May Patients with Recurrent Venous Disease Benefit from Sequential Treatment More than Those without Previous Intervention? A Single-Center Retrospective Study on the Safety and Efficacy of Abdominal and Pelvic Veins Embolization in Sequential Approach.

Background/Objective: The endovenous embolization of insufficient abdominal/pelvic veins is the preferred method of treatment. Also, it seems to be crucial in the treatment of lower limb vein insufficiency, particularly in recurrent disease. This study aimed to evaluate of pelvic vein embolization safety and its impact on the short-term outcome in the sequential treatment of venous disease. Methods: A retrospective analysis involved data from 506 female patients with venous disease involving abdominal and pelvic veins. All records were extracted from the medical database and included patient history, imaging reports as well as pre- and post-operative surveys. Results: Among the patients analyzed, 37.2% underwent some venous intervention in the past, with significant differences in symptom severity between groups. The embolization procedure revealed a high safety profile, with no serious complications. Pain during and after the procedure was generally low, with significantly lower pain scores in patients with recurrence. In patients who required left renal vein venoplasty a 1.7-fold increased risk of lumbar pain after embolization and venoplasty procedure was observed. Overall, 66.6% of patients reported improvement in pelvic symptoms and 72.1% experienced improvement in leg symptoms. The full sequential treatment protocol (abdominal, pelvic, and leg compartment) demonstrated superior outcomes in leg symptom improvement compared to embolization alone. Conclusions: Pelvic vein embolization is a safe and effective method of treatment, significantly improving both pelvic and leg symptoms, particularly in patients with a history of previous interventions in lower limb veins. Further studies are warranted to validate our findings and further refine treatment protocols.

The roles of organic amendments and plant treatments in soil polychlorinated biphenyl dissipation under oxic and sequential anoxic-oxic conditions.

Understanding polychlorinated biphenyl (PCB) degradation in sequential anaerobic-aerobic remediation is crucial for effective remediation strategies. In this study, microcosm and greenhouse experiments were conducted to dissect the effects of organic amendments (carbon-based) and plant treatments (ryegrass) on soil PCB dissipation under oxic and sequential anoxic-oxic conditions. We analyzed the soil bacterial community in greenhouse experiments using high-throughput sequencing to explore plant-pollutant-microbe interactions. Microcosm results showed that organic amendments alone did not facilitate aerobic PCB removal, but significantly accelerated PCB dechlorination under anoxic conditions altering the profiles of PCB congeners. In standard greenhouses, plant treatments substantially increased PCB dissipation to 50.8 ± 3.9%, while organic amendments aided phytoremediation by promoting plant growth, increasing PCB removal to 65.9 ± 3.2%. In sequential anaerobic-aerobic greenhouses, plant growth was inhibited by flooding treatment while flooding stress was markedly alleviated by organic amendments. Plant treatments alone during sequential treatments did not lead to PCB dissipation; however, dissipation was significantly promoted following organic amendments, achieving a removal of 41.2 ± 5.7%. This PCB removal was primarily due to anaerobic dechlorination during flooding (27.8 ± 0.5% removal), rather than from plant growth stimulation in subsequent planting phase. Co-occurrence network and functional prediction analyses revealed that organic amendments recruited specific bacterial clusters with distinct functions under different conditions, especially stimulating plant-microbe interactions and xenobiotics biodegradation pathways in planted systems. The findings provide valuable guidance for the design of practical remediation strategies under various remedy scenarios, such as in arable or paddy fields.

Nab-paclitaxel plus S-1 followed by gemcitabine-oxaliplatin as first-line alternating sequential treatment of pancreatic ductal adenocarcinoma.

