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Background: Androgen receptor signaling inhibitors (ARSis), when administered sequentially or in combination with docetaxel and androgen deprivation therapy (ADT), have been shown to enhance overall survival (OS) and progression-free survival (PFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Nonetheless, the optimal sequence for administering chemotherapy and ARSis remains to be determined. Objective: To compare the efficacy of ARSis sequential therapy with ARSis combined therapy for mHSPC, and to evaluate the efficacy and safety of different combination regimens. Methods: The PubMed, Embase, Cochrane Central, and ClinicalTrials.gov databases were searched from their inception through 14 July 2024, to identify eligible phase III randomized clinical trials (RCTs) evaluating the combination or sequential use of docetaxel + ADT with abiraterone, enzalutamide, apalutamide, or darolutamide. The outcomes of interest included OS, PFS, time to prostate-specific antigen (PSA) progression, grade 3–5 adverse events (AEs), and serious adverse events (SAEs). Results: Five RCTs involving 2836 patients were included in the analysis. When comparing ARSis sequential therapy to ARSis combined therapy, no significant differences were observed in OS (Hazard Ratio (HR): 1.17, 95% Confidence Interval (CI): 0.69–1.96), PFS (HR: 1.03, 95% CI: 0.47–2.22), or time to PSA progression (HR: 0.48, 95% CI: 0.03–7.69). Within the different ARSis combined regimens, the triple therapies involving enzalutamide, abiraterone, and darolutamide demonstrated comparable efficacy and safety profiles in the overall population, and their efficacy in patients with high-volume disease or low-volume disease was also similar. Conclusion: ARSis sequential therapy did not significantly differ from ARSis combined therapy in improving OS and PFS among patients with mHSPC, and thus can be considered as a viable treatment option. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Enamel hypoplasia is a disease that results in enamel formation and mineralization abnormalities due to the effects of hereditary or environmental variables during tooth development. Affected teeth may appear to have an aberrant color and structural flaws. Patients often display clinical signs such as tooth defects, tooth sensitivity, and tooth discoloration. The disease can cause patients to feel physically and mentally uncomfortable and negatively impact their ability to chew, swallow, speak, and smile. In this review, the pathophysiology of enamel hypoplasia, which is caused by anomalies in gene regulation and changes in environmental variables, is summarized, along with a list of clinical diagnostic indicators based on the most commonly used disease classifications. The main points are as follows: ① enamel hypoplasia changes only the color and transparency of the affected teeth; ② lesions often occur symmetrically in groups; ③ the age at which systemic diseases or nutritional disorders occur during tooth development can be predicted based on the patient's impaired teeth; and ④ banded or pitted brown depression on the enamel surface can easily be confused with dental fluorosis. It also elaborates on the comprehensive application of tooth bleaching, desensitization, direct or indirect restoration and other treatment modalities according to unique chief complaints by different patients and suggests the use of multidisciplinary cooperative sequential treatment for critical infants and young children. The goal of this review is to provide professionals with the most recent information and advice about enamel hypoplasis. Current literature on this condition is primarily case reports. To further standardize the diagnostic and management approaches for this disease, additional high-quality clinical research and systematic reviews are required.

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. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Prevention & Treatment For Stomatological Diseases is the property of Journal of Prevention & Treatment For Stomatological Diseases Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article discusses the complexities of treating posttraumatic stress disorder (PTSD) and the importance of tailoring therapy to individual patients. The author presents a case study of a man named John who experiences acute stress disorder (ASD) and later develops PTSD after the sudden death of his fiancée. The therapist uses a combination of psychoeducation, cognitive restructuring, and exposure therapy to help John process his guilt and traumatic memories. The article emphasizes the need for therapists to listen to their patients, adapt treatment plans, and acknowledge their own limitations. [Extracted from the article]

Osteoporosis, a prevalent systemic degenerative disease, poses significant challenges to China's national health, particularly due to complications such as fractures. Therapeutic interventions for osteoporosis primarily involve bone resorption inhibitors (antiresorptive) and bone formation promoters (anabolic). Numerous studies underscore the importance of sequential and combination treatments using diverse drug types. Such approaches have shown considerable efficacy in increasing bone mineral density, reducing fracture risk, and preventing the progression of osteoporosis. This article aimed to consolidate various sequential treatment schemes, offering valuable insights for clinicians in their practice. Keywords: Osteoporosis; Sequential treatment; Combination treatment [ABSTRACT FROM AUTHOR]

BackgroundAndrogen receptor signaling inhibitors (ARSis), when administered sequentially or in combination with docetaxel and androgen deprivation therapy (ADT), have been shown to enhance overall survival (OS) and progression-free survival (PFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Nonetheless, the optimal sequence for administering chemotherapy and ARSis remains to be determined.ObjectiveTo compare the efficacy of ARSis sequential therapy with ARSis combined therapy for mHSPC, and to evaluate the efficacy and safety of different combination regimens.MethodsThe PubMed, Embase, Cochrane Central, and ClinicalTrials.gov databases were searched from their inception through 14 July 2024, to identify eligible phase III randomized clinical trials (RCTs) evaluating the combination or sequential use of docetaxel + ADT with abiraterone, enzalutamide, apalutamide, or darolutamide. The outcomes of interest included OS, PFS, time to prostate-specific antigen (PSA) progression, grade 3–5 adverse events (AEs), and serious adverse events (SAEs).ResultsFive RCTs involving 2836 patients were included in the analysis. When comparing ARSis sequential therapy to ARSis combined therapy, no significant differences were observed in OS (Hazard Ratio (HR): 1.17, 95% Confidence Interval (CI): 0.69–1.96), PFS (HR: 1.03, 95% CI: 0.47–2.22), or time to PSA progression (HR: 0.48, 95% CI: 0.03–7.69). Within the different ARSis combined regimens, the triple therapies involving enzalutamide, abiraterone, and darolutamide demonstrated comparable efficacy and safety profiles in the overall population, and their efficacy in patients with high-volume disease or low-volume disease was also similar.ConclusionARSis sequential therapy did not significantly differ from ARSis combined therapy in improving OS and PFS among patients with mHSPC, and thus can be considered as a viable treatment option.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Textile industries are one of the rapidly growing but on the contrary the most polluting industries in terms of the volume and complexity of their effluent discharge. Treatment of textile industry wastewater with turquoise blue dye using sequential electrocoagulation (EC) and adsorption (AD) process and its optimization was attempted in this study. Algal activated carbon (AAC) was used as adsorbent in the treatment process. These two-process parameters were optimized using the response surface methodology and artificial neural network (ANN) for the effective removal of COD (%COD). The experimental results were found to be in good agreement with the predicted results from both RSM and ANN model (R2 values > 0.9). After EC treatment the maximum removal efficiency obtained for COD was 76.97% at an optimal condition of 1.5 A/dm2 current density and 36-min time. Similarly, for AD treatment maximum removal efficiency was acquired under an optimal AAC dosage of 12.9 g/L and time of 44 min. Therefore, the overall removal efficiency obtained for COD was 91.28%. in sequential treatment process. Additionally, color, turbidity and TDS was also removed up to 68.82%, 90.96%, and 16.04%, respectively. This study concludes that the RSM and ANN were adequate statistical tools to predict the effective optimal conditions to attain the maximum COD removal for textile industry effluent using a sequential EC–AD treatment process. [ABSTRACT FROM AUTHOR]

