Atmospheric chemistry of trifluorodicarbonyls initiated by Cl atoms: Reactivity trends, mechanism, and acid formation yields.

Rate coefficients of the gas-phase reactions of Cl atoms with a series of fluorinated diketones (FDKs): CF3C(O)CH2C(O)CH3 (TFP), CF3C(O)CH2C(O)CH2CH3 (TFH) and CF3C(O)CH2C(O)CH(CH3)2 (TFMH), have been measured at (298 ± 2) K and under atmospheric pressure. The experiments were performed using the relative-rate method with a GC-FID detection system. From different determinations and references used, the following rate coefficients were obtained (in cm3/(molecule·sec)): k4(TFP + Cl) = (1.75 ± 0.21) × 10-10, k5(TFH + Cl) = (2.05 ± 0.23) × 10-10, k6(TFMH + Cl) = (2.71 ± 0.34) × 10-10. Reactivity trends of FDKs were discussed and Free Energy Relationships analysis was developed. The expression lgkOH = 1.68 lgkCl + 5.71 was obtained for the reactivity of the studied FDKs together with similar unsaturated VOCs with Cl and OH radicals Additionally, acetic acid (CH3C(O)OH) and trifluoroacetic acid (CF3C(O)OH) were positively identified and quantified as degradation products using in situ FTIR spectroscopy. According to the identified products, atmospheric chemical mechanisms were proposed. The atmospheric implications of the studied reactions were assessed by the estimation of the tropospheric lifetimes of TFP, TFH, and TFMH concerning their reaction with Cl atoms to be 48, 41, and 31 hours, respectively. The relatively short residence in the atmosphere of the fluorocarbons studied will have a local/regional impact with restricted transport. Global warming potential (GWP(20yr)) calculated for the studied fluoro diketones were 0.014, 0.003 and 0.001 for TFP, TFH and TFMH, respectively with a negligible contribution to the greenhouse effect.

A M-PEEK rod system to stabilize spinal motion after graded facetectomy: a finite element study.

BACKGROUND: Resecting the facet joint to relieve nerve pain can lead to spinal instability, deformity, and abnormal pressure on the anterior of the intravertebral disc. To mitigate these issues, surgeons often limit the amount of bone removed during facetectomy or stabilize the spine by fusion to maintain lumbar stability. This study aimed to assess how a M-PEEK rod system influenced the stability of the lumbar spine during graded facetectomy. METHODS: Facetectomy was performed on a validated L1-L5 finite element model which was then simulated both with and without the M-PEEK rod system. RESULTS: In extension, models implanted with M-PEEK in the interspinous space of L3/L4 experienced a 35.2% decrease in range of motion (ROM) at L3/L4, while others saw an 8.4-24.8% increase. For axial rotation, the ROM at L3/L4 increased by 2.2-5.4% in models with the M-Rod, and by 4.9-12.9% in models without the implant. In lateral flexion, the ROM at L3/L4 increased by 8.4-14.3% in models without a PEEK M-Rod (facetectomy only), with adjacent segments experiencing a 6.5% decrease in ROM in the implanted models. Overall, the difference in ROM between the intact and implanted models was minimal. CONCLUSIONS: Facetectomy involving the removal of 50% or more of the facet joint significantly increases range of motion and maximum intradiscal pressure, potentially accelerating disc degeneration, as shown in our finite element study. Stabilizing the segment with an M-PEEK rod may limit excessive motion, providing stability and maintaining intradiscal pressure closer to that of an intact model.

Biomechanical Study on the Comparison of Synthetic Materials for Cranio-Orbital Fracture Repair.

OBJECTIVE: For analyzing the mechanical properties of 2 cranio-orbital repair materials under distinct external impacts by finite element analysis and evaluating the stability of various repair materials. METHODS: Based on the computed tomography images of the patients with cranio-orbital fractures, three-dimensional models of the normal craniomaxillofacial models were established by segmenting them with Mimics 19.0, Geomagic Studio 12.0, and UG 12.0, respectively, to build the finite element models of titanium repair fixation and the poly-ether-ether-ketone repair fixation. The models were then simulated by Ansys 19.2, with divergent impact forces to analyze the stresses and displacements of the repair materials, as well as the internal fixation system, and to make a comparison on the stability of the distinct repair materials. RESULTS: The titanium mesh is stable at impact forces ≤1500 N. Furthermore, the poly-ether-ether-ketone mesh and the internal fixation system are resistant to fracture and displacement at impact forces of up to 3000 N. CONCLUSION: By simulating distinct mechanical environments, the biomechanical finite element analysis method can digitally assess the mechanical properties of cranio-orbital repair materials and objectively evaluate the stability of the repair materials and the internal fixation system.

