Molecular forecasting of domoic acid during a pervasive toxic diatom bloom.

In 2015, the largest recorded harmful algal bloom (HAB) occurred in the Northeast Pacific, causing nearly 100 million dollars in damages to fisheries and killing many protected marine mammals. Dominated by the toxic diatom Pseudo-nitzschia australis, this bloom produced high levels of the neurotoxin domoic acid (DA). Through molecular and transcriptional characterization of 52 near-weekly phytoplankton net-tow samples collected at a bloom hotspot in Monterey Bay, California, we identified active transcription of known DA biosynthesis (dab) genes from the three identified toxigenic species, including P. australis as the primary origin of toxicity. Elevated expression of silicon transporters (sit1) during the bloom supports the previously hypothesized role of dissolved silica (Si) exhaustion in contributing to bloom physiology and toxicity. We find that coexpression of the dabA and sit1 genes serves as a robust predictor of DA one week in advance, potentially enabling the forecasting of DA-producing HABs. We additionally present evidence that low levels of iron could have colimited the diatom population along with low Si. Iron limitation represents an overlooked driver of both toxin production and ecological success of the low-iron-adapted Pseudo-nitzschia genus during the 2015 bloom, and increasing pervasiveness of iron limitation may fuel the escalating magnitude and frequency of toxic Pseudo-nitzschia blooms globally. Our results advance understanding of bloom physiology underlying toxin production, bloom prediction, and the impact of global change on toxic blooms.

Evidence for seasonal migration by a cryptic top predator of the deep sea.

BACKGROUND: In ecosystems influenced by strong seasonal variation in insolation, the fitness of diverse taxa depends on seasonal movements to track resources along latitudinal or elevational gradients. Deep pelagic ecosystems, where sunlight is extremely limited, represent Earth's largest habitable space and yet ecosystem phenology and effective animal movement strategies in these systems are little understood. Sperm whales (Physeter macrocephalus) provide a valuable acoustic window into this world: the echolocation clicks they produce while foraging in the deep sea are the loudest known biological sounds on Earth and convey detailed information about their behavior. METHODS: We analyze seven years of continuous passive acoustic observations from the Central California Current System, using automated methods to identify both presence and demographic information from sperm whale echolocation clicks. By integrating empirical results with individual-level movement simulations, we test hypotheses about the movement strategies underlying sperm whales' long-distance movements in the Northeast Pacific. RESULTS: We detect foraging sperm whales of all demographic groups year-round in the Central California Current System, but also identify significant seasonality in frequency of presence. Among several previously hypothesized movement strategies for this population, empirical acoustic observations most closely match simulated results from a population undertaking a "seasonal resource-tracking migration", in which individuals move to track moderate seasonal-latitudinal variation in resource availability. DISCUSSION: Our findings provide evidence for seasonal movements in this cryptic top predator of the deep sea. We posit that these seasonal movements are likely driven by tracking of deep-sea resources, based on several lines of evidence: (1) seasonal-latitudinal patterns in foraging sperm whale detection across the Northeast Pacific; (2) lack of demographic variation in seasonality of presence; and (3) the match between simulations of seasonal resource-tracking migration and empirical results. We show that sperm whales likely track oceanographic seasonality in a manner similar to many surface ocean predators, but with dampened seasonal-latitudinal movement patterns. These findings shed light on the drivers of sperm whales' long-distance movements and the shrouded phenology of the deep-sea ecosystems in which they forage.

Discovery of 1,3,4-oxadiazoles with slow-action activity against Plasmodium falciparum malaria parasites.

To achieve malaria eradication, new preventative agents that act differently to front-line treatment drugs are needed. To identify potential chemoprevention starting points we screened a sub-set of the CSIRO Australia Compound Collection for compounds with slow-action in vitro activity against Plasmodium falciparum. This work identified N,N-dialkyl-5-alkylsulfonyl-1,3,4-oxadiazol-2-amines as a new antiplasmodial chemotype (e.g., 1 96 h IC50 550 nM; 3 96 h IC50 160 nM) with a different action to delayed-death slow-action drugs. A series of analogues were synthesized from thiotetrazoles and carbomoyl derivatives using Huisgen 1,3,4-oxadiazole synthesis followed by oxidation of the resultant thioethers to target sulfones. Structure activity relationship analysis of analogues identified compounds with potent and selective in vitro activity against drug-sensitive and multi-drug resistant Plasmodium parasites (e.g., 31 and 32 96 h IC50 <40 nM; SI > 2500). Subsequent studies in mice with compound 1, which had the best microsomal stability of the compounds assessed (T1/2 >255 min), demonstrated rapid clearance and poor oral in vivo efficacy in a P. berghei murine malaria model. These data indicate that while N,N-dialkyl-5-alkylsulfonyl-1,3,4-oxadiazol-2-amines are a novel class of slow-acting antiplasmodial agents, the further development of this chemotype for malaria chemoprophylaxis will require pharmacokinetic profile improvements.

