Timing of Toxicities and Non-relapse Mortality Following CAR T Therapy in Myeloma.

BACKGROUND: BCMA-directed chimeric antigen receptor T-cell (CAR T) therapies, including idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have transformed the treatment landscape for relapsed-refractory multiple myeloma (RRMM), offering remarkable efficacy with hallmark toxicity risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The FDA mandates a 4-week monitoring period at the treatment center as part of a Risk Evaluation and Mitigation Strategy (REMS) to monitor and manage these toxicities, which, while prudent, may add unnecessary challenges related to access and socioeconomic disparities. OBJECTIVE: We sought to assess CRS and ICANS onset and duration, as well as causes of non-relapse mortality (NRM) in real-world BCMA CAR T recipients in order to better inform future changes to the monitoring guidelines for CAR T recipients. STUDY DESIGN: This is a retrospective study across four academic centers that examined 129 ide-cel and cilta-cel recipients that received CAR T cell infusions from May 2021 to June 2023. Infusion and toxicities were managed per institutional guidelines in accordance with previously published guidelines. RESULTS: While differences were noted in the incidence and duration of CRS/ ICANS between ide-cel and cilta-cel, late-onset CRS and ICANS were rare after 2 weeks following infusion (0% and 1.6%, respectively). NRM was driven by hemophagocytic lymphohistiocytosis and infections in the early follow-up period (1.1% until Day 29), then by infections through three months post-infusion (1.2%). Our findings suggest that 25% of patients had to relocate for 4 weeks due to distance from the treatment center. CONCLUSIONS: With the low risk of CRS and ICANS after 2 weeks, a flexible shorter monitoring period may be reasonable, emphasizing collaboration with referring oncologists to improve NRM.

Comparison of biosimilar filgrastim and originator filgrastim for peripheral blood stem cell mobilization for allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Nivestym, a biosimilar granulocyte colony-stimulating factor (G-CSF) to the originator filgrastim (Neupogen), is now being used for the mobilization of peripheral blood stem cells (PBSC) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aim to compare the efficacy of Nivestym and Neupogen for PBSC mobilization in healthy allogeneic donors. METHODS: We conducted a retrospective single-center study including 541 adult allo-HSCT donors receiving Nivestym (January 2013-July 2020), or Neupogen (July 2020-June 2023) for donor PBSC mobilization. Bivariate analysis was conducted using SPSS version 28. Statistical significance was determined at a p-value <.05. RESULTS: Our study included 541 allo-HSCT donors who received Neupogen (n = 345, 64%) or Nivestym (n = 196, 36%) for PBSC mobilization. The median age was 47 years (range 17-76). The median donor weight was 86 kg (95% confidence interval [CI]: 87-91). Donors receiving Neupogen had similar pre-G-CSF white blood cell count, CD34+ percentages, and circulating CD34+ count compared with donors receiving Nivestym. The Neupogen group had similar median PBSC product total neutrophil count, CD34+ percentage, absolute CD34+ count, and infused CD34+ dose compared with the Nivestym group. For donors aged 35 years or younger, the median CD34+ dose was higher in donors who received Neupogen compared with Nivestym (6.9 vs. 6.3 million cells/kg, p = .044). CONCLUSIONS: Nivestym demonstrated similar efficacy for PBSC mobilization compared with Neupogen among allo-HSCT donors. In donors aged 35 years or younger, a slightly lower PBSC product CD34+ count was noted with Nivestym compared with Neupogen.

Preparation of medium- and long-chain triacylglycerols rich in n-3 polyunsaturated fatty acids by bio-imprinted lipase-catalyzed interesterification.

Medium and long-chain triacylglycerol (MLCT) rich in n-3 polyunsaturated fatty acids (PUFAs) were obtained in three-hour interesterification of fish oil with medium-chain triacylglycerol (MCTs), using lipase bio-imprinted with surfactant as a catalyst. Initially, for bio-imprinted lipase preparation, the interesterification reaction conditions were optimized, resulting in a lipase with 1.47 times higher catalytic activity compared to control (non-bio-imprinted). Afterwards, the reaction conditions for MLCT synthesis were optimized, using bio-imprinted lipase as a catalyst. The reaction reached equilibrium within first three hours at 70 °C temperature, 4 wt% lipase load, and molar ratio of substrate 1:1.5. Under these conditions, final product contained 18.52% MCT, 56.65% MLCT, and 24.83% long-chain triacylglycerol (LCT). To reduce the MCT content, a solvent extraction process was performed, yielding 2.42% MCT, 56.19% MLCT, and 41.39% LCT. The obtained structured lipids (SLs), enriched in n-3 PUFAs, offer significant health benefits, enhanced bioavailability, with potential applications in functional foods and nutraceuticals.

