Citations

Background: Static ice storage (SIS) has long been accepted as the conventional lung preservation method, assuming to maintain 4 °C temperature. Although never directly confirmed by temperature measurements, this assumption has been widely accepted. We aimed to measure lung and preservation temperature with SIS in porcine experiments and clinical observations. Methods: Porcine lungs were preserved with SIS for 8 h (group I, n = 3) and 3 h followed by 10 °C storage (group II, n = 3). Tissue (tissueT°), first bag preservation solution (psT°) and second bag saline (salineT°) temperature were monitored. In clinical lungs (n = 4), psT° was monitored during SIS. Surface (surfaceT°) and core (coreT°) temperature were assessed before and after SIS (n = 62). Results: After 4 h in porcine lung group I, average tissueT° was 0.66 °C, psT° was 0.12 °C and salineT° was −0.02 °C. After 3 h in group II, average tissueT° was 1.90 °C, psT° was 0.57 °C and salineT° was 2.33 °C. In clinical observations, psT° was below 4 °C after 9–13 min and 0 °C after 78–267 min. After SIS, median surfaceT° was 1.25 °C (min-max; −3.2–9.2 °C) and coreT° was 1.45 °C (−0.4–4.8 °C). Conclusions: SIS leads to rapid temperature drops below 4 °C, approaching 0 °C within 2–4 h. The post-SIS lung temperature shows considerable variability and does not consistently remain at the commonly assumed 4 °C, posing potential freezing injury to donor lungs.

Abstract There are multiple underlying etiologies of patellar instability including both osseous and soft‐tissue factors. Obligate flexion dislocation consists of lateral dislocation of the patella, occurring each time the knee flexes. This generally results from a predominantly lateral contracture of the extensor mechanism and can be technically challenging to manage. Quadricepsplasty can be of particular clinical utility for obligate flexion dislocation and constitutes a realignment of the proximal soft‐tissue attachments of the patella. The described technique features isolation of the 4 muscles of the quadriceps and subsequent stepwise lengthening of the vastus lateralis, advancement of the vastus medialis obliquus, and Z‐lengthening of the rectus femoris and vastus intermedius. This technique can be used in isolation or in combination with other procedures, such as medial patellofemoral ligament reconstruction, to surgically address patellofemoral maltracking. Technique Video video See video under supplementary data.

Abstract Despite the availability of effective vaccines and a recent decrease in annual deaths, COVID-19 remains a leading cause of death. Serological studies provide insights into host immunobiology of adaptive immune response to infection, which holds promise for identifying high-risk individuals for adverse COVID-19 outcomes. We investigated correlates of anti-nucleocapsid antibody responses following SARS-CoV-2 infection in a US population-based meta-cohort of adults participating in longstanding National Institutes of Health–funded cohort studies. Anti-nucleocapsid antibodies were measured from dried blood spots collected between February 2021 and February 2023. Among 1419 Collaborative Cohort of Cohorts for COVID-19 Research participants with prior SARS-CoV-2 infection, the mean age (standard deviation) was 65.8 (12.1), 61% were women, and 42.8% self-reported membership in a race/ethnicity minority group. The proportion of participants reactive to nucleocapsid peaked at 69% by 4 months after infection and waned to only 44% ≥12 months after infection. Higher anti-nucleocapsid antibody response was associated with older age, Hispanic or American Indian Alaskan Native (vs White) race/ethnicity, lower income, lower education, former smoking, and higher anti-spike antibody levels. Asian race (vs White) and vaccination (even after infection) were associated with lower nucleocapsid reactivity. Neither vaccine manufacturer nor common cardiometabolic comorbidities were not associated with anti-nucleocapsid response. These findings inform the underlying immunobiology of adaptive immune response to infection, as well as the potential utility of anti-nucleocapsid antibody response for clinical practice and COVID-19 serosurveillance.

