Sequential Therapy Research Articles

Dalbavancin as sequential therapy in infective endocarditis: Real-life experience in elder and comorbid patients

ObjectivesThis study aimed to evaluate the effectiveness of dalbavancin as sequential therapy in patients with infective endocarditis (IE) due to gram positive bacteria (GPB) in a real-life heterogenous cohort with comorbid patients. MethodsA single center retrospective cohort study including all patients with definite IE treated with dalbavancin between January 2017 and February 2022 was developed. A 6-month follow-up was performed. The main outcomes were clinical cure rate, clinical and microbiological relapse, 6-month mortality, and adverse effects (AEs) rate. ResultsThe study included 61 IE episodes. The median age was 78.5 years (interquartile range [IQR] 63.2–85.2), 78.7% were male, with a median Charlson comorbidity index of 7 (IQR 4–9) points. Overall, 49.2% suffered native valve IE. The most common microorganism was Staphylococcus aureus (26.3%) followed by Enterococcus faecalis (21.3%). The median duration of initial antimicrobial therapy and dalbavancin therapy were 27 (IQR 20–34) and 14 days (IQR 14–28) respectively. The total reduction of hospitalization was 1090 days. The most frequent dosage was 1500mg of dalbavancin every 14 days (96.7%). An AE was detected in 8.2% of patients, only one (1.6%) was attributed to dalbavancin (infusion reaction). Clinical cure was achieved in 86.9% of patients. One patient (1.6%) with Enterococcus faecalis IE suffered relapse. The 6-month mortality was 11.5%, with only one IE-related death (1.6%). ConclusionThis study shows a high efficacy of dalbavancin in a heterogeneous real-world cohort of IE patients, with an excellent safety profile. Dalbavancin allowed a substantial reduction of in-hospital length of stay.

Real world outcomes of sequential ADC therapy in metastatic breast cancer: Patients treated with sacituzumab govitecan and trastuzumab deruxtecan.

1085 Background: Sacituzumab govitecan (SG) and trastuzumab deruxtecan (TDXd) are antibody drug conjugates (ADCs) that are approved for the treatment of HER2 low metastatic breast cancer (MBC). Both carry payloads which inhibit topoisomerase 1, and it is unknown whether these ADCs retain clinical activity when used sequentially to each other. Here we present a retrospective study of patients treated with both SG and TDXd at our institution and report real world progression free survival (PFS), clinical factors associated with longer PFS, and whether ADC sequence impacts outcome. Methods: All patients with MBC treated at MSKCC who had received both SG and TDXd (in any order) were eligible for inclusion. Clinicopathological and demographic data were obtained from retrospective chart review. PFS was determined clinically and calculated using Kaplan-Meier survival analysis. Univariate and multivariate associations of survival were assessed using Cox proportional hazards models. Results: Eighty-five patients met eligibility per the criteria above: 54 with estrogen receptor positive (ER+) MBC and 31 with triple negative breast cancer (TNBC). 33 patients received SG followed by TDXd (14 ER+, 19 TNBC), and 52 received TDXd followed by SG (40 ER+, 12 TNBC). Median age at time of second ADC treatment (ADC2) was 59 among all patients, 62 among SG first, and 58 among TDXd first. This cohort was heavily pre-treated, with median 5 prior therapies at the time of first ADC (ADC1) and 7 at the time of ADC2. Both the SG first and TDXd first cohorts had median 1 line of intervening therapy between ADCs. In the SG first group, median ADC2 (TDXd) PFS was 3.5 months (95%CI 2.7-7.7), and in the TDXd first group median ADC2 (SG) was 2.8 months (95%CI 2.6-3.7). On multivariate analysis, neither ADC sequence (SG first vs. TDXd first, HR 1.30, 95%CI 0.71-2.37, p=0.4) nor ER status (TNBC vs. ER+, HR 1.21, 95%CI 0.63-2.32, p=0.6) showed statistically significant differences in ADC2 PFS between these groups. Instead, later treatment line at the time of ADC2 was significantly associated with shorter ADC2 PFS (continuous, HR 1.11, 95%CI 1.01-1.23, p=0.03). To separately evaluate differences in PFS for each ADC depending upon whether it was first or follow-up therapy, median ADC1 vs. ADC2 PFS is summarized by ADC (Table). Conclusions: In this heavily pre-treated patient cohort, the clinical activity of both SG and TDXd appear modest in the ADC2 setting. Further studies are needed to confirm these findings and to determine whether payload cross-resistance may undermine the benefit of sequential ADC therapy. [Table: see text]