Objective Evaluate the effect of an integrated teaching model of oral preclinical practice based on endodontic-restorative sequential treatment to provide a reference for the exploration of the teaching mode of the stomatology specialty. Methods This retrospective study was reviewed and approved by the Ethics Committee. The study was divided into 2 groups. There were 450 2018-grade and 2019-grade students in the discipline integration teaching method (DIT) group, and a preclinical practice course (root canal therapy and fixed prosthetic treatments were integrated into an endodontic-restorative sequential treatment) using the DIT method was applied. There were 443 2016-grade and 2017-grade students in the traditional teaching method (TT) group, and a TT preclinical practice course (root canal therapy and fixed prosthetic treatments training courses were taught separately) was applied. Both groups were taught by the same two teachers. The scores of clinical skills examination and treatment planning were compared between the two groups. In addition, students in the two groups were asked to complete the questionnaires about the teaching methods, and students in Group DIT and their teachers were asked to complete the questionnaires on their degree of satisfaction with the DIT method in the preclinical course. Results Students in the DIT group had an average score of 90.2 ± 4.16 in the practical skill evaluation, which was higher than that of the TT group (86.3±3.57) (P = 0.001). In the case analysis, 91.8% (413/450) of the students in the DIT group successfully planned the treatment, compared to a significantly lower rate in the TT group of 74.7% (331/443) (P = 0.001). The questionnaire results showed that recognition degrees of cultivated clinical thinking, improved indication analysis ability, improved operational skills, stimulated enthusiasm for learning, and improved autonomous learning were higher in the DIT group than in the TT group, and both teachers (2/2) and 98.4% (443/450) of students recognized the DIT method. Conclusions The DIT method significantly improved students’ learning quality and ability, proved effective in the endodontic-restorative sequential treatment practice course and was more acceptable to teachers and students. The DIT method is more effective than the TT method in improving students’ clinical thinking and operation ability.

Objective To evaluate the impact of the 'point to downstream hospital multi-department' emergency medical consortium model between Peking Union Medical College Hospital (PUMCH) and Beijing Longfu Hospital on the treatment of critically ill patients. Methods Clinical data of ICU patients at Beijing Longfu Hospital from December 2018 to November 2020 were retrospectively collected. The patients were categorized into two groups based on whether the emergency medical consortium was established: the pre-establishment group (December 2018 to November 2019) and the post-establishment group (December 2019 to November 2020). Clinical data, disease spectrum, examination/treatment utilization, and in-hospital mortality were compared between the two groups. Results A total of 350 ICU patients meeting the inclusion and exclusion criteria were included in this study. The pre-establishment group comprised 126 patients, while the post-establishment group had 224 patients(including 162 transferred via the consortium). In the pre-establishment group, the disease spectrum primarily consisted of common critical illnesses, with the top three diseases being acute cardiovascular diseases (34.1%), severe pneumonia (25.4%), and post-surgical cases (19.0%). In the post-establishment group, there was a greater diversity in the disease spectrum, with the top three diseases being severe pneumonia (31.2%), renal dysfunction (13.8%), and acute cerebrovascular disease (9.8%). Compared to the pre-establishment group, the post-establishment group had a lower average age [68.50(57.00, 79.00) years vs. 78.00(68.25, 84.00) years, P < 0.001], higher acute physiology and chronic health evaluation Ⅱ score [18.00(14.00, 24.00) points vs. 15.00(12.00, 22.75) points, P=0.005] and sequential organ failure assessment (SOFA) score [5.00(3.00, 7.25) points vs. 3.00(2.00, 6.00) points, P < 0.001], higher rates of central venous catheterization (52.7% vs. 20.6%, P < 0.001), continuous renal replacement therapy(22.3% vs. 4.0%, P < 0.001), vasoactive drug use (21.4% vs. 11.9%, P=0.037), and epinephrine usage (17.0% vs. 7.1%, P=0.015), and hospital stay [(11.61±9.41)days vs. (10.06±7.63)days, P=0.260], hospital costs [(18 982.35(9251.80, 51 677.59) CNY vs. 39 113.11(19 500.03, 68 981.90) CNY, P=0.067], and in-hospital mortality (12.1% vs. 10.3%, P=0.753) showed no significant changes. Furthermore, after the establishment of the emergency medical consortium, the ICU of Beijing Longfu Hospital admitted and treated 25 cases of difficult-to-treat patients (no difficult-to-treat patients were seen before the establishment of the emergency medical consortium) and used a number of new technologies, including bedside bronchoscopy in 9 cases and bedside ultrasound examination in 105 cases. Multivariable Logistic regression analysis results indicated that after adjusting for factors such as age and SOFA score, the establishment of the emergency medical consortium had no significant impact on in-hospital mortality among ICU patients (OR=0.994, 95% CI: 0.401-2.464, P=0.990). Conclusions After the establishment of the 'point to downstream hospital multi-department' emergency medical consortium between PUMCH and Beijing Longfu Hospital, the complexity and severity of diseases treated in Beijing Longfu Hospital's ICU increased, but the in-hospital mortality rate did not significantly rise. The emergency medical consortium model may contribute to enhancing the capacity for treating critically ill patients in downstream hospitals.

