Safety Of Treatment In Patients Research Articles

First-line treatment for advanced or metastatic EGFR mutation-positive non-squamous non-small cell lung cancer: a network meta-analysis

BackgroundSeveral head-to-head meta-analyses have compared the efficacy and safety of different first-line treatments in patients with EGFR mutation-positive (M+) advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC). However, there is a lack of comprehensive evaluation encompassing multiple treatment strategies. Our objective is to conduct a network meta-analysis that includes various treatment modalities, enabling both direct and indirect comparisons for a more thorough assessment.MethodsWe conducted a search of PubMed, Embase, Cochrane Library, and Web of Science databases from inception until May 8, 2024, to identify eligible randomized controlled trials (RCTs). The primary endpoints were progression-free survival (PFS) and overall survival (OS), while secondary outcomes included objective response rate (ORR) and grade 3 or higher adverse events (≥3AEs). Stata 15.0 and R 4.3.2 software were utilized for the network meta-analysis.ResultsA total of 30 RCTs, comprising 8654 participants, were included. The study encompassed the following 19 treatments: Chemotherapy; Afatinib; Afatinib + Cetuximab; Apatinib + Gefitinib; Befotertinib; Cetuximab + Chemotherapy; Erlotinib; Erlotinib + Bevacizumab; Erlotinib + Chemotherapy; Gefitinib; Gefitinib + Chemotherapy; Gefitinib + Olaparib; Icotinib; Icotinib + Chemotherapy; Lazertinib; Naquotinib; Osimertinib; Osimertinib + Bevacizumab; Osimertinib + Chemotherapy. The network meta-analysis results indicated that, in terms of PFS, Osimertinib + Chemotherapy (SUCRAs: 93.4%) and Osimertinib (SUCRAs: 84.61%) were the most effective. Regarding OS, Lazertinib (SUCRAs: 89.72%), Gefitinib (SUCRAs: 72.07%), and Osimertinib + Chemotherapy (SUCRAs: 70.74%) emerged as the top three options. Afatinib (SUCRAs: 92.27%) was associated with the best ORR improvement. For ≥3AEs, Afatinib (SUCRAs: 74.93%) and Osimertinib (SUCRAs: 69.42%) were likely the best choices.ConclusionCurrent evidence suggests that, considering both survival and safety, Osimertinib stands out as the preferred first-line treatment for untreated EGFR M + advanced or metastatic nsq-NSCLC. Notably, the combination of Osimertinib with chemotherapy demonstrated superior survival benefits. However, due to the limitations in the number and quality of included studies, these conclusions await further validation through more high-quality research.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024562981, identifier CRD42024562981.

Efficacy and safety of multi-day antiemetic treatment for patients undergoing multi-day chemotherapy: a systematic review of Clinical Practice Guidelines for Antiemesis 2023 from Japan Society of Clinical Oncology.

A standardized multi-day antiemetic regimen for multi-day chemotherapy remains elusive. This systematic review evaluated the efficacy and safety of multi-day antiemetic regimens in patients undergoing multi-day intravenous chemotherapy. We conducted a comprehensive search of PubMed, Cochrane Library, and Ichushi-Web databases for relevant studies published from January 1990 to December 2020. We included studies comparing multi-day and single-day antiemetic regimens for preventing chemotherapy-induced nausea and vomiting. No studies directly comparing multi-day versus single-day antiemetic regimens were found. Despite expanding control group criteria beyond "single-day antiemetic therapy" limited high-quality studies and variations in cancer types, chemotherapy regimens, and antiemetic treatments precluded meta-analysis. Among the included studies, some randomized controlled trials (RCTs) focused on complete response and vomiting rates. Two studies comparing two- and three-drug combinations reported higher complete response and no-vomiting rates with the three-drug regimen. Limited RCTs explored "nausea control" and "cost," and assessing "adverse events" proved challenging due to inconsistent reporting. The research on multi-day antiemetic therapy is limited, necessitating further investigation. Nonetheless, our findings suggest that three-drug combination therapy, including aprepitant, may offer superior antiemetic efficacy compared to two-drug regimens. Multi-day antiemetic therapy is strongly recommended during multi-day intravenous administration of cytotoxic anticancer drugs.

