Beyond VEGF: Angiopoietin-Tie Signaling Pathway in Diabetic Retinopathy.

Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin-Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies.

Hypotension prediction index guided goal-directed therapy to reduce postoperative acute kidney injury during major abdominal surgery: study protocol for a multicenter randomized controlled clinical trial.

BACKGROUND: Acute kidney injury (AKI) is a significant postoperative complication associated with increased mortality and hospital costs. Hemodynamic strategies, such as goal-directed therapy, might reduce AKI risk. Predicting and proactively managing intraoperative hypotension may be helpful. This trial aims to investigate if a preemptive hemodynamic strategy guided by the hypotension prediction index (HPI) can decrease the incidence of moderate-to-severe AKI within 30 days following major elective abdominal surgery. METHODS: This is an open-label, controlled, multicenter, randomized clinical trial that involves daily patient follow-up until hospital discharge. Inclusion criteria are patients aged over 65 and/or categorized as ASA III or IV physical status, undergoing major elective abdominal surgery (general, urological, or gynecological procedures) via laparoscopic or open approach under general or combined anesthesia. INTERVENTION: In the intervention group, hemodynamic management will be based on the HPI and the advanced functional hemodynamic variables provided by the Hemosphere platform and the AcumenIQ® sensor (Edwards Lifesciences). The primary outcome is the incidence of moderate-to-severe AKI within 7 days post-surgery. Secondary outcomes include postoperative complications and 30-day mortality. DISCUSSION: This study explores the potential of HPI-guided hemodynamic management in reducing AKI after major elective abdominal surgery, with implications for postoperative outcomes and patient care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05569265. Registered on October 6, 2022.

Efficient bioremediation of indigo-dye contaminated textile wastewater using native microorganisms and combined bioaugmentation-biostimulation techniques.

In this work, the bioremediation of wastewater from the textile industry with indigo dye content was carried out using combined bioaugmentation, bioventilation, and biostimulation techniques. Initially, the inoculum was prepared by isolating the microorganisms from the textile wastewater in a 2 L bioreactor. Then, the respirometry technique was implemented to determine the affinity of the microorganisms and the substrate by measuring CO2 and allowed the formulation of an empirical mathematical model for the growth kinetics of the microorganism. Finally, the bioremediation was carried out in a 3 L bioreactor obtaining an indigo dye removal efficiency of 20.7 ± 1.2%, 24.0 ± 1.5%, and 29.7 ± 1.1% for equivalent wavelengths of 436 nm, 525 nm, and 620 nm. The chemical oxygen demand showed an average reduction of 88.9 ± 2.5%, going from 470.7 ± 15.6 to 52.3 ± 10.7 ppm after 30 days under constant agitation and aeration. A negative generalized exponential model was fitted to assess the affinity of the microorganism with the wastewater as a substrate by evaluating the production of CO2 during the bioremediation. Bioremediation techniques improve water discharge parameters compared to chemical treatments implemented in the industry, reducing the use of substances that can generate secondary pollution. Bioaugmentation, biostimulation, and bioventing of the textile wastewater in this study demonstrate the potential of these combined techniques to serve as an efficient alternative for indigo-contaminated wastewater in the textile industry.

Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia.

Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3+ T-cells to engage and lyse CD19+ target cells. Here we demonstrate that subcutaneous (SC) blinatumomab can provide high efficacy and greater convenience of administration. In the expansion phase of a multi-institutional phase 1b trial (ClinicalTrials.gov, NCT04521231), heavily pretreated adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) received SC blinatumomab at two doses: (1) 250 µg once daily (QD) for week 1 and 500 µg three times weekly (TIW) thereafter (250 µg/500 µg) or (2) 500 µg QD for week 1 and 1000 µg TIW thereafter (500 µg/1000 µg). The primary endpoint was complete remission/complete remission with partial hematologic recovery (CR/CRh) within two cycles. At the data cutoff of September 15, 2023, 29 patients were treated: 14 at the 250 µg/500 µg dose and 13 at 500 µg/1000 µg dose. Data from two ineligible patients were excluded. At the end of two cycles, 12 of 14 patients (85.7%) from the 250 µg/500 µg dose achieved CR/CRh of which nine patients (75.0%) were negative for measurable residual disease (MRD; <10-4 leukemic blasts). At the 500 µg/1000 µg dose, 12 of 13 patients (92.3%) achieved CR/CRh; all 12 patients (100.0%) were MRD-negative. No treatment-related grade 4 cytokine release syndrome (CRS) or neurologic events (NEs) were reported. SC injections were well tolerated and all treatment-related grade 3 CRS and NEs responded to standard-of-care management, interruption, or discontinuation. Treatment with SC blinatumomab resulted in high efficacy, with high MRD-negativity rates and acceptable safety profile in heavily pretreated adults with R/R B-ALL.