Abstract 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.

Hydrogels have been recognized for their versatile in regenerative medicine; however, their inadequate mechanical and osteogenic properties have limited their applicability in bone tissue engineering (BTE). Hence, we present a novel approach to address this issue by developing sulfated methacrylate hyaluronic acid hydrogels (SMeHA@CM) doped with alendronate (ALN), calcium ions (Ca2+), and magnesium ions (Mg2+). This hydrogel system incorporates sequential physical and chemical crosslinking to facilitate the treatment of bone defects. Physical crosslinks form between the SO32−, ALN, and Ca2+/Mg2+ ions, resulting in nanocluster crosslinking and complete filling of irregular bone defects. Subsequently, the methacrylate groups within the polymer chain undergo polymerization under ultraviolet light irradiation, forming the second stage of chemical crosslinking in the SMeHA@CM hydrogel. These chemical crosslinks contribute strong chemical bonds, enhancing biomechanical strength, and stable support for bone regeneration. The SMeHA@CM hydrogel exhibits remarkable osteogenic capacity, primarily attributed to the cooperative action of SO32− and Mg2+ ions, which promote the recruitment of bone marrow stem cells and angiogenesis. Furthermore, the sustained release of SO32−-ALN-Ca2+/Mg2+ nanoclusters from the hydrogel system offers additional benefits for bone regeneration. Moreover, both in-vitro and in-vivo assessments confirm the significant potential of the newly developed SMeHA@CM hydrogel for applications in BTE.

Simple Summary: Third-line or further treatments are rarely given to patients with refractory mCRC. In this regard, two noteworthy innovative therapy options, with varying toxicity profiles and statistically significant improvements in overall survival (OS), progression-free survival (PFS), and disease control, are regorafenib (R) and trifluridine/tipiracil (T). This study is a subset analysis of a larger retrospective study that we have already published, with the aim of evaluating patient outcomes when R and T were administered in that order. The purpose of this analysis was to evaluate the relationship between survival outcomes and the first drug treatment duration (<3 months, 3 to <6 months, and ≥6 months) in patients who had received the regorafenib-to-trifluridine/tipiracil sequence or vice versa. Our substudy found that administering R three to six months prior to T can prolong both OS and PFS in comparison to the opposite sequence. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Prevention & Treatment For Stomatological Diseases is the property of Journal of Prevention & Treatment For Stomatological Diseases Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract 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.

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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Systemic juvenile idiopathic arthritis (sJIA) is a complex and difficult to cure condition with high disability and mortality rates. Herein, we report the case of a patient with sJIA who was treated with sequential tocilizumab (TCZ) and tofacitinib treatment. The patient was a 4-year-old girl hospitalised with fever accompanied by multiple joint swelling and pain in June 2020. Laboratory tests revealed a white blood cell count of 15.3 × 109/L, platelet count of 676.8 × 109/L, haemoglobin of 91.8 g/L, serum ferritin level of 1103.8 U/L, erythrocyte sedimentation rate of 85.0 mm/h, C-reactive protein level of 146.0 g/L and interleukin (IL)-6 level of 288.0 pg/ml. Rheumatoid factor and autoantibodies test results were negative, and she was diagnosed with sJIA. The patient was started on a combination of ibuprofen, methotrexate and TCZ, and her fever decreased to the normal range without any recurrence. Painful joint swelling had resolved significantly at 3-month follow-up. Janus kinase (JAK) inhibitors inhibit the effects of several cytokines, particularly IL-6, and are economical and convenient. Therefore, we selected tofacitinib to replace TCZ in this case, while the other drugs remained unchanged. Arthritis symptoms disappeared gradually after 9-month follow-up. In May 2021, the patient was hospitalised owing to a slight recurrence of the upper respiratory tract infection. She was administered one intravenous infusion of TCZ along with a switch to oral tofacitinib, which quickly relieved the symptoms. In March 2022, the patient’s condition was stable. The curative effect of sequential TCZ and tofacitinib treatment was remarkable. IL-6 inhibitors sequential to JAK inhibitors could be a new option in the treatment of systemic juvenile idiopathic joints.

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. [ABSTRACT FROM AUTHOR]

Introduction: Thrombotic thrombocytopenia purpura (TTP) associated with systemic lupus erythematous (SLE), features the appearance of inhibitory autoantibodies against ADAMTS13. Rituximab and belimumab (BEL), as both targeting B cells, seem to be an optimal therapy to induce clinical remission, prevent relapse of disease and contribute to glucocorticoid induction. However, the clinical outcome of SLE‐TTP treated with sequential therapy between rituximab and BEL remain elusive. Case Series: We reported the clinical outcomes of 4 patients diagnosed with SLE‐TTP who were administrated a combination of corticosteroids, plasma exchange, and rituximab at stage of induction. BEL was utilized to rapidly reduce the reliance on these agents and prevent relapse of TTP at maintenance stage. Ultimately, 4 patients fully recovered with a SLE Disease Activity Index score of 0 and reached the goal at dose of prednisolone <7.5 mg/d without relapse. Conclusion: Sequential treatment of rituximab and BEL could be an encouraging approach in treatment of SLE‐TTP and rapid glucocorticoid reduction. [ABSTRACT FROM AUTHOR]

