The effect of ship-induced wave trains on periphytic algal communities in the littoral zone of a large regulated river (River Danube, Austria).

Riverine ecosystems are profoundly influenced by hydrological dynamics and natural flow regimes, which dictate the temporal variability of water levels and the amplitude of fluctuations. Human activities, particularly navigation and hydropower generation, have significantly altered these natural patterns, leading to detrimental impacts on the physical, chemical, and biological integrity of river ecosystems. The littoral zone, in particular, is highly susceptible to anthropogenic disturbances, experiencing disruptions in biological activity and biogeochemical processes. This study evaluates the effects of ship-induced wave trains on the structural and functional properties of periphytic algal communities in a regulated river environment. Using data from the Austrian Danube River, periphytic algae's immediate and long-term responses to wave events generated by different types of ships were investigated. Immediate reactions of periphytic algae to wave trains were characterized by reductions in the effective quantum yield of PS II, indicating stress-induced down-regulation of photosystem II photochemistry. Abrasion and remobilization of periphytic algae due to wave action led to increased resuspension of chlorophyll-a into the water column. Furthermore, ship-induced wave trains influenced the pigment composition of periphyton, with photoprotective mechanisms being activated in response to fluctuating light conditions. Long-term effects of wave impact on periphytic algae biomass varied depending on water depth and exposure to aerial stress. While wave action mitigated desiccation stress in shallow areas, it resulted in biomass reduction and alterations in community composition in deeper zones. Notably, the occurrence of diatoms decreased in wave-impacted areas, potentially shifting the community towards Chlorophyceae dominance. Overall, this study underscores the complexity of ship-induced wave impacts on riverine ecosystems and highlights the importance of considering both immediate and long-term responses of periphytic algal communities. Understanding these dynamics is crucial for informing sustainable management strategies aimed at mitigating the adverse effects of navigation activities on riverine biodiversity and ecosystem functioning.

The Case of Dolutegravir Plus Darunavir Antiretroviral Regimens: Is It Always Useful to Double the Drug Doses? A Short Communication.

BACKGROUND: Antiretroviral drug combinations affect dolutegravir trough concentrations. Here, the authors focused on dolutegravir plus booster darunavir antiretroviral regimens to investigate the effect of the booster and/or timing of drug administration on dolutegravir and darunavir plasma trough concentrations. METHODS: This retrospective observational study included consecutive people with HIV (PWH) receiving dolutegravir plus booster darunavir antiretroviral regimens for at least 3 months, with at least one assessment of dolutegravir and darunavir plasma trough concentrations. RESULTS: A total of 200 drug therapeutic drug monitoring results from 116 PWH were included. Dolutegravir and darunavir trough concentrations ranged, respectively, from 70 to 3648 mcg/L and from 102 to 11,876 mcg/L. The antiretroviral drug combination associated with the highest dolutegravir trough concentration was dolutegravir plus darunavir/cobicistat, both once daily (1410 ± 788 mcg/L), whereas dolutegravir once daily plus darunavir/ritonavir twice daily had the lowest trough concentrations (686 ± 481 mcg/L). Doubling the dose of dolutegravir did not significantly increase drug trough concentrations compared with that of once-daily regimens. Instead, the highest darunavir trough concentrations were with ritonavir (2850 ± 1456 mcg/L, P < 0.05 versus cobicistat-based regimens). Doubling the drug dose resulted in a significant increase in the darunavir trough concentration (4445 ± 2926 mcg/L, P < 0.05). CONCLUSIONS: Dolutegravir trough concentrations were significantly reduced in PWH receiving darunavir/ritonavir twice daily. This evidence should be carefully considered in clinical conditions requiring higher dolutegravir exposure, such as in the presence of drug-drug interactions with drugs known to reduce dolutegravir bioavailability or in highly experienced PWH.

Heterogeneity of Salmonella enterica lipopolysaccharide counteracts macrophage and antimicrobial peptide defenses.