Minimal numerical ingredients describe chemical microswimmers' 3-D motion.

The underlying mechanisms and physics of catalytic Janus microswimmers is highly complex, requiring details of the associated phoretic fields and the physiochemical properties of catalyst, particle, boundaries, and the fuel used. Therefore, developing a minimal (and more general) model capable of capturing the overall dynamics of these autonomous particles is highly desirable. In the presented work, we demonstrate that a coarse-grained dissipative particle-hydrodynamics model is capable of describing the behaviour of various chemical microswimmer systems. Specifically, we show how a competing balance between hydrodynamic interactions experienced by a squirmer in the presence of a substrate, gravity, and mass and shape asymmetries can reproduce a range of dynamics seen in different experimental systems. We hope that our general model will inspire further synthetic work where various modes of swimmer motion can be encoded via shape and mass during fabrication, helping to realise the still outstanding goal of microswimmers capable of complex 3-D behaviour.

Feasibility of Forward Osmosis to Recover Textile Dyes Using Single Salts and Multicomponent Draw Solutions.

The textile industry generates large volumes of water characterized mainly by an intense color coming from dyes that are difficult to process due to their synthetic base and the presence of aromatic components. Due to the stricter regulation on the discharge of these effluents, in order to reduce dye waste before discharge into natural channels, alternatives are being sought to manage this wastewater. In this work, the concentration of dyes in simulated wastewater from the textile industry was studied by forward osmosis (with a cellulose triacetate CTA membrane), with the aim of concentrating the dye for its future recovery and reincorporation into the production process. Two dyes of different nature were evaluated to study the efficiency of the proposed process, using NaCl and reverse osmosis brine from a model seawater desalination solution as extraction solutions. It was observed that dye type (reactive or direct) and their charge influence the color rejection with the forward osmosis membrane used. It was able to concentrate the dyes in the feed solution up to approximately 55% with the reverse osmosis brine from the model seawater desalination solution. Finally, the results demonstrate that the FO process is a promising option for concentrating dyes present in wastewater from the textile industry in order to reuse them in the dyeing process.

Early-Phase Perceptions of COVID-19's Impact on Ophthalmology Practice Patterns: A Survey from the Pan-American Association of Ophthalmology.

Purpose: The COVID-19 pandemic affected medical practice worldwide due to interventions to prevent spreading. Its effect on ophthalmology practices in Latin America has not yet been explored. We aimed to assess the perceptions about the pandemic from countries' ophthalmological national and subspecialty retina societies affiliated to the Pan-American Association of Ophthalmology (PAAO). Patients and Methods: A survey-based study of leaders of national ophthalmological and retinal societies was conducted. The survey was sent by email to 30 societies, from which 20 responded (12 countries, 66.6% response rate). It included closed- and open-ended questions about (1) operational capacity and precautions, (2) telemedicine and virtual care, (3) procedures, and (4) post-pandemic considerations. Results: There was a marked decline in ophthalmology patient visits (80-95%) and elective surgeries (90%) during 2020 compared to before the pandemic. Precautions like temperature checks, mask usage, and social distancing were widely implemented while personal protective equipment (PPE) availability varied. Telemedicine use was limited due to lack of experience with it. Reopening plans focused on maintaining precautions and gradually resuming activities. Economic and security concerns were raised, and adherence to guidelines was emphasized. Respondents acknowledged the need to adapt to a "new normal". Long duration drugs, fewer imaging studies, and shorter wait times were preferred; however, availability of long duration drugs was limited. Conclusion: The pandemic impacted ophthalmology in Latin America, with reduced patient visits, procedures, and surgeries. Delayed treatment and complications were likely the result of the pandemic.