Statin therapy improves locomotor muscle microvascular reactivity in patients with heart failure with preserved ejection fraction.

Peripheral microvascular dysfunction has been documented in patients with heart failure with preserved ejection fraction (HFpEF), which may be related to elevated levels of inflammation and oxidative stress. Unfortunately, few strategies have been identified to effectively ameliorate this disease-related derangement. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10 mg daily) on lower limb microvascular reactivity, functional capacity, and biomarkers of inflammation and oxidative stress in patients with HFpEF (statin, n = 8, 76 ± 6 yr; placebo, n = 8, 68 ± 9 yr). The passive limb movement (PLM)-induced hyperemic response and 6-min walk test (6MWT) distance were evaluated to assess ambulatory muscle microvascular function and functional capacity, respectively. Circulating biomarkers were also measured to assess the contribution of changes in inflammation and redox balance to these outcomes. The total hyperemic response to PLM, assessed as leg blood flow area under the curve (LBFAUC), increased following the statin intervention (pre, 60 ± 68 mL; post, 164 ± 90 mL; P < 0.01), whereas these variables were unchanged in the placebo group (P = 0.99). There were no significant differences in 6MWT distance following statin or placebo intervention. Malondialdehyde (MDA), a marker of lipid peroxidation, was significantly reduced following the statin intervention (pre, 0.68 ± 0.10; post, 0.51 ± 0.11; P < 0.01) while other circulating biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to a diminution in oxidative stress.NEW & NOTEWORTHY This was the first study to investigate the impact of statin administration on locomotor muscle microvascular function in patients with HFpEF. In support of our hypothesis, the total hyperemic response to PLM, assessed as leg blood flow area under the curve, increased, and malondialdehyde, a marker of oxidative damage, was reduced following the statin intervention. Together, these data provide new evidence for the efficacy of statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to reduced oxidative stress.

Efficacy of Activity Trackers in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a common, complex syndrome associated with elevated morbidity and mortality. Patients with HFpEF have a high prevalence of comorbidities, including hypertension, diabetes mellitus, and obesity, which are closely related to the underlying mechanisms of the disease. Lifestyle modification with weight loss and physical activity can improve risk factors and functional outcomes in HFpEF. We sought to observe daily physical activity and determine whether utilizing an activity tracker can enhance functional status in HFpEF patients. METHODS: We performed a prospective analysis of 57 patients with HFpEF from 2021 to 2023 at a single academic medical center who utilized a Fitbit to record one year of daily step activity. The patients were evaluated in the ambulatory setting for an initial visit and subsequently at intervals of 3, 6, and 12 months to gather vitals, labs, physical exam, and functional measurements, including the Six-Minute Walk Test (6MWT) and Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12). Associations between variables were assessed using Pearson's r correlation using Stata 18.0. RESULTS:  Of the 49 patients who completed the study, the mean age was 68.1 ± 10.2 years, with 67% of patients identifying as female. The average BMI was 36.4 ± 8.6 kg/m2. Across each time interval, the median numbers of steps per day were 4,113 (2,517-6,520) (1-3 months), 4,583 (2,532-6,326) (4-6 months), and 3,957 (2,942-5,982) (7-12 months). There was no statistically significant variation in daily step count (p=0.06). We observed a statistically significant increase of 66 (6-200) feet in the 6MWT (p= 0.002) from baseline (1,175 (910-1,400)) to 12 months (1,321 (1,000-1,550)). The daily step count was highly correlated with the 6MWT across all time points (1-3 months: r= .70, p< .001; 4-6 months: r= .61, p< .001; 7-12 months: r= .69, p< .001). The total KCCQ-12 scores increased by 6.8 (-4.2-19.8) points (p=0.005) from baseline (60.1 (41.7-73.4)) to 12 months (69.8 (50-84.4)). Among the sub-categories of the questionnaire, we observed a positive correlation between physical limitation scores and daily step count (1-3 months: r= .47, p=.001; 4-6 months: r= .63, p< .001; 7-12 months: r= .56, p= .001). Of interest, one patient who was taking over 15,000 daily steps scored their physical limitation 10-20 points lower than those taking less than half the steps and had one of the lowest quality of life scores in the cohort, reflecting the subjective nature of heart failure (HF) symptoms. CONCLUSION: Fitbit technology offers a convenient means to monitor real-time physical activity in patients with HFpEF. Utilizing a Fitbit to record daily step activity enhances health-related quality of life in this population. In contrast to the improved average total KCCQ-12 score, we did not observe a clinically significant increase in the 6MWT over the course of the year. Our findings establish the utility of daily step count as a valuable surrogate for six-minute walk distance.

