Citations

Abstract Home parenteral nutrition (HPN) is a life‐sustaining therapy traditionally used as a bridge to enteral autonomy or intestinal transplantation. Increasingly, it is used for intractable feeding intolerance (IFI), which can occur near the end of life (EOL) in children with severe neurological impairment (SNI). In these cases, HPN use differs from its historical role and requires tailored outpatient planning. We report a retrospective case series of four children with SNI who developed IFI and received HPN as part of their EOL care. The pediatric palliative care team (PPCT) was involved in all cases during HPN decision‐making and planning. The pediatric nutrition support team (PNST) and PPCT collaborated to provide individualized, goal‐directed care. Patients ranged from 1 to 12 years old, with HPN durations between 5 weeks and 2 years. All were enrolled in hospice while receiving HPN. Plans were made through shared decision‐making, reflecting each family's values, and included tailored approaches to laboratory monitoring, febrile episodes, line care, growth assessment, and follow‐up. HPN at EOL requires careful ethical consideration, particularly of autonomy because families often find comfort in providing nutrition. IFI is often unanticipated, and prognoses are uncertain. With the combined expertise of PNST and PPCT, HPN can be used meaningfully at EOL, supporting family values, easing suffering, and creating space for peace and connection.

Background and Purpose Informed consent (IC) practices for endovascular thrombectomy (EVT) in acute stroke are not well elucidated. We investigated the roles and specialties of those obtaining EVT IC, aiming to provide insights for enhancing the process. Methods We conducted a survey from July- December 2023 among acute stroke care clinicians. Utilizing Qualtrics, we disseminated a questionnaire through various national and international online platforms. This analysis summarizes the characteristics of individuals who obtain IC at respondents’ institution. Results Among 168 respondents, 71% were staff physicians, 70% practiced in the US and 70% worked at academic centers. Neurology (77%) was the most common specialty obtaining EVT IC, followed by neurosurgery (41%), radiology (30%) and emergency medicine (EM) (10%). Staff physicians were the most frequently involved (61%), followed by fellows (43%), residents (48%) and advanced practice providers (APPs) (36%). Comparatvely, non-US institutions were more likely to utilize neurologists alone (50% vs 31%, P = 0.016) and staff physicians (76% vs 54%, P = 0.008), while US institutions more often utilized neurosurgeons (51% vs 18%, P < 0.001), APPs (43% vs 18%, P = 0.002) and residents (56% vs 28%, P = 0.001). Non-academic institutions used EM (25% vs 5%, P < 0.001) and APPs (50% vs 31%, P = 0.031), while academic institutions commonly utilized neurosurgeons (48% vs 18%, P = 0.001), residents (59% vs 13%, P < 0.001) and fellows (52% vs 18%, P < 0.001). Conclusion Neurologists and staff physicians are the primary providers obtaining EVT IC, with variations based on region and institution type. Future efforts to optimize the IC process should integrate various specialties and be widely adaptable.

ABSTRACT Beyond the arboviruses they transmit to humans and animals, mosquitoes harbour diverse viral communities that shape infection and immunity dynamics. Understanding how these communities shift within mosquito populations across time and space has important implications for how we anticipate and manage arboviral disease epidemics. Here, we examined the viromes of rural and sylvatic mosquito species sampled longitudinally across two years from countries representing South America, Africa, and Southeast Asian geographies to quantify the relative contributions of host and ecological factors in shaping their virome dynamics. We found that virus diversity and virome composition are strongly influenced by host phylogeny and spatial factors and show limited temporal variation. By examining virus similarity networks across mosquito species and biogeographies, we observed frequent instances of within- and cross-genus Culex - Anopheles virus sharing in Madagascar. Taken together, these findings inform the development and implementation strategies of any virome-based vector control technology and raise new evolutionary questions on how host generalism shapes the spatial prevalence of viruses and their potential for disease emergence.