The Predictors of Patient Safety Culture in Hospital Setting: A Systematic Review.

Patient safety (PS) is a global public health concern. It is estimated that 10% of patients experience preventable harm while hospitalized. Patient safety culture (PSC) has been recognized as essential to improving PS, drawing inspiration from other high-risk industries. In PS research, however, PSC poses conceptual challenges, with inconsistent terminology, a lack of definitions, and limited use of substantiating theory. Despite these challenges, PSC remains widely used in PS research and practice, as it is seen as a potential gateway to understanding sociotechnical complex aspects of the healthcare system and improving safe patient treatment and care. This review explores the concept of PSC in a hospital setting. How PSC is used as an outcome, thus exploring the theoretical position underpinning PSC, which predictors impact PSC, and how these predictors are related to PSC. Using a search of 3 electronic databases, 23 studies that met the inclusion criteria were selected for review. The review identified 81 predictors of PSC. Study population, unit of analysis and method varied widely. PSC as an outcome was assessed based on one of 4 surveys. Thus, the underpinning position of the PSC construct is dominated by an organizational/managerial approach. The large number of predictors explored and the range in outcome measures, units of analysis, and methods make it hard to establish any causal relationship. We argue that studies closer to actual practices in the messy conditions of clinical practice are needed.

Efficacy and Safety of Ivabradine for Patients With AcuteHeart Failure: Meta-Analysis of Randomized Controlled Trials.

The efficacy and safety of Ivabradine for patients with acute heart failure (AHF) is controversial, and there are few clinical trials addressing this topic. We performed this meta-analysis to evaluate efficacy and safety of Ivabradine treatment for patients with acute heart failure. We obtained data for controlled trials using the PubMed, Cochrane Library, EMBASE, and Clinical Trials.gov databases. The efficacy endpoints included change in heart rate, brain natriuretic peptide (BNP) levels, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, ejection fraction (EF) values, and a 6-min walk distance. The safety endpoints included mortality, cardiogenic mortality, incidents of hospital readmission, bradycardia, and atrial fibrillation. Ten randomized controlled trials (RCTs) met our criteria, and data from 656 patients were included for the study. Ivabradine treatment significantly decreased heart rate and BNP and NT-proBNP levels compared with those seen in the control group. EF values were significantly increased upon ivabradine treatment. No significant differences were observed in the endpoints of the 6-min walk distance, all-cause mortality, cardiogenic mortality, incidents of hospital readmission, bradycardia, and atrial fibrillation data between ivabradine treated and control groups. Ivabradine can reduce heart rate and BNP and NT-pro BNP levels and elevate EF values and 6-min walk distance data significantly in acute heart failure patients. It also exhibits a stable safety profile, with similar risks of all-cause mortality, cardiogenic mortality, incidents of readmission, and major adverse cardiovascular effects compared with those of the control group.