Salmonella enterica is comprised of over 2,500 serovars, in which non-typhoidal serovars (NTS), Enteritidis (SE), and Typhimurium (STM) are the most clinically associated with human infections. Although NTS have similar genetic elements to cause disease, phenotypic variation including differences in lipopolysaccharide (LPS) composition may control immune evasion. Here, we demonstrate that macrophage host defenses and LL-37 antimicrobial efficacy against SE and STM are substantially altered by LPS heterogeneity. We found that SE evades macrophage killing by inhibiting phagocytosis while STM survives better intracellularly post-phagocytosis. SE-infected macrophages failed to activate the inflammasomes and subsequently produced less interleukin-1ß (IL-1ß), IL-18, and interferon λ. Inactivation of LPS biosynthesis genes altered LPS composition, and the SE LPS-altered mutants could no longer inhibit phagocytosis, inflammasome activation, and type II interferon signaling. In addition, SE and STM showed differential susceptibility to the antimicrobials LL-37 and colistin, and alteration of LPS structure substantially increased susceptibility to these molecules. Collectively, our findings highlight that modification of LPS composition by Salmonella increases resistance to host defenses and antibiotics.

Overview of the role of purinergic signaling and insights into its role in cancer therapy.

Innovation of cancer therapy has received a dramatic acceleration over the last fifteen years thanks to the introduction of the novel immune checkpoint inhibitors (ICI). On the other hand, the conspicuous scientific knowledge accumulated in purinergic signaling since the early seventies is finally being transferred to the clinic. Several Phase I/II clinical trials are currently underway to investigate the effect of drugs interfering with purinergic signaling as stand-alone or combination therapy in cancer. This is supporting the novel concept of "purinergic immune checkpoint" (PIC) in cancer therapy. In the present review we will address a) the basic pharmacology and cell biology of the purinergic system; b) principles of its pathophysiology in human diseases; c) implications for cell death, cell proliferation and cancer; d) novel molecular tools to investigate nucleotide homeostasis in the extracellular environment; e) recent developments in the pharmacology of P1, P2 receptors and related ecto-enzymes; f) P1 and P2 ligands as novel diagnostic tools; g) current issues in PIC-based anti-cancer therapy. This review will provide an appraisal of the current status of purinergic signaling in cancer and will help identify future avenues of development.

Light has a principal role in the Arabidopsis transcriptomic response to the spaceflight environment.

The Characterizing Arabidopsis Root Attractions (CARA) spaceflight experiment provides comparative transcriptome analyses of plants grown in both light and dark conditions within the same spaceflight. CARA compared three genotypes of Arabidopsis grown in ambient light and in the dark on board the International Space Station (ISS); Col-0, Ws, and phyD, a phytochrome D mutant in the Col-0 background. In all genotypes, leaves responded to spaceflight with a higher number of differentially expressed genes (DEGs) than root tips, and each genotype displayed distinct light / dark transcriptomic patterns that were unique to the spaceflight environment. The Col-0 leaves exhibited a substantial dichotomy, with ten-times as many spaceflight DEGs exhibited in light-grown plants versus dark-grown plants. Although the total number of DEGs in phyD leaves is not very different from Col-0, phyD altered the manner in which light-grown leaves respond to spaceflight, and many genes associated with the physiological adaptation of Col-0 to spaceflight were not represented. This result is in contrast to root tips, where a previous CARA study showed that phyD substantially reduced the number of DEGs. There were few DEGs, but a series of space-altered gene categories, common to genotypes and lighting conditions. This commonality indicates that key spaceflight genes are associated with signal transduction for light, defense, and oxidative stress responses. However, these key signaling pathways enriched from DEGs showed opposite regulatory direction in response to spaceflight under light and dark conditions, suggesting a complex interaction between light as a signal, and light-signaling genes in acclimation to spaceflight.

