Initial Weeks Research Articles

The effect of implementing a dialysis start unit on modality decision among patients with unplanned start kidney replacement therapy.

Many individuals start dialysis in an acute setting with suboptimal pre-dialysis education. These individuals are often treated with central venous catheter insertion and initiation of in-center hemodialysis and only a minority will transfer to a home-based therapy. The dialysis start unit is a program performing in-center hemodialysis in a separate space while providing support and education on chronic kidney disease and treatment options in the initial weeks of kidney replacement therapy. We aimed to assess the uptake of home dialysis therapies between 2013 and 2021 among patients who started acute inpatient hemodialysis at University Health Network, Toronto and underwent dialysis at the dialysis start unit. This is a retrospective observational cohort study based on prospectively collected data. Patients' demographics were obtained from electronic charts. In the dialysis start unit, all patients received dialysis modality education by a nurse educator, dedicated home dialysis nurses, and the allied health care team. During 2013-2021, 122 patients were dialyzed in the dialysis start unit and included in the study. Among those patients, 68 patients ultimately chose home dialysis (57 peritoneal dialysis and 11 home hemodialysis). Fifty-four patients continued in-center hemodialysis. Patients adopting home dialysis were less likely to have diabetes and hypertension as the etiology of kidney failure and more likely to have glomerulonephritis or vasculitis. Dialysis modality education is implementable in advanced chronic kidney disease. Individualized education and care after unplanned start dialysis can potentially enhance home dialysis choice and utilization.

Subchronic particulate matter exposure underlying polyhexamethylene guanidine phosphate–induced lung injury: Quantitative and qualitative evaluation with chest computed tomography

Our study was to explore the effects of subchronic particulate matter (PM) exposure on lung injury induced by polyhexamethylene guanidine phosphate (PHMG-p) in a rat model. Specifically, we investigated pulmonary inflammation, fibrosis, and tumor formation using chest computed tomography (CT), and histopathologic examination. PHMG-p was administered intratracheally to 20 male rats. After an initial week of PHMG-p treatment, the experimental group (PM group) received intratracheal administration of PM suspension, while the control group received normal saline. This regimen was continued for 10 weeks to induce subchronic PM exposure. Chest CT scans were conducted on all rats, followed by the extraction of both lungs for histopathological analysis. All CT images underwent comprehensive quantitative and qualitative analyses. Pulmonary inflammation was markedly intensified in rats subjected to subchronic PM exposure in the PM group compared to those in the control. Similarly, lung fibrosis was more severe in the PM group as observed on both chest CT and histopathologic examination. Quantitative chest CT analysis revealed that the mean lesion volume was significantly greater in the PM group than in the control group. Although the incidence of bronchiolo-alveolar hyperplasia was higher in the PM group compared to the control group, this difference was not statistically significant. In summary, subchronic PM exposure exacerbated pulmonary inflammation and fibrosis underlying lung injury induced by PHMG-p.

Advancements in Predictive Tools for Primary Graft Dysfunction in Liver Transplantation: A Comprehensive Review.

Orthotopic liver transplantation stands as the sole curative solution for end-stage liver disease. Nevertheless, the discrepancy between the demand and supply of grafts in transplant medicine greatly limits the success of this treatment. The increasing global shortage of organs necessitates the utilization of extended criteria donors (ECD) for liver transplantation, thereby increasing the risk of primary graft dysfunction (PGD). Primary graft dysfunction (PGD) encompasses early allograft dysfunction (EAD) and the more severe primary nonfunction (PNF), both of which stem from ischemia-reperfusion injury (IRI) and mitochondrial damage. Currently, the only effective treatment for PNF is secondary transplantation within the initial post-transplant week, and the occurrence of EAD suggests an elevated, albeit still uncertain, likelihood of retransplantation urgency. Nonetheless, the ongoing exploration of novel IRI mitigation strategies offers hope for future improvements in PGD outcomes. Establishing an intuitive and reliable tool to predict upcoming graft dysfunction is vital for early identification of high-risk patients and for making informed retransplantation decisions. Accurate diagnostics for PNF and EAD constitute essential initial steps in implementing future mitigation strategies. Recently, novel methods for PNF prediction have been developed, and several models for EAD assessments have been introduced. Here, we provide an overview of the currently scrutinized predictive tools for PNF and EAD evaluation strategies, accompanied by recommendations for future studies.