7563 Investigation of the safety of GH treatment for Noonan syndrome -single center experience

Abstract Disclosure: M. Ishimaru: None. S. Fukui: None. E. Tanimoto: None. C. Nakamura: None. N. Ujita: None. H. Miyagi: None. H. Doi: None. M. Igarashi: None. T. Kashima: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None. [Background] Growth hormone (GH) treatment for Noonan syndrome (NS) was approved in Japan in 2017. Although there have been no reports of serious adverse reactions associated with GH treatment for NS, there have been reports of myocardial thickening and warnings about malignant tumours which might be related to GH treatment. [Objective] To investigate the short- and long-term safety of GH treatment in patients with NS treated with GH at our hospital. [Methods and results] Medical records of 21 patients with NS (12 males and 9 females) treated with GH at our hospital from August 2006 to April 2023 were investigated retrospectively. Genetic diagnosis was performed in 13 patients, the others were clinically diagnosed. The patients ranged in age from 3 y 1 m to 11 y 6 m at the start of treatment, and the duration of treatment ranged from 11 m to 9 y 5 m. 2 patients had existing hypertrophic cardiomyopathy (HCM), and no patients experienced malignant neoplasmas or other hematologic abnormalities before treatment. The height was on average -3.60 SD at the start of treatment and had improved to an average of -2.10 SD at the most recent measurement. GH treatment was well-tolerated and no new severe adverse events were observed except for two who developed HCM after initiation of GH treatment. One patient developed HCM at the age of 17y and 0 m, 7 y 4 m after starting treatment. The treatment was continued in consultation with a cardiologist and completed at the age of 17 y and 4 m. Another patient was diagnosed as HCM 2 years and 3 months after the start of treatment. At the age of 7 y 2 m, 3 y 5 m after starting treatment, GH treatment was temporarily stopped by the cardiologist's decision. [Discussion] More than half of the children with Noonan syndrome have been reported to have short stature, indicating the effectiveness of GH treatment. Improvement of short stature has also been observed in our GH-treated cases. On the other hand, malignant tumours occur more frequently in NS and 50% of patients, with or without cardiomyopathy, are reported to have abnormal electrocardiograms. Long-term effect of GH and long-acting GH treatment on neoplasm formation and/or cardiac diseases should be carefully monitored. [Conclusion] The safety issues of GH treatment in Noonan syndrome should be monitored carefully. Presentation: 6/3/2024

S1881 Long-Term Efficacy and Safety of Open-Label Seladelpar Treatment in Patients With Primary Biliary Cholangitis: Interim Results for 2 Years From the ASSURE Study

S1881 Long-Term Efficacy and Safety of Open-Label Seladelpar Treatment in Patients With Primary Biliary Cholangitis: Interim Results for 2 Years From the ASSURE Study

S1446 Efficacy and Safety of Long-Term Mirikizumab Treatment in Patients With Moderate to Severe Crohn’s Disease

S1446 Efficacy and Safety of Long-Term Mirikizumab Treatment in Patients With Moderate to Severe Crohn’s Disease

S1050 Efficacy and Safety of Upadacitinib Maintenance Treatment in Patients With Moderately to Severely Active Crohn’s Disease: Two Year Results From the U-ENDURE Long-Term Extension Study

S1050 Efficacy and Safety of Upadacitinib Maintenance Treatment in Patients With Moderately to Severely Active Crohn’s Disease: Two Year Results From the U-ENDURE Long-Term Extension Study

Efficacy and safety of palliative treatment in patients with autoimmune liver disease-associated hepatocellular carcinoma

Introduction and ObjectivesAutoimmune liver diseases (AILD) are rare causes hepatocellular carcinoma (HCC), and data on the efficacy and tolerability of anti-tumor therapies are scarce. This pan-European study aimed to assess outcomes in AILD-HCC patients treated with tyrosine kinase inhibitors (TKIs) or transarterial chemoembolization (TACE) compared with patients with more common HCC etiologies, including viral, alcoholic or non-alcoholic fatty liver disease. Materials and Methods107 patients with HCC-AILD (AIH:55; PBC:52) treated at 13 European centres between 1996 and 2020 were included. 65 received TACE and 28 received TKI therapy. 43 (66 %) were female (median age 73 years) with HCC tumor stage BCLC A (34 %), B (46 %), C (9 %) or D (11 %). For each treatment type, propensity score matching was used to match AILD to non-AILD-HCC on a 1:1 basis, yielding in a final cohort of 130 TACE and 56 TKI patients for comparative analyses of median overall survival (mOS) and treatment tolerability. ResultsHCC-AILD patients showed comparable mOS to controls for both TACE (19.5 vs. 22.1 months, p = 0.9) and TKI (15.4 vs. 15.1 months, p = 0.5). Adverse events were less frequent in AILD-HCC patients than controls (33 % % vs. 62 %, p = 0.003). For TKIs, there were no significant differences in adverse events (73% vs. 86%, p = 0.2) or interruption rates (44% vs. 36 %, p = 0.7). ConclusionsIn summary, this study demonstrates comparable mOS for AILD-HCC patients undergoing local and systemic treatments, with better tolerability than HCC of other causes. TKIs remain important therapeutic options for AILD-HCC patients, particularly given their exclusion from recent immunotherapy trials.