Society for Cardiovascular Magnetic Resonance 2023 Cases of SCMR Case Series.

"Cases of SCMR" is a case series on the SCMR website (https://www.scmr.org) for the purpose of education. The cases reflect the clinical presentation, and the use of cardiovascular magnetic resonance (CMR) in the diagnosis and management of cardiovascular disease. The 2023 digital collection of cases are presented in this manuscript.

Cellular prion protein acts as mediator of amyloid beta uptake by caveolin-1 causing cellular dysfunctions in vitro and in vivo.

INTRODUCTION: Cellular prion protein (PrPC) was implicated in amyloid beta (Aß)-induced toxicity in Alzheimer's disease (AD), but the precise molecular mechanisms involved in this process are unclear. METHODS: Double transgenic mice were generated by crossing Prnp knockout (KO) with 5xFAD mice, and light-sheet microscopy was used for whole brain tissue analyses. PrPC-overexpressing cells were developed for in vitro studies, and microscopy was used to assess co-localization of proteins of interest. Surface-plasmon resonance (SPR) was used to investigate protein-binding characteristics. RESULTS: In vivo, PrPC levels correlated with reduced lifespan and cognitive and motor function, and its ablation disconnected behavior deficits from Aß levels. Light-sheet microscopy showed that PrPC influenced Aß-plaque burden but not the distribution of those plaques. Interestingly, caveolin-1 (Cav-1) KO neurons significantly reduced intracellular Aß-oligomer (Aßo) uptake when compared to wild-type neurons. DISCUSSION: The findings shed new light on the relevance of intracellular Aßo, suggesting that PrPC and Cav-1 modulate intracellular Aß levels and the Aß-plaque load. HIGHLIGHTS: PrPC expression adversely affects lifespan and behavior in 5xFAD mice. PrPC increases Aß1-40 and Aß1-42 levels and Aß-plaque load in 5xFAD mice. Cav-1 interacts with both PrPC and Aß peptides. Knocking out Cav-1 leads to a significant reduction in intracellular Aß levels.

Tuning the B-CLL microenvironment: evidence for BAG3 protein- mediated regulation of stromal fibroblasts activity.

The Bcl2-associated athanogene-3 (BAG3) protein, a critical regulator of cellular survival, has been identified as a potential therapeutic target in various malignancies. This study investigates the role of BAG3 within stromal fibroblasts and its interaction with B-cell chronic lymphocytic leukemia (B-CLL) cells. Previous research demonstrated that BAG3 maintains the active state of pancreatic stellate cells (PSCs) and aids pancreatic ductal adenocarcinoma (PDAC) spread via cytokine release. To explore BAG3's role in bone marrow-derived stromal fibroblasts, BAG3 was silenced in HS-5 cells using siRNA. In co-culture experiments with PBMCs from B-CLL patients, BAG3 silencing in HS-5 cells increased apoptosis and decreased phosphorylation of BTK, AKT, and ERK in B-CLL cells, thus disrupting their pro-survival key signaling pathways. The observation of fibroblast-activated protein (FAP) positive cells in infiltrated bone marrow specimens co-expressing BAG3 further support the involvement of the protein in fibroblast-mediated tumor survival. Additionally, BAG3 appears to support B-CLL survival by modulating cytokine networks, including IL-10 and CXCL12, which are essential for leukemic cell survival and proliferation. A robust correlation between BAG3 expression and the levels of CXCL12 and IL-10 was observed in both co-cultures and patient specimens. These findings point out the need for a more in-depth comprehension of the intricate network of interactions within the tumor microenvironment and provide valuable insights for the selection of new potential therapeutic targets in the medical treatment of CLL.

Overexpression of BAG3 (Bcl2-associated athanogene 3) in serum and skin of patients with systemic sclerosis.

