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Objective: To evaluate the safety of COVID-19 vaccines in patients with multiple sclerosis (MS) by assessing their impact on serum neurofilament light chain (sNfL) levels as a marker of neuroaxonal damage. Methods: Single-center observational longitudinal study including patients with MS who consecutively received their initial vaccination against SARS-CoV-2 at Hospital Universitario Ramón y Cajal, following the first national immunization program in Spain. Serum samples were collected at baseline and after receiving the second dose of the vaccine. sNfL levels were quantified using the single molecule array (SIMOA) technique. Adverse events, including clinical or radiological reactivation of the disease, were recorded. Results: Fifty-two patients were included (median age, 39.7 years [range, 22.5-63.3]; 71.2% female). After SARS-CoV-2 vaccination, no increased inflammatory activity, either determined by the presence of relapses and/or new MRI lesions and/or high sNfL levels, was detected. Accordingly, there was no difference between median sNfL levels before and after vaccination (5.39 vs. 5.76 pg/ml, p=0.6). Despite this, when looking at baseline patient characteristics before vaccination, younger age associated with disease activity after vaccination (OR 0.87, 95% CI: 0.77-0.98, p=0.022). Larger studies are needed to validate these results. Conclusion: COVID-19 vaccines did not cause reactivation of disease at a clinical, radiological or molecular level, thus suggesting that they are safe in MS patients.

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Introduction: Alemtuzumab is a highly effective pulsed immune reconstitution therapy for multiple sclerosis (MS). Aim: To evaluate serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) in patients with relapsing-remitting MS who have been treated with Alemtuzumab over the course of 2 years. Methods: This prospective study involved MS patients treated with Alemtuzumab at a referral MS center. Both sNfL and sGFAP were analyzed at baseline and then again at 6, 12, and 24 months post-treatment using the single molecule array (SiMoA) technique. We also recruited matched healthy controls (HCs) for comparison. Results: The study included 46 patients (with a median age of 34.2 [Interquartile range (IQR), 28.7-42.3] years, 27 of which were women [58%]) and 76 HCs. No differences in demographic characteristics were observed between patients and HC. The median disease duration was 6.22 (IQR, 1.56-10.13) years. The median annualized relapse rate before treatment was 2 (IQR, 1-3). At baseline, sNfL and sGFAP levels were higher in MS patients (median of 18.8 [IQR, 10.7-52.7] pg/ml and 158.9 [IQR, 126.9-255.5] pg/ml, respectively) when compared to HC (6.11 [IQR, 2.03-8.54] pg/ml and 91.0 [72.6-109] pg/ml, respectively) (p<0.001 for both comparisons). The data indicates that 80% of patients had high (≥10 pg/ml) sNfL values at baseline. We observed a significant decrease in sNfL levels at 6 (65%, p = 0.02), 12 (70.8%, p<0.001), and 24 (78.1%, p<0.001) months. sNfL reached similar levels to HC only after 24 months of Alemtuzumab treatment. During the follow-up period, no changes were identified in the sGFAP values. Conclusion: Alemtuzumab leads to the normalization of sNfL values in MS patients after 2 years of treatment, with no apparent effect on sGFAP values.

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BACKGROUND: Tapping speed (TS) correlates with baseline disability scales in people with multiple sclerosis (pwMS). OBJECTIVE: The study aimed to address if progression independent of relapse activity (PIRA) could be predicted by first-month measurement of TS. METHODS: Prospective study including pwMS in one referral MS center. Consecutive patients were included and keys/second (Keys/s) were passively measured each day using an in-house smartphone application for 1 month. Median, mean, and maximum keys/s were obtained. Multivariate logistic regression models (including keys/s, age, sex, and baseline disability scores) were obtained for prediction of a PIRA event after 1 year. RESULTS: Overall, 59 patients were included in the final analysis (64.4% women, median age of 44.5 years). However, 10 patients presented a PIRA event, without differences regarding baseline characteristics between PIRA and no-PIRA groups. PIRA group presented lower median keys/s (2 vs 4 keys/s, p = 0.002) and mean keys/s (2.8 vs 4.6, p = 0.008), while maximum keys/s were similar (p = 0.32). A median ⩽ 3 keys/s was independently associated with PIRA (aOR = 16.8, p = 0.03), as did a mean ⩽ 3.7 keys/s (aOR = 17, p = 0.02). These differences were not detected regarding other variables analyzed. CONCLUSION: Low median or mean keys/s obtained during initial month of assessment were indicative of a PIRA event within the next year.