BACKGROUND: Alternating sequential administration of drugs may be a promising approach to overcome chemotherapy resistance in advanced pancreatic ductal adenocarcinoma (PDAC). METHODS: This study was an open-label, single-arm, and prospective trial included patients with untreated advanced PDAC. They received 2 cycles of NS regimen (nab-paclitaxel:125 mg/m2, intravenously injected on days 1 and 8, plus S-1:40-60 mg, orally twice per day for 1-14 days) followed by 2 cycles of GemOx regimen (gemcitabine, intravenously injected on days 1 and 8, and oxaliplatin: 130 mg/m2, intravenously injected on day 1). The primary efficacy endpoint was a progression-free survival rate at 6 months (PFSR-6m). The secondary efficacy endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Specific mRNA transcripts were used to explore survival associated genes. RESULTS: Forty-two patients received a minimum of one treatment cycle, and of these, 30 patients completed one alternating treatment consisting of 4 cycles. The PFSR-6m was 71% (95% CI = 58%-87%). The median PFS and OS were 6.53 months (95% CI = 6.03-8.43) and 11.4 months (95% CI = 9.8-14.4), respectively. Common grades 3-4 hematological AEs included neutropenia 30.9%, leukopenia 26.2%, anemia 2.4%, and thrombocytopenia in 11.9%. Patients with OS > 10 months showed high expression of HLA-DQA2 while melanoma-associated antigen genes (MAGE) were notably upregulated in patients with OS < 10 months. CONCLUSION: The alternating sequential administration of the NS and GemOx regimens may be a novel approach for first-line chemotherapy in patients with advanced PDAC requiring further study (ClinicalTrials.gov Identifier: ChiCTR1900024867).

Head-to-head comparison of treatment sequences in advanced pancreatic cancer-Real-world data from the prospective German TPK clinical cohort study.

There are no clear guidelines regarding the optimal treatment sequence for advanced pancreatic cancer, as head-to-head phase III randomised trials are missing. We assess real-world effectiveness of three common sequential treatment strategies by emulating a hypothetical randomised trial. This analysis included 1551 patients with advanced pancreatic cancer from the prospective, clinical cohort study Tumour Registry Pancreatic Cancer receiving FOLFIRINOX (n = 613) or gemcitabine/nab-paclitaxel (GEMNAB; n = 938) as palliative first-line treatment. We used marginal structural modelling to compare overall survival (OS) and time to deterioration (TTD) of health-related quality of life (HRQoL) between three common first- to second-line treatment sequences, adjusting for time-varying potential confounding. The sequences were: FOLFIRINOX→GEMNAB, GEMNAB→FOLFOX/OFF and GEMNAB→nanoliposomal irinotecan (NALIRI) + 5-fluorouracil. Outcome was also calculated stratified by patients' prognostic risk according to the Pancreatic Cancer Score. Median OS and TTD of HRQoL independent of risk were 10.7 [8.9, 11.9] and 6.4 [4.8, 7.7] months for FOLFIRINOX→GEMNAB, 8.4 [7.4, 9.7] and 5.8 [4.6, 7.1] months for GEMNAB→FOLFOX/OFF and 8.9 [7.8, 10.4] and 4.6 [4.1, 6.1] months for GEMNAB→NALIRI+5-fluorouracil. Compared to FOLFIRINOX→GEMNAB, OS and TTD were worse for poor-risk patients with GEMNAB→FOLFOX/OFF (OS: HR 2.09 [1.47, 2.98]; TTD: HR 1.97 [1.19, 3.27]) and those with GEMNAB→NALIRI+5-fluorouracil (OS: HR 1.35, [0.76, 2.39]; TTD: HR 2.62 [1.56, 4.42]). Brackets denote 95%-confidence intervals. The estimated real-world effectiveness of the three treatment sequences evaluated were largely comparable. Poor-risk patients might benefit from intensified treatment with FOLFIRINOX→GEMNAB in terms of clinical and patient-reported outcomes. Future randomised trials on sequential treatments in advanced pancreatic cancer are warranted.