Sequential treatment of osteoporosis has been increasingly mentioned in recent years. However, the corresponding systematic review has not been reported. This study aims to systematically review and assess all full-text pharmacoeconomic studies of sequential treatment for osteoporosis. A comprehensive literature search was performed using PubMed, EMBASE (Ovid), CNKI, and Wanfang Database to identify original articles, published before June 17, 2022. The quality of included articles was evaluated by the updated Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases International Osteoporosis Foundation (ESCEO-IOF). In general, ten articles were included in this review. For the comparison between sequential treatment and bisphosphonate monotherapy, more than 75% of studies demonstrated the sequential treatment was cost-effective or dominant, with the exception of sequential treatment involving teriparatide. When the comparisons occurred between the two sequential treatment groups, the sequential treatments associated with either abaloparatide or romosozumab were cost-effective or dominant compared to the sequential treatment involving teriparatide. Several major key drivers of cost-effectiveness included drug cost, medication persistence and adherence, drug effect on fracture risk, offset effect, time horizon, and baseline fracture risk. The most of studies were identified as high quality in CHEERS (2022) and ESCEO-IOF. The cost-effectiveness of sequential treatment for osteoporosis is influenced by multiple factors. Generally, the sequential treatments involving abaloparatide, romosozumab, denosumab, and bisphosphonates may be considered as the preferred option for osteoporosis with high fracture risk, while the sequential treatment with teriparatide was not a cost-effectiveness strategy. The ESCEO-IOF and CHEER (2022) increase the transparency, comparability, extrapolation, and quality of research, engage patients and the general public in research on health services and policies, and help improve the quality of health technology assessment. [ABSTRACT FROM AUTHOR]

This paper summarized the nursing measures for a patient with chronic obstructive pulmonary disease complicated with type II respiratory failure treated by sequential non-invasive positive pressure ventilation via nasal high-flow oxygen therapy. Nursing interventions were carried out in the following ways: non-invasive positive pressure ventilation, medication nursing, enteral nutrition support, pipeline maintenance, skin care and psychological nursing and other issues. Efforts were made to improve the respiratory failure status and various vital signs, control of carbon dioxide retention and reduce the occurrence of complications. By providing patients with a constant, adjustable, high-speed breathing gas mixture formed from air and oxygen, it was aimed to crush the gas left in the nasal cavity, oral cavity and pharynx, and significantly reduce the amount of carbon dioxide inhaled during the next inhalation. The application of sequential treatment with transnasal high-flow oxygen therapy has achieved positive therapeutic results in patients with hypoxic respiratory failure. (本文总结经鼻高流量氧疗序贯无创正压通气治疗1例慢性阻塞性肺疾病(COPD)合并Ⅱ型呼吸衰竭患者的护理干预措施, 主要从无创正压通气护理、用药护理、肠内营养支持、管路护理、皮肤护理及心理护理等方面进行干预, 旨在改善患者呼吸衰竭状况和各项生命体征, 控制二氧化碳潴留病情, 减少并发症的发生。通过为患者提供恒定的、可调节的高速空氧混合气体, 冲刷患者呼气末残留在鼻腔、口腔及咽部的解剖无效腔的气体, 可明显减少患者下一次吸气时吸入的二氧化碳的含量。经鼻高流量氧疗序贯治疗的应用, 对低氧性呼吸衰竭患者具有积极的治疗效果。)

The tyrosine kinase inhibitor (TKI) cabozantinib might impede the growth of the sunitinib-resistant cell lines by targeting MET and AXL overexpression in metastatic renal cell carcinoma (mRCC). We studied the role of MET and AXL in the response to cabozantinib, particularly following long-term administration with sunitinib. Two sunitinib-resistant cell lines, 786-O/S and Caki-2/S, and the matching 786-O/WT and Caki-2/WT cells were exposed to cabozantinib. The drug response was cell-line-specific. The 786-O/S cells were less growth-inhibited by cabozantinib than 786-O/WT cells (p-value = 0.02). In 786-O/S cells, the high level of phosphorylation of MET and AXL was not affected by cabozantinib. Despite cabozantinib hampering the high constitutive phosphorylation of MET, the Caki-2 cells showed low sensitivity to cabozantinib, and this was independent of sunitinib pretreatment. In both sunitinib-resistant cell lines, cabozantinib increased Src-FAK activation and impeded mTOR expression. The modulation of ERK and AKT was cell-line-specific, mirroring the heterogeneity among the patients. Overall, the MET- and AXL-driven status did not affect cell responsiveness to cabozantinib in the second-line treatment. The activation of Src-FAK might counteract cabozantinib activity and contribute to tumor survival and may be considered an early indicator of therapy response. [ABSTRACT FROM AUTHOR]

Systemic juvenile idiopathic arthritis (sJIA) is a complex and difficult to cure condition with high disability and mortality rates. Herein, we report the case of a patient with sJIA who was treated with sequential tocilizumab (TCZ) and tofacitinib treatment. The patient was a 4-year-old girl hospitalised with fever accompanied by multiple joint swelling and pain in June 2020. Laboratory tests revealed a white blood cell count of 15.3 × 109/L, platelet count of 676.8 × 109/L, haemoglobin of 91.8 g/L, serum ferritin level of 1103.8 U/L, erythrocyte sedimentation rate of 85.0 mm/h, C-reactive protein level of 146.0 g/L and interleukin (IL)-6 level of 288.0 pg/ml. Rheumatoid factor and autoantibodies test results were negative, and she was diagnosed with sJIA. The patient was started on a combination of ibuprofen, methotrexate and TCZ, and her fever decreased to the normal range without any recurrence. Painful joint swelling had resolved significantly at 3-month follow-up. Janus kinase (JAK) inhibitors inhibit the effects of several cytokines, particularly IL-6, and are economical and convenient. Therefore, we selected tofacitinib to replace TCZ in this case, while the other drugs remained unchanged. Arthritis symptoms disappeared gradually after 9-month follow-up. In May 2021, the patient was hospitalised owing to a slight recurrence of the upper respiratory tract infection. She was administered one intravenous infusion of TCZ along with a switch to oral tofacitinib, which quickly relieved the symptoms. In March 2022, the patient's condition was stable. The curative effect of sequential TCZ and tofacitinib treatment was remarkable. IL-6 inhibitors sequential to JAK inhibitors could be a new option in the treatment of systemic juvenile idiopathic joints. [ABSTRACT FROM AUTHOR]

