Clinical Safety Research Articles

Clinical evaluation of 3D PEEK implants for skull bone defects repair: a single center case serious

BackgroundCustom-designed 3D-printed polyetheretherketone (PEEK) implants have emerged as a promising option for skull bone defect repair. This study aimed to evaluate the clinical outcomes, feasibility, and safety of using 3D-printed PEEK implants in patients with skull defects.MethodsA retrospective case series was conducted at Menoufia University Hospital, reviewing the medical records of patients who underwent cranioplasty between January 2022 and December 2023. Patients aged 18–65 years with skull bone defects due to trauma, surgical resection, or congenital anomalies were included. All patients underwent preoperative CT scans for custom implant design using computer-aided design (CAD) software. The 3D-printed PEEK implants were fabricated and implanted during surgery. Primary outcome measures included successful implant integration and structural stability, while secondary outcomes assessed complications and patient satisfaction.ResultsThirteen patients (76.9% male, mean age 45.8 years) were included. The majority of defects were caused by trauma (76.9%). The mean time to cranioplasty was 6 ± 2 months, and the average operative time was 143 ± 34 min. Mean blood loss was 265 ± 97 cc, and the average hospital stay was 2.85 ± 0.9 days. Complications included dural tears in 38.5% of cases, while no immediate postoperative complications were reported. Late complications included one case of convulsions (7.7%) and one superficial infection (7.7%). Radiographic follow-up confirmed successful implant integration in all patients.Conclusion3D-printed PEEK implants provide a feasible and effective solution for skull bone defect repair, with favorable outcomes and manageable complication rates. These custom implants offer a personalized approach to cranioplasty, but larger studies with longer follow-up are needed to validate these findings.

Pharmacodynamic Elucidation of Pelargonium zonale (L.) L'Hér. ex Aiton for its Folkloric Claims in Diarrhea and Asthma via in Vitro, in Vivo and in Silico Methods

Ethnopharmacological relevance Pelargonium zonale (L.) L'Hér. ex Aiton ( P.zonale) is used against various cardiovascular, gastrointestinal and respiratory diseases involving smooth muscles relaxation. It is traditionally used for the treatment of diarrhea, gastropathy, and toothache. Aim of study The current study was designed to validate its conventional applications, we conducted the investigational studies to evaluate the potential mode of operation in the management of disorders pertaining to the cardiovascular system, respiratory tract, and gastrointestinal tract via in-vitro, in-vivo and in-silico studies. Material and methods The bioactive compounds were identified via HPLC done by using a binary-gradient solvent system containing of C-18 column (250 × 4.6 mm, 5 µm), flow rate of 0.8 ml/min, and run time of 36 min was used for the illumination of P.zonale crude extract chromatogram. These compounds were predicted spasmolytic and bronchodilation potential in molecular docking. Invitro methods confirmed the spasmolytic and bronchodilator effects. Analgesic, anti-inflammatory and antidiarrheal experiments were conducted in in-vivo studies. Results Experimental investigations have disclosed that it possesses antidiarrheal, anti-inflammatory, and analgesic attributes. In vitro examinations of this botanical specimen demonstrated its spasmolytic, vasorelaxant, ionotropic, and bronchodilator activities, which involve adrenergic, muscarinic, and potassium ion channels by alleviating sustained contractions induced by phenylephrine (1 µM), carbamylcholine (1 µM), and KCl (25 mM L−1) respectively. The properties associated with the opening of potassium channels were validated by conducting repeat experiments in the presence of tetraethylammonium (TEA) and glibenclamide (GB), which confirmed the activation of voltage-activated and ATP-sensitive potassium channels. Both in vitro and in vivo investigations reveal the existence of significant smooth muscle relaxant activity, further corroborated by in silico studies. Conclusion In vitro and in vivo studies reveal substantial capacities for smooth muscle relaxation, which encompass bronchodilation, spasmolytic activity, and vasodilation, with these observations being corroborated by molecular docking analyses. However, further studies are needed to define the clinical significance and safety treatment with P.zonale.

Valemetostat and trastuzumab deruxtecan (T-DXd) in previously treated advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive gastric cancer or gastro-esophageal junction (GEJ) adenocarcinoma.

TPS508 Background: Valemetostat tosylate (valemetostat), a novel and selective dual inhibitor of enhancer of zeste homolog (EZH)2 and EZH1, has demonstrated clinical efficacy and tolerability in multiple hematologic cancers (200 mg orally [PO] once daily [QD]). EZH2 inhibition by valemetostat is expected to upregulate DNA/RNA helicase Schlafen 11 expression and sensitize tumor cells to DNA damaging agents such as topoisomerase I inhibitor antibody–drug conjugates (ADCs). Topoisomerase inhibitors cause DNA strand breaks, which may synergize with valemetostat. HER2 gene amplification or protein expression has been associated with gastric cancer (GC) and GEJ adenocarcinoma. Patients with HER2+ locally advanced or metastatic gastric adenocarcinoma who progress after first line treatment have poor prognosis and limited therapeutic options. T-DXd is approved globally for HER2+ locally advanced or metastatic GC previously treated with a trastuzumab-based regimen. This study evaluates the clinical activity and safety of valemetostat in combination with T-DXd in patients with GC or GEJ adenocarcinoma as part of a Master Protocol trial evaluating valemetostat in combination with ADCs in solid tumors. Methods: This global, phase 1b, multicenter, open-label Master Protocol study (NCT06244485) will enroll ~ 70 patients per sub-protocol in multiple regions, including the US and Japan. The gastric cohort enrolls patients with previously treated advanced or metastatic HER2+ GC or GEJ adenocarcinoma. The dose-escalation (Part 1) will determine the recommended dose for expansion (RDE), combining valemetostat 50–200 mg PO QD with T-DXd 5.4 or 6.4 mg/kg intravenously every 3 weeks. The dose-expansion (Part 2) will assess the efficacy of valemetostat + T-DXd at the RDE. Primary endpoints include safety and tolerability in Part 1 and the objective response rate in Part 2. Secondary endpoints include response duration, progression-free and overall survival, pharmacokinetics, and HER2 expression by immunohistochemistry and in situ hybridization with clinical response. An interim futility analysis will be performed when 20 patients are enrolled with ≥ 6 months of follow-up. Clinical trial information: NCT06244485 .