Global burden of metabolic diseases, 1990-2021.

BACKGROUND: Common metabolic diseases, such as type 2 diabetes mellitus (T2DM), hypertension, obesity, hypercholesterolemia, and metabolic dysfunction-associated steatotic liver disease (MASLD), have become a global health burden in the last three decades. The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) data enables the first insights into the trends and burdens of these metabolic diseases from 1990 to 2021, highlighting regional, temporal and differences by sex. METHODS: Global estimates of disability-adjusted life years (DALYs) and deaths from GBD 2021 were analyzed for common metabolic diseases (T2DM, hypertension, obesity, hypercholesterolemia, and MASLD). Age-standardized DALYs (mortality) per 100,000 population and annual percentage change (APC) between 1990 and 2021 were estimated for trend analyses. Estimates are reported with uncertainty intervals (UI). RESULTS: In 2021, among five common metabolic diseases, hypertension had the greatest burden (226 million [95 % UI: 190-259] DALYs), whilst T2DM (75 million [95 % UI: 63-90] DALYs) conferred much greater disability than MASLD (3.67 million [95 % UI: 2.90-4.61]). The highest absolute burden continues to be found in the most populous countries of the world, particularly India, China, and the United States, whilst the highest relative burden was mostly concentrated in Oceania Island states. The burden of these metabolic diseases has continued to increase over the past three decades but has varied in the rate of increase (1.6-fold to 3-fold increase). The burden of T2DM (0.42 % [95 % UI: 0.34-0.51]) and obesity (0.26 % [95 % UI: 0.17-0.34]) has increased at an accelerated rate, while the rate of increase for the burden of hypertension (-0.30 % [95 % UI: -0.34 to -0.25]) and hypercholesterolemia (-0.33 % [95 % UI: -0.37 to -0.30]) is slowing. There is no significant change in MASLD over time (0.05 % [95 % UI: -0.06 to 0.17]). CONCLUSION: In the 21st century, common metabolic diseases are presenting a significant global health challenge. There is a concerning surge in DALYs and mortality associated with these conditions, underscoring the necessity for a coordinated global health initiative to stem the tide of these debilitating diseases and improve population health outcomes worldwide.

Variation in Lip Shape and Aesthetics in the Young Female Population: A Statistical Atlas Study.

Background: The distribution of lip shapes in young females and how morphological variation relates to attractiveness are poorly defined. Objectives: We hypothesized that among young female lip images generated by a statistical atlas model, those with more full lips compared with those with less full lips would be perceived as more attractive as measured by anonymous survey participants. Method: A statistical atlas of lip morphology was created using photographs of 700 women aged 18-35 years. The average lip shape was determined by coregistering and averaging images. Morphological variation was analyzed using principal component analysis. The relationship between attractiveness and observed lip morphologies was assessed using publicly distributed surveys. Results: In total, 428 survey responses were obtained. We developed a statistical model of variation of lip shape in the population and its relationship to attractiveness. The most attractive lips were significantly fuller than the average shape in the population, with greater vertical height and surface area. Conclusion: A statistical atlas can provide a visual guide to variation in lip shape in the population. The most attractive lip shapes vary significantly from the population average, lending support to procedures that increase lip height and surface area.

Post-polypectomy surveillance: follow-up recommendations from the Alberta Colorectal Cancer Screening Program.