Catalytic prenyl conjugate additions for synthesis of enantiomerically enriched PPAPs.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of >400 natural products with a broad spectrum of bioactivity, ranging from antidepressant and antimicrobial to anti-obesity and anticancer activity. Here, we present a scalable, regio-, site-, and enantioselective catalytic method for synthesis of cyclic ß-prenyl ketones, compounds that can be used for efficient syntheses of many PPAPs in high enantiomeric purity. The transformation is prenyl conjugate addition to cyclic ß-ketoesters promoted by a readily accessible chiral copper catalyst and involving an easy-to-prepare and isolable organoborate reagent. Reactions reach completion in just a few minutes at room temperature. The importance of this advance is highlighted by the enantioselective preparation of intermediates previously used to generate racemic PPAPs. We also present the enantioselective synthesis of nemorosonol (14 steps, 20% yield) and its one-step conversion to another PPAP, garcibracteatone (52% yield).

[Analysis of polyetheretherketone framework on the stress distribution of implant-supported fixed maxillary prosthesis: 3-D finite element analysis].

PURPOSE: To analyze the stress distribution of polyetheretherketone framework of implant-supported fixed maxillary prosthesis by three-dimensional finite element method. METHODS: Three dimensional finite element model of implant-supported fixed maxillary prosthesis was established. Polyetheretherketone as framework material, resin, zirconia, PEEK, baked plastic and lithium silicate were used to make crown prosthesis as experimental group, pure titanium and monolithic zirconia prosthesis model was used as control group. The feasibility of PEEK framework was analyzed by loading 150N axially and obliquely on the first molar, and the maximum compressive stress, minimum tensile stress and von Mises principal stress of the framework, crown, screw, implant, cortical and cancellous bone were measured and compared. RESULTS: Under axially loading, the von Mises stress in the monolithic zirconia and lithium silicate crowns were 361 MPa and 295 MPa, while the stress in resin and PEEK crowns were 35 MPa and 37 MPa, respectively. The screw von Mises stress of the experimental group was 694-724 MPa, which was much higher than 61 MPa of the control group.The maximum and minimum stresses of the screw appeared in the resin crown and PEEK crown group. Under oblique loading,von Mises stress of the framework in the experimental group was lower than that in the control group, but the maximum stress appeared in the resin crown and PEEK crown. von Mises stresses of monolic zirconia and lithium disilicate crowns in the experimental group were higher than that of resin and PEEK crowns. von Mises stress of the implant in the experimental group was twice that of the control group. von Mises stress in screw of the experimental group was much higher than that of the control group, and the maximum stress was 22 times that of the control group. The stresses of cancellous bone and cortical bone in the experimental group were twice that of the control group, and the differences were larger than that under vertical loading. CONCLUSIONS: In order to reduce the stress of crowns,resin or PEEK materials are preferred to be used as the crown prosthesis when PEEK was framework of implant-supported fixed maxillary prosthesis. Reducing the cantilever and lateral force may avoid excessive stress in screw.

[Case of Acute Pancreatitis during Eribulin Mesilate Therapy for Metastasis of Breast Cancer].

We report the case of a 46-year-old Japanese woman diagnosed with Stage Ⅳ right breast cancer, cT1cN1M1(ovarian and peritoneal metastases). We administered bevacizumab+paclitaxel as the first-line treatment. In the 13th course, the peritoneal dissemination progressed, and the regimen was changed to eribulin(1.4 mg/m2)as the second-line treatment. During the second course, abdominal distension developed and was resolved during follow-up. However, abdominal distension and pain were observed from day 9 of the fourth course. Based on the results of blood chemistry and CT scans, she was diagnosed with acute pancreatitis(CT Grade 1)and was admitted to the hospital. After fasting and fluid replacement therapy, her clinical symptoms and laboratory data improved, and was discharged from the hospital 8 days later. She had no history of excessive alcohol consumption and no evidence of biliary disease, and was considered having eribulin-induced pancreatitis.