Lactational performance, ruminal fermentation, and enteric gas emission of dairy cows fed an amylase-enabled corn silage in diets with different starch concentrations

This study investigated the effects of feeding an amylase-enabled corn silage (ACS) on the performance and enteric gas emissions in lactating dairy cows. Following a 2-wk covariate period, 48 mid-lactation Holstein cows were assigned to 1 of 3 treatments in a 10-wk randomized complete block design experiment. Treatments were diets containing the same proportion of corn silage (40% of dietary DM) as follows: (1) a conventional hybrid corn silage control (CON), (2) ACS replacing the control silage (ADR), and (3) the ADR diet replacing soybean hulls with ground corn grain to achieve the same dietary starch concentration as CON (ASR). Control corn silage and ACS were harvested on the same day and contained 40.3% and 37.1% DM and (% of DM): 37.2% and 41.0% NDF and 37.1% and 30.0% starch, respectively. Enteric gas emissions were measured using the GreenFeed system. Two cows were culled due to health-related issues during the covariate period. Ruminal fluid was collected from 24 cows (8 per treatment) using the orogastric ruminal sampling technique. When compared with CON, cows fed ADR had increased DMI during experimental wk 3, 4, and 9, but treatment did not affect milk or ECM milk yields (39.0 kg/d on average; SEM = 0.89). Compared with CON, feed efficiency (per unit of milk, but not ECM) tended to be lower for ADR, whereas milk true protein concentration (a tendency) and yield were lower for ASR. Milk urea N was decreased by both ADR and ASR diets relative to CON. Compared with CON, daily CH4 emission and emission intensity were increased by ADR but not ASR. Total protozoal count tended to be increased by both diets formulated with ACS when compared with control corn silage. Total-tract digestibility of dietary NDF was greater for ASR, and that of ADF was greater for both ADR and ASR versus CON. The molar proportion of acetate (a tendency) and acetate-to-propionate ratio were increased by ADR, but not ASR, when compared with CON. Replacement of CON with ACS (having lower starch concentration) in the diet of dairy cows increased DMI during the initial weeks of the experiment, maintained ECM, tended to decrease feed efficiency, and increased enteric CH4 emissions, likely due to increased intake of digestible fiber, compared with CON.

Mortality and Associated Risk Factors Among People Living With HIV With Kaposi Sarcoma: A5263/AMC066 and A5264/AMC067.

AIDS-related Kaposi sarcoma (AIDS-KS) remains a leading cause of morbidity and mortality among people living with HIV in Africa. Mortality among people with AIDS-KS on antiretroviral therapy remains high compared with people on antiretroviral therapy who do not have AIDS-KS. People living with HIV with Kaposi sarcoma (KS) who participated in 2 randomized trials (A5263/AMC066 [advanced stage] and A5264/AMC067 [mild-to-moderate stage]) conducted by AIDS Clinical Trials Group/AIDS Malignancy Consortium in low- and middle-income countries. We estimated mortality rates over the trial period. Cox proportional hazards regressions were used to identify baseline characteristics associated with mortality and compared mortality rates between participants who had KS progression within 12 weeks of treatment initiation (early progression of KS [KS-PD]) and those who did not. Of the 329 and 189 eligible participants in A5263/AMC066 and A5264/AMC067, 71 (21.6%) and 24 (12.7%) died, respectively. In both trials, hypoalbuminemia was associated with increased hazards of death compared with normal albumin; A5263/AMC066: mild hypoalbuminemia (adjusted hazard ratio [aHR] = 3.01; 95% CI: 1.42 to 6.29), moderate hypoalbuminemia (aHR = 5.11; 95% CI: 2.54 to 10.29), and severe hypoalbuminemia (aHR = 14.58; 95% CI: 6.32 to 35.60), and A5264/AMC067: mild hypoalbuminemia (aHR = 5.66; 95% CI: 1.90 to 16.93) and moderate hypoalbuminemia (aHR = 7.02; 95% CI: 2.57 to 19.15). The rate of death was higher among participants who had early KS-PD than those without early KS-PD in A5263/AMC066 (HR = 5.09; 95% CI: 1.71 to 15.19) but not in A5264/AMC067 (HR = 1.74; 95% CI: 0.66 to 4.62). Albumin measurements may be used to identify individuals at higher risk of death after initiating KS treatment and for evaluation of interventions that can reduce AIDS-KS mortality.