In 2013, the Alberta Colorectal Cancer Screening Program (ACRCSP) initially published recommendations for post-colonoscopy follow-up and polypectomy. Over time, emerging evidence and evolving surveillance guidelines from various expert groups necessitated a comprehensive review to align with the healthcare landscape in Alberta. To accomplish this, an expert panel was convened. Using the Agree II tool, we identified high-quality Clinical Practice Guidelines that were relevant to the Alberta medical context. Recommendations from these guidelines were adapted to fit the specific needs of Alberta. Recognizing inconsistencies and gaps within the existing guidelines, we conducted targeted literature reviews to ensure a comprehensive and evidence-based approach to our recommendations. Our revised recommendations build upon the assumption that a high-quality index colonoscopy has been performed at baseline. They are intended to enhance the quality of care and reduce unnecessary procedures. As well, they align with the growing consensus in the scientific literature that individuals with low-risk tubular adenomas may not require aggressive colonoscopy surveillance. The updated Alberta recommendations aim to provide clear recommendations for practicing endoscopists, referring physicians, and their patients. They address crucial questions such as determining which patients should commence surveillance via colonoscopy and which individuals should return to average-risk screening using the fecal immunochemical test (FIT). Additionally, our recommendations outline the appropriate surveillance intervals for those requiring continued monitoring.

A pilot feasibility study comparing large language models in extracting key information from ICU patient text records from an Irish population.

BACKGROUND: Artificial intelligence, through improved data management and automated summarisation, has the potential to enhance intensive care unit (ICU) care. Large language models (LLMs) can interrogate and summarise large volumes of medical notes to create succinct discharge summaries. In this study, we aim to investigate the potential of LLMs to accurately and concisely synthesise ICU discharge summaries. METHODS: Anonymised clinical notes from ICU admissions were used to train and validate a prompting structure in three separate LLMs (ChatGPT, GPT-4 API and Llama 2) to generate concise clinical summaries. Summaries were adjudicated by staff intensivists on ability to identify and appropriately order a pre-defined list of important clinical events as well as readability, organisation, succinctness, and overall rank. RESULTS: In the development phase, text from five ICU episodes was used to develop a series of prompts to best capture clinical summaries. In the testing phase, a summary produced by each LLM from an additional six ICU episodes was utilised for evaluation. Overall ability to identify a pre-defined list of important clinical events in the summary was 41.5 ± 15.2% for GPT-4 API, 19.2 ± 20.9% for ChatGPT and 16.5 ± 14.1% for Llama2 (p = 0.002). GPT-4 API followed by ChatGPT had the highest score to appropriately order a pre-defined list of important clinical events in the summary as well as readability, organisation, succinctness, and overall rank, whilst Llama2 scored lowest for all. GPT-4 API produced minor hallucinations, which were not present in the other models. CONCLUSION: Differences exist in large language model performance in readability, organisation, succinctness, and sequencing of clinical events compared to others. All encountered issues with narrative coherence and omitted key clinical data and only moderately captured all clinically meaningful data in the correct order. However, these technologies suggest future potential for creating succinct discharge summaries.

Long-distance communication can enable collective migration in a dynamic seascape.

Social information is predicted to enhance the quality of animals' migratory decisions in dynamic ecosystems, but the relative benefits of social information in the long-range movements of marine megafauna are unknown. In particular, whether and how migrants use nonlocal information gained through social communication at the large spatial scale of oceanic ecosystems remains unclear. Here we test hypotheses about the cues underlying timing of blue whales' breeding migration in the Northeast Pacific via individual-based models parameterized by empirical behavioral data. Comparing emergent patterns from individual-based models to individual and population-level empirical metrics of migration timing, we find that individual whales likely rely on both personal and social sources of information about forage availability in deciding when to depart from their vast and dynamic foraging habitat and initiate breeding migration. Empirical patterns of migratory phenology can only be reproduced by models in which individuals use long-distance social information about conspecifics' behavioral state, which is known to be encoded in the patterning of their widely propagating songs. Further, social communication improves pre-migration seasonal foraging performance by over 60% relative to asocial movement mechanisms. Our results suggest that long-range communication enhances the perceptual ranges of migrating whales beyond that of any individual, resulting in increased foraging performance and more collective migration timing. These findings indicate the value of nonlocal social information in an oceanic migrant and suggest the importance of long-distance acoustic communication in the collective migration of wide-ranging marine megafauna.