Efficacy Analysis of Hypofractionated Radiotherapy for Oligometastatic Tumors: A Retrospective Study.

Metastasis remains a major cause of death among patients with malignant tumors. Radiotherapy is one of the main modalities of cancer treatment. The rapid development of radiotherapy technology has enabled the widespread application of hypofractionated radiotherapy (HFRT) in clinical practice. This study aimed to evaluate the effect of HFRT on the survival and safety of patients with oligometastatic tumors. We conducted a retrospective study that involved 65 patients with well-controlled primary tumors and 1-5 metastatic foci treated at the study site between January 2020 and December 2022. Patients were aged >18 years and had a ≥ 6-month life expectancy. The patients received standard treatments plus HFRT for all metastatic foci. The dose fractionation regimen was adjusted according to the location and size of the patient's metastatic foci. The planning gross tumor volume of HFRT was 82.93 cm3 (range: 10.12-562.80 cm3), and the radiation dose range was 20 Gy/5 F-60 Gy/15 F. Progression-free survival (PFS), overall survival (OS), local control rates, and incidence of adverse events of the patients were observed. Among the 65 patients, the median follow-up time, PFS, and OS were 26 months (95% CI: 0.80-37.50), 15 months (95% CI: 9.36-20.64), and 28 months (95% CI: 16.71-39.29), respectively. The 1- and 2-year PFS were 53.8% and 40.0%, respectively, while the 1- and 2-year OS rates were 73.8% and 56.9%, respectively. In total, 13.8%, 55.4%, 20.0%, and 13.8% of patients showed complete response, partial response, stable disease, and progressive disease, respectively. Four patients developed grade 3 or worse adverse events, and no treatment-related deaths occurred. HFRT showed favorable clinical efficacy and safety in patients with oligometastatic tumors, generally achieving a good OS rate. Further randomized trials should be conducted.

Phase II study of modulation of sorafenib (SOR)-induced autophagy using hydroxychloroquine (HCQ) in advanced hepatocellular cancer (HCC).

586 Background: SOR is the first systemic therapy approved for advanced HCC, but has shown only modest improvements in survival. Resistance to SOR in pre-clinical models has been attributed to autophagy induction. Autophagy inhibition with HCQ enhanced SOR-induced cell death and apoptosis in early pre-clinic and clinical studies. Data from the phase I study of SOR plus HCQ in advanced solid tumors at showed clinical safety and efficacy. Therefore, we conducted a prospective study to evaluate efficacy of SOR and HCQ in advanced HCC patients (pts) (NCT03037437) and report the final efficacy analysis. Methods: Prospective phase II study of SOR 400 mg po BID + HCQ 400 mg daily in pts with advanced HCC (CP A-B8 cirrhosis). Cohort 1: first-line SOR/HCQ. Cohort 2: add HCQ upon progressing on SOR. CP B pts started at 200 mg BID, with dose escalation as tolerated. Cycle = 4 weeks. Primary endpoint: mTTP. Secondary endpoints: mOS, objective response rate (ORR) by RECIST; AEs (NCI-CTCAEv3.0); PD analysis for markers of autophagy and immunity. Pts evaluable for efficacy if completed C1. Historically, the mTTP for patients treated with sorafenib is 5.5 mo (SHARP trial). We predicted the addition of HCQ will improve mTTP by 50% to 8.2 months. Results: N=33 completed C1. Median age 64.1 years SD 8.6 (46- 80). 88% Male; 58% Hispanics. ECOG 0-1: 100%. CP B cirrhosis: 35%. Etiology of cirrhosis: HCV 68%, ETOH 32%, NASH 11%. BCLC B 19%, C 81%. AFP>400: 43%, PVT: 27%, extrahepatic/metastases: 68%, post-transplant: 27%. N=5 (14%) were in cohort 2 (prior SOR). Reason off study: PD (n=21), toxicity (n=5), lost to f/u (n=1), withdrew (n=3). mTTP is 8.0 months (95% CI: 4.0-19.0). mOS 10.0 months (95% CI: 6.0-22.0). ORR (CR+PR): 27%. Best response: CR n=1 (3%), PR n=8 (24%), SD n=14 (42%). 4+ cycles: n=19 (58%). AE on treatment: grade 1 (68%), 2 (24%), 3 (7%), 4 (0.6%), 5 (0.3%). No Gr 4/5 related to SOR or HCQ. Dose interruption (20%), dose reduction (10%). Conclusions: SOR/HCQ had a better mTTP (8.0 months) than historical control (mTTP=5.5 months, p=0.03), and the trial met its primary endpoint. SOR/HCQ ORR (27%) was higher than historically SOR alone (ORR 2%, SHARP) in pts with advanced HCC, predominantly BCLC C, with CP A and B cirrhosis (35%), and was tolerable. While immune checkpoint inhibitors (ICIs) are taking the forefront in advanced HCC, SOR/HCQ may still have a role in patients with CP B cirrhosis, post-transplant, or contraindications to ICIs. Further, analysis of predictive markers of response is ongoing. Clinical trial information: NCT03037437 .