Current Roles of Ramucirumab in the Sequential Treatment of Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: The treatment algorithm for systemic therapies for advanced hepatocellular carcinoma (HCC) has changed dramatically; however, the therapeutic landscape for sequential second-line or later-line treatments, including ramucirumab, remains controversial. This study aimed to investigate the role of ramucirumab for treating HCC. PATIENTS AND METHODS: We retrospectively analyzed data from 17 patients with advanced HCC who received ramucirumab, and 8 of them who received lenvatinib re-administration after ramucirumab treatment failure. RESULTS: The median overall survival of 17 patients treated with ramucirumab was 11.5 months. The median ratios of the 1-month post-treatment α-fetoprotein (AFP) levels and albumin-bilirubin (ALBI) scores to the pre-treatment AFP levels and ALBI scores following ramucirumab treatment were 0.880 and 0.965, respectively. The median ratios of the 1-month post-treatment AFP and ALBI levels to the pre-treatment levels were 1.587 and 0.970 for mALBI grade 1/2a, and 1.313 and 0.936 for mALBI grade 2b/3, respectively. Six of the eight patients who received lenvatinib rechallenge treatment exhibited a decrease in AFP levels one month post-lenvatinib treatment. Deterioration of liver function 3 months post-lenvatinib treatment was noted in five of the eight patients who received lenvatinib rechallenge treatment after ramucirumab. CONCLUSION: Ramucirumab may be equally useful in patients with unresectable HCC who have poor liver function or whose liver function is aggravated by other therapies. Rechallenge treatment with lenvatinib after ramucirumab may be a valid treatment option for HCC.

Reducing citrus effluent toxicity: Biological-electrochemical treatment with diamond anode.

One challenge of the citrus industry is the treatment and disposal of its effluents due to their high toxicity, substantial organic load, and consequent resistance to conventional biotechnological processes. This study introduces a novel approach, using electrochemical oxidation with a boron-doped diamond anode to efficiently remove organic compounds from biodegraded pulp wash (treated using the fungus Pleurotus sajor-caju.) The findings reveal that employing a current density of 20 mA cm-2 achieves notable results, including a 44.1% reduction in color, a 70.0% decrease in chemical oxygen demand, an 88.0% reduction in turbidity, and an impressive 99.7% removal of total organic carbon (TOC) after 6 h of electrolysis. The energy consumption was estimated at 2.93 kWh g-1 of removed TOC. This sequential biological-electrochemical procedure not only significantly reduced the mortality rate (85%) of Danio rerio embryos but also reduced the incidence of morphologically altered parameters. Regarding acute toxicity (LC50) of the residue, the process demonstrated a mortality reduction of 6.97% for D. rerio and a 40.88% lethality decrease for Lactuca sativa seeds. The substantial reduction in toxicity and organic load observed in this study highlights the potential applicability of combined biological and electrochemical treatments for real agroindustrial residues or their effluents.

Real-world sequential treatment patterns and clinical outcomes among patients with advanced urothelial carcinoma in Japan.

OBJECTIVES: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment. METHODS: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. RESULTS: At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. CONCLUSIONS: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.

High Thermoelectric Performance in Solution-Processed Semicrystalline PEDOT:PSS Films by Strong Acid-Base Treatment: Limitations and Potential.

Thermoelectric (TE) generation with solution-processable conducting polymers offers substantial potential in low-temperature energy harvesting based on high tunability in materials, processes, and form-factors. However, manipulating the TE and charge transport properties accompanies structural and energetic disorders, restricting the enhancement of thermoelectric power factor (PF). Here, solution-based strong acid-base treatment techniques are introduced to modulate the doping level of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) thin films with preserving its molecular orientation, enabling to achieve a remarkably high PF of 534.5 µW m-1  K-2 . Interestingly, theoretical modeling suggested that further de-doping can increase the PF beyond the experimental value. However, it is impossible to reach this value experimentally, even without any degradation of PEDOT crystallinity. Uncovering the underlying reason for the limitation, an analysis of the relationship among the microstructure-thermoelectric performance-charge transport property revealed that inter-domain connectivity via tie-chains and the resultant percolation for transport are crucial factors in achieving high TE performance, as in charge transport. It is believed that the methods and fundamental understandings in this work would contribute to the exploitation of conducting polymer-based low-temperature energy harvesting.

Investigation of pre-treatment techniques on spent substrate of Pleurotus ostreatus for enhanced biobutanol production using Clostridium acetobutylicum MTCC 11274.