OBJECTIVES: BAG3 (Bcl2-associated athanogene3) is able to induce the transformation of cancer-associated fibroblasts to alpha smooth muscle actin (a-SMA) positive (+) myofibroblasts. In systemic sclerosis (SSc), a-SMA+ myofibroblasts also play an important role in the progression of fibrosis in the skin and involved internal organs. The aim of the study was to investigate whether BAG3 is overexpressed in SSc and may be a biomarker of fibrogenesis. METHODS: BAG3 serum levels were measured in 106 patients with SSc, 47 with the limited (lc) and 59 the diffuse (dc) SSc, and in age- and sex-matched healthy controls (HC). BAG3 levels were then compared according to their clinical subset, nailfold video-capillaroscopic (NVC) patterns, interstitial lung disease (ILD, and correlated with modified Rodnan skin score (mRSS) and global disease activity. BAG3 expression was also investigated in skin biopsies of 8 dcSSc patients. RESULTS: BAG3 serum levels were significantly higher in dcSSc (143.3 pg/mL, 95%CI 78-208.5) than in HC (0.68 pg/mL, 95%CI 0.13-1.23), and were significantly higher in patients with late NVC pattern and ILD but did not correlate with disease activity and mRSS. Of note, BAG3 was strongly expressed in the skin biopsies of dcSSc patients. CONCLUSIONS: BAG3 is overexpressed in dcSSc patients and may contribute to skin and organ fibrosis by prompting the transition of fibroblasts into myofibroblasts and increasing their survival. Thus, BAG3 may play an important role in SSc fibrotic pathogenesis and be a potential biomarker of fibrosis. Further research on its role as a therapeutic target is warranted.

Analyzing pain patterns in the emergency department: Leveraging clinical text deep learning models for real-world insights.

OBJECTIVE: To determine the incidence of patients presenting in pain to a large Australian inner-city emergency department (ED) using a clinical text deep learning algorithm. MATERIALS AND METHODS: A fine-tuned, domain-specific, transformer-based clinical text deep learning model was used to interpret free-text nursing assessments in the electronic medical records of 235,789 adult presentations to the ED over a three-year period. The model classified presentations according to whether the patient had pain on arrival at the ED. Interrupted time series analysis was used to determine the incidence of pain in patients on arrival over time. We described the changes in the population characteristics and incidence of patients with pain on arrival occurring with the start of the Covid-19 pandemic. RESULTS: 55.16% (95%CI 54.95%-55.36%) of all patients presenting to this ED had pain on arrival. There were differences in demographics and arrival and departure patterns between patients with and without pain. The Covid-19 pandemic initially precipitated a decrease followed by a sharp, sustained rise in pain on arrival, with concurrent changes to the population arriving in pain and their treatment. DISCUSSION: Applying a clinical text deep learning model has successfully identified the incidence of pain on arrival. It represents an automated, reproducible mechanism to identify pain from routinely collected medical records. The description of this population and their treatment forms the basis of intervention to improve care for patients with pain. The combination of the clinical text deep learning models and interrupted time series analysis has reported on the effects of the Covid-19 pandemic on pain care in the ED, outlining a methodology to assess the impact of significant events or interventions on pain care in the ED. CONCLUSION: Applying a novel deep learning approach to identifying pain guides methodological approaches to evaluating pain care interventions in the ED, giving previously unavailable population-level insights.

Preclinical Pharmacokinetics in Tumors and Normal Tissues of the Antigene PNA Oligonucleotide MYCN-Inhibitor BGA002.