Update of phase 1b/2 study of muzastotug (ADG126, an anti-CTLA-4 SAFEbody) in combination with pembrolizumab in advanced/metastatic MSS CRC.

193 Background: ADG126 is an anti-CTLA-4 IgG1 masked antibody with cleavable masking peptides that is preferentially activated in the tumor microenvironment, which in turn binds to a unique epitope to block CTLA-4 function, prime T cells and deplete Tregs. We previously reported that repeated dosing of the IO doublet therapy ADG126 plus pembrolizumab (Pembro) was well-tolerated with promising clinical efficacy in 3L MSS CRC patients (pts) free of liver metastasis (NCT05405595) 1,2 . Here we update clinical safety and efficacy of the study as result of continued dose optimization for the IO doublet therapy. Methods: This is a Phase 1b/2, open-label, multicenter dose escalation (DE) and expansion (EXP) study. Primary endpoints were safety and tolerability. Secondary endpoints were PK, ADA, ORR, DCR, DOR, PFS and OS. Results: A total of 72 pts were dosed with ADG126/Pembro (Table). 27.8% pts had ≥ 3 prior therapies and 6.9% pts had prior IO therapies. There was no Grade 4/5 TRAE, and MTD was not reached. Grade 3 TRAEs were 5.9% (1/17), 16.2% (6/37), 33% (4/12) for 10 mg/kg Q6W, 10 mg/kg Q3W and 20 mg/kg loading dose (LD) & cohorts, respectively. Repeated dosing of ADG126 at 20 mg/kg (Q3W)/Pembro was not well-tolerated. In MSS CRC EXP cohorts, ADG126 of 10 mg/kg Q3W/Pembro treatment resulted in 4 confirmed PRs (n=24 EE), 17% ORR (95% CI: 5-37%), 75% DCR, 4.7-mon mPFS and OS rate of 88% (6 mons) and 75% (9 mons). Subgroup analysis revealed that in pts without liver and peritoneal metastasis (NLPM), ADG126 of 10 mg/kg Q6W/Pembro (10 EE) showed 70% SD and ~ 100% OS (6 and 9 mons); ADG126 of 10 mg/kg Q3W/Pembro (17 EE) showed 24% ORR (4 PR (95% CI: 7-50%)), 88% DCR, 47% CBR, 8.5-mon mPFS and OS rate of 89% (6 mons) and 83% (9 mons). Detailed safety and efficacy results, including those from ADG126 20 mg/kg LD cohort, will be reported. Conclusions: Extensive effort on ADG126 dose optimization, aided by PK-informed dosing strategy, suggested that ADG126 10 mg/kg Q6W and Q3W are appropriate dose/regimen for the IO doublet; this is supported by the well-balanced safety and efficacy (ORR, PFS and OS) profile observed in MSS CRC. ADG126 20 mg/kg Q3W appears to have reached safety ceiling for the IO doublet. The totality of the data further verifies that ADG126 possesses potential best-in-class therapeutic index, and provides basis for continued development of the IO doublet in MSS CRC and for additional exploration of the IO doublet in combination with SOCs/other anti-cancer agents in broader patient populations. Clinical trial information: NCT05405595 . Patient number for safety and efficacy evaluation. Evaluated for ADG126 Dose/Pembro* 10 mg/kg Q6W 10 mg/kg Q3W 20 mg/kg Q3W 20 mg/kg LD & Overall Safety (all pts of DE & EXP) 17 37 6 12 72 Efficacy (MSS CRC NLM, EXP) 10 24 / 5 39 *200mg, Q3W, IV; & 20 mg/kg LD: 20 mg/kg x1 cycle followed by 10 mg/kg Q3W. NLM: liver metastasis-free; DE: Dose Escalation; EXP: Dose Expansion; EE: efficacy evaluable. Data cut date: Aug 30, 2024.

First out-of-bed mobilisation in adults with severe acquired brain injury in Scandinavian neurointensive care units: A survey of current clinical practice (FOOBScan).

The harm-benefit balance for early out-of-bed mobilisation of patients with severe acquired brain injury (ABI) in neurointensive care units (neuro-ICUs) is unclear, and there are no clinical guidelines. This study aimed to survey the current clinical practice and perceptions among clinicians involved in first out-of-bed mobilisation in Scandinavian neuro-ICUs. This was a cross-sectional, anonymous, web-based survey; the reporting follows the recommended CROSS checklist. Clinicians involved in the first out-of-bed mobilisation in all 14 Scandinavian neuro-ICUs were eligible to participate. The questionnaire was distributed to local contact persons. Respondents were asked about their clinical practice regarding the first out-of-bed mobilisation, and perceived harms and benefits of early mobilisation. One hundred eighty clinicians (53% nurses, 31% physicians, and 14% therapists) completed the questionnaire. Eighty-one percent indicated that more than half of patients underwent their first out-of-bed mobilisation in the neuro-ICU. More respondents from Denmark than the remaining countries indicated that both physicians, nurses and physiotherapists contributed to the decision on when to mobilise. Intracranial pressure, cerebral perfusion pressure, sedation, presence of vasospasm and arterial blood pressure were the most used safety clinical indicators for deciding about mobilisation. Clinicians stated several positive effects of mobilisation, for example, improved bowel movements, level of consciousness, motor function, and reduced risk of pneumonia, contractures, delirium, and deep vein thrombosis. Mobilisation out of bed is frequently performed in patients with severe ABI in Scandinavian neuro-ICUs. The perceived clinical safety indicators for mobilisation were ICP, CPP, level of sedation, presence of vasospasms, and ABP.

