The risk analysis index demonstrates exceptional discrimination in predicting frailty's impact on neurosurgical length of stay quality metrics.

BACKGROUND: Quality measures determine reimbursement rates and penalties in value-based payment models. Frailty impacts these quality metrics across surgical specialties. We compared the discriminatory thresholds for the risk analysis index (RAI), modified frailty index-5 (mFI-5) and increasing patient age for the outcomes of extended length of stay (LOS [eLOS]), prolonged LOS within 30 days (pLOS), and protracted LOS (LOS > 30). METHODS: Patients ≥18 years old who underwent neurosurgical procedures between 2012 and 2020 were queried from the ACS-NSQIP. We performed receiver operating characteristic analysis, and multivariable analyses to examine discriminatory thresholds and identify independent associations. RESULTS: There were 411,605 patients included, with a median age of 59 years (IQR, 48-69), 52.2% male patients, and a white majority 75.2%. For eLOS: RAI C-statistic 0.653 (95% CI: 0.652-0.655), versus mFI-5 C-statistic 0.552 (95% CI: 0.550-0.554) and increasing patient age C-statistic 0.573 (95% CI: 0.571-0.575). Similar trends were observed for pLOS- RAI: 0.718, mFI-5: 0.568, increasing patient age: 0.559, and for LOS>30- RAI: 0.714, mFI-5: 0.548, and increasing patient age: 0.506. Patients with major complications had eLOS 10.1%, pLOS 26.5%, and LOS >30 45.5%. RAI showed a larger effect for all three outcomes, and major complications in multivariable analyses. CONCLUSION: Increasing frailty was associated with three key quality metrics that is, eLOS, pLOS, LOS > 30 after neurosurgical procedures. The RAI demonstrated a higher discriminating threshold compared to both mFI-5 and increasing patient age. Preoperative frailty screening may improve quality metrics through risk mitigation strategies and better preoperative communication with patients and their families.

The Weight of Frailty in Neurosurgery Patients: Analyzing the Combined Effect of Frailty and Body Mass Index on 30-Day Postoperative Mortality.

OBJECTIVE: There is a rising prevalence of overweight and obese persons in the US, and there is a paucity of information about the relationship between frailty and body mass index. Therefore, we examined discrimination thresholds and independent relationships of the risk analysis index (RAI), modified frailty index-5 (mFI-5), and increasing patient age in predicting 30-day postoperative mortality. METHODS: This retrospective American College of Surgeons National Surgical Quality Improvement Program analysis compared all overweight or obese adult patients who underwent neurosurgery procedures between 2012 and 2020. We compared discrimination using receiver operating characteristic curve analysis for RAI, mFI-5, and increasing patient age. Furthermore, multivariable analyses, as well as subgroup analyses by procedure type i.e., spine, skull base, and other (vascular and functional) were performed, and reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 315,725/412,909 (76.5%) neurosurgery patients, with a median age of 59 years (interquartile range: 48-68), predominately White 76.7% and male 54.3%. Receiver operating characteristic analysis for 30-day postoperative mortality demonstrated a higher discriminatory threshold for RAI (C-statistic: 0.790, 95%CI: 0.782-0.800) compared to mFI-5 (C-statistic: 0.692, 95%CI: 0.620-0.638) and increasing patient age (C-statistic: 0.659, 95%CI: 0.650-0.668). Multivariable analyses showed a dose-dependent association and a larger magnitude of effect by RAI: frail patients OR: 11.82 (95%CI: 10.57-13.24), and very frail patients OR: 31.19 (95%CI: 24.87-39.12). A similar trend was observed in all subgroup analyses i.e., spine, skull base, and other (vascular and functional) procedures (P ≤ 0.001). CONCLUSIONS: Increasing frailty was associated with a higher rate of 30-day postoperative mortality, with a dose-dependent effect. Furthermore, the RAI had a higher threshold for discrimination and larger effect sizes than mFI-5 and increasing patient age. These findings support RAI's use in preoperative assessments, as it has the potential to improve postoperative outcomes through targeted interventions.