Addressing global energy demand, researchers sought eco-friendly biobutanol production from lignocellulosic waste biomass. In the present research work, five different pre-treatment methods viz., Microwave, Ultrasound, Alkali, Acid, and Hybrid, were investigated to explore its biobutanol production potential by utilizing Pleurotus ostreatus spent as substrate. The compositional and physico-chemical changes of the pre-treated Spent Mushroom Substrate (SMS) were assessed using SEM, FTIR, and XRD. Hybrid pre-treatment (Microwave, Alkali, Ultrasound) showed higher delignification when compared to conventional pre-treatment method. Hybrid pre-treated SMS resulted in higher total reducing sugars (521.53 ± 1.84 mg/g) than indigenous SMS (267.89 ± 1.53 mg/g). Fermentation of hybrid pre-treated SMS with Clostridium acetobutylicum MTCC 11274 produced the highest biobutanol concentration (9.84 ± 0.03 g/L) and yielded 0.38 ± 0.02 g/g of biobutanol. This study revealed that hybrid pre-treatment could be a promising solution for enhanced biobutanol production using SMS biomass.

Photothermal-Controllable Microneedles with Antitumor, Antioxidant, Angiogenic, and Chondrogenic Activities to Sequential Eliminate Tracheal Neoplasm and Reconstruct Tracheal Cartilage.

The optimal treatment for tracheal tumors necessitates sequential tumor elimination and tracheal cartilage reconstruction. This study introduces an innovative inorganic nanosheet, MnO2 /PDA@Cu, comprising manganese dioxide (MnO2 ) loaded with copper ions (Cu) through in situ polymerization using polydopamine (PDA) as an intermediary. Additionally, a specialized methacrylic anhydride modified decellularized cartilage matrix (MDC) hydrogel with chondrogenic effects is developed by modifying a decellularized cartilage matrix with methacrylic anhydride. The MnO2 /PDA@Cu nanosheet is encapsulated within MDC-derived microneedles, creating a photothermal-controllable MnO2 /PDA@Cu-MDC microneedle. Effectiveness evaluation involved deep insertion of the MnO2 /PDA@Cu-MDC microneedle into tracheal orthotopic tumor in a murine model. Under 808 nm near-infrared irradiation, facilitated by PDA, the microneedle exhibited rapid overheating, efficiently eliminating tumors. PDA's photothermal effects triggered controlled MnO2 and Cu release. The MnO2 nanosheet acted as a potent inorganic nanoenzyme, scavenging reactive oxygen species for an antioxidant effect, while Cu facilitated angiogenesis. This intervention enhanced blood supply at the tumor excision site, promoting stem cell enrichment and nutrient provision. The MDC hydrogel played a pivotal role in creating a chondrogenic niche, fostering stem cells to secrete cartilaginous matrix. In conclusion, the MnO2 /PDA@Cu-MDC microneedle is a versatile platform with photothermal control, sequentially combining antitumor, antioxidant, pro-angiogenic, and chondrogenic activities to orchestrate precise tracheal tumor eradication and cartilage regeneration.

Retrospective Correlation between First Drug Treatment Duration and Survival Outcomes in Sequential Treatment with Regorafenib and Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer: A Real-World Subgroup Analysis.

Background: Patients with refractory metastatic colorectal cancer (mCRC) rarely receive third-line or further treatment. In this context, regorafenib (R) and trifluridine/tipiracil (T) are two important novel therapeutic choices with statistically significant increases in overall survival (OS), progression-free survival (PFS), and disease control, with different toxicity profiles. This study is a subgroup analysis of our larger retrospective study, already published, whose objective was to assess the outcomes of patients when R and T were given sequentially. Patients and Methods: The study involved thirteen Italian cancer centers on a 10-year retrospective observation (2012-2022). In this subgroup analysis, we focused our attention on the correlation between the first drug treatment duration (<3 months, 3 to <6 months and ≥6 months) and survival outcomes in patients who had received the sequence regorafenib-to-trifluridine/tipiracil, or vice versa. Results: The initial study included 866 patients with mCRC who received sequential T/R, or R/T, or T or R alone. This analysis is focused on evaluating the impact of the duration of the first treatment in the sequence on clinical outcomes (OS, PFS) and includes 146 and 116 patients of the T/R and R/T sequences, respectively. Based on the duration of the first drug treatment, subgroups for the T/R sequence included 27 patients (18.4%) who received T for <3 months, 86 (58.9%) treated for 3 to <6 months, and 33 (22.6%) treated for ≥6 months; in the reverse sequence (R as the first drug), subgroups included 18 patients (15.5%) who received their first treatment for <3 months, 62 (53.4%) treated for 3 to <6 months, and 35 (31.0%) treated for ≥6 months. In patients who received their first drug treatment for a period of 3 to <6 months, the R/T sequence had a significantly longer median OS (13.7 vs. 10.8 months, p = 0.0069) and a longer median PFS (10.8 vs. 8.5 months, p = 0.0003) than the T/R group. There were no statistically significant differences between groups with first drug treatment durations of <3 months and ≥6 months. Conclusions: Our analysis seems to suggest that the administration of R for a period of 3 to <6 months before that of T can prolong both OS and PFS, as compared to the opposite sequence.