Utility of minimally invasive percutaneous arthrodesis of the sacroiliac joint for the treatment of low back pain: systematic review of the literature.

The surprising increase observed in recent years in the use of minimally invasive sacroiliac joint arthrodesis techniques as a treatment for low back pain justifies an objective review of this results. carry out a systematic review of the literature to evaluate the clinical results of patients with low back pain treated with percutaneous arthrodesis of the SIJ. Systematic review. Systematic search of the medical literature. The words used in the Search were: "Hollow screw system", "percutaneous sacroiliac joint stabilization", "sacroiliac joint", "minimally invasive", "sacroiliac pain", "sacroiliac dysfunction". With logical connectors such as "and", "not" and "or". Pubmed, Scopus, Embase, Ovid, EBSCO host and google scholar. The search extended from the beginning of the databases until September 2024. The "Rayyan" program was used to collect the information and facilitate the analysis process. Systematic review from the literature, clinical trials, observational studies and case series. They followed PRISMA principles. 661 articles were found, of which 108 articles were duplicates. The criteria (Inclusion/Exclusion) were applied to the 553 articles identified based on the independent reading of the summaries by each of the authors on the Rayyan platform and 434 articles were excluded. The 119 selected articles were completely reviewed to finally obtain 102 articles included in the review. Epidemiological data were extracted into an Excel table, methodological and related to clinical results and safety of procedures made. The Prisma checklist for systematic reviews was applied in each article. The epidemiological quality of the articles was evaluated based on the checklists STROBE and CONSORT. The results regarding clinical improvement were overwhelming. However, most of the studies were sponsored by industry and with a limited population and follow-up not always prolonged. Although the clinical results regarding the effectiveness of SIJ fusion are forceful for their effectiveness, we recommend considering some aspects for their analysis and especially long-term studies.

Clinical utility and diagnostic accuracy of a novel handheld ultrasound device for cardiac evaluation in non-cardiology settings

Abstract Background During consultation rounds in non-cardiology departments the cardiologist is confronted with clinical questions which often require further evaluation with echocardiography. Transporting a cart-based standard echocardiography (SE) machine to this end is unpractical, and referral to the echocardiography laboratory is routine practice in most cases. Recently, technological advances have enabled the development of handheld ultrasound devices (HUDs) that are equipped with M-mode, color and spectral Doppler capabilities, on top of improved 2D image quality. The use of such novel HUDs in non-cardiology settings may reduce the referrals for SE exam and expedite clinical workflow for those patients, but data on clinical safety and accuracy of such approach are lacking. Purpose The aim of this study was to evaluate the clinical utility and diagnostic accuracy of a novel HUD for cardiac evaluation during consultation rounds in non-cardiology settings. Methods The study comprised 102 consecutive patients (age 66±17 years, 52% male) from non-cardiology departments of a tertiary hospital who were referred for an echocardiogram after cardiology consultation. All patients were scanned with the HUD by the consulting cardiologist and subsequently underwent an exam with a SE machine by an echocardiographer. For each patient the consulting cardiologist noted whether the findings of the HUD were adequate for final diagnosis, as well as the image quality and the time required to perform the focused cardiac exam using the HUD. The following parameters were assessed: 1) LV size and function, 2) RV size and function, 3) significant (more than moderate) valvular heart disease (VHD), 4) pericardial effusion, and 5) inferior vena cava (IVC) size and collapse. Results In 86 (84%) patients, it was possible to successfully answer the clinical question by the HUD examination alone. In 71 (70%) patients no further examination with SE was deemed as necessary. The HUD image quality was good in 24 patients, moderate in 59 patients, bad in 18 patients, and non-diagnostic in 1 patient. The mean time required per patient for the focused cardiac exam with the HUD was 5.7±2.2 minutes. The prevalence of abnormal echo findings in the study population is presented in Table 1. There was excellent agreement for the detection of abnormal LV size and function (k=0.936), abnormal RV size and function (k=0.928), pericardial effusion (k=0.936), and abnormal IVC size and collapse (k=0.960). There was good agreement for significant VHD (k=0.735). In 5 cases the clinical question was not answered even after the SE examination and further cardiac imaging was needed (3 transesophageal echo, 1 contrast echo, 1 CT pulmonary angiography). Conclusion A novel HUD can provide accurate detection of cardiac abnormalities during consultation rounds in non-cardiology settings. Its use in clinical practice may be a valuable alternative to SE for most patients in non-cardiology departments.

P-144. The Introduction of Antimicrobial Prescription Guidance and Patient Education for a Medical Brigade to Honduras