Theoretical Model for the Prediction of Water Flux during the Concentration of an Olive Mill Wastewater Model Solution by Means of Forward Osmosis.

Currently, understanding the dynamics of the interaction between the agents in a process is one of the most important factors regarding its operation and design. Membrane processes for industrial wastewater management are not strangers to this topic. One such example is the concentration of compounds with high added value, such as the phenolic compounds present in olive mill wastewater (OMW). This process is a viable option, thanks to the forward osmosis (FO) process, osmotically driven by a saline stream. In this context, the transport of the solute and the solvent through the FO membranes, although essential to the process, remains problematic. This paper presents a study to predict, by means of a theoretical model, the water flux for two membranes (a cellulose triacetate flat sheet and a polyamide hollow fiber with integrated aquaporin proteins) with different characteristics using a sodium chloride solution as the draw solution (DS). The novelty of this model is the consideration of the contribution of organic compounds (in addition to the inorganic salts) to the osmotic pressure in the feed side. Moreover, the geometry of the modules and the characteristics of the membranes were also considered. The model was developed with the ability to run under different conditions, with or without tyrosol (the compound chosen as representative of OMW phenolic compounds) in the feed solution (FS), and was fitted and evaluated using experimental data. The results presented a variability in the model prediction, which was a function of both the membrane used and the FS and DS, with a greater influence of tyrosol observed on the permeate flux in the flat cellulose triacetate membrane.

Nitrogen recovery from sludge centrate by membrane contactor: Influence of operating parameters and cleaning conditions.

In urban wastewater treatment, the sludge generated is treated by anaerobic digestion, to be subsequently dehydrated by centrifuges. Currently, the liquid fraction obtained in this dehydration process is recirculated at the head of the treatment plant. However, its high nitrogen and phosphorus content makes it an effluent with high added value. The recovery of these nutrients could be an excellent alternative for the production of fertilizers or other industrial applications. In this study, the use of a liquid-liquid phase membrane contactor is presented as a favorable solution for the recovery of ammoniacal nitrogen from sludge centrated. The polypropylene hollow fiber membrane was evaluated considering its ammonia removal and recovery capacity. For this, different parameters were evaluated: the influence of the type and concentration of the acid solution, the wastewater pH, the flow rates of feeding and the acid stripping solution, and the contact time. Results showed that with a contact time of 65 min, ammonia removal and recovery percentages of the order of 90% were achieved. The flow rates of the stripping and feed solutions together with the acid concentration did not have a significant influence on the removal but on the recovery. Concerning used acid, sulphuric and phosphoric acid solutions achieved better results than nitric acid solution. The most critical parameter was the pH, obtaining the highest removal and recovery of ammonium at the highest pH. Finally, a stable cleaning protocol was obtained, between preventive and moderate cleanings to avoid severe cleanings, keeping the membrane at its maximum capacity.

Clinical outcomes after CPX-351 in patients with high-risk acute myeloid leukemia: A comparison with a matched cohort from the Spanish PETHEMA registry.

BACKGROUND: CPX-351 is approved for the treatment of therapy related acute myeloid leukemia (t-AML) and AML with myelodysplastic related changes (MRC-AML). The benefits of this treatment over standard chemotherapy has not been addressed in well matched cohorts of real-life patients. METHODS: Retrospective analysis of AML patients treated with CPX-351 as per routine practice. A propensity score matching (PSM) was used to compare their main outcomes with those observed in a matched cohort among 765 historical patients receiving intensive chemotherapy (IC), all of them reported to the PETHEMA epidemiologic registry. RESULTS: Median age of 79 patients treated with CPX-351 was 67 years old (interquartile range 62-71), 53 were MRC-AML. The complete remission (CR) rate or CR without recovery (CRi) after 1 or 2 cycles of CPX-351 was 52%, 60-days mortality 18%, measurable residual disease <0.1% in 54% (12 out of 22) of them. Stem cell transplant (SCT) was performed in 27 patients (34%), median OS was 10.3 months, and 3-year relapse incidence was 50%. Using PSM, we obtained two comparable cohorts treated with CPX-351 (n = 52) or IC (n = 99), without significant differences in CR/CRi (60% vs. 54%) and median OS (10.3 months vs. 9.1 months), although more patients were bridged to SCT in the CPX-351 group (35% vs. 12%). The results were confirmed when only 3 + 7 patients were included in the historical cohort. In multivariable analyses, SCT was associated with better OS (HR 0.33 95% CI: 0.18-0.59), p < 0.001. CONCLUSION: Larger post-authorization studies may provide evidence of the clinical benefits of CPX-351 for AML in the real-life setting.