Using sequential pharmacotherapy for the treatment of osteoporosis: an update of the literature.

INTRODUCTION: Osteoporosis, which is characterized by compromised bone density and heightened susceptibility to fractures, is a substantial public health concern, especially among the aging population. Underdiagnosis, undertreatment, and therapy non-adherence contribute to its impact. Anabolic and dual-action agents like teriparatide, abaloparatide, and romosozumab have emerged as effective treatments, allowing rapid gains in bone mineral density (BMD) and reducing fracture risk. However, administering treatments in the correct order is paramount, with an 'anabolic first' approach gaining traction for patients at high risk of fractures. This strategy involves starting anabolic therapies, followed by antiresorptive agents as maintenance therapy. It is important to note that the effectiveness of anabolic agents differs between treatment-naive and previously treated patients: tailored treatment approaches are therefore necessary. This comprehensive strategy adheres to clinical guidelines, emphasizing individualized care, early intervention, and patient-centered management to mitigate the burden of osteoporosis and enhance patients' quality of life. AREA COVERED: The aim of this review is to summarize recent evidence on the sequential treatment of osteoporosis and to provide recommendations on the best treatment strategies. EXPERT OPINION: Effective treatments, such as anabolic agents, are key in high-risk patients, who require an 'anabolic first' approach. Sequential therapy, specifically tailored to a patient's history, can help to optimize prevention and management of fractures.

Combining phages and antibiotic to enhance antibiofilm efficacy against an in vitro dual species wound biofilm.

Chronic wound management is extremely challenging because of the persistence of biofilm-forming pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, which are the prevailing bacterial species that co-infect chronic wounds. Phage therapy has gained an increased interest to treat biofilm-associated infections, namely when combined with antibiotics. Here, we tested the effect of gentamicin as a co-adjuvant of phages in a dual species-biofilm wound model formed on artificial dermis. The biofilm-killing capacity of the tested treatments was significantly increased when phages were combined with gentamicin and applied multiple times as multiple dose (three doses, every 8 h). Our results suggest that gentamycin is an effective adjuvant of phage therapy particularly when applied simultaneously with phages and in three consecutive doses. The multiple and simultaneous dose treatment seems to be essential to avoid bacterial resistance development to each of the antimicrobial agents.

A critical review on environmental risk and toxic hazards of refractory pollutants discharged in chlorolignin waste of pulp and paper mills and their remediation approaches for environmental safety.