OBJECTIVE: To identify distinct phenotypes of acute respiratory distress syndrome (ARDS) developing after hematopoietic cell transplantation (HCT), using routinely available clinical data at ICU admission. DESIGN: Multicenter retrospective cohort study using latent class analysis. SETTING: ICUs across three Mayo Clinic campuses (Minnesota, Florida, and Arizona). PATIENTS: A total of 166 adult patients who developed ARDS within 120 days following HCT (96 allogeneic, 70 autologous). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Model selection was based on multiple metrics including Bayesian information criteria, entropy, and Vuong-Lo-Mendell-Rubin Likelihood Ratio testing. A two-class model optimally described the cohort. Class 1 (n = 81) was characterized by worse hypoxemia (P/F ratio 157 vs. 210, p = 0.002), higher Pco 2 (41 vs. 36 mm Hg, p < 0.001), and higher bilirubin (1.4 vs. 0.9 mg/dL, p < 0.001) compared with class 2 (n = 85). Both classes included a mix of transplant types, transcending a simple autologous/allogeneic dichotomy, although class 1 had more allogeneic recipients (70.4% vs. 45.9%, p = 0.001). Although time-from-transplant was not a class-defining variable, class 1 occurred later after transplant (30.0 vs. 11.9 d, p < 0.001) with higher frequency of idiopathic pneumonia syndrome (14.8% vs. 2.4%, p = 0.004). Class 2 had more frequent neutropenia (leukocytes 0.4 vs. 5.9 × 109, p < 0.001) and higher frequency of peri-engraftment respiratory distress syndrome (29.4% vs. 9.9%, p = 0.005). Outcomes were significantly worse for class 1 (90-d mortality: 72.8% vs. 48.2%, p = 0.001). An exploratory parsimonious model had good classification accuracy (0.90) using just six variables: leukocyte count, platelet count, bilirubin, Pco 2, body mass index, and temperature. CONCLUSIONS: ARDS after HCT comprises two distinct phenotypes with distinct clinical characteristics and outcomes. These phenotypes align with recognized post-HCT lung injury syndromes and may reflect different underlying biological processes. This framework provides a foundation for investigating targeted therapeutic approaches.

OBJECTIVE The role of amputation and myoelectric prosthetic fitting for hand function in traumatic pan–brachial plexus injury (pBPI) continues to evolve. This study evaluated the function and activity performance of patients with traumatic pBPI who underwent amputation and prosthetic fitting with a myoelectric prosthesis (MEP) for hand function. METHODS A retrospective analysis of adult patients who underwent elective amputation after sustaining a pBPI followed by MEP for hand function was performed. Demographics, mechanisms of injury, amputation details, and outcomes were collected from medical records. The Disabilities of the Arm, Shoulder and Hand (DASH) outcome measure was used to evaluate the impact of impairment, the visual analog scale (VAS) to assess pain, and the Activities Measure for Upper Limb Amputees (AM-ULA) to determine functional activity performance pre- and post-MEP usage. Follow-up time, prosthesis usage, satisfaction, and site of electrical signal used were recorded. Paired t-tests were used to compare outcomes. RESULTS Twenty-one adult patients with pBPI (90% male, mean age 32 years at the time of BPI) underwent amputations and were fitted with MEPs for hand function controlled by nonintuitive signals. Fifteen patients underwent a trans-radial amputation and 6 underwent a trans-humeral amputation. While all patients sought improved terminal grasp function, 3 patients subsequently declined prosthetic fitting after amputation. Of the 18 patients who underwent myoelectric prosthetic hand fittings, linear transducers activated by the contralateral shoulder protraction were used in 66% of patients, and traditional electrode signals from ipsilateral nonintuitive muscle were used in 33% to control MEP grasp function. Disability (DASH) and pain (VAS) scores significantly improved after amputation (p = 0.04 and p < 0.01, respectively). AM-ULA scores showed a significant improvement in activity performance after application of the MEP, with an average increase of 23 points from 0 points on a 40-point scale before amputation and prosthetic fitting (p < 0.0001). Daily users of the MEP averaged 6 hours per day and reported the prosthesis was useful during daily activities with great satisfaction at an average of 22 months of follow-up. CONCLUSIONS Amputation followed by MEP fitting in adult traumatic pBPI significantly improved function, reduced pain, and had a high prosthetic usage. The AM-ULA, a tool for quantitatively evaluating activity performance, was applied to measure the bimanual functional activity performance of patients before and after using MEPs, which revealed a significant improvement. Patients reported using their prosthetics daily with a high satisfaction rate with functional terminal grasp and release.