Field-Pulse-Induced Annealing of 2D Colloidal Polycrystals.

Two-dimensional colloidal crystals are of considerable fundamental and practical importance. However, their quality is often low due to the widespread presence of domain walls and defects. In this work, we explored the annealing process undergone by monolayers of superparamagnetic colloids adsorbed onto fluid interfaces in the presence of magnetic field pulses. These systems present the extraordinary peculiarity that both the extent and the character of interparticle interactions can be adjusted at will by simply varying the strength and orientation of the applied field so that the application of field pulses results in a sudden input of energy. Specifically, we have studied the effect of polycrystal size, pulse duration, slope and frequency on the efficiency of the annealing process and found that (i) this strategy is only effective when the polycrystal consists of less than approximately 10 domains; (ii) that the pulse duration should be of the order of magnitude of the time required for the outer particles to travel one diameter during the heating step; (iii) that the quality of larger polycrystals can be slightly improved by applying tilted pulses. The experimental results were corroborated by Brownian dynamics simulations.

Rheology of Pseudomonas fluorescens biofilms: From experiments to predictive DPD mesoscopic modeling.

Bacterial biofilms mechanically behave as viscoelastic media consisting of micron-sized bacteria cross-linked to a self-produced network of extracellular polymeric substances (EPSs) embedded in water. Structural principles for numerical modeling aim at describing mesoscopic viscoelasticity without losing details on the underlying interactions existing in wide regimes of deformation under hydrodynamic stress. Here, we approach the computational challenge to model bacterial biofilms for predictive mechanics in silico under variable stress conditions. Up-to-date models are not entirely satisfactory due to the plethora of parameters required to make them functioning under the effects of stress. As guided by the structural depiction gained in a previous work with Pseudomonas fluorescens [Jara et al., Front. Microbiol. 11, 588884 (2021)], we propose a mechanical modeling by means of Dissipative Particle Dynamics (DPD), which captures the essentials of topological and compositional interactions between bacterial particles and cross-linked EPS-embedding under imposed shear. The P. fluorescens biofilms have been modeled under mechanical stress mimicking shear stresses as undergone in vitro. The predictive capacity for mechanical features in DPD-simulated biofilms has been investigated by varying the externally imposed field of shear strain at variable amplitude and frequency. The parametric map of essential biofilm ingredients has been explored by making the rheological responses to emerge among conservative mesoscopic interactions and frictional dissipation in the underlying microscale. The proposed coarse grained DPD simulation qualitatively catches the rheology of the P. fluorescens biofilm over several decades of dynamic scaling.

Racial-Ethnic Disparities in Benzodiazepine Prescriptions for Anxiety in US Emergency Departments.

BACKGROUND/OBJECTIVES: Benzodiazepines are commonly used to treat anxiety and panic disorders. White patients are more likely to receive a benzodiazepine prescription than non-White patients in different medical settings. Racial-ethnic disparities have also been found in prescription of opioids from the emergency room. It is not known whether racial disparities in benzodiazepine prescriptions exist at the emergency department level. This study aims to analyze the relationship between benzodiazepine prescriptions for anxiety in an emergency department setting. DESIGN: Data for this cross-sectional study was obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS) Years 2009-2018. Patients ≥ 18 years of age presenting to the emergency department with anxiety were identified. Adjusted survey logistic regression was conducted to evaluate the patient characteristics and receipt of benzodiazepines. RESULTS: This study analyzed 1,174,556,119 emergency department (ED) visits out of which 2.8% had a diagnosis of anxiety disorder. Prevalence of anxiety was higher in the following groups: females, younger age range (18-34 years old), and non-Hispanic (NH) White. Rates of benzodiazepine prescription for patients with anxiety were higher for NH-White and Hispanic patients at 29% and 28% respectively than for NH-Black and NH-Other (24% and 21% respectively). Compared to NH-White patients, NH-Black patients were 36% less likely to be prescribed a benzodiazepine (prevalence ratio (PR) = 0.64; 95% confidence interval (CI) = 0.54-0.76) and Hispanic patients were 19% less likely to be prescribed a benzodiazepine (PR = 0.81; 95% CI = 0.68-0.96). Age, sex, or type of insurance did not show a statistically significant influence in the prescription of benzodiazepines. CONCLUSIONS: These findings reveal that NH-Black and Hispanic patients with anxiety are significantly less likely to be prescribed benzodiazepines than their NH-White counterparts in the ED. Further studies are needed to determine the root causes of these health disparities and strategies to combat them.