Real world data of 177 Lutetium-PSMA-617 for metastatic castration resistant prostate cancer (mCRPC): Analysis of patients treated from 2 large reference centers.

e17050 Background: 177Lu-PSMA-617 was recently approved for the treatment of patients with mCRPC in the USA. While treatment is associated with improved survival, responses to therapy are lower in patients with visceral metastasis and with FDG avid disease. In this study, we aim to characterize response to the therapy trying to optimize patient selection for 177Lu-PSMA-617. Methods: Patients treated from 2020 to 2023 in 2 large oncology centers in Brazil were analyzed. Our primary endpoint was to investigate the PSA response rate. Secondary endpoints included overall survival (OS), time to next sequential therapies (TNST) and PSA response in patients with visceral disease. Patients were treated after being submitted to a double image consisting of PET-CT PSMA and a PET-CT FDG (as indicated by the TheraP trial, Hoffman et al.) confirming disease uptake without divergent disease. Results: A total of 32 patients with mCRPC were included in this analysis. The median age was 73 years. Median number of prior lines of therapy for mCRPC was 3 with 20 receiving more than one androgen receptor signaling inhibitor (ARSI) and 5 receiving more than one taxane. The percentage with a PSA response was 48,5% and visceral disease was present in 56,3% of patients. Response rate for pts with visceral disease versus non-visceral was 21,9% vs 43,8%. The Medians of TNST and OS were respectively 7 and 9,6 months. The characteristics of patients with and without a PSA response are detailed in the table. Conclusions: Our cohort, characterized by advanced age, extensive prior treatments, and elevated PSA values, exhibited a PSA response that aligns with patients treated in randomized trials. Notably, our patients with visceral disease demonstrated a lower PSA response. [Table: see text]

EVOLVE-HNSCC: A global phase 3 study of volrustomig as sequential therapy for unresected locally advanced head and neck squamous cell carcinoma (LA-HNSCC) following definitive concurrent chemoradiotherapy (cCRT).

TPS6120 Background: Currently there are no approved maintenance therapies for patients (pts) with unresected LA-HNSCC following definitive cCRT. The PD-1 inhibitors pembrolizumab and nivolumab are licensed for treatment of pts with recurrent or metastatic HNSCC who have progressed on or after a platinum-based therapy. Dual inhibition of CTLA-4 and PD-L1 is approved in solid tumors including renal cell carcinoma (RCC), NSCLC, and melanoma, and has shown a numerical trend towards improved survival in first-line pts with recurrent/metastatic HNSCC whose tumors express PD-L1. Volrustomig (MEDI5752) is a monovalent, PD-1/CTLA-4 bispecific, humanized IgG1 monoclonal antibody engineered to specifically inhibit PD-1, with increased CTLA-4 blockade on PD-1+ activated T cells compared to PD-1– resting peripheral T cells. In a first-in-human phase 1/2 study (NCT03530397), volrustomig monotherapy showed promising efficacy with acceptable tolerability in advanced clear cell RCC and in combination with chemotherapy in advanced NSCLC. The phase 3, randomized, open-label, multicenter, eVOLVE-HNSCC study will evaluate the efficacy and safety of sequential therapy with volrustomig compared with observation in pts with unresected LA-HNSCC who have not progressed after receiving definitive cCRT (NCT06129864). Methods: Key eligibility criteria include histologically or cytologically confirmed, unresected LA-HNSCC with no evidence of metastatic disease, i.e. AJCC 8th edition (TNM staging system) stage IVA/B cancers of the hypopharynx, oral cavity, larynx or HPV-negative oropharynx, or stage III HPV-positive oropharynx cancer; age ≥18 years; WHO/ECOG performance score of 0 or 1; and adequate organ and bone marrow function. Key exclusion criteria include requiring further treatment with curative intent after definitive cCRT, resected LA-HNSCC, recurrent/metastatic disease, and >1 primary tumor. Following initial screening and definitive cCRT (cisplatin or carboplatin + paclitaxel or carboplatin + 5-FU, plus concomitant radiotherapy), approximately 1145 pts whose disease has not progressed within 12 weeks of the last dose of cCRT will be randomized 1:1 to Arm A or B. Arm A will receive volrustomig intravenously every 3 weeks for a maximum of 12 months or 18 cycles, or until RECIST v1.1-defined radiological progressive disease (PD) or unacceptable toxicity. Arm B will undergo observation for a maximum of 12 months or until PD. The primary endpoint is PFS in pts with PD-L1-expressing tumors. Secondary endpoints include PFS in all randomized pts, OS in pts with PD-L1-expressing tumors and in all randomized pts, PFS2, safety, patient-reported outcomes, pharmacokinetics, and immunogenicity. Exploratory biomarker analyses will also be conducted. Enrollment began in December 2023. Clinical trial information: NCT06129864 .