MODL-11. LOW-GRADE GLIOMA 3D PATIENT-DERIVED ORGANOID PLATFORM AS TRANSFORMATIVE TOOL FOR TUMOR BIOLOGY AND TRANSLATIONAL RESEARCH

Abstract Unlike many high-grade tumors, low-grade glioma (LGG) has faced challenges in advancing scientific and clinical breakthroughs, affected by the limited capacity to develop representative preclinical tumor models. Major barriers to establishing traditional LGG cell culture systems have been cellular senescence and the need to introduce additional genetic modifications to obtain cultured growth. Such LGG models, while extremely valuable, require extensive periods for development and result in clonally selected lines which may not present the complexity of LGG tumor biology. To mitigate such challenges in LGG model development and address the need for three-dimensional tissue cultures, we have successfully generated organoids from fresh tissue specimens obtained from surgical resection. We have demonstrated success of this method on various pediatric brain tumor histologies and have expanded these approaches successfully to LGG. Through such efforts, we have developed 14 LGG tumors’ organoid models as well as other low-grade tumor’s models such as craniopharyngioma, schwannoma, meningioma, optic glioma, and oligodendroglioma. The tissue was processed immediately post-extraction and cultured in media solution on rotating platform. Organoid growth was observed within 1-3 weeks of initiation and tested for growth for up to 3 months. Phenotypic analysis revealed organoid cell composition representing clinical histology. The immune component was preserved in organoids for up to 40 days. MAPK pathway activity, a hallmark marker for KIAA-BRAF fusion positive pilocytic astrocytoma was preserved for up to 4 weeks. Our successful deployment of three-dimensional patient-tissue derived organoids provides for an efficient, simple workflow for the generation of unique and transformative preclinical models for the LGG field. Supported by the Children’s Brain Tumor network’s open science model, 3D organoids will provide investigations with broader resources for LGG tumor biology preclinical testing and support translational studies on behalf of the development of novel clinical trials.

LGG-51. SYSTEMIC IMMUNE TOXICITY OF BRAF AND MEK-INHIBITORS IN CHILDREN: A PAN-CANADIAN SERIES

Abstract BACKGROUND BRAF/MEK-inhibitors have been transformative for pediatric gliomas with RAS/MAPK pathway aberrations. The RAS/MAPK pathway has a complex role in immune regulation. Though well-known in adults, the systemic immune-related adverse effects (irAE) of BRAF/MEKi in children are not widely reported. METHODS We performed a retrospective chart review for irAE following BRAF/MEKi in children treated at SickKids between 2016-2023. Additional patients were included through a pan-Canadian survey. RESULTS 136 patients on BRAF/MEKi were included (MEKi: 74%, BRAFi: 13%, BRAF+MEKi: 13%); irAE was reported in 6/136 (4.5%). One additional patient was included through the national survey. Median age was 14 years (range: 7-16). Male:female was 3:4. Three patients were on BRAFi, and two each on MEKi, and BRAF+MEKi. Early events developing within weeks of drug initiation included hyper-immune systemic inflammatory responses in three children on BRAFi and one child on MEKi. There was no evidence of any concomitant infection. Two children needed intensive care and showed evidence of multi-organ dysfunction. Delayed irAE developing after months to years on therapy included multi-systemic sarcoid-like reaction, parasympathetic dysautonomia (both on BRAF+MEKi) and brachial neuritis/Parsonage-Turner syndrome (MEKi). Management included drug holidays, dose reductions, and immunosuppressive treatment with steroids. Long-term steroids were needed in two of these seven patients. CONCLUSIONS Pediatric oncologists need to be aware of rare yet possibly under-reported systemic immune toxicity in children treated with BRAF/MEKi. They can present acutely, or while on chronic therapy. Management may be challenging in view of issues with rebound tumor growth on stopping some of these drugs, with select patients needing concomitant, long-term immunosuppressive therapy. Genetic susceptibility and biomarkers may need to be systematically studied in future clinical trials of novel RAS/MAPK inhibitors. Continued surveillance and reporting are needed for the marketed compounds, especially for children on long-term use of these inhibitors.

Assessment of tissue response in vivo: PET-CT imaging of titanium and biodegradable magnesium implants

