post-processing for deep grey matter. We discuss the clinical relevance of deep grey matter injury and specific regions of interest within the deep grey matter. We highlight unanswered questions and propose future directions, with the aim of focusing research priorities towards better methods, analysis, and interpretation of results.

Juxtacortical susceptibility changes in progressive multifocal leukoencephalopathy at the gray-white matter junction correlates with iron-enriched macrophages.

OBJECTIVE: Describe magnetic resonance imaging (MRI) susceptibility changes in progressive multifocal leukoencephalopathy (PML) and identify neuropathological correlates. METHODS: PML cases and matched controls with primary central nervous system lymphoma (PCNSL) were retrospectively identified. MRI brain at 3 T and 7 T were reviewed. MRI-pathology correlations in fixed brain autopsy tissue were conducted in three subjects with confirmed PML. RESULTS: With PML (n = 26 total, n = 5 multiple sclerosis natalizumab-associated), juxtacortical changes on susceptibility-weighted imaging (SWI) or gradient echo (GRE) sequences were noted in 3/3 cases on 7 T MRI and 14/22 cases (63.6%) on 1.5 T or 8/22 (36.4%) 3 T MRI. Similar findings were only noted in 3/25 (12.0%) of PCNSL patients (odds ratio (OR) 12.83, 95% confidence interval (CI), 2.9-56.7, p < 0.001) on 1.5 or 3 T MRI. On susceptibility sequences available prior to diagnosis of PML, 7 (87.5%) had changes present on average 2.7 ± 1.8 months (mean ± SD) prior to diagnosis. Postmortem 7 T MRI showed SWI changes corresponded to areas of increased iron density along the gray-white matter (GM-WM) junction predominantly in macrophages. CONCLUSION: Susceptibility changes in PML along the GM-WM junction can precede noticeable fluid-attenuated inversion recovery (FLAIR) changes and correlates with iron accumulation in macrophages.

Role of medical thoracoscopy in the treatment of complicated parapneumonic effusions.

OBJECTIVE: The role of medical thoracoscopy in the treatment of pleural infections is increasingly being recognized. This study was done to assess the role of medical thoracoscopy in the management of carefully selected subset of patients with complicated parapneumonic effusions (PPEs). MATERIALS AND METHODS: We analyzed retrospective data of 164 thoracoscopic procedures performed at our center on patients with complicated PPE in the past 10 years. Patients were subjected to medical thoracoscopy based on ultrasonographic stratification and a computed tomography (CT) thorax. Medical thoracoscopy was performed after an intercostal block under conscious sedation with midazolam (2 mg) and fentanyl (50 mcg) and local anesthesia with lignocaine 2% (10-15 ml), through a single port 10 mm diameter thoracoscope. RESULTS: A total of 164 patients (119 males and 45 females) underwent medical thoracoscopy during the study period. The mean age was 47.4 ± 15.9 (median, 50; range, 16-86). The final diagnosis by thoracoscopy was bacterial empyema in 93 patients and tuberculosis in 71 patients. Medical thoracoscopy was successful without subsequent intervention in 160 (97.5%) patients, two patients underwent a second procedure, in the form of decortication, and two patients died due to sepsis. There were no major procedure-related complications that required intervention. CONCLUSION: Early adhesiolysis and drainage of fluid using medical thoracoscopy should be considered in patients with multiloculated complicated PPE after careful radiological (ultrasonography and CT) stratification, as a more cost-effective and safe method of management.

Yield of pleural biopsy in different types of tubercular effusions.

INTRODUCTION: The yield of mycobacteria is shown to be very low in pleural effusions as it is a pauci-bacillary disease. The present study looked at the yield of mycobacterium tuberculosis (MTB) in terms of GeneXpert for acid fast bacilli (AFB) and culture using a medical thoracoscopy guided biopsy and analysed whether the yield increases in more complicated effusions. MATERIALS AND METHODS: This is a retrospective analysis of patients who underwent medical thoracoscopy for tubercular pleural effusions at our institute over the last 5-years. Patients who had no or minimal thin septations were considered as simple effusions and were subjected to semi-rigid thoracoscopy (n = 61). While patients who had multiple loculations and thick septations were considered as complicated effusions and were subjected to rigid thoracoscopy (n = 64). We considered granuloma on a biopsy as the standard for diagnosis of Tuberculosis (TB). Xpert MTB/RIF and The BACTEC MGIT was used for culture. RESULTS: Out 125 patients with granulomatous inflammation on biopsy, 56 (44.8%) were positive for either GeneXpert or culture for MTB. Only GeneXpert was positive in 43 and only culture was positive in 13. Amongst 61 patients with simple effusion, 14 had either GeneXpert for AFB or AFB culture being positive and 9 out of these patients had GeneXpert for MTB detected on biopsy sample. Only culture was positive in 5 patients. In complicated pleural effusion group either GeneXpert or culture for mycobacterium was positive in 42 (65.6%) out of 64 patients. Only GeneXpert was positive in 34 and culture alone was positive in 8 patients. CONCLUSION: The yield of MTB increases as the pleural effusion becomes more complicated. GeneXpert in a biopsy sample is a useful marker for MTB yield especially in a complicated effusion.

Multiple sclerosis management during the COVID-19 pandemic.

BACKGROUND: People with multiple sclerosis (MS) may be at higher risk for complications from the 2019 coronavirus (COVID-19) pandemic due to use of immunomodulatory disease modifying therapies (DMTs) and greater need for medical services. OBJECTIVES: To evaluate risk factors for COVID-19 susceptibility and describe the pandemic's impact on healthcare delivery. METHODS: Surveys sent to MS patients at Cleveland Clinic, Johns Hopkins, and Vall d'Hebron-Centre d'Esclerosi Múltiple de Catalunya in April and May 2020 collected information about comorbidities, DMTs, exposures, COVID-19 testing/outcomes, health behaviors, and disruptions to MS care. RESULTS: There were 3028/10,816 responders. Suspected or confirmed COVID-19 cases were more likely to have a known COVID-19 contact (odds ratio (OR): 4.38; 95% confidence interval (CI): 1.04, 18.54). In multivariable-adjusted models, people who were younger, had to work on site, had a lower education level, and resided in socioeconomically disadvantaged areas were less likely to follow social distancing guidelines. 4.4% reported changes to therapy plans, primarily delays in infusions, and 15.5% a disruption to rehabilitative services. CONCLUSION: Younger people with lower socioeconomic status required to work on site may be at higher exposure risk and are potential targets for educational intervention and work restrictions to limit exposure. Providers should be mindful of potential infusion delays and MS care disruption.