Abstract Background Antimicrobial resistance is a global problem that requires active interventions to combat. Misusage of antimicrobials contributes to the development of multi-drug resistant organisms that can be fatal. Many can be purchased over the counter in countries outside of the US, and medical brigades often provide a source of these drugs. PODEMOS is a medical brigade partnered with The Ohio State University College of Medicine and travels to Honduras twice yearly. Since this brigade prescribes antimicrobials for a variety of disease states, this project aimed to create guidelines on antimicrobial usage and community education materials to ensure that PODEMOS is not contributing to further resistance. Patient Education Antimicrobial Resistance This flyer was distributed to patients on the PODEMOS medical brigade to educate the community on antimicrobial resistance. Methods First, current literature on antimicrobial resistance was reviewed to understand the scope of the problem in Central America. Data was collected on antimicrobial consumption and community education within Honduras and surrounding area. Secondly, common infectious diseases encountered during the PODEMOS medical brigades were identified and the current drug formulary was reviewed in comparison to current treatment guidelines on UpToDate. Medical Brigade Treatment Guidelines The image shows a portion of the guidelines that were created for PODEMOS medical brigades, with this example being for upper respiratory infections. Results Results of our initial literature review indicated that there is no current standard of tracking antimicrobial usage in Honduras. There is also limited awareness and education on antimicrobial resistance. There were 16 common infectious disease states encountered on PODEMOS brigades which were used as basis for creating guidelines for students and providers on future brigades. These included information on clinical diagnosis, treatment protocols, and medication safety. Also, the drug formulary for PODEMOS was updated to include two antimicrobials that will lessen contribution to drug resistance. Lastly, a flyer was created with information to educate the community on antimicrobial resistance. Conclusion Guidance for the proper usage of antimicrobials is paramount in combating drug resistance. By creating treatment protocols and patient education materials, this project aimed to prevent contribution to antimicrobial resistance and improve the care of patients on future PODEMOS medical brigades. Prospectively, data will be collected on usage of these guidelines and patient understanding of antimicrobial resistance. Disclosures All Authors: No reported disclosures

Innovative Antibiotic Therapies for Carbapenem-Resistant Gram-Negative Bacterial Infections: Clinical Efficacy, Safety, and Comparative Studies

This review provides an overview of recent research and advancements in infection prevention and the treatment of drug-resistant bacterial diseases. Cefiderocol, a novel siderophore cephalosporin, has demonstrated effectiveness against carbapenem-resistant bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. Clinical trials, including APEKS-NP and CREDIBLE-CR, affirm its efficacy for hospital-acquired pneumonia (HAP) but highlight concerns over increased mortality due to severe renal complications. Cefiderocol has shown superior outcomes in complicated urinary tract infections (cUTI) compared to imipenem–cilastatin. A comparison of colistin monotherapy versus combination therapy with meropenem for carbapenem-resistant infections revealed no significant improvement in clinical outcomes with combination therapy but noted delays in resistance development. Colistin–rifampicin combination therapy showed potential benefits for colistin-resistant Acinetobacter baumannii, although results were not statistically significant. SPR206, a polymyxin derivative, and durlobactam, a β-lactamase inhibitor, show promise in addressing these resistant strains, with durlobactam demonstrating efficacy in combination with sulbactam and imipenem–cilastatin. Additional studies investigated antibiotic strategies for resistant infections, including cefoperazone–sulbactam versus combination therapy with tigecycline, and examined infection-prevention strategies in surgical settings, comparing chlorhexidine–alcohol and povidone–iodine. This research highlights the importance of optimizing treatment regimens and infection-control measures across various healthcare settings, including neonatology and surgical care.

P-1659. Clinical and Safety Outcomes of Uniform Thrice-Weekly Daptomycin Dosing Based on Adjusted Body Weight in Patients Receiving Intermittent Hemodialysis

Abstract Background Limited evidence exists on optimal dosing of daptomycin (DAP) in patients receiving intermittent dialysis (HD). Current labeling recommends every 48 hour (q48h) dosing which often causes additional DAP doses to be given throughout the week when the schedules become unaligned. Alternatively, current recommendations for thrice weekly dosing suggest a larger dose for the 72-hour interdialytic interval, which makes operationalization difficult within current inpatient electronic systems. Methods A retrospective observational cohort study comparing clinical and safety outcomes of adult patients receiving DAP with HD was performed between 01/2021 and 04/2024. Updated dosing recommendations for DAP with HD was modified on 1/2023 to indication based uniform adjusted body weight (AdjBW) dosing with each HD session compared to the previous recommendation of q48h based on total body weight. Clinical outcomes included microbiologic recurrence and escalation of dose or antibiotic therapy. Safety outcomes included CK elevation and development of rhabdomyolysis. Patients were excluded if they were on DAP prior to admission or received < 2 DAP doses. Results In total, 79 patients met inclusion. BMI, acuity of infection, length of stay, and duration of therapy were similar between the q48h (n=42) and the with each HD groups (n=37). There was a significant reduction in total weekly AdjBW DAP received in the with each HD group (23.8mg/kg vs 28.8 mg/kg, p < .0001) despite a higher utilization of the 8 mg/kg strategy (64.9% vs 26.2%). There was no significant difference in the clinical failure (5.4% vs 4.8%, p = 0.90) or safety outcomes (0% vs 6.5%, p = 0.12) between the post- and pre-groups, including after propensity matching based on BMI, AdjBW dose received, and receipt of source control. Conclusion Utilizing uniform DAP doses with each HD compared to standard q48h frequency in patients receiving HD did not result in worse clinical or safety outcomes while reducing the overall weekly exposure to DAP. This strategy further supports the use of AdjBW as the preferred dosing weight for DAP, including in HD patients, who have been underrepresented in previous studies. This method could also be useful in the outpatient setting to help optimize DAP exposure. Disclosures All Authors: No reported disclosures

The Prevention and Treatment of Postoperative Delirium in the Elderly: A Narrative Systematic Review of Reviews.