To study in vivo the bioactivity of biodegradable magnesium implants and other possible biomaterials, we are proposing a previously unexplored application of PET-CT imaging, using available tracers to follow soft tissue and bone remodelling and immune response in the presence of orthopaedic implants. Female Wistar rats received either implants (Ti6Al7Nb titanium or WE43 magnesium) or corresponding transcortical sham defects into the diaphyseal area of the femurs. Inflammatory response was followed with [18F]FDG and osteogenesis with [18F]NaF, over the period of 1.5 months after surgery. An additional pilot study with [68Ga]NODAGA-RGD tracer specific to αvβ3 integrin expression was performed to follow the angiogenesis for one month.[18F]FDG tracer uptake peaked on day 3 before declining in all groups, with Mg and Ti groups exhibiting overall higher uptake compared to sham. This suggests increased cellular activity and tissue response in the presence of Mg during the initial weeks, with Ti showing a subsequent increase in tracer uptake on day 45, indicating a foreign body reaction. [18F]NaF uptake demonstrated the superior osteogenic potential of Mg compared to Ti, with peak uptake on day 7 for all groups. [68Ga]NODAGA-RGD pilot study revealed differences in tracer uptake trends between groups, particularly the prolonged expression of αvβ3 integrin in the presence of implants.Based on the observed differences in the uptake trends of radiotracers depending on implant material, we suggest that PET-CT is a suitable modality for long-term in vivo assessment of orthopaedic biomaterial biocompatibility and underlying tissue reactions. Statement of significanceThe study explores the novel use of positron emission tomography for the assessment of the influence that biomaterials have on the surrounding tissues. Previous related studies have mostly focused on material-related effects such as implant-associated infections or to follow the osseointegration in prosthetics, but the use of PET to evaluate the materials has not been reported before. The approach tests the feasibility of using repeated PET-CT imaging to follow the tissue response over time, potentially improving the methodology for adopting new biomaterials for clinical use.

Efficacy of macozinone in mice with genetically diverse susceptibility to Mycobacterium tuberculosis infection

Host heterogeneity in pulmonary tuberculosis leads to varied responses to infection and drug treatment. The present portfolio of anti-TB drugs needs to be boosted with new drugs and drug regimens. Macozinone, a clinical-stage molecule targeting the essential enzyme, DprE1, represents an attractive option. Mice (I/St, B6, (AKRxI/St)F1, B6.I-100 and B6.I-139) genetically diverse susceptibility to Mycobacterium tuberculosis (Mtb) H37Rv infection were subjected to aerosol- or intravenous infection to determine the efficacy of macozinone (MCZ). They were treated with macozinone or reference drugs (isoniazid, rifampicin). Lung and spleen bacterial burdens were measured at four and eight weeks post-infection. Lung histology was evaluated at four weeks of treatment. Treatment with macozinone resulted in a statistically significant reduction in the bacterial load in the lungs and spleen as early as four weeks after treatment initiation in mice susceptible or resistant to Mtb infection. In the TB hypoxic granuloma model, macozinone was more potent than rifampicin in reducing the CFU counts. However, histopathological analysis revealed significant lung changes in I/St mice after eight weeks of treatment initiation. Macozinone demonstrated efficacy to varying degrees across all mouse models of Mtb infection used. These results should facilitate its further development and potential introduction into clinical practice.

CD20-bispecific antibodies improve response to CD19-CAR T cells in lymphoma in vitro and CLL in vivo models

AbstractRelapse after anti-CD19 chimeric antigen receptor (CD19-CAR) occurs in a substantial proportion of patients with lymphoid malignancies. We assessed the potential benefits of co-administering CD20-targeting bispecific antibodies (CD20-BsAbs) with CD19-CAR T cells with the aim of enhancing immunotherapeutic efficacy. Addition of CD20-BsAbs to cocultures of CD19-CARs and primary samples of B-cell malignancies, comprising malignant B cells and endogenous T cells, significantly improved killing of malignant cells and enhanced the expansion of both endogenous T cells and CD19-CAR T cells. In an immunocompetent mouse model of chronic lymphocytic leukemia, relapse after initial treatment response frequently occurred after CD19-CAR T-cell monotherapy. Additional treatment with CD20-BsAbs significantly enhanced the treatment response and led to improved eradication of malignant cells. Higher efficacy was accompanied by improved T-cell expansion with CD20-BsAb administration and led to longer survival with 80% of the mice being cured with no detectable malignant cell population within 8 weeks of therapy initiation. Collectively, our in vitro and in vivo data demonstrate enhanced therapeutic efficacy of CD19-CAR T cells when combined with CD20-BsAbs in B-cell malignancies. Activation and proliferation of both infused CAR T cells and endogenous T cells may contribute to improved disease control.

Brain health in preterm infants: importance of early-life pain and analgesia exposure.