Use of scaffolds based on polyetheretherketone tubular implant in the treatment of a gunshot multifragmentary fracture of the proximal part of the shoulder with a bone defect: a case report.

BACKGROUND: In connection with the war in Ukraine and the use of modern high-energy weapons by the enemy, the nature of injuries have changed. These changes require improvement of approaches to the treatment of patients with gunshot and mine-explosive bone defects. CASE PRESENTATION: We present the case of treatment of a 28-year-old Ukranian man with a gunshot multifragmentary fracture of the proximal humerus with a bone defect using three-dimensional printing of a polyetheretherketone frame (scaffold) for alloplastic material. The analysis of this case expands the possibilities of using three-dimensional printing technologies of polyetheretherketone scaffolds in the treatment of significant bone defects. CONCLUSION: Modern military trauma requires individualized treatment for each patient. The use of individual polyetheretherketone scaffolds in the treatment of a gunshot multifragmentary fracture with a bone defect has a positive clinical effect.

Ketogenic Approaches for the Treatment of Alzheimer's Disease.

Dementia represents one of the largest and most urgent public health problems across the globe. Modeling projections have estimated that delaying the onset of Alzheimer's disease (AD) by 6 months would reduce the prevalence by 5%, while a delay of 12 months would reduce the prevalence by 10%. One approach to achieving a delay in the onset of AD is to investigate lifestyle interventions that could be widely implemented with a favorable risk-benefit relationship and socioeconomic profile. Amongst such interventions, there is increasing evidence to support the use of ketogenic interventions in AD. Indeed, it is well known that cerebral glucose metabolism is impaired in AD, even at a preclinical stage, and a growing body of literature suggests that these findings may represent a primary pathogenic mechanism leading to neurodegeneration. Ketones are readily taken up by the brain and can serve as an alternative energy source for neurons and glia, hypothetically bypassing the glucose uptake deficit in AD. In this invited review we discuss the preclinical as well as clinical work aiming to increase ketones as a primary intervention in AD, including variations of the ketogenic diet, medium chain triglyceride supplementation, and newer, more experimental approaches.

A comparative quantitative assessment of 3D-printed PEKK and PEEK thin meshes in customized alveolar bone augmentation.

OBJECTIVE: Customized nonabsorbable membranes are widely used in severe alveolar bone defects and provide sufficient and precise regenerated bone tissue for subsequent dental implant placement. Although 3D-printed polyetheretherketone (PEEK) meshes have confirmed successful use in clinical cases, the performance of a PEEK mesh is not satisfactory. Compared with PEEK, polyetherketoneketone (PEKK) has better mechanical and processing properties. However, whether PEKK is suitable for making customized membranes remains unclear. The objectives of this study were (1) to evaluate the printing precision, surface characteristics, mechanical characteristics and biocompatibility of the PEKK mesh and (2) to compare the properties of the PEKK and PEEK meshes. MATERIALS AND METHODS: Both PEKK and PEEK meshes were designed and manufactured via additive manufacturing technology combined with computer-aided design (CAD). The printing precision was evaluated with a high-resolution extraoral scanner. The surface characteristics were evaluated with a contact angle system and three-dimensional optical microscopy. The mechanical characteristics were evaluated via three-point bending tests and tensile tests. The biocompatibility was evaluated with a CCK-8 assay, live/dead viability assay and qRT-PCT. RESULTS: Compared with the PEEK mesh, the PEKK mesh exhibited better control in terms of the thickness and aperture area. Both the PEKK mesh and the PEEK mesh had a hydrophobic surface, but the PEKK mesh had a smoother surface. Compared with the PEEK mesh, the PEKK mesh has better compression and tensile properties. Both the PEKK mesh and the PEEK mesh had good biocompatibility. The proliferation of cells on the PEKK mesh was slightly lower than that on the PEEK mesh. CONCLUSIONS: Compared with PEEK mesh, PEKK mesh has greater printing accuracy, smoother surfaces, better mechanical properties and similar biocompatibility and is expected to be used in the production of customized barrier membranes for the augmentation of severe bone defects. To ensure the stability of the mesh for clinical application, it is best to control the aperture diameter of the PEKK mesh to less than 2 mm with a thickness of 0.2 µm.