Postoperative delirium (POD) is a common complication after major surgeries, posing significant challenges to patient recovery and outcomes, particularly among the elderly. A narrative systematic review was conducted to assess the clinical effectiveness and safety of interventions aimed at preventing and treating POD. A review of the literature from 2017 to September 29, 2023, was conducted using MEDLINE, EMBASE, and CINAHL. Systematic reviews, with or without meta-analyses, as well as practice guidelines, were included. Participants were adults, ≥60 years. The methodological quality of included reviews was appraised using AMSTAR 2. After the search strategy identified 2295 references, 36 review studies were selected. Multicomponent interventions, incorporating both pharmacological and nonpharmacological approaches, demonstrate promise, particularly in hip fracture patients. Notably, dexmedetomidine emerges as a potential preventive measure, showing a notable reduction in delirium incidence following cardiac surgery. While several pharmacological interventions show potential, evidence remains inconclusive, necessitating further investigation. Similarly, varying anesthesia type and monitoring methods has mixed outcomes on delirium prevention. Despite methodological variations and quality appraisal limitations, this review underscores the importance of multicomponent interventions and the potential efficacy of dexmedetomidine in mitigating POD. Integration of evidence-based protocols into clinical practice is advocated to improve patient outcomes. However, the complex interplay between intervention components calls for further research to optimize delirium management strategies. The strength of evidence associated with multicomponent interventions and dexmedetomidine use should require a genuine commitment from health care institutions to support their integration into efficient strategies to prevent and treat POD. Ongoing research is vital to uncover their full potential and refine clinical protocols, ultimately enhancing patient care outcomes.

P-65. Results from A Phase 2 Clinical Trial for Treatment of Bone And Joint Infections with Afabicin, A First-in-Class Selective Anti-Staphylococcal Antibiotic

Abstract Background Staphylococci are the most common causative pathogens in bone and joint infections (BJI). Treatment for BJI is a major clinical challenge, with recurrent and persistent infections occurring in 40% of patients. Afabicin is the most advanced FabI inhibitor in clinical development and has the potential to be the first microbiome-sparing anti-staphylococcal antibiotic. Currently, a Phase 2 trial in BJI (NCT03723551) is enrolling patients to be treated for 3-6 weeks with afabicin or standard of care (SoC). Results of the first cohort in this study (2-3 weeks treatment) are presented here Methods In an ongoing multicenter, open-label, Phase 2 study, the safety, tolerability, and efficacy of afabicin was compared to those of SoC, in the treatment of patients with BJI. Patients with osteomyelitis, septic arthritis, or prosthetic joint infections were randomized (5 afabicin: 1 SoC) to receive IV and oral treatment for 14 to 21 days. Afabicin treatment (55 mg IV/ 80 mg PO BID) was compared to a pre-defined SoC treatment. Results Twenty patients were included in microbiological intent-to-treat (mITT) population and were treated for up to 21 days with afabicin or SoC (17 afabicin and 3 SoC). The mean treatment duration was 20.1 days for afabicin and 19.7 days for SoC. Overall, osteomyelitis was the most common diagnosis (85%). The most frequent baseline pathogen was Staphylococcus aureus (19 patients), and 18 patients had methicillin-sensitive S. aureus. All 20 patients were treatment responders at End of Treatment (EoT) visit. The clinical response at 4 weeks post EoT was 13 of 15 patients in the afabicin arm, consistent with patient exposure being above PK/PD targets derived from non-clinical modeling. All 3 patients in the SOC arm achieved clinical response at 4 weeks post EoT. At 12 weeks post EoT, the clinical response rate was 13 of 15 patients in the afabicin arm and 2 of 3 patients in the SoC arm. A similar safety profile was observed in the afabicin arm versus SoC arm. Conclusion The clinical response rate and safety profile of 2-3 weeks treatment of staphylococcal BJI with afabicin was comparable to SoC. These data support exploring longer durations of treatment in the study. Additionally, the impact of Afabicin on BJI patient’s gut microbiota will be explored. Disclosures Alireza Shamaei Tousi, PhD, Debiopharm International: Salary Moritz Marquardt, n/a, Debiopharm International: Salary Annick Menetrey, n/a, Debiopharm International: Salary Justyna Nowakowska, n/a, Debiopharm International: Salary Justine Dao, n/a, Debiopharm International: Salary David Cameron, PhD, Debiopharm International S.A.: Salary Charlotte Catala-Goldschmidt, n/a, Debiopharm International: Salary Ricardo Chaves, n/a, Debiopharm International S.A.: Salary

Use of a mini 3D transesophageal echocardiogram (TEE) probe in adult patients for outpatient TEE: initial experience in a national tertiary hospital