"Everyday" exposures in the neonatal period, such as pain, may impact brain health in preterm infants. Specifically, greater exposure to painful procedures in the initial weeks after birth have been related to abnormalities in brain maturation and growth and poorer neurodevelopmental outcomes in preterm infants. Despite an increasing focus on the importance of treating pain in preterm infants, there is a lack of consensus of optimal approaches to managing pain in this population. This may be due to recent findings suggesting that commonly used analgesic and sedative medications in preterm infants may also have adverse effects of brain maturation and neurodevelopmental outcomes. This review provides an overview of potential impacts of pain and analgesia exposure on preterm brain health while highlighting research areas in need of additional investigations for the development of optimal pain management strategies in this population.

Efectos de la dieta alta en calorías y el ejercicio físico en el pez cebra (Danio rerio)

Zebrafish are becoming a valid model for investigating obesity and its associated disorders within a scientific context. The comprehension of the metabolic parameters linked to heightened body mass, adiposity, and energy expenditure stands as an indispensable endeavor in unraveling metabolic requisites among vertebrates. In this particular investigation, a cohort of 48 zebrafish specimens was scrutinized to determine the impact of physical exercise when subjected to a hypercaloric diet. The subjects were categorized into four distinct groups, each group respectively assigned to maintenance diets (GM, n=12, and GMex, n=12) or hypercaloric diets (GH, n=12, and GHex, n=12), with or without concurrent engagement in physical exercise. Applying a one-way ANOVA, with a significance level of P ≤ 0.05, the results revealed noteworthy findings. Among the GMex group, regarding body mass, a statistically significant variance was observed during the initial week (0.30g ± 0.10). This disparity demonstrated a reduction of 30.83% in the subsequent week, 33.59% in the fourth week, and 40.01% in the sixth week. Similarly, within the GH group, the analysis of variance unveiled significant deviations in body mass (in grams) from the inception of the study (0.32g ± 0.07), in comparison to measurements from the sixth through the thirteenth weeks. The GHex group exhibited significant differences in body mass between the first week (0.27g ± 0.08) and the subsequent weeks, extending until the thirteenth week. Furthermore, discernible variations in the length (in centimeters) of the zebrafish specimens were recorded, with statistical significance observed from the ninth (3.29cm ± 0.33) to the thirteenth weeks (3.61cm ± 0.33). The implementation of a hypercaloric diet yielded an augmentation in body mass. Additionally, the combination of this dietary regimen with physical exercise further contributed to an augmentation in the length of the zebrafish specimens. Collectively, the proposed model exhibited the capability to induce discernible metabolic effects, thereby enhancing our understanding of the intricate interplay between diet, exercise, and metabolic dynamics.

Effectiveness of remote monitoring in improving CPAP compliance and the impact of preexisting organisation of standard care: a randomised controlled trial

Purpose Continuous positive airway pressure (CPAP) is often the treatment of choice for obstructive sleep apnea (OSA). Short-term adherence and early perceived benefits are the best predictors of long-term adherence. The aim of this study was to determine the effect of telemonitoring in the first period of treatment with CPAP (auto-titrating PAP) on compliance and the long-term outcome.MethodsPatients aged between 18–75 years old with symptomatic severe OSA (apnea–hypopnea index (AHI) ≥ 30) requiring CPAP therapy were included in this single-blind, single-centre, randomised, controlled trial. They were divided into 2 groups (telemonitored standard clinical care versus standard clinical care without telemonitoring).ResultsA total of 230 patients (115 patients/group) were included (mean age 54 ± 16.6 years, BMI 32.6 ± 5.4 kg/m2, ESS 13.1 ± 6.2, AHI 47.5 ± 14.8/hr). At week 10 compliance was similar in both groups (telemonitoring vs control 6:27 and 6:35 h, respectively, p = 0.57), as were AHI (2.4; 2.4/hr, p = 0.89) and ESS (5.8; 4.9, p = 0.22). The number of contacts of a patient with a healthcare professional was significantly higher during the follow-up from week 3 until week 10 (0.25; 0.13, p = 0.03). The number of patients who could be evaluated after 1 year was equally distributed in both groups (104; 104, p = 1.00), as were compliance (6:43; 6:49 h, p = 0.59) and residual AHI (1.9; 2.2/hr, p = 0.41).ConclusionsIn patients with severe OSA with standard intensive follow-up during the initial weeks of CPAP therapy and good compliance, telemonitoring did not improve CPAP compliance nor the clinical outcome in the short or long term. The practical consequences can be highly relevant for patients and healthcare professionals.