Immune Mediators Important for a Protective Secondary Response to Babesia microti.

Babesia microti (B. microti) is a tick-transmitted protozoan parasite that invades red blood cells. It is the primary cause of human babesiosis in the US. The severity of babesiosis caused by B. microti infection can range from asymptomatic to fatal. Risk factors for severe disease include general immune suppression, advanced age (>50) and lack of a spleen. However, severe disease can occur in the absence of any known risk factors. The degree to which tick-transmitted B. microti infection confers protection from subsequent exposure is largely unexplored. This is an important question as both the prevalence and geographic range of tick-transmitted B. microti infection continues to increase and individuals in endemic regions may have multiple exposures over their lifetime. In the current study we used a mouse model to evaluate the degree to which primary infection with B. microti protected against secondary challenge with the same parasite strain. We show that CD4 T cells, and to a lesser extent B cells, contribute to protection. However, mice exhibited significant protection from secondary parasite challenge even in the absence of either CD4 T cells or B cells. The protection mediated by CD4 T cells did not depend on their production of IFN-γ as mice with a targeted gene deletion for the IFN-γ receptor remained fully protected against secondary challenge. Other factors including inducible nitric oxide synthase (iNOS) and the adaptor protein MyD88, important for toll-like receptors, IL-18 and IL-1 signaling, were not important for protection against primary or secondary challenge with B. microti. Thus, our study shows that resolution of primary infection with B. microti results in robust protection against secondary challenge with parasites, at least in the short term. Further studies are needed to evaluate the length of protection and the degree to which protection is impacted by parasite heterogeneity. Although we show an important role for CD4 T cells in protection against secondary challenge, our results suggest that no single aspect of the immune system is solely responsible for adequate protection against secondary challenge with B. microti.

Effect of chronic antiplatelet therapy on clinical outcomes of endovascular thrombectomy for treatment of acute ischemic stroke.

OBJECTIVE: The objective of this study was to investigate the prognostic significance of chronic antiplatelet therapy (APT) usage in acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT). Long-term APT may enhance recanalization but may also predispose patients to an increased risk of hemorrhagic transformation. METHODS: Weighted hospitalizations for anterior-circulation AIS treated with EVT were identified in a large United States claims-based registry. Baseline clinical characteristics and outcomes were compared between patients with and without chronic APT usage prior to admission. Multivariable logistic regression analysis was performed to assess adjusted associations between APT and study endpoints. RESULTS: This analysis identified 36,560 patients, of whom 8170 (22.3%) were on a chronic APT regimen prior to admission. These patients were older and demonstrated a higher burden of comorbid disease, but had similar stroke severity on presentation in comparison with those not on APT. On unadjusted analysis, patients with prior APT demonstrated higher rates of favorable outcomes (24.3% vs 21.5%, p < 0.001), lower rates of mortality (7.0% vs 10.1%, p < 0.001), and lower rates of any intracranial hemorrhage (ICH; 20.3% vs 24.2%, p < 0.001), but no difference in rates of symptomatic ICH (sICH). Following multivariable adjustment for baseline clinical characteristics including age, acute stroke severity, and comorbidity burden, prior APT was associated with favorable outcome (adjusted odds ratio [aOR] 1.21, 95% CI 1.17-1.24, p < 0.001) and a lower likelihood of mortality (aOR 0.73, 95% CI 0.70-0.77, p < 0.001), without an increased likelihood of ICH (any ICH aOR 0.84, 95% CI 0.81-0.87, p < 0.001; sICH aOR 0.92, 95% CI 0.82-1.03, p = 0.131). CONCLUSIONS: Retrospective evaluation of patients with AIS treated with EVT using registry-based data demonstrated an association of prior APT usage with favorable outcomes, without an increased risk of hemorrhagic transformation.

Dural Closure Techniques and Cerebrospinal Fluid Leak Incidence After Resection of Primary Intradural Spinal Tumors: A Systematic Review.