Abstract Background The effect of the sequential combination of chemotherapy and immune checkpoint inhibitors (ICIs) remains unclear. Here, we evaluated the efficacy of different chemotherapy regimens administered after ICIs in advanced non‐small cell lung cancer (NSCLC), compared to the same regimens administered without previous ICIs. Methods We retrospectively included all patients treated between 2015 and 2019 for an advanced NSCLC, receiving a salvage chemotherapy just after ICI (CAI group) comparing them to ICI naive patients (CWPI group) undergoing the same chemotherapy at Bordeaux University Hospital. The primary outcome was the time to treatment discontinuation (TTD), and secondary endpoints were overall survival (OS) and overall response rate (ORR). Results A total of 152 patients were included, with 34/23 (CAI/CWPI) receiving paclitaxel/bevacizumab (PB), 24/11 paclitaxel (P), 27/12 gemcitabine (G) and 6/15 pemetrexed (PE). Characteristics were comparable, except for CAI treated with PB (more patients with an ECOG PS ≤1 [p

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. [Display omitted] • Plant treatments enhance PCB dissipation in standard greenhouses. • Organic amendments aid phytoremediation in standard greenhouses. • Sequential anoxic-oxic greenhouses do not favor phytoremediation. • Organic amendments stimulate PCB dechlorination and plant-microbe interactions. Synopsis: This study revealed different roles of organic amendments in promoting soil PCB transformation under oxic and sequential anoxic–oxic conditions. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

The significant increase in global Landfill Leachate is a pressing challenge directly linked to the growing global population. Among the strategies for landfill leachate treatment, advanced oxidation processes using sulfate radical (SR-AOP) have gained considerable interest, despite the challenge of nitrate generation during ammonia oxidation. This study introduces a sequential treatment method that combines adsorption and a UV/PMS/Fe2+ system to assess its impact on COD (Chemical Oxygen Demand) and ammonia removal efficiencies. The results show that the sequential process achieves optimal COD and ammonia removal rates of 88 % and 88.3 % respectively. The increase in UV 254 absorbance removal during the adsorption phase indicates the removal of UV quenching substances (UVQS), supporting the effectiveness of using adsorption as a pretreatment for the UV-assisted systems (UV/PMS/Fe2+). Additionally, analysis using Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) reveals that the adsorption treatment before the SR-AOP process not only enhances COD and ammonia removal efficiencies, but also eliminates heavy metals such as vanadium (V), titanium (Ti), zinc (Zn), and aluminum (Al) present in leachate. Moreover, the higher BOD/COD ratio suggests improved biodegradability of the effluent. When compared to other systems at optimal conditions, the sequential adsorption and UV/PMS/Fe2+ systems demonstrate superior performance, focusing on removing refractory matter and reducing ammonia content, especially effective at a pH level of 7.25. Analysis using Excitation-Emission Matrix (EEM) shows a shift from primary peaks in raw leachate spectra associated with humic and fulvic acid-like compounds to lower-intensity peaks from fulvic-like small molecule materials in the treated effluent. [Display omitted] • Sequential adsorption and UV/PMS/Fe2+ treatment removes 88 % COD and 88.3 % ammonia from leachate. • The best system performance is in neutral environmental conditions. • The process also eliminates heavy metals like V, Ti, Zn, and Al, improving overall treatment efficiency. • EEM fluorescence spectra changes indicate removal of humic and fulvic compounds, enhancing effluent biodegradability. [ABSTRACT FROM AUTHOR]

Abstract Background The goal of this study was to investigate the effects of treatment with Saccharomyces boulardii and Lactobacillus reuteri on the eradication of Helicobacter pylori and Adverse effects (AEs) of the treatment. Results This study was a double-blind, randomized, placebo-controlled trial. And, eradication of H. pylori was reported comparing quadruple therapy include of PPI (proton pomp inhibitor), bismuth subcitrate, clarithromycin, and amoxicillin versus quadruple therapy supplemented with S. boulardii and L. reuteri DSMZ 17648. For this aim, a total of 156 patients were included in the current study; and patients positive for H. pylori infection (n = 156) were randomly assigned to 3 groups: 52 patients (Group P) received conventional quadruple therapy plus L. reuteri, 52 patients (Group S) received conventional quadruple therapy plus S. boulardii daily, for 2 weeks, and 52 patients were in the control group (Group C). At the end of the treatment period, all the subjects continued to take proton pump inhibitor (PPI) alone for 14 days, and then, no medication was given for 2 weeks again. During follow-up, gastrointestinal symptoms were assessed using an evaluation scale (Glasgow dyspepsia questionnaire [GDQ]), and AEs were assessed at 7, 14, 21, and 28 days. As a result, all patients completed the treatment protocol in all groups by the end of the study. Additionally, eradication therapy was effective for 94.2% of subjects in Group S, 92.3% of subjects in Group P, and 86.5% of subjects in the control group, with no differences between treatment arms. In Group S, the chance of developing symptoms of nausea (OR = 2.74), diarrhea (OR = 3.01), headache (OR = 10.51), abdominal pain (OR = 3.21), and anxiety (OR = 3.58) was significantly lower than in the control group (p

Abstract Background Testicular germ cell tumours (TGCTs) are the most commonly diagnosed malignancy in young men. Although cisplatin has been shown to be effective to treat TGCT patients, long-term follow-up has shown that TGCT survivors who accepted cisplatin treatment suffered from a greater number of adverse reactions than patients who underwent orchiectomy alone. As metformin has shown an anticancer effect in various cancers, we investigated whether metformin could enhance the effects of cisplatin to treat TGCTs. Methods The anticancer effects of different treatment strategies consisting of metformin and cisplatin in TCam-2 and NTERA-2 cells were assessed in vitro and in vivo. First, we used a colony formation assay, CCK-8 and MTT assays to explore the viability of TGCT cells. Flow cytometry was used to assess the cell cycle and apoptosis of TGCTs. Then, Western blotting was used to detect the protein expression of TGCTs cells after different treatments. In addition, a xenograft model was used to investigate the effects of the different treatments on the proliferation of TGCT cells. Immunohistochemistry assays were performed to analyse the expression of related proteins in the tissues from the xenograft model. Results Metformin inhibited the proliferation of TCam-2 and NTERA-2 cells by arresting them in G1 phase, while metformin did not induce apoptosis in TGCT cells. Compared with cisplatin monotherapy, the CCK-8, MTT assay and colony formation assay showed that sequential treatment with metformin and cisplatin produced enhanced anticancer effects. Further study showed that metformin blocked the cells in G1 phase by inducing phosphorylated YAP1 and reducing the expression of cyclin D1, CDK6, CDK4 and RB, which enhanced the chemosensitivity of cisplatin and activated the expression of cleaved caspase 3 in TGCTs. Conclusions Our study discovers the important role of YAP1 in TGCTs and reports a new treatment strategy that employs the sequential administration of metformin and cisplatin, which can reduce the required cisplatin dose and enhance the sensitivity of TGCT cells to cisplatin. Therefore, this sequential treatment strategy may facilitate the development of basic and clinical research for anticancer therapies to treat TGCTs.