Higher final speed in 30–15 intermittent fitness tests correlates with soccer's locomotor demands, not heart rate responses in small-sided soccer games

This study aimed to achieve two objectives: firstly, to analyze the relationships between aerobic fitness, as represented by the VIFT, and the heart rate and locomotor responses of youth male soccer players across various teams; and secondly, to compare players with lower and higher VIFT in terms of performance outcomes extracted during small-sided games (SSGs). A total of twenty-six youth male soccer players, aged 16.5 ± 0.32 years, with 3.4 ± 1.1 years of experience, voluntarily participated in the study. These players belonged to two regional-level tier 2 teams (trained/developmental). In the initial week of observation, the 30–15 Intermittent Fitness Test was implemented to measure the final velocity (VIFT) achieved by the players. Subsequently, the 5v5 format of play was conducted twice a week over two consecutive weeks, during which heart rate responses and locomotor demands were measured. The Pearson product-moment correlation test revealed a significant correlation between VIFT and the total distance covered during the 5v5 format (r = 0.471 [95% CI: 0.093; 0.721], p = 0.015). Conversely, small and non-significant correlations were identified between VIFT and mean heart rate (r = 0.280 [95% CI: − 0.126; 0.598]; p = 0.166), VIFT and peak heart rate (r = 0.237 [95% CI: − 0.170; 0.569]; p = 0.243), as well as VIFT and high-speed running (r = 0.254 [95% CI: − 0.153; 0.580]; p = 0.211). Players with higher VIFT demonstrated a significantly greater total distance, with a large effect size (+ 6.64%; p = 0.015; d = 1.033), compared to those with lower VIFT. Our findings suggest that improved performance in VIFT may lead to covering more distance in 5v5 matches. However, the lack of significant associations between VIFT and heart rate levels during SSGs suggests that they are not strongly correlated, possibly because VIFT is more closely linked to locomotor profile. As a practical implication, coaches may consider organizing players during SSGs based on their VIFT if the goal is to standardize locomotor demands.

Impact of pandemic mobility restrictions on kidney transplant patients' experience: lessons on quality of care.

Patient perspectives on their post-operative health are acknowledged as valuable healthcare outcomes and should be scrupulously considered when designing interventions for patient-centered healthcare. Yet, following the COVID-19 lockdown and in the absence of standardized guidelines on how to best provide virtual chronic care to kidney transplant recipients, little is known about how this unique population coped and managed to comply with public health indications during confinement. This study addresses this shortcoming by examining the experiences of patients from a tertiary hospital in Spain during the initial weeks of the lockdown decreed by the national government. Specifically, we focus our attention on the perceptions and experiences of these patients by retrieving robust qualitative and quantitative data: the former based on a thematic analysis of focus group transcripts, the latter obtained from a large-scale survey. Our findings identify opportunities for improvement in the quality of care and point to the provisions that might be made when facing future pandemics or lockdown-requiring situations. As healthcare services navigate evolving landscapes, our findings on the experience of kidney transplant recipients should enable hospital services to improve the quality of care they are able to provide to such patients during periods of restricted mobility, especially those associated with future disease emergencies, and considering that home confinement is often part of the natural course of post-operative care of these patients.

Rapid decrease in IL-1Ra and IP-10 plasma levels following tuberculosis treatment initiation

ObjectivesMonitoring tools that could provide quick predictions of tuberculosis (TB) treatment outcomes are urgently needed. Here, we assessed whether the evolution of selected biomarkers of innate immunity may help monitoring TB treatment response within 2 weeks of treatment initiation. MethodsANRS12394-LILAC-TB was a proof-of-concept prospective study: adults with a rifampicin-susceptible TB who are HIV-negative and HIV-infected documented by a positive Xpert MTB/RIF test were enrolled in Cambodia and Côte d'Ivoire. Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interferon-γ–induced protein-10 and clusters of differentiation (CD) (scavenging CD163) were measured by commercial enzyme-linked immunosorbent assay kits. A Wilcoxon test for paired data was used for longitudinal comparisons. ResultsA total of 55 patients were enrolled (women: 31%, median age: 37 years; median CD4 count in the 10 of 13 participants with HIV: 53 cells/mm3). Overall, 83% were considered in TB treatment success. Compared with baseline, the IL-1Ra plasma levels significantly decreased as soon as week (W) 1, independent of HIV status (−71% in HIV-positive vs −33% in HIV-negative; P <0.001). The IP-10 plasma levels significantly decreased at W1 and W2 compared with baseline (P <0.0001); however, that decrease was less marked in participants with HIV. ConclusionsOur findings suggest that measuring IL-1Ra plasma levels with a standard enzyme-linked immunosorbent assay technique at baseline and then 1 week after TB treatment onset could help clinicians to quickly assess TB treatment response.