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The potential of combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict disability worsening in multiple sclerosis (MS) remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their response to disease-modifying treatments (DMTs). This multicentre study, conducted across thirteen European hospitals, spanned from July 15, 1994, to August 18, 2022, with follow-up until September 26, 2023. We enrolled MS patients who had serum samples collected within 12 months from disease onset and before initiating DMTs. Multivariable regression models were used to estimate the risk of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and Expanded Disability Status Scale (EDSS) score of 3. Of the 725 patients included, median age was 34.2 years (IQR, 27.6-42.4), and 509 patients (70.2%) were female. Median follow-up duration was 6.43 years (IQR, 4.65-9.81). Higher sNfL values associated with an elevated risk of RAW (HR of 1.45; 95% CI 1.19-1.76; P < 0.001), PIRA (HR of 1.43; 95% CI 1.13-1.81; P = 0.003), and reaching an EDSS of 3 (HR of 1.55; 95% CI 1.29-1.85; P < 0.001). Moreover, higher sGFAP levels were linked to a higher risk of achieving an EDSS score of 3 (HR of 1.36; 95% CI 1.06-1.74; P = 0.02) and, in patients with low sNfL values, to PIRA (HR of 1.86; 95% CI 1.01-3.45; P = 0.04). We further examined the combined effect of sNfL and sGFAP levels. Patients with low sNfL and sGFAP values (NLGL) exhibited a low risk of all outcomes and served as reference. Untreated patients with high sNfL levels showed a higher risk of RAW, PIRA, and reaching an EDSS of 3. Injectable or oral DMTs reduced the risk of RAW in these patients but failed to mitigate the risk of PIRA and reaching an EDSS of 3. Conversely, high-efficacy DMTs counteracted the heightened risk of these outcomes, except for the risk of PIRA in patients with high sNfL and sGFAP levels. Patients with low sNfL and high sGFAP values (NLGH) showed an increased risk of PIRA and achieving an EDSS of 3, which remained unchanged with either high-efficacy or other DMTs. In conclusion, evaluating sNfL and sGFAP levels at disease onset in MS may identify distinct phenotypes associated with diverse immunological pathways of disability acquisition and therapeutic response.

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Background Applying topical vancomycin has shown a decrease in the likelihood of surgical site infections (SSIs) in surgeries linked to a heightened risk of severe and resistant infections. Nevertheless, the effectiveness of this prophylactic approach has not been assessed in open ankle surgeries with internal fixation. Objective This study aimed to assess whether topical vancomycin diminishes the risk of SSI in patients with ankle fractures undergoing open reduction with internal fixation. Methods A randomized, controlled, double-blind clinical trial was carried out. Patients were divided into two groups in a 1:1 ratio. The control group received the standard prophylactic treatment with IV cephalothin 1 g, while the intervention group was administered topical vancomycin (1 g) in addition to the standard prophylactic treatment. The main outcomes were the SSI rates at 14 days, 28 days, and three months post-surgery, based on relevant clinical signs and laboratory tests. Results One hundred thirty-two patients were randomized (51.2% female), with 66 subjects included in each intervention arm. A total of 97.7% of them completed the study. Both groups were homogeneous in baseline characteristics. There were two SSIs in both the vancomycin group (3.3%) and the control group (3.5%), with no statistical differences (p = 0.945). The microorganisms isolated as causal agents were Staphylococcus aureus and Acinetobacter baumannii. By the three-month follow-up, no infections were noted in both intervention groups. Conclusion These results indicate that the topical administration of vancomycin may not represent an advantage in preventing SSI in ankle fractures requiring open reduction with internal fixation at the three-month postoperative stage.