Though osteoporosis is a significant cause of disability worldwide, treatment with pharmacologic agents decreases risk of fragility fracture. Though these treatments act through the bone remodeling system to improve bone mass, it is unclear if they alter the response of bone to mechanical loading at the level of the osteocyte. This pre-clinical study determined the relationship between microstructural bone tissue properties and osteocyte lacunar size and density to strain around osteocytes with standard osteoporosis treatment or sequential therapies. Six-month-old female ovariectomized (OVX) Sprague-Dawley rats were cycled through various sequences of pharmacological treatments [alendronate (Aln), raloxifene (Ral) and human parathyroid hormone-1,34 (PTH)] for three month intervals, over nine months. Linear nanoindentation mapping was used to determine Young's modulus in perilacunar and bone matrix regions around cortical bone osteocyte lacunae. Measurements of lacunar diameter and density were completed. Treatment-related differences in Young's modulus in the perilacunar and bone matrix regions were not observed. We confirmed previous data that showed that the bone matrix region was stiffer than the perilacunar matrix region. Whole bone material properties were correlated to perilacunar matrix stiffness. Finite element models predicted a range of mechanical strain amplification factors estimated at the osteocyte across treatment groups. In summary, though the perilacunar matrix near cortical osteocyte lacuna is not as stiff as bone matrix further away, osteoporosis treatment agents do not affect the stiffness of bone tissue near osteocyte lacunae.

Introduction: To compare survival outcomes of radiotherapy (RT) prior to transcatheter arterial chemoembolization (TACE) (RT + TACE) with TACE followed with RT (TACE + RT) in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). Methods: A randomized controlled study was conducted from August 2016 to December 2019 on patients with unresectable HCC and PVTT. The patients were randomly assigned to RT + TACE group or TACE + RT group in a 1:1 ratio. Evaluation of therapeutic effects on the primary tumor was based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST), while that on PVTT was based on the changing of Cheng's PVTT classification. The primary end-point was overall survival (OS). Results: The 120 patients who entered this study were evenly assigned to two groups. In the intention-to-treat (ITT) population, the OS rates for RT + TACE group at 1, 2 and 3 years were 61.7%, 27.4% and 15.6%, compared with 45.0%, 16.1% and 4.7% in TACE + RT group. The median OS was increased in patients with RT + TACE compared with those who had TACE + RT with a marginally significance (15.4 versus 11.5 months, HR = 0.68, 95% CI 0.46–1.01, p = 0.054). The median progression-free survival (PFS) in RT + TACE group was 6.6 months versus 4.2 months in TACE + RT group (HR = 0.66, 95% CI 0.46–0.96, p = 0.030). The corresponding disease control rate (DCR) at 3 months was 86.7% versus 66.7% (p = 0.017) and 61.7% versus 46.7% (p = 0.099) at 6 months. In subgroup analyses, RT + TACE was associated with better OS (HR, 0.48; 95% CI 0.33–0.99, p = 0.048) and PFS (HR, 0.55; 95% CI 0.33–0.93, p = 0.026) versus TACE + RT among patients with type III/IV PVTT. There were 3 patients in RT + TACE group and 2 in TACE + RT group had adverse events ≥ grade 3. Conclusion: Applying RT prior to TACE provided better survival outcomes than TACE followed by RT for patients with HCC and PVTT, which may act as an optimized regional modality to further improve local control rates (Trial registration: ChiCTR ChiCTR2000033573.) [ABSTRACT FROM AUTHOR]

Simple Summary: For patients with advanced basal cell carcinoma (aBCC) limited treatment options are available. In this situation, hedgehog inhibitors (HHIs) are approved as first-line treatment. Upon treatment failure or intolerance, a second-line treatment with PD1 inhibitors (PD1i) is an option. However, no third-line treatment is established. Therefore, we collected data of patients with aBCC, who received HHI reinduction following PD1i-failure. In our cohort of 12 patients, initial HHI treatment led to partial response in 8 and disease stabilization in 4 patients. Eventual HHI discontinuation was mostly due to tumor progression. Second-line PD1i resulted in a partial response in only one patient. Four out of the twelve patients responded to HHI reinduction, with the longest follow-up period being 29 months. Thus, a sequential treatment with HHI reinduction can be a feasible treatment option in a subgroup of patients with aBCC after treatment failure of first-line HHIs as well as of second-line PD1i. For patients with advanced basal cell carcinoma (aBCC) first-line treatment with hedgehog inhibitors (HHIs) and second-line treatment with PD1 inhibitors (PD1i) is available, offering combination and sequencing options. Here, we focus on the efficacy and safety of HHI reinduction after PD1i failure. Retrospective data analysis was performed with 12 patients with aBCC (locally advanced (n = 8)/metastatic (n = 4)). These patients (male:female 6:6, median age 68 years) initially received HHIs, leading to complete/partial response (66%) or stable disease (33%). Median treatment duration was 20.8 (2–64.5) months until discontinuation due to progression (n = 8), adverse events (n = 3), or patient request (n = 1). Subsequent PD1 inhibition (pembrolizumab 42%, cemiplimab 58%) yielded a partial response (8%), stable disease (33%), or progression (59%). Median treatment duration was 4.1 (0.8–16.3) months until discontinuation due to progression (n = 9), adverse events (n = 1), patient request (n = 1), or missing drug approval (n = 1). HHI reinduction resulted in complete/partial response (33%), stable disease (50%), or progression (17%). Median treatment duration was 3.6 (1–29) months. Response duration in the four responding patients was 2–29+ months. Thus, a subgroup of patients with aBCC responded to reinduction of HHI following PD1i failure. Therefore, this sequential treatment represents a feasible treatment option. [ABSTRACT FROM AUTHOR]