Correction to "Mitigation of Salinity Stress and Lead Toxicity in Maize by Exogenous Application of the Sorghum Water Extract".

[This corrects the article DOI: 10.1021/acsomega.3c09495.].

Phase-specific strategies and interventions to enhance medication adherence across different phases in ADHD: a systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis assessed the characteristics, types, and impact of interventions to improve adherence to attention-deficit hyperactivity disorder (ADHD) medications within the context of the three phases of adherence, namely, initiation, implementation, and discontinuation. METHODS: PubMed, Psychological Information Database, Embase, International Pharmaceutical Abstracts, and Google Scholar were systematically searched for relevant trials using appropriate search terms. Interventions were classified as educational, behavioural, affective, and multifaceted. Data was pooled using odds ratios and proportions. RESULTS: Seventeen studies were included in this review. In a pooled analysis of four RCTs, interventions did not significantly improve medication adherence (OR = 2.32; 95%-Confidence Interval=CI = 0.91-5.90; p = 0.08). In seven non-randomized trials, a pooled proportion of people who adhered to ADHD medication was considerably higher in the intervention group (85%, 95%CI = 78%-91%) than in the control group (47%, 95%CI = 33%-61%). Interventions varied in terms of study design, methods and their impact on different phases of adherence. CONCLUSIONS: Despite some promising results, the lack of consideration of phase-specific adherence factors may limit the effectiveness and sustainability of interventions to improve adherence in clinical practice. Future interventions should be phase-specific, guided by factors which are pertinent to each phase. Meanwhile, clinicians should choose or tailor interventions based on individual needs and preferences.

Green-synthesized lignin nanoparticles enhance Zea mays resilience to salt stress by improving antioxidant metabolism and mitigating ultrastructural damage.

Soil salinity poses a substantial threat to agricultural productivity, resulting in far-reaching consequences. Green-synthesized lignin nanoparticles (LNPs) have emerged as significant biopolymers which effectively promote sustainable crop production and enhance abiotic stress tolerance. However, the defensive role and underlying mechanisms of LNPs against salt stress in Zea mays remain unexplored. The present study aims to elucidate two aspects: firstly, the synthesis of lignin nanoparticles from alkali lignin, which were characterized using Field Emission Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM), Fourier Infrared Spectroscopy (FT-IR) and Energy Dispersive X-Ray Spectroscopy (EDX). The results confirmed the purity and morphology of LNPs. Secondly, the utilization of LNPs (200 mg/L) in nano priming to alleviate the adverse effects of NaCl (150 mM) on Zea mays seedlings. LNPs significantly reduced the accumulation of Na+ (17/21%) and MDA levels (21/28%) in shoots/roots while increased lignin absorption (30/31%), resulting in improved photosynthetic performance and plant growth. Moreover, LNPs substantially improved plant biomass, antioxidant enzymatic activities and upregulated the expression of salt-tolerant genes (ZmNHX3 (1.52 & 2.81 FC), CBL (2.83 & 3.28 FC), ZmHKT1 (2.09 & 4.87 FC) and MAPK1 (3.50 & 2.39 FC) in both shoot and root tissues. Additionally, SEM and TEM observations of plant tissues confirmed the pivotal role of LNPs in mitigating NaCl-induced stress by reducing damages to guard cells, stomata and ultra-cellular structures. Overall, our findings highlight the efficacy of LNPs as a practical and cost-effective approach to alleviate NaCl-induced stress in Zea mays plants. These results offer a sustainable agri-environmental strategy for mitigating salt toxicity and enhancing crop production in saline environments.

Assessing the Efficacy and Long-Term Outcomes of Surgical Intervention Versus Radiotherapy: A Comprehensive Systematic Review and Meta-Analysis of Prostate Cancer Treatment Modalities.