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Background: The objective was to compare dosimetry in left-sided breast cancer (LSBC) patients receiving deep inspiration breath hold (DIBH) radiotherapy (RT) with free-breathing (FB) treatment plans. Materials and methods: Voluntary DIBH with a spirometer-based video-assisted system and CT-simulation were performed under FB and DIBH conditions on 40 LSBC patients, segmented according Duane's atlas. IMRT plans kept the same dosimetric goals on FB and DIBH conditions. Target, lungs and heart volumes were measured. Planning target volume (PTV) dose distribution, organs at risk (OARs) dose/volume parameters, including cardiac substructures, were calculated. Results: Lungs and left-lung volumes increased in DIBH conditions (ΔV = 1637.8 ml ± 555.3 and 783.5 ml ± 286.4, respectively). Heart volume slightly decreased in apnea (p = 0.04), but target volumes, CTV and PTV were similar in FB or DIBH plans. PTV dose coverage was similar irrespective of respiratory conditions (median D50% = 41.1 Gy vs 41.0 Gy, p = 0.665; V95% = 96.9% vs. 97%). Mean dose for the whole heart (MHD), left ventricle (LV), and LV segments were significantly reduced in DIBH plans. V20 values for heart subvolumes were significantly different only for those that received considerable doses (apical and anterior). DIBH plans provided significantly smaller doses (Dmax, D2%, and V20) to the LAD artery. Conclusion: Important dosimetric improvements can be achieved with DIBH technique for LSBC patients, reducing the dose to the LAD artery and heart, particularly to the segments closer to the chest wall. Apical/anterior LV segments, should be considered as separate organ at risk in breast RT.

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OBJECTIVE: Gossip-evaluative talk about an absent third party-exists in surgical residency programs. Attending surgeons may engage in gossip to provide residents with feedback on performance, which may contribute to bias. Nevertheless, the perspectives of attending surgeons on gossip has not been studied. DESIGN: In this qualitative study, semi-structured interviews about gossip in surgical training were conducted with attending surgeons. We performed a reflexive thematic analysis of transcripts with a grounded theory approach to describe attendings' perceptions of their role in gossip within surgical residency. SETTING: Interviews were conducted from September 23, 2023, to November 27, 2023 via Zoom™. PARTICIPANTS: Eighteen surgery attendings associated with 7 surgical training programs were interviewed. RESULTS: Six themes were developed: 1) Attendings typically view gossip with a negative lens; thus, well-intended conversations about resident performance that meet the academic definition of gossip are not perceived as gossip; 2) Gossip can damage attendings' reputations as surgeons and educators; 3) Mitigating the negative impacts of gossip by maintaining accurate and objective standards of honest communication is hard; 4) Attendings express concerns about hearing other attendings' impressions of residents prior to formulating their own opinion; 5) The surgical hierarchy restricts the volume and content of gossip that reaches attendings, which may limit their knowledge of program culture; and 6) It is very difficult to mitigate gossip at the program level. Ultimately, attendings utilize gossip (e.g. triangulating their experience) with the goal of providing residents feedback. CONCLUSIONS: Defining important conversations about resident performance as gossip should not discourage these critically important conversations but rather underscore the importance of combating harmful gossip through 3 behaviors: 1) committing to objective communication; 2) limiting or reframing information about resident performance that is shared with attendings who have yet to formulate their own opinions; and 3) regulating gossip in particular high-stakes microenvironments (e.g. the operating room).

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The residency match process can be overwhelming. We are the Collaboration of Surgical Education Fellows (CoSEF), a multi-institutional group of surgical residents. Our perspectives represent our current experiences as residents at academic programs, but all authors recently underwent the general surgery resident interview and match process, during which they interviewed at programs of all kinds. Based on our collective experiences, we aim to highlight program attributes that applicants should consider to find their perfect match.