Template based segmental mandibulectomy with nerve preservation and patient-specific PEEK plate reconstruction in a dog.

A 7-year-old French Bulldog presented with an acanthomatous ameloblastoma affecting approximately 30% of the right mandibular body. We utilized a patient-specific 3D-printed surgical template to perform lateral fenestration of the mandible and elevation of the inferior alveolar nerve (IAN), facilitating nerve preservation during subsequent segmental mandibulectomy. The resulting critical-sized bone defect was anatomically stabilized using a patient-specific polyetheretherketone (PEEK) bridging plate. The recovery process was uneventful, with maintained occlusion and orofacial sensitivity.Similar to cases in humans with ameloblastoma, preserving orofacial sensitivity through the preservation of the inferior alveolar nerve seems feasible in dogs. Consequently, potential negative consequences of permanent regional denervation, which are unavoidable in traditional mandibulectomy, can be avoided. Bridging the ostectomy with a PEEK plate, offering advantages such as radiolucency, absence of imaging artifacts, and a modulus of elasticity similar to bone, proved to be functional in this canine patient, with no signs of complications observed up to the latest follow-up at 6 months.

Study on hybrid 3D printing and milling process for customized polyether-ether-ketone components.

Polyether-ether-ketone (PEEK) has been widely applied in various fields due to its excellent mechanical properties and biocompatibility. The efficient and high-quality customized manufacturing of PEEK components are investigated in this study by the hybrid 3D printing and milling process. At first, the alternating hybrid process is selected and verified by comparing two typical hybrid process categories and conducting experiments, respectively. Second, a set of procedures are designed to automate the engineering application of the hybrid process trying to avoid the disadvantages of manual programing. Then, considering the tool length and possible interferences during the hybrid process, a model segmentation algorithm, namely, the exchange principle of avoiding interference (EPAI) is proposed. Based on the introduced EPAI and the programing language Python, the additive and subtractive hybrid manufacturing (ASHM) data processing procedure is proposed and realized by post-processing of the conventional 3D printing codes. Finally, the feasibility experiments have been conducted. The experimental results verify the hybrid manufacturing process in the fabrication of parts with complex internal features. The surface roughness Ra and dimensional error L of the parts have been reduced by 75.5% and 85.2%, respectively, while the shear strength τ has been increased by 14.1%. Compared with conventional milling process, the material consumption is reduced by 48.7%.

AB081. Experience using CFR-PEEK implants in metastatic and primary spine tumour surgery: a single centre retrospective study.

BACKGROUND: Titanium has been the conventional implant material of choice for fixation in both primary and metastatic spine tumour surgeries (MSTS). However, these implants result in artefact generation during post-operative computed tomography (CT) or magnetic resonance imaging (MRI), resulting in poor planning of radiotherapy (RT) and suboptimal tumour surveillance. Carbon fibre-reinforced polyetheretherketone (CFR-PEEK) implants have gained momentum for instrumentation in MSTS due to their radiolucent properties. This in turn does not sacrifice the biomechanical strength of the implants. In this study, we compared the peri-operative outcomes, post operative imaging artefacts and dosimetricdata of CFR-PEEK implants to titanium implants to asses for potential benefits in post-operative RT planning in patients who underwent MSTS. METHODS: This is a retrospective study involving 42 patients operated for MSTS. Patient-related data including demographics, tumour pathology, intra-operative data, functional outcome, and RT-related data were collected for both groups. All patients were followed-up post-operatively for a minimum of 2 years or until demise, whichever was earlier. RESULTS: In our study, 20 (47.6%) patients had CFR-PEEK implants, while 22 (52.4%) of patients had titanium implants used for MSTS. Both groups of patients had similar clinical outcomes for pain and overall survival predictability pre-operatively (P>0.05). Mean number of levels instrumented by titanium screws were 6.8±2.93, while for the CFR-PEEK screws were 4.07±1.05. Mean volume of artefact generated during post operative CT was 75.1±43.4 mm3 in titanium group and 13.3±14.2 mm3 in CFR-PEEK group (P=0.005). The mean time taken to contour the artefacts was 17.3±5.84 minutes in the titanium group, while the CFR-PEEK group took 9.60±7.17 minutes (P=0.049). CONCLUSIONS: Our study suggests that carbon fibre reinforced PEEK screws significantly reduce artefact generation and the time taken to contour them during post-operative RT planning, while delivering equivalent clinical and functional outcomes as compared to standard titanium implants.