Abstract Background The mini 3D TEE probe, initially developed for pediatric patients, is now being utilized for adult patients due to its smaller size and clear 2D & 3-dimensional imaging and Doppler studies, potentially limiting anesthesia use and procedural complications. Purpose This study aimed to analyze the clinical profiles and outcomes of adult patients who underwent an outpatient TEE using a mini 3D TEE probe, including image quality and ease of use. Proper evaluation is vital for patient safety, and this initial study aims to determine the mini 3D TEE probe's applicability and safety in adults, potentially guiding future clinical practice. Methods This was a retrospective cross-sectional, and observational study. Medical records were reviewed, including demographic and clinical profiles, echocardiographic data, and procedural and safety outcomes. For each patient, two operators rated ease of use and all imaging modalities on a 5-point scale, from 1 (very difficult/poor) to 5 (very easy/good). Results Eight adult patients were included in the study to undergo a comprehensive TEE using a mini 3D TEE probe. Most patients were female (63%) with a median age of 28.5 years (IQR 5.13), with valvular heart diseases (38%), congenital heart diseases (38%), and heart failure (50%). Most patients had an ASA Physical Classification of Class II (38%) or III (38%). Indications for TEE were primarily suspected congenital heart disease with inadequate transthoracic echo (63%) and pre-intervention evaluation of valvular structures (63%). The probe insertion was rated very easy (100%), and handling was mostly very easy (87.5%). 2D, 3D, 2D color, continuous, and pulsed wave Dopplers were rated very good (100%), with 87.5% rating 3D color flow Doppler as very good. All patients received local pharyngeal anesthesia, with only half of the patients given low-dose intravenous midazolam. The median procedure time for a full study was 40 minutes (IQR 17). After the procedure, all patients were fully awake and recovered (median recovery time 4.5 minutes, IQR 1.88), with only minor post-TEE complications like pharyngeal irritation (13%) and hoarseness (13%). No major morbidities, GI bleeding, esophageal perforation, arrhythmia, respiratory compromise, or mortality occurred. All patients were discharged after recovery with a median outpatient length of stay of 47 minutes (IQR 15.25). Conclusion The mini 3D TEE probe demonstrates ease of use and excellent imaging quality for adult patients across all imaging modalities. It is safe to use and can be performed with local pharyngeal anesthesia alone or with mild intravenous sedation, with no significant post-procedural complications. This study supports the mini 3D TEE probe's applicability and safety in adult patients, suggesting its potential for broader clinical application in cardiovascular diagnostics. A larger scale prospective study is recommended to further confirm these preliminary findings.

Updated Bayesian network meta-analysis on the efficacy and safety of PD−1 versus PD−L1 inhibitors in first−line treatment with chemotherapy for extensive−stage small-cell lung cancer

ObjectiveTo compare the efficacy and safety of programmed cell death 1 inhibitors plus chemotherapy (PD-1 + Chemo) and programmed cell death ligand 1 inhibitors plus chemotherapy (PD-L1 + Chemo) for the treatment of extensive-stage small-cell lung cancer (ES-SCLC).MethodsWe performed a meta-analysis of relevant data using R software, considering overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events (TRAES).ResultsPD-1 + Chemo (OS: hazard ratio [HR] 0.71; PFS: HR 0.59) and PD-L1 + Chemo (OS: HR 0.72; PFS: HR 0.73) significantly prolonged survival and did not increase the incidence of grade ≥3 TRAEs compared with chemotherapy. Indirect comparisons showed no significant difference in clinical efficacy (OS: HR 0.99, 95% CI: 0.86–1.1; PFS: HR 0.80, 95% CI: 0.61–1.0) or safety (HR 1.0, 95% CI: 0.93–1.1) between PD-1 + Chemo and PD-L1 + Chemo. Non-cumulative probability ranking plot ranking results showed that PD-1 + Chemo ranked first in OS and PFS. Patients with PD-L1 expression levels < 1%, PD-1 + Chemo showed a trend of disadvantage (OS: HR 1.3; PFS: HR 1.2), whereas for patients with PD-L1 expression levels ≥ 1%, PD-1 + Chemo showed a trend of advantage (OS: HR 0.85; PFS: HR 0.85).ConclusionsPD-1 + Chemo and PD-L1 + Chemo significantly prolonged OS and PFS in patients with ES-SCLC and did not significantly increase the incidence of grade ≥ 3 TRAES. The efficacy and safety profiles of PD-1 + Chemo and PD-L1 + Chemo appear to be similar.

Microwave ablation for liver metastases from colorectal cancer: A comprehensive review of clinical efficacy and safety.

Microwave ablation (MWA) is emerging as a highly effective treatment for colorectal liver metastases (CRLMs). This review explores the advantages of MWA compared to other ablative techniques such as radiofrequency ablation and cryoablation and highlights its clinical efficacy, safety, and technical considerations. MWA offers significant benefits, including higher intratumoral temperatures, larger ablation zones, and reduced susceptibility to the heat-sink effect, which make it particularly suitable for tumors near large blood vessels. This review details the patient selection criteria, procedural approaches, and the use of advanced imaging techniques to improve the precision and effectiveness of MWA. Clinical outcomes indicate that MWA achieves high rates of complete tumor ablation and long-term survival with a favorable safety profile. This review is significant because it provides updated insights into the expanding role of MWA in treating unresectable CRLM and its potential as an alternative to surgical resection for resectable tumors. By summarizing recent studies and clinical trials, this review highlights the comparative effectiveness, safety, and integration with systemic therapies of MWA. In conclusion, MWA is a promising treatment option for CRLM and offers outcomes comparable to or better than those of other ablative techniques. Future research should focus on optimizing technical parameters, integrating MWA with systemic therapies, and conducting large-scale randomized controlled trials to establish standardized treatment protocols. Advancing our understanding of MWA will enhance its application and improve long-term survival and quality of life for patients with CRLM.

Clinical Outcomes and Safety Profiles of Generic Versus Brand-Name Clopidogrel in Patients Following Coronary Artery Stent Placement.

Coronary artery disease remains a significant global health issue and is a leading cause of mortality. Dual antiplatelet therapy, including clopidogrel, is essential for preventing stent thrombosis after coronary artery stenting. This study assessed the comparative efficacy and safety of generic versus brand-name clopidogrel in a large Taiwanese cohort. A retrospective cohort study was conducted using the National Health Insurance database, identifying patients who underwent coronary stenting and received either generic or brand-name clopidogrel between January 1, 2008, and December 31, 2021. Propensity score matching was employed to balance baseline characteristics. The primary efficacy outcome was a composite of myocardial infarction, ischemic stroke, or cardiovascular death over a two-year follow-up. The primary safety outcome was major bleeding requiring hospitalization. A total of 211,509 patients were included, of which 2686 received generic clopidogrel and 208,823 received brand-name clopidogrel. After matching, 2686 patients from each group were analyzed. The hazard ratio for the primary efficacy outcome was 0.92 (95% confidence interval: 0.78-1.10), indicating no significant difference between the two groups. The subdistribution hazard ratio for the primary safety outcome was 1.06 (95% confidence interval: 0.84-1.33), suggesting no significant difference in bleeding risk. Subgroup analyses showed consistent results across various patient demographics and clinical conditions. In conclusion, among patients undergoing coronary stenting, the risks of ischemic and bleeding events were comparable between those receiving generic and brand-name clopidogrel.