STUDY DESIGN: This is a systematic review of primary intradural spinal tumors (PIDSTs) and the frequency of postoperative cerebrospinal fluid (CSF) leaks. OBJECTIVE: This study aimed to compare CSF leak rates among techniques for dural watertight closure (WTC) after the resection of PIDSTs. SUMMARY OF BACKGROUND DATA: Resection of PIDSTs may result in persistent CSF leak. This complication is associated with infection, wound dehiscence, increased length of stay, and morbidity. Dural closure techniques have been developed to decrease the CSF leak rate. METHODS: A PubMed search was performed in 2022 with these inclusion criteria: written in English, describe PIDST patients, specify the method of dural closure, report rates of CSF leak, and be published between 2015 and 2020. Articles were excluded if they had <5 patients. We used standardized toolkits to assess the risk of bias. We assessed patient baseline characteristics, tumor pathology, CSF leak rate, and dural closure techniques; analysis of variance and a 1-way Fisher exact test were used. RESULTS: A total of 4 studies (201 patients) satisfied the inclusion criteria. One study utilized artificial dura (AD) and fibrin glue to perform WTC and CSF diversion, with lumbar drainage as needed. The rate of CSF leak was different among the 4 studies (P=0.017). The study using AD with dural closure adjunct (DCA) for WTC was associated with higher CSF leak rates than those using native dura (ND) with DCA. There was no difference in CSF leak rate between ND-WTC and AD-DCA, or with any of the ND-DCA studies. CONCLUSIONS: After resection of PIDSTs, the use of autologous fat grafts with ND resulted in lower rates of CSF leak, while use of fibrin glue and AD resulted in the highest rates. These characteristics suggest that a component of hydrophobic scaffolding may be required for WTC. A limitation included articles with low levels of evidence. Continued investigation to understand mechanisms for WTC is warranted. LEVEL OF EVIDENCE: Level 3.

Bilateral Knee Lyme Arthritis in Children: A Report of 3 Cases.

CASES: Three patients presented with bilateral knee pain, effusion, decreased range of motion, and difficulty ambulating. Synovial analysis demonstrated leukocytosis in bilateral knees with positive serum enzyme-linked immunosorbent assay. All cases were managed with antibiotics and anti-inflammatories. One patient developed chronic Lyme arthritis and underwent arthroscopic synovectomy. CONCLUSION: Bilateral knee arthritis is a possible presentation of Lyme disease in children. Accurate diagnosis and treatment with antibiotics and anti-inflammatories can lead to satisfactory outcomes. Arthroscopic synovectomy may be indicated if conservative treatment fails.

Concomitant Ruxolitinib and Ibrutinib for Graft-Versus-Host Disease (GVHD): The First Reported Use in Pediatric Patients.

Allogeneic hematopoietic stem cell transplant (alloHSCT) can be a life-saving treatment for patients with hematological disorders but far too often carries the feared complication of graft-versus-host disease (GVHD). The first-line treatment of GVHD is typically corticosteroids, but steroid-refractory chronic GVHD (cGVHD) has led to the Food and Drug Administration (FDA) approval of ruxolitinib (Jakafi), ibrutinib (Imbruvica), and belumosudil (Rezurock). Patient 1 was a four-year-old female diagnosed with natural killer (NK) cell dysfunction who underwent alloHSCT with cells from a 9/10 National Marrow Donor Program (NMDP) donor and subsequently developed chronic GVHD (cGVHD) of the skin and gut. This cGVHD was refractory to steroids and ibrutinib but improved with the administration of concomitant ibrutinib and ruxolitinib. Patient 2 was a one-year-old male with sickle cell anemia. The patient was transplanted under a haploidentical protocol from the mother but developed bronchiolitis obliterans organizing pneumonia (BOOP) and pathology-confirmed GVHD. This cGVHD was steroid-refractory and resolved with the administration of concomitant ibrutinib and ruxolitinib. To our knowledge, this is the first reported use of concomitant ruxolitinib and ibrutinib in pediatric patients. The combination was well tolerated with no significant adverse events. Neither patient had to discontinue these drugs. We propose a further investigation into this dual therapy in cGVHD either compared to steroids or as a second-line option.