Stability studies of ß-Amino- and ß-Hydroxy difluoromethyl ketones in rat serum and rat liver microsomes.

Although difluoromethyl ketones are used as tools in chemical biology and leads in drug discovery, the metabolic stability of these compounds is generally uncharacterized and must be inferred from in vivo pharmacological assays. In order to address this gap which impedes their wider use, we have synthesized and performed metabolic stability studies for thirty-nine ß-amino and ß-hydroxy difluoromethyl ketones. These investigations provide structure-stability relationships of the difluoromethyl ketones following incubation with rodent serum and liver microsomes.

Elevated blood-ethanol concentration promotes reduction of aliphatic ketones (acetone and ethyl methyl ketone) to secondary alcohols along with slower oxidation to aliphatic diols.

Many people convicted for drunken driving suffer from an alcohol use disorder and some traffic offenders consume denatured alcohol for intoxication purposes. Venous blood samples from people arrested for driving under the influence of alcohol were analyzed in triplicate by headspace gas chromatography (HS-GC) using three different stationary phases. The gas chromatograms from this analysis sometimes showed peaks with retention times corresponding to acetone, ethyl methyl ketone (2-butanone), 2-propanol, and 2-butanol in addition to ethanol and the internal standard (1-propanol). Further investigations showed that these drink-driving suspects had consumed an industrial alcohol (T-Red) for intoxication purposes, which contained > 90% w/v ethanol, acetone (~ 2% w/v), 2-butanone (~ 5% w/v) as well as Bitrex to impart a bitter taste. In n = 75 blood samples from drinkers of T-Red, median concentrations of ethanol, acetone, 2-butanone, 2-propanol and 2-butanol were 2050 mg/L (2.05 g/L), 97 mg/L, 48 mg/L, 26 mg/L and 20 mg/L, respectively. In a separate GC analysis, 2,3-butanediol (median concentration 87 mg/L) was identified in blood samples containing 2-butanone. When the redox state of the liver is shifted to a more reduced potential (excess NADH), which occurs during metabolism of ethanol, this favors the reduction of low molecular ketones into secondary alcohols via the alcohol dehydrogenase (ADH) pathway. Routine toxicological analysis of blood samples from apprehended drivers gave the opportunity to study metabolism of acetone and 2-butanone without having to administer these substances to human volunteers.

Heparin-modified polyether ether ketone hollow fiber membrane with improved hemocompatibility and air permeability used for extracorporeal membrane oxygenation.

To expand the selection of raw material for fabricating extracorporeal membrane oxygenation (ECMO) and promote its application in lung disease therapy, polyether ether ketone hollow fiber membrane (PEEK-HFM) with designable pore characteristics, desired mechanical performances, and excellent biocompatibility was selected as the potential substitute for existing poly (4-methyl-1-pentene) hollow fiber membrane (PMP-HFM). To address the platelet adhesion and plasma leakage issues with PEEK-HFM, a natural anticoagulant heparin was grafted onto the surface using ultraviolet irradiation. Additionally, to explore the substitutability of the heparin layer while considering cost and scalability, a heparin-like layer composed of copolymers of acrylic acid and sodium p-styrenesulfonate was also constructed on the surface of PEEK-HFM Even though the successful grafting of heparin and heparin-like layers on the PEEK-HFM surface reduced the pore parameters, improvements in surface hydrophilicity also prevented the platelet-adhesion phenomenon and improved the anticoagulant behaviour, making it a viable alternative for commercial PMP-HFMs in ECMO production. Furthermore heparin-modified and heparin-like modified PEEK-HFMs demonstrated similar performance, indicating that synthetic layers can effectively replace natural heparin. This study holds practical and instructive significance for future research and the application of membranes in the development of oxygenators.

A Surface-Mediated Biomimetic Porous Polyether-Ether-Ketone Scaffold for Regulating Immunity and Promoting Osteogenesis.