BACKGROUND: Spinal cord involvement is infrequently reported in primary central nervous system vasculitis (PCNSV). This study describes the clinical findings, therapeutic responses, and outcomes of spinal cord involvement in a large cohort of patients with PCNSV. METHODS: We retrospectively studied 216 consecutive patients with PCNSV evaluated at the Mayo Clinic from 1983 to 2023. Spinal cord involvement was documented by histological examination or imaging. The clinical, laboratory, radiological, and pathological findings, along with management and outcomes, were compared between patients with and without spinal cord involvement. RESULTS: Of 216 patients, 10 (4.6%) had spinal cord involvement, with cerebral involvement in 9 cases. One patient (0.5%) had isolated spinal cord vasculitis. Histological evidence of vasculitis was found in all 10, with necrotizing vasculitis in 5 (50%). Magnetic resonance imaging showed thoracic abnormalities in 8 patients, cervical spine involvement in 2, conus medullaris involvement in 3, and cauda equina enhancement in 4. Compared with the 206 patients without spinal cord involvement, those with spinal cord vasculitis were more likely to present with paraparesis/tetraparesis ( P <0.001) and necrotizing vasculitis ( P =0.01) and less likely with hemiparesis ( P =0.006) and granulomatous vasculitis ( P =0.03). Patients with spinal cord involvement were more likely to have at least 1 relapse ( P <0.001) or more ( P <0.001). No differences between the 2 groups were observed regarding long-term remission, therapy response, and high disability scores (modified Rankin Scale score, 4–6) or death at last follow-up. Spinal cord involvement was associated with meningeal enhancement on brain imaging (odds ratio, 10.50) and the presence of lymphoma (odds ratio, 6.49), specifically Hodgkin lymphoma diagnosed simultaneously with PCNSV. Spinal involvement was negatively associated with increasing age (odds ratio, 0.64) and cerebral infarction on imaging (odds ratio, 0.08). CONCLUSIONS: Spinal cord involvement defines a distinct subset of patients with PCNSV.

ABSTRACTObjectiveIntrathecal fluorescein (IF) is effective for localizing nasal cerebrospinal fluid (CSF) leaks along the skull base during endoscopic exploration, with largest studies reporting sensitivities ranging from 66%–93%. Due to reports of intraoperative and postoperative neurologic complications such as seizures and paralysis, surgeons often dilute the fluorescein and inject it intrathecally slowly over a variable amount of time. However, no study has assessed whether rapid IF administration causes the aforementioned risks or whether it affects its accuracy in identifying CSF leaks intraoperatively.MethodsA prospective study was conducted from 2015 to 2024, where all patients undergoing endoscopic exploration and/or repair of CSF rhinorrhea had 0.1 mL of 10% fluorescein (10 mg) mixed with 3–5 mL of patients' CSF injected rapidly via the lumbar drain over a few seconds.ResultsOf the 82 included patients, the mean age was 53.8 ± 15.2 years, and 84% were female. Sixty‐nine patients underwent successful endoscopic CSF leak repairs, and 13 had negative endoscopic explorations. Rapid IF injection was 80% sensitive (20% false negative rate) and 100% specific for identifying CSF leaks, and it caused no seizures, paralysis, or other neurologic complications.ConclusionCompared to prior reports of slow low‐dose IF injection for CSF leak localization, rapid IF injection yielded similar efficacy (80% sensitivity) with no IF‐related complications. Rapid IF injection was safe and effective but should be corroborated by future studies.Level of Evidence4.