Peritonitis Due to Appendicitis Related to Mercury Sequestration: An Unusual Peruvian Case Report.

Elemental mercury ingestion caused by folk practices is rare and usually harmless. Nevertheless, some complications related to mercury ingestion have been reported such as appendicitis related to mercury sequestration and poisoning leading to systemic toxicity. Patients usually present with nausea, vomiting, and abdominal tenderness. Mercury sequestration in the appendix depends on its anatomy and mercury physical properties, both of which may lead to appendicitis, resulting in subsequent peritonitis leading to multiple and severe surgical complications. A 26-year-old Peruvian man complaining of vomiting and abdominal pain after ingestion of elemental mercury as part of a folk practice presented to the emergency department. Physical exam was remarkable for rigid abdomen and diffuse rebound sign. A clinical diagnosis of peritonitis was made. The patient was taken to the operating room where an open appendectomy and peritoneal lavage were performed. On gross inspection, a silver foreign body within the perforated appendix was seen by the surgical team. The patient developed multiple surgical complications leading to multiple organ failure and death. Clinicians should be aware that mercury ingestion is usually benign. However, severe complications may develop. Early surgical and medical intervention should be initiated promptly to achieve better outcomes. We present the first case of peritonitis due to appendicitis related to mercury sequestration in the appendix.

Co-designing a behavioural intervention for reducing the impact of chemotherapy-induced peripheral neuropathy symptoms: An evidence- and theory-driven approach.

OBJECTIVE: This study aims to co-design an evidence- and theory-based behavioural intervention to reduce the impact of chemotherapy-induced peripheral neuropathy (CIPN) symptoms on patients' quality of life. METHODS: Guided by the Medical Research Council Framework for developing and evaluating complex interventions, our intervention development process was guided by (a) findings of systematic reviews, (b) inductive analysis of 39 h of observational fieldwork, 12 patient and 11 clinician interviews, (c) deductive analysis using the Common-Sense Model to develop a Self-Regulation Model of CIPN and (d) 17 patients and 18 clinicians co-designing the intervention. RESULTS: CIPN perception and coping behaviours were highlighted as processes to target when co-designing an intervention. The processes targeted in our intervention are CIPN perception and coping behaviours, namely, (a) self-monitoring of symptoms, (b) communicating and early reporting of symptoms to clinicians, (c) participating in making chemotherapy dose reduction decisions with their clinicians and (d) engaging in self-management and safety strategies to reduce impact of CIPN symptoms. To address these, a behavioural intervention was deemed suitable. CONCLUSION: We developed a self-regulation model of CIPN and a logic model for documenting the proposed mechanism of action of our co-designed behavioural intervention for reducing impact of CIPN symptoms.

Co-designing a cancer care intervention: reflections of participants and a doctoral researcher on roles and contributions.