There is controversy regarding the most effective primary treatment of choice for prostate cancer (PCa) in terms of patient outcomes, such as surgery or radiotherapy (RT). This study evaluated the comparative efficacy and long-term outcomes of radical prostatectomy (RP) and RT for PCa treatment. A thorough literature review of relevant databases was conducted, focusing on academic and clinical studies published from 2019 onwards. The inclusion criteria included randomized controlled trials (RCTs) and other observational studies comparing survival outcomes in patients treated with surgery and RT. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines to provide an overview of the data. We selected 19 studies based on the inclusion criteria. Of the total 19 studies, 12 advocated RP as the preferred treatment to improve survival outcomes in patients with PCa. The results of our synthesis showed that prostate cancer-specific mortality (PCSM) was lower in patients treated with RT. The total effect size for the analysis was calculated as Z=1.19 (p-value=0.23). The heterogeneity in the studies was as follows: Tau2=0.09, Chi2=20.25, df=4, I2=80%. Moreover, overall survival (OS) was shown to be higher in patients who underwent prostatectomy. The combined effect for the analysis was found to be: HR=0.97 (0.93, 1.01). The total effect was calculated as Z=1.33 (p-value= 0.18). The heterogeneity was found to be Tau2=0.00, Chi2=1.33, df=2, and I2=0%. However, overall mortality (OM) was shown to be independent of the treatment modality. RT is the preferred strategy for PCa treatment, as it balances efficacy and long-term outcomes. Clinical decision-making should consider individual patient characteristics and future research should delve into specific subpopulations and long-term outcomes to further refine the treatment guidelines.

Successful treatment with fludarabine and cyclophosphamide in a VEXAS syndrome patient with associated myelodysplastic syndrome: a case report and systematic review.

Vacuoles, E1 syndrome, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a chronic inflammatory disorder that affects various organ systems. It is associated with hematologic malignancies and is generally refractory to therapies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for selected patients. We report a case wherein systemic and hematological manifestations completely resolved in a patient with VEXAS and associated myelodysplastic syndrome (MDS), following the administration of fludarabine and cyclophosphamide as part of the preparation for allo-HSCT. We conducted a systematic literature review and included 86 patients with VEXAS syndrome and associated MDS. Most cases presented with musculoskeletal involvement (71%) and anemia (72%) with lower-risk MDS. Most patients responded to corticosteroids (CS) but had a recurrence of symptoms with CS taper and were refractory to other immunosuppressive agents. Hypomethylating agents and Janus kinase inhibitors achieved a complete response in some cases. Further research is needed to develop more effective treatment strategies.

Real-time navigation of mecanum wheel-based mobile robot in a dynamic environment.

Path planning and control of a mobile robot, in a dynamic environment, has been an important research topic for many years. In this paper an algorithm for autonomous motion of a mobile robot is proposed, with mecanum wheels, to reach a goal while avoiding obstacles through the shortest path in a dynamic environment. The proposed method uses a hybrid A⁎ and a velocity obstacle algorithms for path planning and obstacle avoidance. The A⁎ algorithm is implemented to explore the shortest path from starting position to the goal while avoiding all the static obstacles. However, in real time applications the dynamic obstacles need to be avoided, therefore, for such a case velocity obstacle algorithm is unified with the A⁎ algorithm. Initially, the proposed algorithm is verified through simulations. Then it is implemented using experimental setup in real time environment using single and multiple static obstacles as well as on a dynamic obstacle. It can be observed that the robot reaches the goal, effectively by avoiding static and dynamic obstacles. Moreover, the performance of the proposed work is evaluated through qualitative comparison between proposed method and recently published work, showing that the proposed algorithm is gives better features than existing work. In the end, the possible application of mobile robot having mecanum wheels with proposed path planning method is also given in the paper.

Intraoperative renal replacement therapy during liver transplantation in children: Safety, efficacy and impact on survival.

BACKGROUND: Intraoperative Continuous Renal Replacement Therapy (iCRRT) can prevent life-threatening complications, facilitate fluid management, and maintain metabolic homeostasis during liver transplantation (LT) in adults. There is a paucity of data in pediatric LT. We evaluated the safety, efficacy, and impact on survival of iCRRT in pediatric LT. METHODS: We conducted a retrospective cohort study of all children requiring CRRT pre-OLT at a quaternary children's hospital from 2014 to 2022. Demographic characteristics, intraoperative events, and post-LT outcomes were compared between those who received iCRRT and those who did not. RESULTS: Out of 306 patients who received LT, 30 (10%) were supported with CRRT at least 24 h prior to LT, of which 11 (36%) received iCRRT. The two cohorts were similar in demographics, diagnosis of liver disease, and severity of illness. The iCRRT patients experienced massive blood loss and increased transfusion requirements. There was no difference in intraoperative metabolic balance. One-year post-LT mortality rates were similar. CONCLUSION: ICRRT is safe in critically ill children with pre-LT renal dysfunction. It optimizes fluid and blood product resuscitation while maintaining metabolic homeostasis. Candidates need to be carefully chosen for this highly resource-intensive therapy to benefit this fragile population.