(037) CATCHING THE CURVE: LEVERAGING DISEASE PHASES FOR OPTIMAL COLLAGENASE THERAPY IN PEYRONIE’S PATIENTS

Abstract Introduction In the United States, collagenase clostridium histolyticum (CCH) injections are widely used as a treatment for patients with Peyronie’s disease (PD). While CCH is an approved treatment for PD, it is unclear from existing evidence if initiating this intervention during the acute phase vs the later chronic phase leads to different outcomes. Objective We sought to investigate the effectiveness and safety of CCH treatment in patients with PD, comparing outcomes between those in the active versus stable phase of the disease. Methods We performed an IRB-approved single-center retrospective study from 2009-2023 on patients with CCH injections for PD. Clinical and demographic information was extracted from patient medical records. Patients were stratified into two groups based on the phase of their disease at the time of treatment: active (acute) phase or stable (chronic) phase. Both groups were compared Pearson's Chi-square or Fisher's exact tests for categorical data. Results This study included 169 patients with a mean age of 57.9 (SD: 8.63). The patient cohort is summarized in Table 1. Of these, 144 and 25 patients received CCH in the chronic and acute phases, respectively. No significant difference was observed between the change in curvature of the active and stable phase (-7.4 [SD:14.73] vs. -7.82 [SD:16.04], p = 0.37, respectively). No significant difference was observed in curve improvement between the two phases (p = 0.864), indicating that treatment was equally effective in both phases. More patients in the stable phase had progression to surgery (p = 0.032). In terms of side effects, the incidences of bruising (p = 0.368), swelling (p = 0.811), pain (p = 0.846), hematoma (p = 0.479), and fracture (p = 0.457) did not differ significantly between the active and stable phases. The chi-square test results for new ED and loss of length should be interpreted cautiously due to small size cell counts. Conclusions These results suggest that CCH injection is a viable treatment option for PD patients in both the active and stable phases, with comparable efficacy in improving penile curvature deformity. Further prospective studies with larger sample sizes are warranted to validate these findings. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Disclosures: Consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast, Halozyme Investor: Sprout.

Efficacy and Safety of Early Treatment with Glibenclamide in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized Controlled Trial.

This study aims to investigate the efficacy and safety of glibenclamide treatment in patients with acute aneurysmal subarachnoid hemorrhage (aSAH). The randomized controlled trial was conducted from October 2021 to May 2023 at two university-affiliated hospitals in Beijing, China. The study included patients with aSAH within 48h of onset, of whom were divided into the intervention group and the control group according to the random number table method. Patients in the intervention group received glibenclamide tablet 3.75mg/day for 7days. The primary end points were the levels of serum neuron-specific enolase (NSE) and soluble protein 100B (S100B) between the two groups. Secondary end points included evaluating changes in the midline shift and the gray matter-white matter ratio, as well as assessing the modified Rankin Scale scores during follow-up. The trial was registered at ClinicalTrials.gov (identifier NCT05137678). A total of 111 study participants completed the study. The median age was 55years, and 52% were women. The mean admission Glasgow Coma Scale was 10, and 58% of the Hunt-Hess grades were no less than grade III. The baseline characteristics of the two groups were similar. On days 3 and 7, there were no statistically significant differences observed in serum NSE and S100B levels between the two groups (P > 0.05). The computer tomography (CT) values of gray matter and white matter in the basal ganglia were low on admission, indicating early brain edema. However, there were no significant differences found in midline shift and gray matter-white matter ratio (P > 0.05) between the two groups. More than half of the patients had a beneficial outcome (modified Rankin Scale scores 0-2), and there were no statistically significant differences between the two groups. The incidence of hypoglycemia in the two groups were 4% and 9%, respectively (P = 0.439). Treating patients with early aSAH with oral glibenclamide did not decrease levels of serum NSE and S100B and did not improve the poor 90-day neurological outcome. In the intervention group, there was a visible decreasing trend in cases of delayed cerebral ischemia, but no statistically significant difference was observed. The incidence of hypoglycemia did not differ significantly between the two groups.