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Leukemia is a rare but fatal cancer of the blood. This cancer arises from abnormal bone marrow cells and requires prompt diagnosis for effective treatment and positive patient prognosis. Traditional diagnostic methods (e.g., microscopy, flow cytometry, and biopsy) pose challenges in both accuracy and time, demanding an inquisition on the development and use of deep learning (DL) models, such as convolutional neural networks (CNN), which could allow for a faster and more exact diagnosis. Using specific, objective criteria, DL might hold promise as a tool for physicians to diagnose leukemia. The purpose of this review was to report the relevant available published literature on using DL to diagnose leukemia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles published between 2010 and 2023 were searched using Embase, Ovid MEDLINE, and Web of Science, searching the terms "leukemia" AND "deep learning" or "artificial neural network" OR "neural network" AND "diagnosis" OR "detection." After screening retrieved articles using pre-determined eligibility criteria, 20 articles were included in the final review and reported chronologically due to the nascent nature of the phenomenon. The initial studies laid the groundwork for subsequent innovations, illustrating the transition from specialized methods to more generalized approaches capitalizing on DL technologies for leukemia detection. This summary of recent DL models revealed a paradigm shift toward integrated architectures, resulting in notable enhancements in accuracy and efficiency. The continuous refinement of models and techniques, coupled with an emphasis on simplicity and efficiency, positions DL as a promising tool for leukemia detection. With the help of these neural networks, leukemia detection could be hastened, allowing for an improved long-term outlook and prognosis. Further research is warranted using real-life scenarios to confirm the suggested transformative effects DL models could have on leukemia diagnosis.

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BACKGROUND: Latine people, comprising 18.5% of the US population, constitute the largest ethnic minority group, with nearly one-third self-identifying as having non-English language preference (NELP). Despite the importance of the telephone in health care access, there is limited understanding of how NELP patients navigate telephone calls with primary and specialty care clinics. OBJECTIVE: This qualitative study aims to capture how Spanish speakers with NELP characterize their telephone call experiences with primary and specialty care clinics. DESIGN: Semi-structured interviews were conducted with 24 Spanish-speaking participants from primary care clinics with a sizeable proportion of patients who prefer to communicate in a language other than English at an urban academic medical center in Boston, MA. PARTICIPANTS: Participants were selected from primary care clinics that were well-equipped to serve Spanish-speaking patients. A total of 24 Spanish-speaking patients with NELP, mainly women (83%), with a mean age of 55.8 years, participated. They represented diverse countries of origin, with an average length of time in the USA of 21.7 years. APPROACH: Interview questions prompted participants to describe their telephone call experiences with front desk staff, with attention to interpreter availability, ancillary assistance, health outcomes stemming from a lack of language services, and emotional consequences of language discordance on calls. KEY RESULTS: Patients perceived primary care clinics as providing familiarity and language concordance during telephone interactions, contrasting with specialty care clinics, seen as sources of monolingual English communication. Participants utilized various strategies, such as requesting interpreters, using concise English phrases, or seeking assistance from acquaintances, relatives, or primary care clinic staff, to mitigate language barriers. CONCLUSIONS: The findings underscore significant challenges faced by Spanish-speaking patients with NELP in ambulatory specialty care telephone calls. The study emphasizes the importance of creating inclusive multilingual telephone environments, standardizing interpreter access, and reflecting the diversity of the communities served.

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The reduction in sea ice cover with Arctic warming facilitates shipping through remarkably shorter shipping routes. Automatic identification system (AIS) is a powerful data source to monitor Arctic Ocean shipping. Based on the AIS data from an online platform, we quantified the spatial distribution of shipping through this area, its intensity, and the seasonal variation. Shipping was heterogeneously distributed with power-law exponents that depended on the vessel category. We contextualized the estimated exponents with the analytical distribution of a transit model in one and two dimensions. Fishing vessels had the largest spatial spread, while narrower shipping routes associated with cargo and tanker vessels had a width correlated with the sea ice area. The time evolution of these routes showed extended periods of shipping activity through the year. We used AIS data to quantify recent Arctic shipping, which brings an opportunity for shorter routes, but likely impacting the Arctic ecosystem.