Agro-based pulp and paper mills (PPMs) inevitably produce numerous refractory pollutants in their wastewater, including chlorolignin, chlorophenols, chlorocatechols, chloroguaiacol, cyanide, furan, dioxins, and other organic compounds, as well as various heavy metals, such as nickel (Ni), zinc (Zn), chromium (Cr), iron (Fe), lead (Pb), arsenic (As), etc. These pollutants pose significant threats to aquatic and terrestrial life due to their cytogenotoxicity, mutagenicity, impact on sexual organs, hormonal interference, endocrine disruption, and allergenic response. Consequently, it is crucial to reclaim pulp paper mill wastewater (PPMW) with high loads of refractory pollutants through effective and environmentally sustainable practices to minimize the presence of these chemicals and ensure environmental safety. However, there is currently no comprehensive published review providing up-to-date knowledge on the fate of refractory pollutants from PPMW in soil and aquatic environments, along with valuable insights into the associated health hazards and remediation methods. This critical review aims to shed light on the potential adverse effects of refractory pollutants from PPMW on natural ecosystems and living organisms. It explores existing effective treatment technologies for remediating these pollutants from wastewater, highlighting the advantages and disadvantages of each approach, all in pursuit of environmental safety. Special emphasis is placed on emerging technologies used to decontaminate wastewater discharged from PPMs, ensuring the preservation of the environment. Additionally, this review addresses the major challenges and proposes future research directions for the proper disposal of PPMW. It serves as a comprehensive source of knowledge on the environmental toxicity and risks associated with refractory pollutants in PPMW, making it a valuable reference for policymakers and researchers when selecting appropriate technologies for remediation. The scientific community, concerned with mitigating the widespread risks posed by refractory pollutants from PPMs, is expected to take a keen interest in this review.

Real-world effectiveness of third-line cabazitaxel in patients with metastatic castration-resistant prostate cancer: CARD-like analysis of data from a post-marketing surveillance in Japan.

BACKGROUND: The CARD trial was conducted in patients with metastatic castration-resistant prostate cancer (mCRPC) who had received docetaxel and experienced disease progression within 1 year on an androgen receptor-axis-targeted therapy (ARAT). Subsequent treatment with cabazitaxel had improved clinical outcomes compared with an alternative ARAT. This study aims to confirm the effectiveness of cabazitaxel in real-world patients in Japan and compare their characteristics with those of patients from the CARD trial. METHODS: This was a post-hoc analysis of a nationwide post-marketing surveillance registering all patients who were prescribed cabazitaxel in Japan between September 2014 and June 2015. Included patients had received docetaxel and ≤ 1 year of an ARAT (abiraterone or enzalutamide) prior to receiving cabazitaxel or an alternative ARAT, as their third-line therapy. The primary effectiveness endpoint was the time to treatment failure (TTF) of the third-line therapy. Patients were matched (1:1) from the cabazitaxel and second ARAT arms based on propensity score (PS). RESULTS: Of the 535 patients analysed, 247 received cabazitaxel and 288 the alternative ARAT as their third-line therapy, of which, 91.3% (n = 263/288) received abiraterone and 8.7% (n = 25/288) received enzalutamide as their second third-line ARAT. Patients in the cabazitaxel and second ARAT arms had TNM classification of M1 or MX in 73.3% and 68.1%, Gleason score of 8-10 in 78.5% and 79.2% and mean (standard deviation) serum PSA levels of 483 (1370) and 594 (1241) ng/mL, respectively. Initial cabazitaxel dose was ≤ 20 mg/m2 in 61.9% (n = 153/247) of the patients in the cabazitaxel arm. The median TTF (95% confidence interval [CI]) of the third-line therapy was 109 (94-128) days for cabazitaxel and 58 (57-66) days for the second ARAT, with a hazard ratio (95% CI) of 0.339 (0.279-0.413) favouring cabazitaxel. Similar results were obtained after PS-matching, with a hazard ratio (95% CI) of 0.323 (95% CI 0.258-0.402) favouring cabazitaxel. CONCLUSIONS: Consistent with the CARD trial, cabazitaxel demonstrated superior effectiveness over a second alternative ARAT in a real-world patient population in Japan, despite the population having more advanced disease status and a lower dose of cabazitaxel being more frequently administered, than in the CARD trial.

Treatment patterns and outcomes associated with sequential and non-sequential use of CDK4 & 6 inhibitors in patients with HR+, HER2- MBC in the real world.