The repair of critical-sized bone defects remains a major challenge for clinical orthopedic surgery. Here, we develop a surface biofunctionalized three-dimensional (3D) porous polyether-ether-ketone (PEEK) scaffold that can simultaneously promote osteogenesis and regulate macrophage polarization. The scaffold is created using polydopamine (PDA)-assisted immobilization of silk fibroin (SF) and the electrostatic self-assembly of nanocrystalline hydroxyapatite (nano-HA) on a 3D-printed porous PEEK scaffold. The SF/nano-HA functionalized surface provides a bone-like microenvironment for osteoblastic cells' adhesion, proliferation, mineralization and osteogenic differentiation. Moreover, the biofunctionalized surface can effectively drive macrophages polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Integrin ß1-specific cell-matrix binding and the activation of Ca2+ receptor-mediated signaling pathway play critical roles in the regulation of macrophage polarization. Compared with the as-printed scaffold, the SF/nano-HA functionalized porous PEEK scaffold induces minimal inflammatory response, enhanced angiogenesis, and substantial new bone formation, resulting in improved osseointegration in vivo. This study not only develops a promising candidate for bone repair but also demonstrates a facile surface biofunctionalization strategy for orthopedic implants to improve osseointegration by stimulating osteogenesis and regulating immunity.

Time to Moderate and Severe Hyperglycemia and Ketonemia Following an Insulin Pump Occlusion.

INTRODUCTION: Insulin pump therapy can be adversely affected by interruption of insulin flow, leading to a rise in blood glucose (BG) and subsequently of blood beta-hydroxybutyrate (BHB) ketone levels. METHODS: We performed a PubMed search for English language reports (January 1982 to July 2024) estimating the rate of rise in BG and/or BHB after ≥ 60 minutes of interruption of continuous subcutaneous insulin infusion (CSII) in persons with type 1 diabetes (PwT1D). We also simulated the rise in BG in a virtual population of 100 adults with T1D following suspension of continuous subcutaneous insulin infusion. RESULTS: We identified eight relevant studies where BG and BHB (seven of these eight studies) were measured following suspension of CSII as a model for occlusion. After 60 minutes post-suspension, the mean extracted rates of rise averaged 0.62 mg/dL/min (37 mg/dL/h) for BG and 0.0038 mmol/L/min (0.20 mmol/L/h) for BHB. Mean estimated time to moderately/severely elevated BG (300/400 mg/dL) or BHB (1.6/3.0 mmol/L) was, respectively, 5.8/8.5 and 8.0/14.2 hours. The simulation model predicted moderately/severely elevated BG (300/400 mg/dL) after 9.25/12, 6.75/8.75, and 4.75/5.75 hours in the virtual subjects post-interruption with small (5th percentile), medium (50th percentile), and large (95th percentile) hyperglycemic changes. DISCUSSION: Clinical studies and a simulation model similarly predicted that, following CSII interruption, moderate/severe hyperglycemia can occur within 5-9/6-14 hours, and clinical studies predicted that moderate/severe ketonemia can occur within 7-12/13-21 hours. Patients and clinicians should be aware of this timing when considering the risks of developing metabolic complications after insulin pump occlusion.

Exogenous ketosis attenuates acute mountain sickness and mitigates normobaric high-altitude hypoxemia.

Acute mountain sickness (AMS) represents a considerable issue for individuals sojourning to high altitudes with systemic hypoxemia known to be intimately involved in its development. Based on recent evidence that ketone ester (KE) intake attenuates hypoxemia, we investigated whether exogenous ketosis might mitigate AMS development and identified underlying physiological mechanisms. Fourteen healthy, male participants were enrolled in two 29-h protocols (simulated altitude of 4,000-4,500 m) receiving either KE or a placebo (CON) at regular timepoints throughout the protocol in a randomized, crossover manner. Physiological responses were characterized after 15 min and 4 h in hypoxia, and the protocol was terminated prematurely upon development of severe AMS (Lake Louise Score ≥ 10). KE ingestion induced a consistent diurnal ketosis (d-ß-hydroxybutyrate, [ßHB] of ∼3 mM), whereas blood [ßHB] remained low (<0.6 mM) in CON. Each participant tolerated the protocol equally long or longer (n = 6 or n = 8, respectively) in KE. Protocol duration increased by 32% on average with KE, and doubled upon KE for severe AMS-developing participants (n = 9). Relative to CON, KE induced a mild metabolic acidosis, hyperventilation, and relative sympathetic dominance. KE also inhibited the progressive hypoxemia that was observed between 15 min and 4 h in hypoxia in CON, while concomitantly increasing cerebral oxygenation and capillary Po2 within this timeframe despite a KE-induced reduction in cerebral oxygen supply. These data indicate that exogenous ketosis attenuates AMS development. The key underlying mechanisms include improved arterial and cerebral oxygenation, in combination with lowered cerebral blood flow and oxygen delivery, and increased sympathetic dominance.NEW & NOTEWORTHY Ketone ester intake attenuated the development of acute mountain sickness at a simulated altitude of 4,000-4,500 m. This likely resulted from a mitigation of arterial and cerebral hypoxemia, reduced cerebral blood flow, and increased sympathetic drive.