BACKGROUND: Patient and Public Involvement is most usually framed in the context of designing, conducting and/or disseminating research. Participatory methods such as Experience-Based Co-Design (EBCD) further allow service users to directly engage in developing, testing and implementing interventions and services alongside healthcare staff. This paper aims to explore how participants in an EBCD project came-over time-to perceive their role and involvement in co-designing a cancer care intervention. METHODS: The findings are based on our reflections, a research diary, email correspondence and fieldnotes from co-design events. Co-design participants who attended most of the ten co-design events took part through written reflections or audio-recorded video calls. Ten reflective pieces were collected from clinicians (n = 4), PPI group members/patient participants (n = 4), a doctoral researcher (n = 1) and a visual illustrator (n = 1). Inductive data analysis of participant reflections was carried out using reflexive thematic analysis. Meeting fieldnotes, email correspondence and the researcher's diary were deductively analysed using the initial themes generated from this inductive analysis. RESULTS: Five main themes were identified: (1) changing perception of roles during the co-design process, (2) defining a 'co-designer', (3) engagement and ownership, (4) role of the research facilitator in maintaining momentum, and (5) perceived benefits of involvement. CONCLUSION: Our findings show the changing perceptions of roles and contributions among participants over time. Patients typically described their role as co-designers in terms simply of sharing their experiences. In contrast, clinicians perceived themselves as co-designers because they were working with patients who were actively involved in decision-making. Levels of engagement were affected by several factors such as time and facilitation, but most participants came to view themselves as co-owners of the intervention. Overall, participants perceived their involvement as a positive experience with clinicians also reporting wider positive impacts on their clinical practice.

Experience-Based Co-Design is a method for helping patients and clinicians work together to improve healthcare services. Studies of participant experiences in projects which use this method and how they perceive the co-designer role are rare. Our study explores how we­patients and clinicians­saw our role and participation as co-designers over time. Our findings are based on our written and verbal reflections of participating in a co-design project aimed at developing an information resource booklet and film for use in cancer care. We also analysed meeting records, email messages between participants and a reflective diary kept by the researcher who was coordinating the project. Our findings show that views of our roles and contributions as co-design participants changed over time. Patients tended to see themselves as 'co-designers' simply because they shared their experiences throughout the co-design process. In contrast, clinicians saw themselves as 'co-designers' because they were working together with patients and making decisions with them. Factors such as time demands, and the skill of the facilitator affected the commitment of participants to co-design activities. Most participants regard the ownership of the newly developed information resources as being shared. Overall, we viewed our participation in the co-design project as a positive experience with results that will benefit clinical practice.

Radical cancer treatment is safe during COVID-19: the real-world experience of a large London-based Comprehensive Cancer Centre during the first wave.

BACKGROUND: During the COVID pandemic, there was a paucity of data to support clinical decision-making for anticancer treatments. We evaluated the safety of radical treatments which were delivered whilst mitigating the risks of concurrent COVID-19 infection. METHODS: Using descriptive statistics, we report on the characteristics and short-term clinical outcomes of patients undergoing radical cancer treatment during the first COVID-19 wave compared to a similar pre-pandemic period. RESULTS: Compared to 2019, the number of patients undergoing radical treatment in 2020 reduced by: 28% for surgery; 18% for SACT; and 10% for RT. Within SACT, 36% received combination therapy, 35% systemic chemotherapy, 23% targeted treatments, 5% immunotherapy and 2% biological therapy. A similar proportion of RT was delivered in 2019 and 2020 (53% vs. 52%). Oncological outcomes were also similar to pre-COVID-19. The COVID-19 infection rates were low: 12 patients were positive pre surgery (1%), 7 post surgery (<1%), 17 SACT patients (2%) and 3 RT patients (<1%). No COVID-19-related deaths were reported. CONCLUSIONS: Whilst there were fewer patients receiving radical anticancer treatments, those who did receive treatment were treated in a safe environment. Overall, cancer patients should have the confidence to attend hospitals and be reassured of the safety measures implemented.

Dynamical anomalies and structural features of active Brownian particles characterized by two repulsive length scales.

In this work, we study a two-dimensional system composed by Active Brownian Particles (ABPs) interacting via a repulsive potential with two length scales-a soft shell and a hard core. Depending on the ratio between the strength of the soft shell barrier and the activity, we find two regimes: If this ratio is much larger or smaller than 1, the observed behavior is comparable with ABPs interacting via a single length scale potential. If this ratio is similar to 1, the two length scales are relevant for both structure and dynamical properties. On the structural side, when the system exhibits a motility induced phase separation, the dense phase is characterized by new and more complex structures compared with the hexatic phase observed in single length scale systems. From the dynamic analysis, we find, to our knowledge, the first manifestation of a dynamic heterogeneity in active particles, reminiscent of the glassy dynamics widely studied in passive colloids.