Charting the Course: Sequencing Immunotherapy for Multiple Myeloma.

Multiple chimeric antigen receptor (CAR) T-cell and bispecific antibody (bsAb) therapies have been approved, demonstrating impressive clinical efficacy in relapsed/refractory multiple myeloma (MM). Currently, these treatment share overlapping approval indications in the relapsed/refractory space, highlighting the importance of optimal selection and sequencing to maximize clinical efficacy. For patients previously unexposed to T-cell-directed therapies, several factors should be weighed when both options are available. These factors include access and logistical challenges associated with CAR T-cell therapy, disease-specific factors such as tempo of disease relapse, in addition to patient-specific factors such as frailty, and distinct toxicity profiles across these agents. Sequential therapy, whether it involves CAR T-cell therapy followed by bsAb or vice versa, has demonstrated clinical efficacy. When sequencing these agents, it is crucial to consider various factors that contribute to treatment resistance with careful selection of treatments for subsequent therapy in order to achieve favorable long-term patient outcomes.

Significance of imaging-detected extranodal extension (iENE) in locally advanced head and neck squamous cell carcinoma (LASCCHN) treated with induction chemotherapy followed by chemoradiotherapy.

6034 Background: Extranodal extension (ENE) of nodal metastasis is a significant prognostic factor in p16-negative SCCHN and is classified as N3b by the AJCC 8th edition. Therefore, pretreatment determination of ENE has significant clinical implications in SCCHN, and iENE has just recently been proposed. We previously discussed association with pathological ENE and iENE (Jpn J Radiol. 2020;38(6):489-506.). However, the role of iENE in non-surgical sequential therapy remains unclear. Methods: We retrospectively reviewed patients with LASCCHN originating from the oropharynx, hypopharynx, and larynx who received enhanced computed tomography (CT), then treated with induction chemotherapy (IC) with paclitaxel, carboplatin, and cetuximab followed by chemoradiotherapy (CRT) from 2013 to 2022 in our hospital. Two radiologists specializing in head and neck cancer blindly annotated the status of iENE in baseline CT images by the previously reported criteria (Oral Oncol. 2022;125:105716.). Multivariate analysis variables for event-free survival (EFS) and overall survival (OS) included the presence or absence of iENE, a response to IC, clinical T-category, performance status, smoking status, etc. Results: In the 88 patients, 67 (76.1%) had iENE and 21 (23.9%) did not at baseline. In the former and latter group, stage II/III/IV were 10.4%/26.9%/62.7% and 0%/28.6%/71.4%, HPV-positive were 37.3% and 28.6%, respectively. With the median follow-up of 37.4 months (range: 6.7-108.8), the former had significantly shorter EFS (3-y EFS: 41.9% vs. 75.6%, hazard ratio [HR]; 2.9 (1.2-7.4), p-value; 0.02) and OS (3-y OS: 72.8% vs. 100%, HR; Inf (0.01-Inf), p-value=0.003). Multivariate analysis identified the presence of iENE (HR for EFS: 2.80, 95%CI: 0.97-8.05, HR for OS: 2.93, 95%CI: 1.01-8.44) and unresponsiveness to IC (HR for EFS: 2.47, 95%CI: 1.31-4.68, HR for OS: 2.87, 95%CI: 1.13-7.26) as mutually independent unfavorable prognostic factors for both EFS and OS. Furthermore, classification based on the two factors could identify the population with a worse prognosis (Table). Conclusions: In the sequential therapy of IC followed by CRT, the current study revealed for the first time that subjects with an iENE at baseline, together with an unsatisfactory response to IC would require special attention, such as more intensified post-treatment follow-up as well as additional therapeutic interventions to improve their prognosis. [Table: see text]

Sequential neoadjuvant chemotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma.