OBJECTIVE Open resective surgery (ORS) has become the standard of care for focal drug-resistant epilepsy (DRE). However, minimally invasive surgical alternatives, such as laser interstitial thermal therapy (LITT), have also been shown to be safe and effective. A meta-analysis comparing both treatments is warranted to assess the benefits of each modality for focal DRE. METHODS A literature search was conducted until March 14, 2024, to identify studies comparing LITT and ORS in patients with DRE. The primary outcomes included seizure freedom (SF), length of hospital stay (LHS), and complication rate (CR). Subgroup analyses were performed based on age, epilepsy etiology, and propensity score–matched (PSM) studies. RESULTS Of 558 articles, 15 cohort studies met the authors’ inclusion criteria, encompassing 3873 patients for analysis. The rate of SF in the LITT group was 52.5% (95% CI 0.453–0.597, I 2 = 47.4%) and 67.1% (95% CI 0.602–0.739, I 2 = 57.4%) for the ORS group. LITT showed a significantly lower rate of SF compared to ORS (risk ratio [RR] 0.78, 95% CI 0.70–0.88, p ≤ 0.0001). However, when PSM studies (RR 0.85, 95% CI 0.63–1.15, p = 0.30) and studies on patients with temporal lobe epilepsy (TLE) (RR 0.88, 95% CI 0.67–1.14, p = 0.34) were analyzed, the SF rates were similar. Patients who underwent LITT had a significantly shorter LHS (mean difference 2.95 days, 95% CI 1.12–4.78, p < 0.00001), lower CR (RR 0.54, 95% CI 0.37–0.79, p < 0.002, I 2 = 32%), lower rate of ischemic stroke (RR 0.15, 95% CI 0.04–0.65, p = 0.01), and lower rate of permanent neurological deficits (RR 0.13, 95% CI 0.05–0.36, p < 0.0001). CONCLUSIONS Across unmatched studies evaluating focal DRE, ORS showed a higher rate of SF. However, pooled matched-cohort analyses showed no difference between interventions in achieving SF, a trend also noted in the authors’ PSM TLE sample. LITT, however, offered significantly shorter LHS and lower CRs. Future prospective studies should match patient populations to control for confounding factors and assess key outcomes, such as postoperative neurocognitive follow-up and quality of life measurements, in order to fully evaluate the risks and benefits of each approach.

Selective inhibitors are essential for targeted therapeutics and for probing enzyme functions in various biological systems. The two main challenges in identifying such protein‐based inhibitors lie in the extensive experimental effort required, including the generation of large libraries, and in tailoring the selectivity of inhibitors to enzymes with homologous structures. To address these challenges, machine learning (ML) is being used to improve protein design by training on targeted libraries and identifying key interface mutations that enhance affinity and specificity. However, such ML‐based methods are limited by inaccurate energy calculations and difficulties in predicting the structural impacts of multiple mutations. Here, we present an ML‐based method that leverages HTS data to streamline the design of selective protease inhibitors. To demonstrate its utility, we applied our new method to find inhibitors of matrix metalloproteinases (MMPs), a family of homologous proteases involved in both physiological and pathological processes. By training ML models on binding data for three MMPs (MMP‐1, MMP‐3, and MMP‐9), we successfully designed a novel N‐TIMP2 variant with a differential specificity profile, namely, high affinity for MMP‐9, moderate affinity for MMP‐3, and low affinity for MMP‐1. Our experimental validation showed that this novel variant exhibited a significant specificity shift and enhanced selectivity compared with wild‐type N‐TIMP2. Through molecular modeling and energy minimization, we obtained structural insights into the variant's enhanced selectivity. Our findings highlight the power of ML‐based methods to reduce experimental workloads, facilitate the rational design of selective inhibitors, and advance the understanding of specific inhibitor–enzyme interactions in homologous enzyme systems.

This study presents the first in vivo intraoperative measurement of the kinetic properties of spastic human muscle. Despite slower relaxation in spastic biceps, the force-frequency relationship was similar to that of the healthy gracilis muscle. This suggests that spasticity does not substantially alter frequency-dependent force summation, possibly due to similar fiber-type compositions and limited changes in calcium handling or myosin isoforms in human spastic muscle.