Epidermolysis Bullosa: Innovative Treatment with Stem Cells, a Systematic Review

Introduction: epidermolysis bullosa is a set of genetic disorders that originate from modifications in certain skin proteins that alter the union and structure of the dermis and epidermis. Clinically, it manifests itself through blisters. However, these lesions can spread to other areas. areas of the body, thus causing the appearance of chronic wounds. The conventional treatment of Epidermolysis Bullosa has not been shown to improve the long-term quality of life of those who suffer from it, which is why researchers propose new therapies that allow improvements in the quality of life of patients, being one of the most promising, the use of stem cells. Methods: randomized clinical trials were selected that evaluated the efficacy and safety of stem cell treatment in patients with Epidermolysis bullosa compared to usual therapy and its cost-effectiveness. Results: based on the selected articles, several variables were measured. Four articles demonstrated the effectiveness of stem cell treatment compared to conventional treatment; two articles measured the economic considerations and access to this new treatment; four articles compared the benefits and disadvantages of using stem cells in patients with Epidermolysis bullosa; and finally, five articles demonstrated the impact that stem cells have in improving the quality of life of patients with Epidermolysis bullosa who undergo this type of therapy. Conclusions: at a global level, the effectiveness of the use of stem cells opens a promising research perspective that seeks to benefit the most vulnerable population affected by this disease, since it plays a key role in the significant reduction of blistering lesions, this represents a positive advance. in the management of the disease, as well as the improvement in its biological, psychological and social sphere, allowing an early introduction to daily activities, generating significant savings of resources for caregivers and for the State. Because, in Latin America, to date there is little research in this area, it should be considered a very promising line of research in the field of Dermatology. Similar situation in the case of Ecuador, where since there are no statistics on patients with this disease, nor data that contribute to the treatment of this vulnerable group, these investigations will provide a solid basis for researchers to adopt this new therapy

Efficacy and Safety of Fruquintinib-Based Treatment in Patients with Refractory Bone and Soft Tissue Sarcoma after Developing Resistance to Several TKIs: A Multicenter Retrospective Study.

Multitargeted tyrosine kinase inhibitors (TKIs) have been approved as second-line therapy in refractory sarcoma, prolonging progression-free survival (PFS) but with short-lived duration of disease control. Fruquintinib is a TKI that specifically inhibits vascular endothelial growth factor receptor-1,2,3 with no metabolism by liver enzymes. In this retrospective study, we assessed the efficacy and safety of fruquintinib-based treatment in patients with refractory sarcoma after developing several lines of TKI resistance. We retrospectively analyzed the clinical data of patients with refractory sarcoma after they had developed several lines of resistance to TKIs and who received fruquintinib-based treatment from November 2021 to August 2023. The primary endpoint was the progression-free survival rate at 4 months (4m-PFSR). Secondary endpoints were the median PFS, overall survival (OS), objective response rate, disease control rate, and adverse effects (AEs). PFS and OS were estimated using the Kaplan-Meier method. A log-rank test was used to compare survival curves between different clinical and pathological factors. Cox proportional hazards analysis was performed to identify PFS-related prognostic factors. We included 124 patients: 56 (45.2%) with osteosarcoma, 28 (22.6%) with Ewing sarcoma, seven (5.6%) with chondrosarcoma, and 33 (26.6%) with soft tissue sarcomas (STS). Only 18 (14.5%) patients received monotherapy with fruquintinib. With a median follow-up time of 6.8 (interquartile range [IQR], 4.6-9.4) months, 22 (17.7%) patients had partial response and 78 (62.9%) had stable disease. The 4m-PFSR was 58.4% (95% confidence interval [CI], 49.6%-67.1%). The median PFS and OS were 4.4 (95% CI, 3.9-5.0) months and 11.4 (95% CI, 10.3-12.5) months. In multivariate analysis, a high hazard ratio for progression was associated with target lesions located outside the lung and bone with 1.79 (95% CI, 1.10-2.93; p = 0.020). Eighty-eight AEs were recorded in 47 (37.9%) patients; the most common were pneumothorax (18/124, 14.5%), diarrhea (8/124, 6.5%), oral mucositis (7/124, 5.6%), and thrombocytopenia (7/124, 5.6%). Fruquintinib may be a potential option for patients with refractory sarcoma after developing several lines of TKI resistance, with a satisfactory efficacy and safety profile in combination therapy. However, the degree of contribution of fruquintinib to results is unclear when combined with other effective substances. Additional prospective trials of fruquintinib should be conducted, especially involving different pathological types and combination regimens.