TPS4209 Background: Patients with borderline resectable (BRPC) and locally advanced unresectable (LAPC) pancreatic cancer have a median OS of 8-20 months unless they undergo margin negative resection. Despite advances in systemic therapy, the prognosis is dismal. The locoregional and distant failure rates are high in post-surgery and therefore neoadjuvant chemotherapy emerged as standard-of-care practice to select the patients for surgery and improve overall clinical outcomes. An effective and tolerable neoadjuvant regimen can facilitate R0 resection by tumor down staging and mitigating the risk for positive margins. A recent SEQUENCE-2 study on sequential treatment with combination of Gemcitabine and nab-paclitaxel (GA) GA followed by modified FOLFOX (mFOLFOX) improved OS (13.2 months) and PFS (9.5 months) in patients with metastatic PDC, compared with the standard GA regimen, with comparable safety profile. Current guidelines suggest modified FOLFIRINOX (mFFX, infusional 5-fluorouracil, oxaliplatin, irinotecan) or GA as the first-line systemic chemotherapeutic regimen in neoadjuvant, adjuvant and palliative setting. These regimens are associated with modest pathological complete response rate. However, there is significant unmet need for management of BRPC and LAPC as the optimal treatment strategy remains undefined. As both of the aforementioned regimens are active and feasible in BRPC and LAPC, we conceptualize that by using both regimens alternating in sequence the rate of R0 resection and pathological response could be improved by overcoming possible resistance to a single backbone. Methods: The aim of this study is to demonstrate the efficacy and feasibility of sequential chemotherapy (GA followed by mFFX) in patients with BRPC (n=34) and LAPC (n=30). To achieve this, we are conducting a non-randomized prospective interventional clinical study with BRPC and LAPC patients treated with alternating cycles of GA and mFFX for 4 months and assessed for clinical outcomes, feasibility and toxicity. The primary objective of this study is to evaluate the efficacy of sequential GA followed by mFFX in improving R0 resection rate in patients with BRPC and LAPC. After four months of sequential neoadjuvant therapy, the patients will proceed to surgery, radiation, or extended course of chemotherapy, off study, as determined by multidisciplinary tumor board consensus or the treating physician. These results will have high translational potential for providing mechanistic insight into tumor response, optimizing current management strategies for pancreatic cancer that could be generalizable to other stages of this cancer. The key eligibility criteria include treatment naive histologically diagnosed BRPC or LAPC with measurable disease, ECOG 0,1, optimal organ function. Clinical trial information: NCT05776524 .

Role of induction chemotherapy in locally advanced oropharyngeal carcinoma in Indian population.

e18026 Background: Head and neck cancer is the third most frequent cancer in Indian men, it is a growing public health problem. Given the numerous disparities in head and neck cancer biology, etiologic and demography between the developing world and the developed world, management guidelines should be based on Indian literature rather than western data. This study aims to define role of Induction chemotherapy in locally advanced oropharyngeal cancer In Indian population by comparing the outcomes which are Overall response rate (O.R.R), Progression free survival (P.F.S), overall survival (O.S) between patients who received Induction chemotherapy followed by CTRT vs CTRT. Methods: Patients who were registered for treatment between jan-2018 to dec-2022 who met the selection criteria were included for the study. Selection criteria: Patients who were diagnosed with Stage III OR IV (a & b, non-metastatic) oropharyngeal squamous cell carcinoma from age group of 20 to 70 who were HPV negative or unknown status were included for study. Total of 50 patients were chosen for the study after stringent selection criteria. Out of 50 ,23 patients received Induction chemotherapy and 27 patients received only CTRT. Results: Overall response rate was analysed using Interim PET CT after Induction chemotherapy and PET CT after 3 to 6 months of CTRT. Complete response and partial response is considered as ORR. It was observed that ORR in sequential therapy arm is 42% and only CTRT arm is 36%, however this is not statistically significant with p value of 0.54. Median PFS for CTRT arm is 8 months and median PFS for IC +CTRT arm is 12 months with p value = 0.97(>0.05) (Log rank test) which is not statistically significant. Median OS for CTRT is 60 months and IC+ CTRT is 18 months. The log rank test has been used for comparing the overall survival outcomes of both the groups , and thus the p-value obtained is 0.56(>0.05), which shows that there is no statistically significant difference in the survival outcome of the two groups. Conclusions: In conclusion, our study on induction chemotherapy in locally advanced head and neck cancer did not identify statistically significant differences in O.R.R, PFS and OS between the two treatment arms which is concordant with MACH- NC updated 2021 data. Several factors, including patient heterogeneity, sample size, treatment protocol, follow-up, duration, may have contributed to these results, it is essential to interpret these results in the context of the study's limitations. [Table: see text]

Reactive oxide species and ultrasound dual-responsive bilayer microneedle array for in-situ sequential therapy of acute myocardial infarction