Introduction: Atezolizumab (ATEZO) plus bevacizumab (BEVA) represents the new standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the second-line treatment after the failure of immunotherapy-based first-line remains elusive. Taking into account the weaknesses of the available evidence, we developed a simulation model based on available phase III randomized clinical trials (RCTs) to identify optimal risk/benefit sequential strategies. Methods: A Markov model was built to estimate the overall survival (OS) of sequential first- and second-line systemic treatments. Sequences starting with first-line ATEZO plus BEVA followed by 5 second-line treatments (sorafenib [SORA], lenvatinib [LENVA], regorafenib, cabozantinib, and ramucirumab) were compared. The probability of transition between states (initial treatment, cancer progression, and death) was derived from RCTs. Life-year gained (LYG) was the main outcome. Rates of severe adverse events (SAEs) (≥ grade 3) were calculated. The incremental safety-effectiveness ratio (ISER) was calculated as the difference in probability of SAEs divided by LYG between the 2 most effective sequences. Results: ATEZO plus BEVA followed by LENVA (median OS, 24 months) or SORA (median OS, 23 months) was the most effective sequence, producing a LYG of 0.50 and 0.42 year, respectively. ATEZO plus BEVA followed by SORA was the safest sequence (SAEs 63%). At a willingness-to-risk threshold of 10% of SAEs for LYG, ATEZO plus BEVA followed by second-line SORA was favored in 72% of cases, while at a threshold of 30% of SAEs for LYG, ATEZO plus BEVA followed by second-line LENVA was favored in 69% of cases. Conclusion: Our simulation model provides a strong rationale to support ongoing trials evaluating second-line tyrosine-kinase inhibitors after first-line ATEZO plus BEVA. Future evidence from ongoing RCTs and prospective real-world studies are needed to prove the net health benefit of sequential treatment options for advanced HCC.

Purpose: Peptide receptor radionuclide therapy (PRRT) and somatostatin analogues (SSAs) are commonly combined as primary treatment for neuroendocrine neoplasms (NEN), and SSAs given as maintenance. We sought to evaluate whether sequential therapy with PRRT followed by SSAs has progression or survival benefits in patients with NEN after disease control by PRRT. Methods: This prospective, randomised, single-centre study had as principal eligibility criteria: unresectable, locally advanced, or metastatic, histologically confirmed well-differentiated NEN; no symptoms/biochemical diagnosis of carcinoid syndrome; no SSAs or ≤ 3 months of SSAs before PRRT; and stable disease or partial or complete response after PRRT. Altogether, 115 patients were randomised 2:1 to an SSA group (n = 74) given octreotide acetate LAR every 4 weeks, or a control group (n = 41) receiving only best supportive care. Octreotide treatment was to stop upon intolerable toxicity or patient refusal, or, at physician/patient discretion, upon NEN progression. The primary endpoint was progression-free survival (PFS), the secondary endpoint, and overall survival (OS). Results: Median (25th–75th percentile) follow-up from the first PRRT activity to death or latest observation was 6.6 (3.18–10.22) years. During that time, 71/115 patients (62%) progressed, 52/74 (70%) in the SSA group, and 19/41 (46%) in the control group (p = 0.01). Eighty-eight/115 patients (76%) died, 58/74 (78%) in the SSA group, and 30/41 (73%) in the control group (p = 0.52). Median (95% CI) PFS was 4.7 (2.8–7.7) years in the SSA group, and 6.4 (4.1–not reached) years in controls. Overall, median OS was 6.6 years. Neither PFS nor OS differed between groups (p = 0.129, p = 0.985, respectively). Conclusions: In patients with disease control after PRRT, subsequent SSA treatment appeared not to be associated with better PFS or OS. Whether to continue SSA administration upon progression after PRRT requires evaluation in a prospective, randomised, controlled multicentre study with a relatively homogeneous sample. [ABSTRACT FROM AUTHOR]

Background: Pemetrexed is common cytotoxic chemotherapy among non-squamous non-small cell lung cancer (non-Sq-NSCLC) patients; however, among epidermal growth factor receptor (EGFR)-positive lung cancer, there is no clear evidence to support the efficacy of sequential treatment with pemetrexed. Material and methods: We performed a post-hoc analysis of subsequent chemotherapies among 144 patients who received the post-protocol treatment in the phase III trial WJTOG 3405 comparing gefitinib to cisplatin plus docetaxel, and analyzed the effect of pemetrexed on overall survival (OS). Results: Patients with treatment including pemetrexed exhibited significantly longer OS in comparison to those without pemetrexed; the median OS in the pemetrexed + and pemetrexed– patients were 40.7 months and 28.0 months, respectively (0.55 of HR [95% CI: 0.38–0.80, p = 0.0020]). On the other hand, other treatments, including docetaxel, TS-1 and paclitaxel showed no significant impact on OS. The multivariate analysis with a time-dependent Cox proportional hazards model showed that treatment including pemetrexed, as well as PS 0 and post-operative recurrence, were independent predictors of a good prognosis. Moreover, among patients who received at least four lines of prior treatment, pemetrexed + treatment also significantly prolonged OS in comparison to pemetrexed– treatment (median OS pemetrexed + vs. pemetrexed–: 44.4 months vs. 32.6 months; HR: 0.55 [95% CI: 0.31–0.94, p = 0.0290]). Conclusions: Sequential treatment including pemetrexed against EGFR-mutated NSCLC might be associated with a better outcome. It was considered that pemetrexed should be administered without fail as a sequential treatment to improve the prognosis of EGFR-mutated NSCLC as well as like EGFR-tyrosine kinase inhibitors. [ABSTRACT FROM AUTHOR]