Efficacy and safety of conservative treatment in patients with neurologically intact thoracolumbar burst fractures: a meta-analysis

Objective. To conduct a meta-analysis of studies focused on the conservative treatment of thoracolumbar burst fractures, and to determine the efficacy and safety of this method in the observed group of patients.Material and Methods. The study was performed following PRISMA guidelines. Inclusion criteria for meta-analysis were as follows: availability of full-text version of the article in English or Russian; A3 or A4 type fractures according to the AOSpine classification, or burst fractures of types IIA, IIB or IIC according to the Denis classification, or a direct indication of the presence of a burst fracture without its classification; absence of neurological deficit; age over 18 years; detailed description of treatment outcomes or complications; and a follow-up for at least one year.Results. The meta-analysis included 29 articles describing the results of treatment of 1107 patients. At the time of admission, the following radiographic parameters were calculated for patients: mean kyphotic angle, 13.6 (95 % CI, 10.8–16.5), degree of vertebral body compression, 39.9 % (95 % CI, 27.7–52.0), and the degree of compression of the spinal canal lumen, 41.7 % (95 % CI, 29.2–54.2). A follow-up examination revealed a significant increase in segmental kyphosis by 3%, in vertebral body compression by 3.7 %, and lysis of bone fragments with a decrease in the degree of spinal canal stenosis by 2 times. The incidence of neurological deficit and progression of thoracic and lumbar spine instability was 5.8 % (95 % CI, 4.1–8.1) and 6.5 % (95 % CI, 4.5–9.3), respectively. Recovery of work ability according to Denis scale was as follows: W1 and W2 – 74.7 % (95 % CI, 63.9–83.1); W3 – 14.1 % (95 % CI, 10.2–19.3); and W4 and W5 – 14.8 % (95 % CI, 8.8–23.9).Conclusion. Conservative treatment of neurologically intact thoracolumbar burst fractures can be an effective and safe option if the angular deformity does not exceed 16 degrees and the anterior vertebral body compression rate is up to 52 %. With conservative therapy, a twofold reduction in spinal canal stenosis was observed due to the lysis of bone fragments. The pooled prevalence of radiculopathy or myelopathy with conservative therapy was 5.8 %. Orthopedic intervention due to the progression of instability of the damaged segment may be required in 6.5 % of patients. More than 90 % of patients returned to full-time work following conservative therapy. Comparative studieson the effectiveness of conservative therapy versus surgical treatment should be continued to form clear recommendations for the choice of treatment tactics for patients with uncomplicated fractures of the thoracic and lumbar spine.

Efficacy and Safety of Pharmacological Treatment in Patients with Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis.