Acute myocardial infarction (AMI) resulting from coronary artery occlusion stands as the predominant cause of cardiovascular disability and mortality worldwide. An all-encompassing treatment strategy targeting pathological processes of oxidative stress, inflammation, proliferation and fibrotic remodeling post-AMI is anticipated to enhance therapeutic outcomes. Herein, an up-down-structured bilayer microneedle (Ce-CLMs-BMN) with reactive oxygen species (ROS) and ultrasound (US) dual-responsiveness is proposed for AMI in-situ sequential therapy. The upper-layer microneedle is formulated by crosslinking ROS-sensitive linker with polyvinyl alcohol loaded with cerium dioxide nanoparticles (CeNPs) featuring versatile enzyme-mimetic activities. During AMI acute phase, prompted by ischemia-induced microenvironmental redox imbalance, this layer swiftly releases CeNPs, which aid in eliminating excessive ROS and catalyzing oxygen gas (O2) production through multiple enzymatic pathways, thereby alleviating oxidative stress-induced damage and modulating inflammation. In AMI chronic repair phase, micro-nano reactors (CLMs) situated in the lower-layer microneedle undergo cascade reactions with the assistance of US irradiation to generate nitric oxide (NO). As a bioactive molecule with pro-angiogenic and anti-fibrotic effects, NO expedites cardiac repair while attenuating adverse remodeling. Additionally, its antiplatelet-aggregating properties contribute to thromboprophylaxis. In-vitro and in-vivo results substantiate the efficacy of this integrated healing approach in AMI management, showcasing promising prospects for advancing infarcted heart repair.

Current Management of Acute Severe Ulcerative Colitis: New Insights on the Surgical Approaches.

Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency with considerable morbidity. Despite recent advances in medical IBD therapy, colectomy rates for ASUC remain high. A scoping review of published articles on ASUC was performed. We collected data, such as general information of the disease, diagnosis and initial assessment, and available medical and surgical treatments focusing on technical aspects of surgical approaches. The most relevant articles were considered in this scoping review. The management of ASUC is challenging; currently, personalized treatment for it is unavailable. Sequential medical therapy should be administrated, preferably in high-volume IBD centers with close patient monitoring and indication for surgery in those cases with persistent symptoms despite medical treatment, complications, and clinical worsening. A total colectomy with end ileostomy is typically performed in the acute setting. Managing rectal stump is challenging, and all individual and technical aspects should be considered. Conversely, when performing elective colectomy for ASUC, a staged surgical procedure is usually preferred, thus optimizing the patients' status preoperatively and minimizing postoperative complications. The minimally invasive approach should be selected whenever technically feasible. Robotic versus laparoscopic ileal pouch-anal anastomosis (IPAA) has shown similar outcomes in terms of safety and postoperative morbidity. The transanal approach to ileal pouch-anal anastomosis (Ta-IPAA) is a recent technique for creating an ileal pouch-anal anastomosis via a transanal route. Early experiences suggest comparable short- and medium-term functional results of the transanal technique to those of traditional approaches. However, there is a need for additional comparative outcomes data and a better understanding of the ideal training and implementation pathways for this procedure. This manuscript predominantly explores the surgical treatment of ASUC. Additionally, it provides an overview of currently available medical treatment options that the surgeon should reasonably consider in a multidisciplinary setting.

Simultaneous versus sequential fractional CO2 laser and subcision combination for management of post-acne atrophic scars: A split-face comparative study.

A combination of fractional CO2 laser and subcision is usually employed for the treatment of post-acne atrophic scars. However, the efficacy and safety of both simultaneous and sequential combination therapies should be explored. To compare the efficacy and safety of simultaneous and sequential fractional CO2 laser and subcision combination therapies for post-acne atrophic scars. This single-blind, split-face clinical trial included 34 patients with post-acne atrophic scars at our institution. Each patient underwent three sessions of subcision combined with fractional CO2 laser, with a 1-month interval between each session. The left side of the face was treated with simultaneous combination therapy, whereas the right side was treated with sequential combination therapy. Treatment efficacy was assessed at 4, 8, and 12 weeks; and 3 and 6 months after the last session. Simultaneous and sequential treatments demonstrated comparable efficacy. Regarding the adverse events, the side of the face undergoing simultaneous treatment experienced longer swelling duration, higher pain levels during laser treatment, and shorter downtime. Despite the longer swelling time and higher pain levels during laser treatment in the simultaneous treatment side, the effectiveness and satisfaction level of the CO2 fractional laser and subcision for treatment of the acne scars were comparable between the two combinations, with a shorter downtime for the simultaneous than for the sequential combination therapy.