Use of Endpoints in Phase III Randomized Controlled Trials for Hematopoietic Stem Cell Transplantation Over the Last 15 Years: A Systematic Review.

This systematic review aimed to evaluate the proportion of primary and secondary endpoints in hematopoietic stem cell transplant (HSCT) phase III randomized clinical trials (RCTs) and analyze their trends in time and study sponsorship status. The Chi-square test and logistic regression analyses were performed using SPSS version 28. A total of 147 HSCT phase III RCTs from 2006 to 2021 reported 197 primary and 600 secondary endpoints. Overall survival (OS, 17 %), progression-free survival (PFS, 15 %), graft versus host disease (GVHD, 8 %), event-free survival (EFS, 8 %), and organ function (8 %) were the most common primary endpoints. GVHD (12.3 %, n = 74), safety/toxicity/adverse events (11.8 %, n = 71), OS (11.5 %, n = 69), PFS (9.3 %, n = 56), and relapse rate (RR; 7.5 %, n = 45) were the most common secondary endpoints during 2006-2021. After 2013, an increase was noted in the use of PFS as a primary endpoint (12 %-18 %, p = 0.196), while the use of OS as a primary endpoint declined (20 %-13 %, p = 0.170). An increase was observed in using the secondary endpoints RR (5 %-10 %, p = 0.047) and NRM (3 %-6 %, p = 0.047). EFS was used more (14 % vs. 4 %, p = 0.012) than ORR (11 % vs. 2 %, p = 0.003) as a primary endpoint in pharmaceutical-compared to non-pharmaceutical-sponsored studies. As secondary endpoints, the use of EFS (4 % vs. 1 %, p = 0.013) and ORR (4 % vs. 1 %, p = 0.028) was higher, whereas that of organ systems/functions (1.5 % vs. 5.5 %, p = 0.022) and GVHD (6.5 % vs. 15 %, p = 0.002) was lower in pharmaceutical-compared to non-pharmaceutical sponsored studies. GVHD-free relapse-free survival was reported as a primary endpoint in 2 % of studies, while only 5 % reported quality of life as a secondary endpoint. We described commonly used endpoints in HSCT phase III RCTs and patterns in their use over time by funding source and study intervention category.

Postoperative outcomes of acute-on-chronic liver failure in infants and children with biliary atresia.

INTRODUCTION: Acute-on-chronic liver failure (ACLF) is associated with increased mortality and morbidity in patients with biliary atresia (BA). Data on impact of ACLF on postoperative outcomes, however, are sparse. METHOD: We performed a retrospective analysis of patients with BA aged <18 years who underwent LT between 2011 and 2021 at our institution. ACLF was defined using the pediatric ACLF criteria: ≥1 extra-hepatic organ failure in children with decompensated cirrhosis. RESULTS: Of 107 patients (65% female; median age 14 [9-31] months) who received a LT, 13 (12%) had ACLF during the index admission prior to LT. Two (15%) had Grade 1; 4 (30%) had Grade 2; and 7 (55%) had Grade ≥3 ACLF. ACLF cohort was younger at time of listing (5 [4-8] vs. 9 [6-24] months; p < .001) and at LT (8 [8-11] vs. 16 [10-40] months, p < .001) compared to no-ACLF group. Intraoperatively, ACLF patients had higher blood loss (40 [20-53] vs. 10 [6-19] mL/kg; p < .001) and blood transfusion requirements (33 [21-69] vs. 18 [7-25] mL/kg; p = .004). Postoperatively, they needed higher vasopressor support (31% vs. 10.6%; p = .04) and had higher total hospital length of stay (106 [45-151] vs. 13 [7-30] days; p = .023). Rate of return to the operating room, hospital readmission rates, and 1-year post-LT survival rates were comparable between the groups. CONCLUSION: Despite higher perioperative complications, survival outcomes for ACLF in BA after LT are favorable and comparable to those without ACLF. These encouraging data reiterate prioritization during organ allocation of these critically ill children for LT.

Predictors of cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation: Insights from a real-world experience.