Complex regional pain syndrome (CRPS) is a disabling condition that usually affects the extremities after trauma or surgery. At present, there is no FDA-approved pharmacological treatment for patients with CRPS. We performed this systematic review and meta-analysis to evaluate the efficacy and safety of pharmacological therapies and determine the best strategy for CRPS. We searched the databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and ClinicalTrials.gov, for published eligible randomized controlled trials (RCTs) comparing pharmacological treatment with placebo in CRPS patients. Target patients were diagnosed with CRPS according to Budapest Criteria in 2012 or the 1994 consensus-based IASP CRPS criteria. Finally, 23 RCTs comprising 1029 patients were included. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty (confidence in evidence and quality of evidence). Direct meta-analysis showed that using bisphosphonates (BPs) (mean difference [MD] -2.21, 95% CI -4.36--0.06, p = 0.04, moderate certainty) or ketamine (mean difference [MD] -0.78, 95% CI -1.51--0.05, p = 0.04, low certainty) could provide long-term (beyond one month) pain relief. However, there was no statistically significant difference in the efficacy of short-term pain relief. Ketamine (rank p = 0.55) and BPs (rank p = 0.61) appeared to be the best strategies for CRPS pain relief. Additionally, BPs (risk ratio [RR] = 1.86, 95% CI 1.34-2.57, p < 0.01, moderate certainty) and ketamine (risk ratio [RR] = 3.45, 95% CI 1.79-6.65, p < 0.01, moderate certainty) caused more adverse events, which were mild, and no special intervention was required. In summary, among pharmacological interventions, ketamine and bisphosphonate injection seemed to be the best treatment for CRPS without severe adverse events.

Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer: A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study

ObjectiveTo report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy. MethodsAnalysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed. ResultsOf the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27–0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19–0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18–1.34). Selinexor treatment was generally manageable, with no new safety signals identified. ConclusionIn the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931).

LBP-040 Long-term efficacy and safety of open-label seladelpar treatment in patients with primary biliary cholangitis (PBC): interimresults for 2 years from the ASSURE study

LBP-040 Long-term efficacy and safety of open-label seladelpar treatment in patients with primary biliary cholangitis (PBC): interimresults for 2 years from the ASSURE study

Efficacy and safety of fruquintinib-based treatment in patients with refractory bone and soft tissue sarcomas after developing resistance to several TKIs: A multicentered retrospective study.

Efficacy and safety of fruquintinib-based treatment in patients with refractory bone and soft tissue sarcomas after developing resistance to several TKIs: A multicentered retrospective study.

Predictors and surgical outcome of hemorrhagic metastatic brain malignancies

PurposeIntracerebral metastases present a substantial risk of tumor-associated intracerebral hemorrhage (ICH). This study aimed to investigate the risk of hemorrhagic events in brain metastases (BM) from various primary tumor sites and evaluate the safety and outcomes of surgical tumor removal.MethodsA retrospective, single-center review of medical records was conducted for patients who underwent BM removal between January 2016 and December 2017. Patients with hemorrhagic BM were compared to those with non-hemorrhagic BM. Data on preoperative predictors, perioperative management, and postoperative outcomes were collected and analyzed.ResultsA total of 229 patients met the inclusion criteria. Melanoma metastases were significantly associated with preoperative hemorrhage, even after adjusting for confounding factors (p = 0.001). Poor clinical status (p = 0.001), larger tumor volume (p = 0.020), and unfavorable prognosis (p = 0.001) independently predicted spontaneous hemorrhage. Importantly, preoperative use of anticoagulant medications was not linked to increased hemorrhagic risk (p = 0.592). Surgical removal of hemorrhagic BM, following cessation of blood-thinning medication, did not significantly affect intraoperative blood loss, surgical duration, or postoperative rebleeding risk (p > 0.096). However, intra-tumoral hemorrhage was associated with reduced overall survival (p = 0.001).ConclusionThis study emphasizes the safety of anticoagulation in patients with BM and highlights the safety of neurosurgical treatment in patients with hemorrhagic BM when blood-thinning medication is temporarily paused. The presence of intra-tumoral hemorrhage negatively impacts survival, highlighting its prognostic significance in BM patients. Further research with larger cohorts is warranted to validate these findings and elucidate underlying mechanisms.

Analysis of the efficacy and safety of bone disease treatment in patients with newly diagnosed multiple myeloma treated with denosumab or zoledronic acid

Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.