What to do when traditional rescue therapies fail in acute severe ulcerative colitis.

Acute severe ulcerative colitis (ASUC) is a medical emergency that affects approximately 25% of patients with ulcerative colitis at some point in time in their lives. Outcomes of ASUC are highly variable. Approximately 30% of patients do not respond to corticosteroids and up to 50% of patients do not respond to rescue therapy (infliximab or cyclosporin) and require emergency colectomy. Data are emerging on infliximab dosing strategies, use of cyclosporin as a bridge to slower acting biologic agents and Janus kinase inhibition as primary and sequential therapy. In this review, we outline contemporary approaches to clinical management of ASUC in the setting of failure to respond to traditional rescue therapies.

Evaluation and Comparison of Different Surgico-chemotherapeutic Regimens for the Treatment of Malignant Canine Mammary Tumours

Background: Cancer has been regarded as the most dreaded disease for both human and animals because of its incurability. Canine mammary tumours are common and major problem encountered by academicians and practicing veterinarians. As a result, the current study was conducted to examine the effectiveness and overall impact of different surgico-chemotherapeutic approaches in treating malignant mammary tumors in dogs. Methods: The investigation involved 18 clinical instances of mammary tumors in different breeds, regardless of age or sex and were divided into three groups of six animals each. In Group S, only surgical excision of tumour was performed while animals of Group SD and Group SV were treated with surgical excision followed by administration of Doxorubicin (30 mg/m2) BSA and Vincristine sulphate (0.025 mg/kg) intravenously alongwith DNS at 7th and 14th post-operative days respectively. Different physiological and haemato-bichemical parameters i.e. Hb, PCV, TLC, TPC, DLC, Serum glucose, TSP, SUN, SC, ALT, AST and ALP were recorded preoperatively, postoperatively and following chemotherapy at 10th, 30th and 60th day intervals. Result: The present study showed transient change in the physiological, haematological and biochemical profiles following surgery and chemotherapy treatment. The histopathological analysis showed more cases of adenocarinoma which were followed by mixed carcinoma. Surgery combined with chemotherapy (doxorubicin and vincristine) resulted in minimal to no reoccurrence with few adverse reactions including inappetance, vomition, anaemia and alopecia. It was concluded that the most effective treatment for malignant mammary tumors in dogs is surgical excision followed by sequential vincristine therapy, which efficiently regresses the tumor without causing relapse.

Assessment of Cefuroxime and Cefuroxime Clavulanic Acid Prescription Practices for Infection Management in Routine Indian Healthcare Settings: Expert Insights

Background: Cefuroxime axetil has shown effectiveness as part of intravenous/oral sequential therapy for community-acquired pneumonia (CAP) treatment, although some countries currently lack dosage recommendations for this regimen. In addition, the perspectives of clinicians were not studied. So, this study evaluated the prescription practice of cefuroxime, and cefuroxime+ clavulanic acid in the management of infections in routine Indian settings. Methods: The cross-sectional survey, titled ‘Cefuroxime & Cefuroxime+Clavulanic acid in Management of Infections: Expert Perspective (CARE) Study’, utilized a 20-item, multiple-response questionnaire to gather expert opinion from specialists regarding the clinical use of cefuroxime and cefuroxime + clavulanic acid in managing infections. The survey encompassed questions about current prescription practices, clinical observations, preferences, and experiences related to the use of these antibiotics in routine settings. Results: Among the 164 clinicians surveyed, 78% of the respondents indicated that cefuroxime was highly effective in managing lower respiratory tract infections. Additionally, 91% of the experts stated that the combination of cefuroxime and clavulanic acid was very effective in managing infections. The majority of clinicians recommended cefuroxime + clavulanic acid as the initial therapy for complicated urinary tract infections (88%), as well as first-line therapy for uncomplicated skin and soft tissue infections (45%) and community-acquired pneumonia (58%). According to 40% of the clinicians, cefuroxime + clavulanic acid was recommended as the initial therapy for 21-30% of patients suspected of methicillin-resistant Staphylococcus aureus infection. Most respondents (88%) preferred cefuroxime + clavulanic acid as the antibiotic for managing Pseudomonas aeruginosa infection. Conclusion: The survey has emphasized the critical role of cefuroxime and cefuroxime + clavulanic acid as antibiotics in managing diverse infections. Clinicians' recognition of their efficacy and preference for combination therapy has underscored the importance of antibiotic stewardship in optimizing patient care.