Thrombospondin-2 (THBS2) is a prevailing prognostic biomarker implicated in different cancer types, such as deadly colorectal, pancreas, and triple-negative breast cancers. While the current methods for cancer-relevant protein detection, such as enzyme-linked immunosorbent assay (ELISA), mass spectrometry, and immunohistochemistry, are feasible at advanced stages, they have shortcomings in sensitivity, specificity, and accessibility, particularly at low concentrations in complex biological fluids for early detection. Here, we propose and demonstrate a modular, in-solution assay design concept, Nanoparticle-Supported Rapid Electronic Detection (NasRED), as a versatile cancer screening and diagnostic platform. NasRED utilizes antibody-functionalized gold nanoparticles (AuNPs) to capture target proteins from a minute amount of sample (<10 µL) and achieve optimal performance with a short assay time by introducing active fluidic forces that act to promote biochemical reaction and accelerate signal transduction. This rapid (15 min) process serves to form AuNP clusters upon THBS2 binding and subsequently precipitate such clusters, resulting in color modulation of the test tubes that is dependent on the THBS2 concentration. Finally, a semiconductor-based, portable electronic device is used to digitize the optical signals for the sensitive detection of THBS2. High sensitivity (femtomolar level) and a large dynamic range (five orders of magnitude) are obtained to analyze THBS2 spiked in PBS, serum, whole blood, saliva, cerebrospinal fluids, and synovial fluids. High specificity is also preserved in differentiating THBS2 from other markers such as cancer antigen (CA) 19-9 and bovine serum albumin (BSA). This study highlights NasRED’s potential to enhance cancer prognosis and screening by offering a cost-effective, accessible, and minimally invasive solution.

Extramedullary multiple myeloma (EMM), defined in this review as soft tissue plasmacytomas resulting from hematogenous spread, is characterized by the ability of MM cells to proliferate outside of the bone marrow microenvironment. It is aggressive, often associated with high-risk cytogenetics and early relapse, and independently portends significantly shorter progression-free and overall survival, even in the era of highly effective immunotherapies. The molecular and microenvironmental factors underlying extramedullary MM dissemination continue to be studied to inform the development of better treatments. In this review, we discuss our current understanding of the biology of EMM, focusing on its distinct molecular and microenvironmental characteristics vis-à-vis MM. We also review the current treatment strategies, acknowledging the paucity of large, randomized studies specific to this population.

Interest in Current Good Manufacturing Practices (cGMP)-grade extracellular vesicles (EVs) is expanding. Some obstacles in this new but rapidly growing field include a lack of standardization and scalability. This review focuses on automated biomanufacturing of EVs in conditioned media collected from cultured mesenchymal stromal cells (MSCs). Different automated cell culture systems are discussed, including factors affecting EV quantity and quality, isolating EVs manufactured in an automated system, and validations needed. The ultimate goal when manufacturing cGMP-grade EVs is to identify a specific application and characterize the EV population in detail. This is achieved by validating every step of the process, choosing appropriate release criteria, and assuring batch-to-batch consistency. Due to the lack of standards in the field, it is critical to ensure that the cGMP-grade EVs meet FDA standards pertaining to identity, reproducibility, sterility, safety, purity, and potency. A closed-system automated bioreactor can be a valuable tool to generate cGMP-EVs in a scalable, economical, and reproducible manner.

Abstract Background The treatment of locally advanced rectal cancer now includes “watch-and-wait” (WW) management for patients who exhibit a clinical complete response (cCR) to total neoadjuvant therapy (TNT). We assessed patients’ knowledge and preferences regarding WW with the goal of incorporating patient input into clinical trial design. Methods Rectal cancer patients in advocacy groups (COLONTOWN/Rectalburgh and Fight CRC) were surveyed regarding perceptions about treatment strategies, tolerable risks of treatment failure, and preferences on clinical trial design. Surveys were initially distributed in 2019, with the shift toward WW prompting re-survey of select questions in 2023. Results All respondents preferred enrollment in trials that incorporated patient input. Most respondents (76%) preferred treatment that incorporated chemotherapy escalation over radiation escalation. Furthermore, when presented with a hypothetical patient who developed a cCR after chemoradiation (without the option for WW), 58% of patients chose surgical treatment (with 100% risk of permanent ostomy and 80% chance of cure) over omission of surgery (with &lt;80% chance of cure). In contrast, when the hypothetical patient developed a cCR after TNT (with an option for WW), 82% of patients opted for selective WW over surgery. Conclusions This work successfully integrated patient advocacy groups as a resource for obtaining patient input. Surveys revealed patients had a strong preference for chemotherapy escalation, for selective WW when offered, and for incorporation of input into future clinical trial design. These findings describe how well-informed patients approach complex medical decision-making and serve as a starting point for future studies seeking to incorporate patient voices.