PURPOSE: Cyclin Dependent Kinase 4 & 6 inhibitors (CDK4 & 6i) have transformed the management of HR+, HER2- metastatic breast cancer (MBC); however, the optimal sequence of these treatments and other systemic therapies for MBC remains unclear. METHODS: This study analyzed electronic medical records from the ConcertAI Oncology Dataset. US patients who received abemaciclib and at least one other systemic line of therapy (LOT) for HR+, HER2- MBC were eligible. Treatment sequences were grouped, and data for two pairs of groups are presented herein (N = 397): Group 1 (1L CDK4 & 6i to 2L CDK4 & 6i) vs. Group 2 (1L CDK4 & 6i to 2L non-CDK4 & 6i), and Group 3 (2L CDK4 & 6i to 3L CDK4 & 6i) vs. Group 4 (2L CDK4 & 6i to 3L non-CDK4 & 6i). Time-to-event outcomes (PFS and PFS-2) were analyzed using Kaplan-Meier method and Cox proportional hazard regression. RESULTS: In the total cohort of 690 patients, the most prevalent sequence was 1L CDK4 & 6i to 2L CDK4 & 6i (n = 165). For the 397 patients across Groups 1-4, sequential CDK4 & 6i demonstrated numerically longer PFS and PFS-2 versus non-sequential CDK4 & 6i. Adjusted results demonstrate that patients in Group 1 demonstrated significantly longer PFS (p = 0.05) versus Group 2. CONCLUSIONS: Although retrospective and hypothesis-generating, these data demonstrate numerically longer outcomes in the subsequent LOT associated with sequential CDK4 & 6i treatment.

Sequential treatment in vulvovaginal atrophy.

Vulvovaginal atrophy (VVA) is a chronic and progressive disease that affects sexuality and quality of life. VVA is preventable and treatable, but requires long-term and often sequential treatment. Sequential treatment consists of designing a strategy that uses one or more medications for a long enough time to achieve the desired benefits with minimal risk and maximum adherence. Currently available therapeutic options consist of topical over-the-counter products (including non-hormonal lubricants and moisturizers applied to the vagina), systemic hormone therapy and estrogens, and prescribed vaginal dehydroepiandrosterone (DHEA). In addition, we have a selective estrogen receptor modulator, ospemifene, and new energy-based treatments (laser and radiofrequency). There are clear differences between the treatments both in the mechanism of action and in the efficacy. Compliance is very low, and patients complain about the use of the vaginal route, often due to its low efficacy, or express fear of the long-term use of estrogens or the price of the treatments. We believe that, as a first option, and for physiological, preventive and efficacy reasons, we should consider the prescription of treatments that work on estrogen receptors. As a second option, there are vaginal moisturizers, which are effective on symptoms but do not prevent or improve conditions. Finally, techniques using heat, which although each time represent a clearer alternative, but on the other hand are the cost and the long-term safety data, give us a third option. Of course, we consider that vulvar moisturizers and lubricants can be used at any time.

Spine or Hip First? Outcomes in Patients Undergoing Sequential Lumbar Spine or Hip Surgery.

BACKGROUND: Lumbar spine pathology frequently coexists in patients who have hip arthrosis. There is controversy on whether lumbar or hip pathology should be first addressed. The purpose of this study was to evaluate the outcomes of sequential lumbar spine (LSP) or hip arthroplasty (THA). METHODS: Using a large national database from 2010 to 2020, we reviewed the records of 241,279 patients who had concurrent hip arthritis and lumbar spine disease defined as spinal stenosis, lumbar radiculopathy, or degenerative disc disease. During the study period, 6,458 (2.7%) patients with concurrent hip/spine disease underwent sequential operative treatment of either the hip joint or lumbar spine within 2 years. The rates of subsequent surgery in either the hip or the spine, opioid requirements, and rates of hip dislocation were determined and analyzed using compared Chi-squared analyses. RESULTS: Patients undergoing THA first had lower risk of subsequent spinal procedure compared to patients who had spinal procedures first (5.7 versus 23.7%, P < .001). This disparity was maintained up to 5 years (P < .001). Opioid requirements at 1 year were highest in patients who underwent spinal procedures only (836 pills/patient) compared to any other group THA only (566 pills/patient), LSP and then THA (564 pills/patient), THA and LSP (586 pills/patient). Also, THA following LSP was associated with significantly higher rates of dislocation compared to patients undergoing THA first (3.2 versus 1.9%, P < .001). CONCLUSION: Total hip arthroplasty first in patients who have concurrent spine disease was associated with lower risk of subsequent surgery, opioid requirement, and risk of postoperative instability compared to patients having lumbar procedure first.