A systematic review on prosthodontic rehabilitation of hemimandibulectomy patients

To restore oral function after tumor excision, practitioners must undertake the enormous challenge of restoring hemimandibulectomy deficits. Depending on the type and extent of mandibular reconstruction (Cantor-Curtis classification), there are many prosthetic treatment options available for the rehabilitation of acquired hemimandibulectomy abnormalities. The objective of this systematic study is to evaluate the range of prosthodontic rehabilitation techniques in relation to the kind of repair and severity of mandibular surgical abnormalities. The databases incorporated for literature search were Google Scholar and Medline (PubMed). Relevant search terms for hemimandibulectomy and reconstruction with prosthetic rehabilitation were used. Two reviewers independently assessed the articles using eligibility criteria; published case reports and case series in the English language and depicting prosthodontic treatment modality of patients greater than 13 years were included. A total of 212 records were identified from the database search of which 29 duplicates were removed.The remaining articles were assessed for eligibility, and 50 articles (comprising 50 cases) were finally included in the study. This review identified a number of prosthetic options, including some novel prosthetic techniques, guiding flange, twin occlusion, palatal ramp, conventional to hybrid partial and complete dentures, and implant-supported prosthesis.The prosthetic options covered in this review included implant-supported prosthesis, guide flange, dual occlusion, palatal ramp, conventional, hybrid, and full dentures, as well as a few cutting-edge prosthetic techniques.As they plan and manage sequential therapy for hemimandibulectomy cases in their daily practice, practitioners and prosthodontists will find this helpful.

Effect of sequential gemcitabine and epirubicin therapy on high-risk non-muscle invasive bladder cancer following transurethral bladder tumour resection

Purpose: To investigate the efficacy of sequential gemcitabine and epirubicin therapy on high-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumour (TURBT). Methods: The records of 100 high-risk NMIBC patients, who underwent TURBT at the Tongling People's Hospital, Tongling City, China between January 2020 and March 2023 were retrospectively analyzed. A total of 46 patients, treated with epirubicin after operation, were assigned to control group, while 54 patients, treated with both gemcitabine and epirubicin, were included in the study group. DKK-1 and YKL-4 levels were assayed by immunomagnetic bead‐based liquid chip technology and enzyme-linked immunosorbent assay, respectively. Furthermore, treatment efficacy was determined and compared between the two groups. Results: There were no significant differences in the pre-treatment DKK-1 and YKL-40 levels between the two groups (p > 0.05). However, both groups experienced a significant drop in post-treatment levels, with significantly lower post-treatment levels in the study group (p < 0.05). There were no significant differences in catheter retention time and hospitalization time between the two groups (p > 0.05). The study group achieved a significantly better overall response rate than the control group. The pre-treatment SF-36 scores of the two groups were similar, while their post-treatment SF-36 scores increased significantly (p < 0.05). Conclusion: Sequential therapy with gemcitabine and epirubicin is effective in the therapy of high-risk NMIBC after TURBT. It significantly lowers DKK-1 and YKL-40 levels, improves postoperative quality of life and reduces the postoperative recurrence rate without increasing adverse reactions and affecting the catheter retention and hospitalization times. A more comprehensive analysis is required to obtain improved outcomes.

Improvements in advanced hepatocellular carcinoma to repeat implementation of primary protocol after cancer progression occurs following sequential systemic therapy and a clinical trial: A case report.

Systemic therapy is recommended for patients with advanced hepatocellular carcinoma (aHCC). However, drug resistance occurs over time when patients receive systemic therapy, resulting in cancer progression. Due to the lack of relevant clinical trials, optimizing subsequent treatments after cancer progression remains elusive. A 52-year-old male patient presented with epigastric discomfort and fatigue for almost 1 month with a past history of chronic hepatitis B virus infection for 30 years. Based on the patient's performance status, tumor status assessed by computed tomography, liver function, he was diagnosed with HCC at BCLC stage C. He first received transarterial chemoembolization (TACE) combined with sintilimab and lenvatinib as first-line treatment and experienced 10-month progression-free survival. After cancer progression, the patient participated in a clinical trial of ABSK-011, a novel fibroblast growth factor receptor 4 inhibitor, with a frustrating result. Then, the patient underwent TACE and received sintilimab plus lenvatinib again. Surprisingly, the tumor had a partial response, and the patient's serum alpha-fetoprotein returned to normal. The combined treatment of TACE plus systemic therapy might be an appropriate subsequent treatment.