Although MYCN has been considered an undruggable target, MYCN alterations confer poor prognosis in many pediatric and adult cancers. The novel MYCN-specific inhibitor BGA002 is an antigene peptide nucleic acid oligonucleotide covalently bound to a nuclear localization signal peptide. In the present study, we characterized the pharmacokinetics (PK) of BGA002 after single and repeated administration to mice using a novel specific enzyme-linked immunosorbent assay. BGA002 concentrations in plasma showed linear PK, with dose proportional increase across the tested dose levels and similar exposure between male and female and between intravenous and subcutaneous route of administration. Repeated dosing resulted in no accumulation in plasma. Biodistribution up to 7 days after single subcutaneous administration of [14C]-radiolabeled BGA002 showed broad tissues and organ distribution (suggesting a potential capability to reach primary tumor and metastasis in several body sites), with high concentrations in kidney, liver, spleen, lymph nodes, adrenals, and bone marrow. Remarkably, we demonstrated that BGA002 concentrates in tumors after repeated systemic administrations in three mouse models with MYCN amplification (neuroblastoma, rhabdomyosarcoma, and small-cell lung cancer), leading to a significant reduction in tumor weight. Taking into account the available safety profile of BGA002, these data support further evaluation of BGA002 in patients with MYCN-positive tumors.

Mismanagement of SARS-CoV-2 Infection Pre Hospitalisation during the Omicron Era: Antibiotics and Steroids Instead of Early Antivirals.

The aim of this study was to assess the prevalence of inappropriate treatment among hospitalised patients affected by SARS-CoV-2 infection before hospital admission during the Omicron era. This single-centre, retrospective observational study included all the patients hospitalised because of SARS-CoV-2 infection during three periods characterised by the Italian prevalence of an Omicron variant of concern: (1) January-May 2022 (BA.1-BA.2), (2) June-October 2022 (BA.5), and (3) November 2022-March 2023 (BQ.1-XBB). Inappropriate treatment was defined as pre-hospitalisation exposure to antibiotics and/or steroids in the absence of a documented bacterial infection or the need for steroid treatment of an underlying medical condition. A total of 931 subjects were hospitalised: 394 in period 1, 334 in period 2, and 203 in period 3. Of the 157 patients undergoing inappropriate treatment (16.9%), 142 (15.3%) received antibiotics and 52 (5.6%) steroids. The proportion of inappropriately treated patients significantly decreased over time, from 23.1% in period 1 to 11.7% in period 2 and 13.3% in period 3 (p < 0.001), and there was a parallel decrease in antibiotic (p < 0.001) and steroid treatment (p < 0.013). Only 13 subjects (1.4%) received early pre-hospitalisation treatment for SARS-CoV-2. A significant proportion of hospitalised COVID-19 patients were exposed to inappropriate treatment before hospital admission.

Impact of a Bundle of Interventions on Quality-of-Care Indicators for Staphylococcus aureus Bacteraemia: A Single-Centre, Quasi-Experimental, Before-After Study.

Staphylococcus aureus bacteraemia (SAB) is a life-threatening bloodstream infection. Improved adherence to quality-of-care indicators (QCIs) can significantly enhance patient outcomes. This quasi-experimental study evaluated the impact of a bundle of interventions on QCI adherence in adult patients with SAB. Additionally, a molecular rapid diagnostic test (mRDT) for S. aureus and methicillin resistance was introduced during weekdays. We compared pre-intervention (January-December 2022) and post-intervention (May 2023-April 2024) data on QCI adherence and time to appropriate treatment. A total of 56 and 40 SAB episodes were included in the pre- and post-intervention periods, respectively. Full QCI adherence significantly increased from 28.6% to 67.5% in the post-intervention period (p < 0.001). The mRDT diagnosed SAB in eight cases (26.6%), but the time to achieve appropriate target therapy did not improve in the post-intervention period (54 h (IQR 30-74) vs. 72 h (IQR 51-83), p = 0.131). The thirty-day mortality rate was comparable between the two periods (17.9% vs. 12.5%, p = 0.476). This study demonstrates that a bundle of interventions can substantially improve adherence to SAB management QCIs.

Customized Vestibular Rehabilitation for Vestibular Schwannoma Excision via Translabyrinthine Approach: A Single-Center Experience.