Systematic review of context-aware digital behavior change interventions to improve health.

Health risk behaviors are leading contributors to morbidity, premature mortality associated with chronic diseases, and escalating health costs. However, traditional interventions to change health behaviors often have modest effects, and limited applicability and scale. To better support health improvement goals across the care continuum, new approaches incorporating various smart technologies are being utilized to create more individualized digital behavior change interventions (DBCIs). The purpose of this study is to identify context-aware DBCIs that provide individualized interventions to improve health. A systematic review of published literature (2013-2020) was conducted from multiple databases and manual searches. All included DBCIs were context-aware, automated digital health technologies, whereby user input, activity, or location influenced the intervention. Included studies addressed explicit health behaviors and reported data of behavior change outcomes. Data extracted from studies included study design, type of intervention, including its functions and technologies used, behavior change techniques, and target health behavior and outcomes data. Thirty-three articles were included, comprising mobile health (mHealth) applications, Internet of Things wearables/sensors, and internet-based web applications. The most frequently adopted behavior change techniques were in the groupings of feedback and monitoring, shaping knowledge, associations, and goals and planning. Technologies used to apply these in a context-aware, automated fashion included analytic and artificial intelligence (e.g., machine learning and symbolic reasoning) methods requiring various degrees of access to data. Studies demonstrated improvements in physical activity, dietary behaviors, medication adherence, and sun protection practices. Context-aware DBCIs effectively supported behavior change to improve users' health behaviors.

Development of a novel, high-throughput screening tool for efficient perfusion-based cell culture process development.

Perfusion technology has been successfully used for the commercial production of biotherapeutics, in particular unstable recombinant proteins, for more than a decade. However, there has been a general lack of high-throughput cell culture tools specifically for perfusion-based cell culture processes. Here, we have developed a high-throughput cell retention operation for use with the ambr® 15 bioreactor system. Experiments were run in both 24 and 48 reactor configurations for comparing perfusion mimic models, media development, and clone screening. Employing offline centrifugation for cell retention and a variable volume model developed with MATLAB computational software, the established screening model has demonstrated cell culture performance, productivity, and product quality were comparable to bench scale bioreactors. The automated, single use, high-throughput perfusion mimic is a powerful tool that enables us to have rapid and efficient process development of perfusion-based cell culture processes.

Canopy structure affects temperature distributions and free convection in moss shoot systems.

PREMISE OF THE STUDY: Nonvascular plants play important roles in exchange of water and heat at the soil-atmosphere interface. Differential evaporative cooling may cause temperature gradients within bryophyte canopies, influencing convective heat and mass transport. Understanding mechanisms that affect fluxes through moss layers should improve models of forest floor function. METHODS: A three-dimensional thermal imaging system measured temperature distributions within moss shoot systems that were used to explore relationships among canopy structure, temperature gradients, evaporation, and conductance to water vapor (gs ). We studied five moss species under dark and light conditions in the lab. Also, these properties were measured in two species that differed in canopy structure during drying. KEY RESULTS: Differential evaporative cooling led to a 1.4 to 5.0°C range in shoot temperatures within canopies. Samples displayed -0.5 to -0.9°C/cm temperature gradients with cooler apical temperatures. Gradient magnitudes did not differ among species, but taller canopies expressed greater temperature differences. Light enhanced both the gradient and the temperature difference. Rates of evaporation were significantly related to canopy height in the light, but not in the dark, although gs was positively associated with canopy height in both. Rayleigh (Ra) numbers characterize whether temperature gradients likely generate free convection. In tall canopies, Ra numbers exceeded the value indicative of free convection and turbulent flow. As plants dried, temperature gradients decreased. CONCLUSIONS: When moss canopies are wet, cooler apical temperatures create thermal instabilities within the canopies that appear sufficient to enhance convective transport of water vapor and heat in tall canopies with low bulk density.