BACKGROUND: We aimed to investigate factors associated with cytomegalovirus (CMV) viremia and CMV disease and its impact on post-transplant outcomes including overall survival (OS) following allogeneic hematopoietic stem cell transplantation (Allo-SCT). METHODS: We conducted a single-center retrospective study including 452 Allo-SCT recipients (matched unrelated donor, MUD 61%; haploidentical, haplo 39%) from 2016 to 2021. Data were analyzed using SPSS v28. Descriptive (chi-square and t-test), Kaplan-Meier and regression analyses were conducted. RESULTS: The median age was 57 years. Sixty-one percent were males and 84.3% were Caucasians. CMV serostatus was positive in 59.1% of recipients. The median follow-up was 24.4 months. CMV viremia and CMV disease were observed in 181 (40%) and 32 (7%) patients, respectively. Among CMV seropositive recipients, 65% developed CMV viremia and 11% were noted to have CMV disease compared to 4% and 1% in seronegative recipients, respectively (p < 0.001). Patients with CMV disease had significantly lower OS than those without CMV disease (median 14.1 months vs. not reached, p = 0.024); however, OS was not associated with CMV viremia (median not reached in both groups, p = 0.640). Letermovir prophylaxis was used in 66% (n = 176/267) of CMV seropositive recipients, but no impact was observed on the incidence of CMV viremia or CMV disease and OS. CONCLUSIONS: CMV disease leads to significantly inferior survival after an allogeneic hematopoietic cell transplantation. Recipient CMV seropositive status was associated with the risk of CMV viremia and CMV disease, and this was not abrogated with the use of Letermovir prophylaxis.

Mitigation of Salinity Stress and Lead Toxicity in Maize by Exogenous Application of the Sorghum Water Extract.

The increased concentration of lead (Pb) in soils is a serious threat to human beings and plants all over the world. Salinity stress is also a major issue across the globe, which limits crop productivity. The use of allelochemicals has become an effective strategy to mitigate the toxic effects of abiotic stresses. Sorghum is an important crop grown across the globe, and it also possesses an appreciably allelopathic potential. Therefore, this study was planned to determine the impacts of the sorghum water extract (SWE) on improving maize growth under Pb and salinity stress. The experiment included different treatments; control, SWE (3%), and different levels of Pb and salinity stress; T1: control, T2: 50 mM NaCl, T3: 100 mM NaCl, T4: 250 µM Pb, and T5: 500 µM Pb. Lead and salinity stress reduced the maize growth by the genesis of reactive oxygen species (ROS), as evidenced by higher production of malondialdehyde (MDA: 39.1 and 32.28%) and hydrogen peroxide (H2O2: 20.62 and 17.81%). Spraying plants with SWE improved the maize growth by increasing antioxidant activities (ascorbate peroxidase: APX, catalase: CAT, peroxidase: POD and superoxide dismutase: SOD), photosynthetic pigments, relative water contents (RWC), osmolyte accumulation (proline, total soluble proteins: TSP, free amino acids: FAA), potassium accumulation, and decreasing MDA, H2O2, sodium, chloride, and Pb accumulation. In conclusion, the application of SWE mitigates adverse impacts of Pb and salinity stresses by improving chlorophyll synthesis and osmolyte accumulation, activating the antioxidant defense system, and preventing the entry of toxic ions.

Fresh Frozen Cartilage in Rhinoplasty Surgery: A Systematic Review of Outcomes.

INTRODUCTION: Cadaveric fresh frozen cartilage provides an enticing alternative to traditional autologous cartilage grafts. This review provides a systematic analysis of existing literature on the use of fresh frozen rib for in rhinoplasties and focuses on clinical and aesthetic outcomes. METHODS: The methodology was designed and registered in the PROSPERO database (CRD42023447166). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline was used to perform this systematic review. RESULTS: Four articles were included, with a total of 554 patients. A total of 477 patients were female (86%). Mean age ranged between 35.8 and 40.6. Mean follow-up ranged from 12.2 to 20.3 months. Only one article had a suitable control (with autologous rib graft). Pooled complications rates were low. Infection occurred in 12 patients (2%), warping in 8 patients (1.4%) and resorption in 3 patients (0.5%). CONCLUSION: Fresh frozen cartilage may be a safe and reliable alternative to autologous rib grafts. Complication rates were comparable to previous systematic reviews of autologous graft and irradiated allograft. Overall, patients reported high satisfaction rates with low rates of revision procedures. Further studies are required to assess both clinical and cost effectiveness against the current gold standard (autologous graft). LEVEL OF EVIDENCE III: Rhinoplasty. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Silicon a key player to mitigate chromium toxicity in plants: Mechanisms and future prospective.