Objectives: To evaluate the effectiveness of intensive customized vestibular rehabilitation after vestibular schwannoma (VS) excision. Methods: 52 patients who underwent VS removal via a translabyrinthine approach from 2020 to 2022 were involved in this study. Bedside examination, video head impulse test (vHIT), functional head impulse test (fHIT), and the dizziness handicap inventory (DHI) were performed before and after the rehabilitation, which consisted of 10 sessions of specifically designed vestibular, visual, and physical integrated training. Results: After rehabilitation, the vHIT showed overall unchanged values on the affected and healthy side. In contrast, the scores of fHIT, which explores the higher connection of the vestibular system with visual and cerebellar pathways, improved on both the pathological and healthy sides after training (p-value 0.004 and 0.000, respectively). The effectiveness of the rehabilitation was reinforced by the DHI scores, which were considerably lower after training. Conclusions: To our knowledge, this is the first study to explore fHIT outcomes after removal of VS, estimating the impact of rehabilitation on the overall compensation process. The outcomes support the role of extensive postsurgical rehabilitation in the compensatory process, even just a few days after surgery.

The P2X7 Receptor is a Master Regulator of Microparticle and Mitochondria Exchange in Mouse Microglia.

Microparticles (MPs) are secreted by all cells, where they play a key role in intercellular communication, differentiation, inflammation, and cell energy transfer. P2X7 receptor (P2X7R) activation by extracellular ATP (eATP) causes a large MP release and affects their contents in a cell-specific fashion. We investigated MP release and functional impact in microglial cells from P2X7R-WT or P2X7R-KO mice, as well as mouse microglial cell lines characterized for high (N13-P2X7RHigh) or low (N13-P2X7RLow) P2X7R expression. P2X7R stimulation promoted release of a mixed MP population enriched with naked mitochondria. Released mitochondria were taken up and incorporated into the mitochondrial network of the recipient cells in a P2X7R-dependent fashion. NLRP3 and the P2X7R itself were also delivered to the recipient cells. Microparticle transfer increased the energy level of the recipient cells and conferred a pro-inflammatory phenotype. These data show that the P2X7R is a master regulator of intercellular organelle and MP trafficking in immune cells.

How to manage adult patients with malaria in the non-endemic setting.

BACKGROUND: The diagnosis and management of malaria in non-endemic countries presents a continuing challenge. Plasmodium falciparum, which is capable of rapidly inducing severe and life-threatening multiorgan disease, is the species most frequently diagnosed in Europe and North America. OBJECTIVES: To summarise the more relevant diagnostic findings and clinical features of malaria observed in non-endemic settings and to provide an update of the key management decision points using three illustrative clinical scenarios of uncomplicated and severe malaria. SOURCES: The discussion is based on a relevant literature search spanning the last 20 years. Recommendations are based on available clinical guidelines including those of the WHO, observational studies conducted in non-endemic settings, and, when available, extrapolation from randomised studies from malaria-endemic settings. CONTENT: The following topics are covered: diagnosis, including the use of molecular biology; clinical characteristics; management with a specific focus on complicated (severe) and uncomplicated malaria; and areas of resistance to available antimalarial drugs. IMPLICATIONS: Malaria imported to non-endemic settings, especially P. falciparum malaria, is sometimes initially overlooked and the delayed diagnosis is responsible for every year of preventable deaths. This review aims to raise awareness of malaria outside endemic countries and to provide clinicians with a practical guide for efficient diagnosis and targeted therapy for the different species involved.

[The Basel model of principle-oriented clinical ethics consultation 2.0 : An introduction for psychiatry]. / Das Basler Modell der prinzipienorientierten klinischen Ethikkonsultation 2.0 : Eine Einführung für die Psychiatrie.