Post-Transplantation Cyclophosphamide After HLA Identical Compared to Haploidentical Donor Transplant in Acute Myeloid Leukemia: A Study on Behalf of GETH-TC.

Post-transplantation cyclophosphamide (PTCY) effectively prevents graft-versus-host disease (GVHD) after unmanipulated HLA-haploidentical hematopoietic stem cell transplantation (HSCT) and achieves low rates of GVHD in HLA-identical transplantation. To compare the outcomes of haploidentical versus HLA identical HSCT in patients undergoing HSCT for acute myeloid leukemia (AML) using PTCY. We conducted a retrospective study of 229 patients undergoing first HSCT for AML using PTCY with additional immunosuppression, 99 from matched sibling or unrelated donor (MSD/MUD) performed in 3 hospitals and 130 from haploidentical donors (haplo group) performed in 20 hospitals within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cellular Therapy. Peripheral blood stem cells were used as graft in 89% of patients; myeloablative conditioning was used in 56%. There were significantly more patients with active disease (5% versus 20%, P = .001), high/very high disease risk index (DRI) (32% versus 67%, P = .000) and prior auto-HSCT (2% versus 11%, P = .010) in the haplo group. Median follow-up was 27 and 62.5 months for MSD/MUD and haplo, respectively. At 2 years, no significant differences were observed in overall survival (OS) (72% versus 62%, P = .07), event-free survival (EFS) (70% versus 54%, P = .055), cumulative incidence of relapse (19% versus 25%, P = .13), non-relapse mortality (14% versus 19%, P = .145), and the composite endpoint of GVHD and relapse-free survival (49% versus 42%, P = .249). Multivariate analysis identified only age and active disease as significant risk factors for OS and EFS; reduced-intensity conditioning, high/very high DRI, and haplo donor were nearly statistically significant for these outcomes. Grade II-IV acute GVHD was lower in MSD/MUD (14% versus 47%, P = .000). Cumulative incidences of grade III-IV acute GVHD (4% versus 9%, P = .14) and moderate-severe chronic GVHD (22% versus 19%, P = .28) were similar. Limitations of our study include limited sample size, differences between haplo and MSD/MUD groups and heterogeneous additional immunosuppression and PTCY timing in MSD/MUD. The use of an HLA-identical donor with PTCY in patients with AML showed lower incidence of clinically significant grade II-IV acute GVHD compared to haplo donors. Further studies with larger sample sizes should be performed to establish a possible benefit of HLA-identical donor on survival. © 2022 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The Impact of COVID-19 on the Delivery of Systemic Anti-Cancer Treatment at Guy's Cancer Centre.

BACKGROUND: This study aimed to assess the outcome of cancer patients undergoing systemic anti-cancer treatment (SACT) at our centre to help inform future clinical decision-making around SACT during the COVID-19 pandemic. METHODS: Patients receiving at least one episode of SACT for solid tumours at Guy's Cancer Centre between 1 March and 31 May 2020 and the same period in 2019 were included in the study. Data were collected on demographics, tumour type/stage, treatment type (chemotherapy, immunotherapy, biological-targeted) and SARS-CoV2 infection. RESULTS: A total of 2120 patients received SACT in 2020, compared to 2449 in 2019 (13% decrease). From 2019 to 2020, there was an increase in stage IV disease (62% vs. 72%), decrease in chemotherapy (42% vs. 34%), increase in immunotherapy (6% vs. 10%), but similar rates of biologically targeted treatments (37% vs. 38%). There was a significant increase in 1st and 2nd line treatments in 2020 (68% vs. 81%; p < 0.0001) and reduction in 3rd and subsequent lines (26% vs. 15%; p = 0.004) compared to 2019. Of the 2020 cohort, 2% patients developed SARS-CoV2 infections. CONCLUSIONS: These real-world data from a tertiary Cancer Centre suggest that despite the challenges faced due to the COVID-19 pandemic, SACT was able to be continued without any significant effects on the mortality of solid-tumour patients. There was a low rate (2%) of SARS-CoV-2 infection which is comparable to the 1.4%-point prevalence in our total cancer population.