Clinical Data Mega-Collection of Obesity and Obesity-Related Trials: Primary Inclusion Criteria from All Studies and Highlights of Clinical Efficacy Analysis of GLP-1 Drugs

Background/Objectives: Obesity is heterogeneous and considered a chronic epidemic with significant un-met needs for management, treatment, and prevention. Methods: In this study, we used LizAI’s software TAITAN (alpha version) for the mega-collection and analysis of clinical data from 10,407 trials addressing obesity and obesity-related diseases and their associated publications, mainly on PubMed. Results: We report an intensive growth of clinical trials until the end of 2024 and highlight the use of the body mass index (BMI) as a critical criterion in clinical participant selection despite its limitations. The significant disparities in races, regions, and the sites of trials across all studies have not been addressed, posing the possibility of research in the far future on the applications of precision medicine in weight management. In the latter parts of this paper, we analyze and discuss the clinical efficacy, mainly focusing on the primary endpoints and benchmarks of the recently FDA-approved once-weekly injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) drugs, including semaglutide and tirzepatide. Both drugs have functioned comparably when considering the 5% weight loss FDA threshold. Tirzepatide outperforms semaglutide and impacts fewer participants as the weight loss level increases from 5 to 20% and has greater effects in different populations, especially in people with type 2 diabetes (T2D). Conclusions: We would, however, like to highlight that (i) the weight loss level should be dependent on the clinically relevant needs of patients, and faster and greater weight loss might not be a win, and (ii) the clinical benefits, safety, and quality of life of patients should be carefully assessed when the weight loss is significant in a short period. In our search, we found that the specificities and impacts of weight loss therapies on organs like the kidneys and heart, different muscle types, bones, and fat accumulation in different parts of body were not investigated or disclosed during the clinical study period and longer term monitoring. In light of scientific needs and remarkable public interest in weight loss, our report provides findings on the buzz around losing weight in clinical trials, and our TAITAN software continues to collect data in real time and enrich its knowledge for future updates.

Efficacy and safety of microsurgery in patients with Gustilo ⅢC open fractures

To analyze the clinical efficacy and safety of microsurgery in patients with Gustilo ⅢC open fractures. A total of 64 patients with Gustilo ⅢC open fractures who were admitted to the hospital bewteen September 2018 and March 2022 were included, and divided into the observation group and the control group, with 32 cases in each one. In the observation group, there were 24 males and 8 females, aged from 29 to 42 years with an average of (36.59±3.24) years. The tibial defect ranged from 2 to 5 cm with an average of (3.41±0.61) cm, and the soft tissue defect area ranged from 34 to 76 cm2 with an average of (58.50±9.44) cm2. This group received microsurgical treatment. In the control group, there were 25 males and 7 females, aged from 27 to 44 years with an average of (37.59±3.21) years. The tibial defect ranged from 2 to 6 cm with an average of (3.59±0.80) cm, and the soft tissue defect area ranged from 36 to 78 cm2 with an average of (59.09±9.53) cm2. This group received conventional staged surgery, with plaster or brace fixation after initial debridement and appropriate internal fixation at a later stage. The Anderson scores, motor ability Fugl-Meyer scale, perioperative indicators, rehabilitation outcomes, and complications were compared between the two groups. The patients were followed up for a duration from 2.5 to 5.5 months with an average of (3.15±1.11) months. In the observation group, 19 patients were rated as excellent, 12 patients as good, 1 patient as fair, and no patients as poor. In the control group, 11 patients were rated as excellent, 13 patients as good, 6 patients as fair, and 2 patients as poor. The difference in outcomes between the two groups was statistically significant (P<0.05). The operation time, the hospitalization time, and the hospitalization cost in the observation group(4.39±0.69) h, (30.22±4.58) d, and (23, 500±3, 300) yuan, respectively were significantly lower than those in the control group(5.01±0.75) h, (33.28±3.74) d, and(30, 200±5, 200) yuan, respectively (P<0.05). Revascularization time(134.25±14.76) h, wound healing time(11.34±1.56) d, and fracture healing time(3.09±0.42) months in the observation group were significantly shorter than those in the control group(P<0.05) which were (189.36±22.17) h, (13.22±2.03) d and (4.02±0.57) months respectively. The motor ability(42.91±5.51) points, sensory function(46.19±3.53) points, and total Fugl-Meyer score(89.09±6.08) in the observation group were significantly higher than those in the control group(P<0.05) which were(35.19±4.27), (34.03±3.79), (69.22±6.32) points respectivdy. In the observation group, there were 1 case of refractory wound and 3 cases of complete nerve injury, which were lower than those in the control group (8 cases and 10 cases, respectively, P<0.05). The number of complications in the observation group was lower than that in the control group (P<0.05). Microsurgical technique can effectively shorten the wound and fracture healing time in patients with Gustilo Ⅲ C open fracture, improve limb movement ability, and reduce the risk of poor prognosis and complications.