BACKGROUND: The effectiveness of clinical ethics counselling in medicine in terms of satisfaction of the participants, support of ethical decision-making, perceived impact on clinical care, moral competence and quality of communication is now empirically well validated. In psychiatry, more and more institutions have structures for clinical ethics consultation as well; however, there is still a lack of evaluative accompanying research on the benefits and differential indications of the various forms and models of clinical ethics counselling in psychiatry. AIM OF THE WORK: The article presents the principles and the step by step application of the principle-oriented clinical ethics consultation according to the Basel model 2.0. MATERIAL AND METHODS: The article is based on material and procedures developed at the Clinical Ethics Unit of the University Hospital Basel and the University Psychiatric Clinics Basel for the principle-oriented clinical ethics consultation according to the Basel model 2.0. RESULTS AND DISCUSSION: Principle-oriented clinical ethics consultation according to the Basel model 2.0 is suitable for dealing with moral issues and conflicts in psychiatric practice and for their ethical reflection; however, further evaluative accompanying research is needed on the benefits and differential indications of this and other models of clinical ethics support in psychiatry.

Hospital-Based Influenza and Pneumococcal Vaccination for Cancer Patients on Active Treatment and Their Family Members during the COVID-19 Pandemic in Italy: A Single-Center Experience.

In patients with cancer, tumor- and treatment-induced immunosuppression are responsible for a four-fold increase in morbidity and mortality caused by influenza and invasive Streptococcus pneumoniae infections compared to the general population. The main oncology societies strongly recommend vaccination in patients with cancer to prevent these infections. However, vaccine hesitancy is a main concern in this population. The aim of this study was to assess the feasibility of in-hospital vaccination for patients under anticancer treatment and their family members (FMs) against influenza and pneumococcal infections during the COVID-19 pandemic in order to increase vaccine coverage. This was a single-center, prospective, observational study conducted at the Department of Oncology of Luigi Sacco University Hospital (Milan, Italy) between October 2020 and April 2021. The main primary outcome was the incidence of influenza-like illness (ILI) and pneumococcal infections. The main secondary outcome was safety. A total of 341 subjects were enrolled, including 194 patients with cancer and 147 FMs. The incidence of ILI was higher among patients than among FMs (9% vs. 2.7%, OR 3.92, p = 0.02). Moreover, two subjects were diagnosed with pneumococcal pneumonia. The most frequent vaccine-related AEs were pain in the injection site (31%) and fatigue (8.7%). In conclusion, this hospital-based vaccination strategy was feasible during the COVID-19 pandemic, representing a potential model to maximize vaccine coverage during a public health emergency.

Establishing targets for goal-directed anesthesia in renal transplantation: A cohort analysis of high-saliency surgical time courses.

Delayed graft function (DGF) increases morbidity and mortality in kidney transplant recipients. Operative parameters, including hemodynamic manipulation through vasopressors and fluids, can impact perfusion to the newly transplanted kidney and influence DGF incidence. We analyzed intraoperative time-series data in 5-minute intervals from kidney transplant recipient operations (N = 545) in conjunction with pretransplant characteristics and postsurgical outcomes, including DGF incidence, 60-day creatinine, and graft survival. Of the operations, 127 DGF events were captured in our cohort from a single academic transplant center (57/278 donations after brainstem death [DBDs], 65/150 donations after circulatory/cardiac death [DCDs], 5/117 live donations). In multiple regression, postanastomosis hypotension defined as mean arterial pressure (MAP) <75 mmHg was a risk factor for DGF independent of conventional predictors of DGF in DCD and DBD kidneys. DCD recipients with DGF had lower average postanastomosis MAP (DGF: 80.1 ± 8.1 mmHg vs no DGF: 76.4 ± 6.7 mmHg, P = .004). Interaction analysis demonstrated above-average doses of vasopressors and crystalloids were associated with improved outcomes when used at MAPs ≤75 mmHg, but they were associated with increased DGF at MAPs >75 mmHg, suggesting that the incidence of DGF can be highly influenced by intraoperative hemodynamic controls. This analysis of surgical time courses has identified potential new strategies for goal-directed anesthesia in renal transplantation.