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In light of the post-genomic era, epigenetics brings about an opportunity to better understand how the molecular machinery works and is led by a complex dynamic set of mechanisms, often intricate and complementary in many aspects. In particular, epigenetics links developmental biology and genetics, as well as many other areas of knowledge. The present work highlights substantial scopes and relevant discoveries related to the development of the term from its first notions. To our understanding, the concept of epigenetics needs to be revisited, as it is one of the most relevant and multifaceted terms in human knowledge. To redirect future novel experimental or theoretical efforts, it is crucial to compile all significant issues that could impact human and ecological benefit in the most precise and accurate manner. In this paper, the reader can find one of the widest compilations of the landmarks and epistemic considerations of the knowledge of epigenetics across the history of biology from the earliest epigenetic formulation to genetic determinism until the present. In the present work, we link the current body of knowledge and earlier pre-genomic concepts in order to propose a new definition of epigenetics that is faithful to its regulatory nature.

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The detrimental effects of ultraviolet radiation (UVR) on human skin are well-documented, encompassing DNA damage, oxidative stress, and an increased risk of carcinogenesis. Conventional photoprotective measures predominantly rely on filters, which scatter or absorb UV radiation, yet fail to address the cellular damage incurred post-exposure. To fill this gap, antioxidant molecules and DNA-repair enzymes have been extensively researched, offering a paradigm shift towards active photoprotection capable of both preventing and reversing UV-induced damage. In the current review, we focused on "active photoprotection", assessing the state-of-the-art, latest advancements and scientific data from clinical trials and in vivo models concerning the use of DNA-repair enzymes and naturally occurring antioxidant molecules.

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Digital health has the potential to expand health care and improve outcomes for patients-particularly for those with challenges to accessing in-person care. The acceleration of digital health (and particularly telemedicine) prompted by the Coronavirus-19 (COVID-19) pandemic facilitated continuity of care in some settings but left many health systems ill-prepared to address digital uptake among patients from underserved backgrounds, who already experience health disparities. As use of digital health grows and the digital divide threatens to widen, healthcare systems must develop approaches to evaluate patients' needs for digital health inclusion, and consequentially equip patients with the resources needed to access the benefits of digital health. However, this is particularly challenging given the absence of any standardized, validated multilingual screening instrument to assess patients' readiness for digital healthcare that is feasible to administer in already under-resourced health systems. This perspective is structured as follows: (1) the need for digital health exclusion risk screening, (2) our convening as a group of stakeholders, (3) our review of the known digital health screening tools and our assessment, (4) formative work with patients regarding their perceptions on language and concepts in the digital health screening tools, and (5) conclusion with recommendations for digital health advocates generated by this collaborative of digital health researchers and operations leaders. There is a need to develop a brief, effective tool to screen for digital health use that can be widely implemented in diverse populations. We include lessons learned from our experiences in developing and testing risk of digital health exclusion screening questions in our respective health systems (e.g., patient perception of questions and response options). Because we recognize that health systems across the country may be facing similar challenges and questions, this perspective aims to inform ongoing efforts in developing health system digital exclusion screening tools and advocate for their role in advancing digital health equity.

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Multiple studies have shown the importance of blood-based biomarkers indicating axonal damage (serum neurofilament light chains [sNfL]) or astroglia activation (serum glial fibrillary acidic protein [sGFAP]) for monitoring different neurological diseases. However, normal values of these variables remain to be clearly defined, partly due to the influence of different demographic factors. We investigated demographic differences in a cohort of healthy volunteers. A cross-sectional study was conducted including 116 healthy controls with ages between 18 and 69 years (67.5% females; n = 79). sNfL and sGFAP concentrations were measured using single-molecule arrays. Age and body mass index affected sNfL values, and age was found to be the most important factor. The normal values changed with age, and we established normal values for individuals younger than 45 years as <10 pg/mL and for controls older than 45 years as <15 pg/mL. We established normal values at <10 pg/mL for individuals younger than 45 years and <15 pg/mL for older individuals. Alternatively, a Z-score of 1.5 was relevant for all controls. sGFAP was only affected by age. Differences in normal values were evident by 55 years. The highest normality limit for sGFAP was 140 pg/mL for controls under 55 years and 280 for older controls. We defined normal levels for sNfL and sGFAP and their corresponding age-associated changes. These data may contribute to the application of such variables in clinical practice.

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