Changes in Fracture Shortening Occur in the First 2 Weeks Following Completely Displaced Adolescent Clavicle Fractures.

Shortening of midshaft clavicle fractures has been described as a critical fracture characteristic to guide treatment. The degree to which shortening may change in the initial weeks following injury has not been well studied. The purpose of this study was to evaluate the change in shortening of adolescent clavicle fractures in the first 2 weeks following injury. This was a multicenter study of prospectively collected data, which was acquired as a part of a cohort study of adolescent clavicle fractures. A consecutive series of patients 10 to 18 years of age with completely displaced diaphyseal clavicle fractures with baseline radiographs 0 to 6 days from the date of injury, as well as 7 to 21 days from the date of injury, were included. Measurements of end-to-end (EES) and cortex-to-corresponding-cortex (CCS) shortening were performed. A total of 142 patients were included. Baseline radiographs were obtained at a mean of 1.0 day following injury with mean EES of 22.3mm, and 69% of patients demonstrating > 20mm of shortening. Follow-up radiographs obtained at a mean of 13.8 days postinjury demonstrated a mean absolute change in EES of 5.4mm. Forty-one percentage of patients had >5mm of change in EES. When analyzing changes in shortening relative to the specific threshold of 20mm, 18 patients (41%) with <20mm EES increased to ≥20mm EES, and 19 patients (19%) with ≥20mm EES decreased to <20mm EES at 2-week follow-up. Clinically significant changes in fracture shortening occurred in 41% of adolescents with completely displaced clavicle fractures in the first 2 weeks after injury. In 26% of patients, this resulted in a change from above or below the commonly used shortening threshold of 20mm, potentially altering the treatment plan by many providers. There is no evidence to suggest that adolescent clavicle fracture shortening affects outcomes, and as such, the authors do not advocate for the use of this parameter to guide treatment. However, among physicians who continue to use this parameter to guide treatment, this study supports that repeat radiographic assessment 2 weeks postinjury may be a better measure of the true shortening of this common adolescent injury. Level IV-case series.

Abstract PO1-17-09: Real-world clinical outcomes in US patients with brain metastases secondary to HR+/HER2- metastatic breast cancer treated with abemaciclib

Abstract Background: Abemaciclib has demonstrated pharmacologically relevant intracranial concentrations and antitumor activity in patients with brain metastases secondary to HR+/HER2- metastatic breast cancer (MBC). However, clinical data is limited, and further assessments are warranted. This retrospective study describes real-world outcomes following abemaciclib initiation in patients with brain metastases secondary to HR+/HER2- MBC. Methods: Data were accessed from the US nationwide Flatiron Health electronic health records-derived de-identified database from 01/01/2011 to 12/31/2021. This real-world study included adult patients with a diagnosis of HR+/HER2- MBC with brain metastases prior to abemaciclib initiation. Patient and treatment characteristics were summarized using descriptive statistics. Kaplan-Meier methods were used to assess clinical outcomes from abemaciclib initiation: time to treatment discontinuation (TTD), progression-free survival (rwPFS), overall survival (rwOS). Intracranial rw best responses were also reported. Results: This study included 82 patients (one male) diagnosed with MBC and brain metastases prior to abemaciclib initiation and the median follow-up was 12.8 months. At data cut-off, 17 (20.7%) patients remained on abemaciclib therapy. Twenty-three (28%) patients received abemaciclib as the first line of therapy for MBC. Of the 82 patients in the study, 68 (82.9%) patients used concomitant endocrine therapy. Prior to abemaciclib initiation, 25 (30.5%) patients received chemotherapy and 33 (40.2%) patients received a CDK4 and 6 inhibitor. Most patients (67.1%) initiated abemaciclib at a dose of 150 mg twice daily. The median time from diagnosis of brain metastasis to abemaciclib initiation was 2.1 months (interquartile range:1.0, 8.0); 16 (19.5%) did not undergo surgical resection or receive radiation to the brain during this time. Sixty-six (80.5%) patients received brain radiation of which 56.1% received stereotactic radiosurgery (SRS) and 47.0% received whole-brain radiation (WBRT) either alone or in combination with craniotomy/metastasectomy, intrathecal chemotherapy, or surgery. The median TTD for abemaciclib was 7.1 months (95% confidence interval [95% CI]: 4.6, 11.3); most common reasons for discontinuation were disease progression (39.0%) or adverse events (29.3%). The median rwPFS was 9.2 months (95% CI: 6.0, 11.6) and median rwOS was 20.8 months (95% CI: 13.9, 26.0). Of the patients where response data were available (n = 51), rw intracranial clinical benefit rate (CBR; complete response [CR]/partial response [PR]/stable disease [SD] ≥24 weeks of abemaciclib initiation) was 62.7% (Table 1). Conclusion: In this real-world study, most patients with brain metastases secondary to HR+/HER2- MBC who initiated abemaciclib treatment received SRS or WBRT prior to or concurrent with abemaciclib initiation. While the clinical outcomes, rwPFS and intracranial CBR were encouraging, these findings should be interpreted with caution due to the nature of the real-world study design. Table 1. Intracranial Real-World Best Responses Citation Format: Wambui Gathirua-Mwangi, Holly Martin, Dan He, Shen Zheng, Kristin Sheffield, Jincy John, Sarah Rybowski, Priscilla Brastianos. Real-world clinical outcomes in US patients with brain metastases secondary to HR+/HER2- metastatic breast cancer treated with abemaciclib [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-17-09.