Chromium is a serious heavy metal (HM) and its concentration in plant-soil interface is soaring due to anthropogenic activities, unregulated disposals, and lack of efficient treatments. High concentration of Cr is toxic to ecosystems and human health. Cr stress also diminishes the plant performance by changing the plant's vegetative and reproductive development that ultimately affects sustainable crop production. Silicon (Si) is the second-most prevalent element in the crust of the planet, and has demonstrated a remarkable potential to minimize the HM toxicity. Amending soils with Si mitigates adverse effects of Cr by improving plant physiological, biochemical, and molecular functioning and ensuring better Cr immobilization, compartmentation, and co-precipitation. However, there is no comprehensive review on the role of Si to mitigate Cr toxicity in plants. Thus, in this present review; the discussion has been carried on; 1) the source of Cr, 2) underlying mechanisms of Cr uptake by plants, 3) how Si affects the plant functioning to reduce Cr toxicity, 4) how Si can cause immobilization, compartmentation, and co-precipitation 5) strategies to improve Si accumulation in plants to counter Cr toxicity. We also discussed the knowledge gaps and future research needs. The present review reports up-to-date knowledge about the role of Si to mitigate Cr toxicity and it will help to get better crop productivity in Cr-contaminated soils. The findings of the current review will educate the readers on Si functions in reducing Cr toxicity and will offer new ideas to develop Cr tolerance in plants through the use of Si.

Liposuction-Only Breast Reduction: A Systematic Review of Outcomes.

INTRODUCTION: Over the past few decades, there have been multiple reports of liposuction assisted breast reduction. This technique appeals to patients due to the limited scars and complication profile, compared to traditional reduction mammaplasty techniques. We aimed to systematically review the literature, to elucidate the outcomes and safety of liposuction-only breast reduction. METHODS: A systematic review was performed using the Ovid (Medline/PubMed) database, in accordance with the PRISMA checklist. RESULTS: In total 7 articles were included within this systematic review. A total of 652 patients were included. Liposuction-only breast reduction appears to lead to improvements in subjective outcome measures, patient satisfaction, and objective outcomes such as moderate breast volume reduction and reduction in breast ptosis. Overall, the procedure had a low complication profile. Liposuction did not preclude further surgery. No evidence of malignancy or difficulty in future breast cancer screening was noted. CONCLUSION: Macromastia leads to a considerable health burden, especially in health-related costs. From the current evidence base, liposuction-only breast reduction appears to be a safe and effective procedure, especially in patients requiring a mild-moderate breast volume reduction and mild ptosis correction. More research is required, with standardised subjective and objective outcome measures, and longer follow-up periods to confirm the effectiveness and safety of this technique. Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Evaluating the photodynamic efficacy of nebulized curcumin-loaded liposomes prepared by thin-film hydration and dual centrifugation: In vitro and in ovo studies.

Lung cancer, one of the most common causes of high mortality worldwide, still lacks appropriate and convenient treatment options. Photodynamic therapy (PDT) has shown promising results against cancer, especially in recent years. However, pulmonary drug delivery of the predominantly hydrophobic photosensitizers still represents a significant obstacle. Nebulizing DPPC/Cholesterol liposomes loaded with the photosensitizer curcumin via a vibrating mesh nebulizer might overcome current restrictions. In this study, the liposomes were prepared by conventional thin-film hydration and two other methods based on dual centrifugation. The liposomes' physicochemical properties were determined before and after nebulization, showing that liposomes do not undergo any changes. However, morphological characterization of the differently prepared liposomes revealed structural differences between the methods in terms of lamellarity. Internalization of curcumin in lung adenocarcinoma (A549) cells was visualized and quantified. The generation of reactive oxygen species because of the photoreaction was also proven. The photodynamic efficacy of the liposomal formulations was tested against A549 cells. They revealed different phototoxic responses at different radiant exposures. Furthermore, the photodynamic efficacy was investigated after nebulizing curcumin-loaded liposomes onto xenografted tumors on the CAM, followed by irradiation, and evaluated using positron emission tomography/computed tomography and histological analysis. A decrease in tumor metabolism could be observed. Based on the efficacy of curcumin-loaded liposomes in 2D and 3D models, liposomes, especially with prior film formation, can be considered a promising approach for PDT against lung cancer.