The Biting Colon: An Unfortunate Nightmare for a Healthy but Anxious Patient.

A 48-year-old female with no significant past medical history presented to the emergency department with an uncommon scenario after accidentally ingesting a three-unit dental bridge, leading to its impaction within the lower gastrointestinal tract. Despite initial conservative management with laxatives aimed at facilitating spontaneous passage, the foreign body remained lodged in the colon. Subsequently, the patient underwent endoscopic intervention via colonoscopy, during which the dental bridge was successfully extracted. This case highlights the complexity of managing foreign body ingestions, particularly when impaction occurs in uncommon locations, such as the colon. We emphasize the importance of individualized care strategies and recognize the potential of endoscopic procedures in resolving clinical scenarios involving foreign body ingestions.

α-Adrenergic regulation of skeletal muscle blood flow during exercise in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) has been characterized by lower blood flow to exercising limbs and lower peak oxygen utilization ( V ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ), possibly associated with disease-related changes in sympathetic (α-adrenergic) signaling. Thus, in seven patients with HFpEF (70 ± 6 years, 3 female/4 male) and seven controls (CON) (66 ± 3 years, 3 female/4 male), we examined changes (%Δ) in leg blood flow (LBF, Doppler ultrasound) and leg V ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ to intra-arterial infusion of phentolamine (PHEN, α-adrenergic antagonist) or phenylephrine (PE, α1-adrenergic agonist) at rest and during single-leg knee-extension exercise (0, 5 and 10 W). At rest, the PHEN-induced increase in LBF was not different between groups, but PE-induced reductions in LBF were lower in HFpEF (-16% ± 4% vs. -26% ± 5%, HFpEF vs. CON; P < 0.05). During exercise, the PHEN-induced increase in LBF was greater in HFpEF at 10 W (16% ± 8% vs. 8% ± 5%; P < 0.05). PHEN increased leg V ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ in HFpEF (10% ± 3%, 11% ± 6%, 15% ± 7% at 0, 5 and 10 W; P < 0.05) but not in controls (-1% ± 9%, -4% ± 2%, -1% ± 5%; P = 0.24). The 'magnitude of sympatholysis' (PE-induced %Δ LBF at rest - PE-induced %Δ LBF during exercise) was lower in patients with HFpEF (-6% ± 4%, -6% ± 6%, -7% ± 5% vs. -13% ± 6%, -17% ± 5%, -20% ± 5% at 0, 5 and 10 W; P < 0.05) and was positively related to LBF, leg oxygen delivery, leg V ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ , and the PHEN-induced increase in LBF (P < 0.05). Together, these data indicate that excessive α-adrenergic vasoconstriction restrains blood flow and limits V ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ of the exercising leg in patients with HFpEF, and is related to impaired functional sympatholysis in this patient group. KEY POINTS: Sympathetic (α-adrenergic)-mediated vasoconstriction is exaggerated during exercise in patients with heart failure with preserved ejection fraction (HFpEF), which may contribute to limitations of blood flow, oxygen delivery and oxygen utilization in the exercising muscle. The ability to adequately attenuate α1-adrenergic vasoconstriction (i.e. functional sympatholysis) within the vasculature of the exercising muscle is impaired in patients with HFpEF. These observations extend our current understanding of HFpEF pathophysiology by implicating excessive α-adrenergic restraint and impaired functional sympatholysis as important contributors to disease-related impairments in exercising muscle blood flow and oxygen utilization in these patients.

A targeted educational intervention increases oral anticoagulation rates in high-risk atrial fibrillation patients.

Background: Anticoagulation is the cornerstone of atrial fibrillation (AF) management for stroke prevention. Recently, we showed that oral anticoagulation (OAC) rates of AF patients in a large U.S. multispecialty health system are >80%. Objective: The purpose of this study was to improve OAC rates in AF patients via an educational intervention targeted to primary care providers with low OAC rates. Methods: Primary care clinicians were stratified by proportions of their AF patients at elevated stroke risk not taking anticoagulation medication. Clinicians with the lowest rates of anticoagulation were assigned to a target group receiving an educational program consisting of E-mail messaging summarizing anticoagulation guidelines. All other clinicians were assigned to a comparison group (CG). Data from a 6-month lead-in phase were compared with a 6-month follow-up period to determine whether the proportion of AF patients treated with OACs had changed. Results: Of the 141 primary care clinicians with patients who met the inclusion criteria, 36 (25.53%) were assigned to the educational group (EG) and 105 (74.47%) to the CG. At baseline, there was a significant difference in percent of high-risk AF patients who were untreated in the EG (20.65%) compared to the high-risk patients who were untreated in the CG (13.64%; P = .001). After the educational intervention, high-risk AF patients without anticoagulation decreased in both EG (15.47%; P = .047) and CG (10.14%; P = .07), with greater absolute reduction in the EG (5.19% vs 3.50%). Conclusion: A targeted education program was associated with increased anticoagulation rates for AF patients at high risk for stroke.