Pre-first-line chemotherapy risk stratification for overall survival in advanced urothelial carcinoma in sequential therapy era.

To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors. A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS. Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified. We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era.

Efficacy analysis of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 inhibitor treatment in hormone receptor positive/human epidermal growth factor receptor 2-low metastatic breast cancer

Objective: To evaluate the efficacy of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment in hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer. Methods: Patients with metastatic breast cancer diagnosed with HR positive/HER2 low expression at the Fifth Medical Center of PLA General Hospital from October 1, 2018 to September 30, 2023 were retrospectively included. All patients received sequential chemotherapy or sequential endocrine therapy combined with targeted drugs after progression on CDK4/6 inhibitor treatment.The median follow-up was 9 months, and the follow-up ended on October 31, 2023. The patients were divided into chemotherapy group (receiving sequential chemotherapy) and endocrine therapy group (receiving sequential endocrine therapy combined with targeted drugs), according to the treatment plan. Information on demographic data, clinical and pathological diagnosis, treatment regimen, and efficacy evaluation was collected. The basic conditions of patients who may affect the curative effect of different treatment schemes were preset as stratified subgroups, including age, progesterone receptor (PR) status, HER2 status, disease-free survival, number of previous endocrine therapy and chemotherapy, and visceral metastasis. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate(CBR) and PFS based on stratification factors. The survival curve was plotted by Kaplan-Meier method, the comparison of PFS between groups was performed by log-rank test, and the comparison of ORR and CBR between groups were performed by χ2 test. Results: A total of 188 patients were included, including 126 patients in the chemotherapy group [all females, aged 29-74 (51±10) years] and 62 patients in the endocrine therapy group [1 male and 61 female, aged 29-77 (51±12) years]. ORR of chemotherapy group was 23.0% (29/126), higher than that of endocrine treatment group [3.2% (2/62)] (P<0.001); The CBR of chemotherapy group and endocrine therapy group were 46.8% (59/126) and 33.9% (21/62), respectively, with no statistical significance (P=0.091). The median PFS of chemotherapy group and endocrine therapy group were 5.0 (95%CI: 4.3-5.7) and 4.0 (95%CI: 1.6-6.4) months, respectively, with no statistical significance (P=0.484). In the preset stratified subgroups, the median PFS of chemotherapy [6.0 (95%CI: 5.4-6.6) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 1.8-2.2) months] (P<0.001) in PR negative patients; In patients who had progressed on over 2 previous endocrine treatments, the median PFS of chemotherapy [5.0 (95%CI: 3.8-6.2) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 0.6-3.4) months] (P=0.045). Conclusions: After progression on treatment with CDK4/6 inhibitors for HR-positive/HER2-low expression metastatic breast cancer, both chemotherapy and endocrine therpy combined with targeted drugs are viable treatment options. However, for patients with PR negative or ≥2 lines of endocrine therapy previously, priority should be accorded to chemotherapy.

Double-Layered Hollow Mesoporous Cuprous Oxide Nanoparticles for Double Drug Sequential Therapy of Tumors.

Cancer stem cells (CSCs) are one of the determinants of tumor heterogeneity and are characterized by self-renewal, high tumorigenicity, invasiveness, and resistance to various therapies. To overcome the resistance of traditional tumor therapies resulting from CSCs, a strategy of double drug sequential therapy (DDST) for CSC-enriched tumors is proposed in this study and is realized utilizing the developed double-layered hollow mesoporous cuprous oxide nanoparticles (DL-HMCONs). The high drug-loading contents of camptothecin (CPT) and all-trans retinoic acid (ATRA) demonstrate that the DL-HMCON can be used as a generic drug delivery system. ATRA and CPT can be sequentially loaded in and released from CPT3@ATRA3@DL-HMCON@HA. The DDST mechanisms of CPT3@ATRA3@DL-HMCON@HA for CSC-containing tumors are demonstrated as follows: 1) the first release of ATRA from the outer layer induces differentiation from CSCs with high drug resistance to non-CSCs with low drug resistance; 2) the second release of CPT from the inner layer causes apoptosis of non-CSCs; and 3) the third release of Cu+ from DL-HMCON itself triggers the Fenton-like reaction and glutathione depletion, resulting in ferroptosis of non-CSCs. This CPT3@ATRA3@DL-HMCON@HA is verified to possess high DDST efficacy for CSC-enriched tumors with high biosafety.