Eribulin plus carboplatin combination for HER2-negative metastatic breast cancer: a multicenter, real-world cohort study.

BACKGROUND: Pre-clinical data suggests a potential synergistic effect of eribulin and platinum. However, clinical data on the combination for metastatic breast cancer (mBC) is lacking. We evaluated the efficacy and safety of eribulin plus carboplatin (ErCb) in patients with mBC. PATIENTS AND METHODS: This multicenter, real-world cohort study included patients with pre-treated metastatic triple negative breast cancer (TNBC) or endocrine-refractory hormone receptor (HR) positive, HER2-negative mBC who received ErCb. Eribulin (1.4 mg/m2) and carboplatin (target AUC = 2) were administered intravenously on day 1 and 8 of 21-day cycle. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. RESULTS: From March 2022 to December 2023, a cohort of 37 patients were recruited to the study. Among them, 22 patients have TNBC and 15 have HR + HER2 - mBC. Of the 22 patients with TNBC, 8 had an initial diagnosis of the HR + HER2 - subtype. The median treatment was 6 cycles (range, 2 - 8 cycles). In the full cohort, TNBC, and HR + HER2 - subgroup, the ORR were 51.4%, 54.5% and 46.7%, the DCR were 81.1%, 81.8% and 80%, and the median PFS were 5 months, 5 months, and 5.2 months, respectively. The median OS was 12.7 months in the entire cohort and 12.8 months in TNBC subgroup. The most common grade 3/4 hematological AEs were neutropenia (37.8%), leukopenia (35.1%), febrile neutropenia (10.8%), thrombocytopenia (5.4%), and anemia (2.7%). No grade 3/4 non-hematological AEs were observed. CONCLUSION: ErCb demonstrated favorable efficacy and tolerability in patients with heavily pre-treated mBC, especially TNBC. The findings of the current study warrant further investigation of the application of this combination in earlier lines of mBC treatment.

Real-world treatment patterns and outcomes in patients with HR+/HER2- metastatic breast cancer treated with chemotherapy in the United States.

BACKGROUND: Until recently, treatment options for patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) and resistance to endocrine therapy were limited to chemotherapy. This real-world study describes treatment patterns and outcomes in patients treated with chemotherapy in the United States before approval of antibody-drug conjugates. PATIENTS AND METHODS: This retrospective, observational study included adults with HR+/HER2- mBC from the ConcertAI Patient360™ Breast Cancer dataset who initiated their first chemotherapy in the metastatic setting between January 2011 and June 2021. Treatment patterns were described; real-world overall survival, time to next treatment or death, and real-world progression-free survival were evaluated for all eligible patients and patients treated with subsequent chemotherapy. Index dates were the start date of each chemotherapy treatment. RESULTS: Among 1545 eligible patients, 76% were white, 12% had Eastern Cooperative Oncology Group performance status ≥2, 38% had de novo mBC, and median age was 61 years (range, 52-69 years). Within the index period, capecitabine was used the most as the first chemotherapy agent and decreased in later treatments, while the use of eribulin increased between first and fourth chemotherapies. Median (95% confidence interval) real-world overall survival was 23.3 months (21.3-25.4 months) from start of first chemotherapy, time to next treatment or death was 6.5 months (5.9-7.1 months), and real-world progression-free survival was 6.9 months (6.4-7.6 months); median times from second, third, and fourth chemotherapies decreased with each additional chemotherapy treatment. CONCLUSIONS: This real-world study demonstrates that for patients with HR+/HER2- mBC, chemotherapy provides relatively limited survival benefit which decreases with each additional chemotherapy line, and highlights the need for improved treatment options.