Correction: Cingulate transcranial direct current stimulation in adults with HIV.

[This corrects the article DOI: 10.1371/journal.pone.0269491.].

Biguanides and glucagon like peptide 1 receptor agonists in the amelioration of post liver transplant weight gain; a scoping review of the mechanism of action, safety and efficacy.

Weight gain post-liver transplant can lead to adverse patient outcomes in the post-transplant period. Pharmacotherapy and other measures can be utilised to reduce the burden and occurrence of weight gain in this population. We explored the mechanism of action, safety, and efficacy of these medications, specifically GLP-1 receptor agonists and metformin, focusing on liver transplant patients. This scoping review was conducted in line with the scoping review structure as outlined by the PRISMA guidelines. Metformin and GLP-1 receptor agonists have been observed to be safe and effective in liver transplant patients. Experimental models have found liver-centric weight loss mechanisms in this drug cohort. There is a paucity of evidence about the use of antihyperglycemics in a post-transplant population for weight loss purposes. However, some small studies have shown strong safety and efficacy data. The evidence in relation to using these medications in patients with metabolic syndrome for weight loss warrants further study in a transplant population.

Performance status at the time of lung retransplant predicts long-term function.

BACKGROUND: Lung retransplantation is offered to select patients with chronic allograft dysfunction. Given the increased risk of morbidity and mortality conferred by retransplantation, post-transplant function should be considered in the decision of who and when to list. The aim of this study is to identify predictors of post-operative disability in patients undergoing lung retransplantation. METHODS: Data were collected from the UNOS national dataset and included all patients who underwent lung retransplant from May 2005-March 2023. Pre- and post-operative function was reported by the Karnofsky Performance Status (KPS) and patients were stratified based on their needs. Cumulative link mixed effects models identified associations between pre-transplant variables and post-transplant function. RESULTS: A total of 1275 lung retransplant patients were included. After adjusting for between-group differences, pre-operative functional status was predictive of post-transplant function; patients requiring Total Assistance ( n = 740) were 74% more likely than No/Some Assistance patients (n = 535) to require more assistance in follow-up (OR 1.74, 95% CI 1.13-2.68, p = .012). Estimated one year survival of Total Assistance patients is lower than No/Some Assistance Recipients (72% vs. 82%, CI 69%-75%; 79%-86%) but similar to overall re-transplant survival (76%, CI 74%-79%). CONCLUSION: Both survival and regain of function in patients requiring Total Assistance prior to retransplant may be higher than previously reported. Pre-operative functional status is predictive of post-operative function and should weigh in the selection, timing and post-operative care of patients considered for lung retransplantation.

Influence of cardiac diagnosis on outcomes of pediatric heart-lung transplantation.

OBJECTIVE: Pediatric Heart-lung transplant (HLTX) is performed for endstage congenital heart disease (CHD) with irreversible pulmonary hypertension or non-congenital heart disease (NCHD) with end-stage heart and lung disease. CHD could influence the outcomes of HTLX due to increased complexity of the operation as compared to NCHD. In this study we evaluated the influence of cardiac diagnosis on outcomes of pediatric HTLX. METHODS: The UNOS database (1987-2022) was queried for primary HTLX in patients <18 years. The data were extracted for demographics, pretransplant characteristics, post-transplant outcomes, and analyzed for the impact of cardiac diagnosis on post-transplant outcomes. Standard statistical tests were used. Survival was compared using the Kaplan-Meier method. RESULTS: Ninety of the 213 patients who underwent HLTX had CHD. There were no demographic differences. Heart listing status was similar but with a higher LAS score for NCHD. NCHD had higher pre-operative life support use (mechanical ventilation, inotropes or dialysis) but the use of ECMO as a bridge to transplantation was similar. Wait-list times were longer for CHD. The ischemic times were similar. Post-transplant dialysis, stroke, prolonged mechanical ventilation, and rejection were similar. Survival at 30-days, 1-year, and long-term survival at 17 years was similar. Non-survivors at 30-days post-transplant were on life support, used ECMO as a bridge, had lower wait-list times, longer ischemic times and had strokes. Non-survivors at 1-year had similar factors in addition to a higher dialysis use. CONCLUSION: Cardiac diagnosis had no impact on outcomes after Pediatric HLTX. Patients on life support or ECMO before transplantation were transplanted faster but with lower survival.