Use of romiplostim for antineoplastic therapy-induced thrombocytopenia in gynecologic and breast cancers

ObjectiveRomiplostim is used to treat chemotherapy-induced thrombocytopenia in a variety of tumor types; however, few studies have examined its use in breast and gynecologic cancers. We evaluated platelet response and durability of response to romiplostim in patients with gynecologic or breast cancer complicated by chemotherapy-induced thrombocytopenia. MethodsWe retrospectively identified 33 patients with gynecologic or breast cancer who received romiplostim between 07/1/2021–07/31/2022 at an academic cancer center. ResultsThirty-three patients met inclusion criteria; 26 (79 %) had breast cancer, 4 (12 %) had ovarian cancer, and 3 (9 %) had endometrial cancer. Twenty patients (61 %) experienced treatment delays and 12 (36 %) required dose reductions prior to starting romiplostim for chemotherapy-induced thrombocytopenia, with some patients experiencing both. Eleven patients (33 %) did not undergo a dose reduction or delay prior to initiation of romiplostim. Median platelet count prior to romiplostim therapy was 53 k/mcL (range, 40.5–78.8). Median platelet count within 3 weeks following initiation of romiplostim was 147 k/mcL (range, 31–562). Twenty-one patients (64 %) achieved platelet correction within 3 weeks, of whom 10 (48 %) resumed anticancer therapy and maintained platelet levels above 100 k/mcL at 8 weeks. Twelve patients did not achieve platelet correction within 3 weeks of romiplostim initiation; 4 (33 %) required a treatment change secondary to persistent thrombocytopenia, 3 (25 %) required a treatment dose reduction, 3 (25 %) were deemed too ill to continue therapy, and 2 (17 %) required a treatment delay. ConclusionsRomiplostim facilitated the resumption of anticancer therapy in 64 % of patients with gynecologic or breast cancer complicated by chemotherapy-induced thrombocytopenia.

Brucellosis-induced peritonitis and abdominal aortitis in a non-endemic area patient on peritoneal dialysis: a case report and literature review

BackgroundBrucella infection is uncommon among peritoneal dialysis (PD) patients in non-endemic areas, and the occurrence of both peritonitis and abdominal aortitis is rare.Case presentationIn December 2023, a 63-year-old male patient undergoing PD was admitted to Shaoxing Second Hospital due to fever, abdominal pain, and cloudy dialysate. Upon physical examination, diffuse mild abdominal pain and tenderness were observed. Subsequent investigation into the patient's medical history revealed consumption of freshly slaughtered lamb from local farmers 3 days prior to the onset of symptoms. Various diagnostic tests, including routine blood tests, procalcitonin levels, and PD fluid analysis, indicated the presence of infection. Abdominal computed tomography (CT) imaging revealed localized lumen widening of the abdominal aorta with surrounding exudative changes. On the sixth day in the hospital, blood and PD fluid cultures confirmed Brucella melitensis infection. The patient was diagnosed with brucella-associated peritonitis and aortitis. Treatment was adjusted to include rifampin and doxycycline for 6 weeks, and the decision was made to keep the PD catheter. Remarkably, the patient exhibited resolution of peritonitis and abdominal aortitis within the initial week of the adjusted treatment. Currently, the patient continues to receive ongoing clinical monitoring.ConclusionBrucella is rare but can cause PD-associated peritonitis and arteritis. Prompt diagnosis and treatment can lead to a good outcome in PD patients. Dual therapy is effective, but the need for catheter removal is unclear. Consider international guidelines and patient factors when deciding on catheter removal.