Background: Following the introduction of immunotherapy (IO) in the first-line (1L) treatment in patients with non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK mutations, increasing real-world data depict how difficult it is to replicate data from clinical trials to clinical practice, with high rates of early treatment failure. In the context of chemo-IO, our study aims to compare platinum-pemetrexed-pembrolizumab combination to platinum-doublet alone in patients with low PD-L1 (<50%). Methods: We retrospectively collected medical records from patients with stage IV non-squamous NSCLC with PD-L1<50%, consecutively treated at our Centre from 2016 to 2021. Patients were grouped according to 1L treatment received: chemo-IO (group A) or platinum-doublet (group B). Survival outcomes were analyzed and compared among the two groups. Results: Overall, 105 patients were included: 49 in group A and 56 in group B. At data cut-off, median follow-up was 12.4 and 34.8 months, with 32/49 and 52/56 events for progression-free survival (PFS) and 21/49 and 29/56 events for overall survival (OS), respectively. No difference in PFS was observed between group B and group A (6.6 versus 8 months, HR 1.12, 95%CI 0.57-1.40). Patients receiving 1L platinum-doublet had significantly longer OS compared to those receiving chemo-IO (median OS 23.8 vs 14.9 months, HR 0.47, 95% CI 1.15- 3.98, p=0.01). 12 month-OS was 58% (95% CI 44-76%) in group A and 78% (95% CI 68-91%) in group B (p=0.040). Subgroup analysis identified KRAS G12C mutation as potentially affecting PFS in patients receiving chemo-IO (HR 0.29, 95% CI 0-10-0.91). The OS benefit of platinum-doublet was consistent across subgroups, with particular benefit in female sex, liver or pleural metastases, PDL1 negative. Overall, only 46.9% of patients with progression received subsequent treatment in group A (15/32), compared to 86.5% in group B (45/ 52, all receiving 2L IO), with no difference in PFS to 2L (group A 3.7months, group B 4.1months, p=0.3). Conclusions: Despite small study population and differential follow-up, our study demonstrates that sequential use of 1L platinum-doublet and 2L IO is not inferior to 1L chemo-IO in non-squamous NSCLC with PD-L1<50%. In addition, we identified subgroups who might benefit differentially from the two approaches. [ABSTRACT FROM AUTHOR]

In Switzerland, physicians do not have national guidelines for metastatic colorectal cancer (mCRC) patient care and utilize international versions for management recommendations. Moreover, information about adherence to these guidelines and real-world practice patterns in Switzerland or other countries is lacking. The Screening and COnsensus based on Practices and Evidence (SCOPE) program were designed by an international expert panel of gastrointestinal oncologists to gather real-world insights in the current clinical setting to manage patients with mCRC who have received prior treatment. We sought to understand general practice patterns, the influence of molecular diagnostics (e.g., testing for KRAS, NRAS, BRAF, and MSI), tumor sidedness, and patient-centric factors on treatment selection utilizing in-person surveys and three hypothetical patient case scenarios. Here, we describe and evaluate the Swiss data from the SCOPE program within the context of an international viewpoint and discuss the findings of our analysis. In general, we find that the real-world clinical decisions of Swiss physicians (SWI) closely follow international (INT) recommendations and guidelines, largely paralleling their regional and international counterparts in using the two approved treatments in the third- and fourth-line settings, namely trifluridine-tipiracil and regorafenib. Finally, our data suggest a tendency toward the use of trifluridine-tipiracil (SWI: 79%; INT: 66%) over regorafenib (SWI: 18%; INT: 18%) as the preferred third-line treatment choice in mCRC patients regardless of KRAS status. [ABSTRACT FROM AUTHOR]

BackgroundFollowing the introduction of immunotherapy (IO) in the first-line (1L) treatment in patients with non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK mutations, increasing real-world data depict how difficult it is to replicate data from clinical trials to clinical practice, with high rates of early treatment failure. In the context of chemo-IO, our study aims to compare platinum-pemetrexed-pembrolizumab combination to platinum-doublet alone in patients with low PD-L1 (

Patients from Asia with non-small-cell lung cancer (NSCLC) often have mutations in the epidermal growth factor receptor (EGFR) gene. While an increasing number of EGFR tyrosine kinase inhibitors (TKIs) are now available for patients with EGFR mutation-positive NSCLC, most patients inevitably develop resistance to the treatment. Evidence from clinical studies suggests that treatment outcomes and resistance mechanisms vary depending on the choice of TKI therapy in the first-line setting. Hence, it is important to develop optimal treatment sequencing strategies that can provide maximum survival benefit for the patient. In this review we present clinical evidence in Asian patients with NSCLC for various EGFR TKIs, with the goal of supporting the optimization of treatment sequencing. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related deaths with high morbidity and mortality. Non–small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 85% of all cases. Fortunately, the development of molecular oncology provides a promising and effective therapeutic strategy for lung cancers, including specific gene mutations/translocations and immune checkpoints, with epidermal growth factor receptor (EGFR) common mutations first and anaplastic lymphoma kinase (ALK) translocations later as the targeted therapy and immune checkpoint inhibitors (ICIs) as immunotherapy. This review summarized the recent therapy advancements of TKIs and ICIs in NSCLC and focused on the clinical effect of combination or sequential treatment so as to provide the effective advice for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

What is known and objective?: Since comprehensive medication has an important role in the initial management of patients presenting with acute primary angle closure, it is necessary to analyse the effect of each drug on alleviating the disease. This study aimed to evaluate the intraocular pressure‐lowering effect of brinzolamide in the sequential treatment of acute primary angle closure. Methods: In this randomized double‐blind controlled trial, a total of 131 eyes of 125 consecutive patients who presented with their first episode of acute primary angle closure were recruited and received sequential treatment. In this treatment, in the absence of remission, anti‐glaucoma drugs, anterior chamber paracentesis and argon laser peripheral iridoplasty are used sequentially. The patients were randomized to receive either brinzolamide or normal saline as a placebo. The primary outcomes were decreased intraocular pressure, success rate and treatment time. Results and discussion: There was no statistically significant difference in the decreased level of intraocular pressure between the two groups at 6, 12 or 24 h after the start of treatment (p‐values were 0.526, 0.206 and 0.130 respectively). The success rate and treatment time were also not significantly different between the groups. No adverse side effects of brinzolamide were observed in the brinzolamide group. What is new and conclusion?: In patients with a first episode of acute primary angle closure, brinzolamide did not improve the effectiveness of the sequential treatment for reducing the intraocular pressure levels or shortening the treatment time within the first 24 h of initiating therapy. [ABSTRACT FROM AUTHOR]