Repair of Full-Thickness Gluteus Maximus Tear With Suture Anchors.

Gluteal tendon tears are a common cause of hip pain. Most commonly, tears occur in the gluteus medius and minimus, and there are well-established nonoperative or operative treatment pathways. In this Technical Note, we describe our technique for repair of a full-thickness gluteus maximus tendon tear using anchor fixation.

IL-10 Differentially Promotes Mast Cell Responsiveness to IL-33, Resulting in Enhancement of Type 2 Inflammation and Suppression of Neutrophilia.

Mast cells (MCs) play critical roles in the establishment of allergic diseases. We recently demonstrated an unexpected, proinflammatory role for IL-10 in regulating MC responses. IL-10 enhanced MC activation and promoted IgE-dependent responses during food allergy. However, whether these effects extend to IgE-independent stimuli is not clear. In this article, we demonstrate that IL-10 plays a critical role in driving IL-33-mediated MC responses. IL-10 stimulation enhanced MC expansion and degranulation, ST2 expression, IL-13 production, and phospho-relA upregulation in IL-33-treated cells while suppressing TNF-α. These effects were partly dependent on endogenous IL-10 and further amplified in MCs coactivated with both IL-33 and IgE/Ag. IL-10's divergent effects also extended in vivo. In a MC-dependent model of IL-33-induced neutrophilia, IL-10 treatment enhanced MC responsiveness, leading to suppression of neutrophils and decreased TNF-α. In contrast, during IL-33-induced type 2 inflammation, IL-10 priming exacerbated MC activity, resulting in MC recruitment to various tissues, enhanced ST2 expression, induction of hypothermia, recruitment of eosinophils, and increased MCPT-1 and IL-13 levels. Our data elucidate an important role for IL-10 as an augmenter of IL-33-mediated MC responses, with implications during both allergic diseases and other MC-dependent disorders. IL-10 induction is routinely used as a prognostic marker of disease improvement. Our data suggest instead that IL-10 can enhance ST2 responsiveness in IL-33-activated MCs, with the potential to both aggravate or suppress disease severity depending on the inflammatory context.

The impact of fluorine-18-fluoroethyltyrosine positron emission tomography scan timing on radiotherapy planning in newly diagnosed patients with glioblastoma.

Background and purpose: Glioblastoma is one of the most common and aggressive primary brain tumours in adults. Though radiation therapy (RT) techniques have progressed significantly in recent decades, patient survival has seen little improvement. However, an area of promise is the use of fluorine-18-fluoroethyltyrosine positron-emission-tomography (18F-FET PET) imaging to assist in RT target delineation. This retrospective study aims to assess the impact of 18F-FET PET scan timing on the resultant RT target volumes and subsequent RT plans in post-operative glioblastoma patients. Materials and Methods: The imaging and RT treatment data of eight patients diagnosed with glioblastoma and treated at a single institution were analysed. Before starting RT, each patient had two 18F-FET-PET scans acquired within seven days of each other. The information from these 18F-FET-PET scans aided in the creation of two novel target volume sets. The new volumes and plans were compared with each other and the originals. Results: The median clinical target volume (CTV) 1 was statistically smaller than CTV 2. The median Dice score for the CTV1/CTV2 was 0.98 and, of the voxels that differ (median 6.5 cc), 99.7% were covered with a 5 mm expansion. Overall organs at risk (OAR) and target dosimetry were similar in the PTV1 and PTV2 plans. Conclusion: Provided the 18F-FET PET scan is acquired within two weeks of the RT planning and a comprehensive approach is taken to CTV delineation, the timing of scan acquisition has minimal impact on the resulting RT plan.