Clinical Advantages Research Articles

RIRS with FV-UAS vs. ESWL for the management of 1–2 cm lower pole renal calculi in obese patients: a prospective study

ObjectiveTo evaluate the efficacy and safety of retrograde intrarenal surgery (RIRS) combined with flexible vacuum-assisted ureteral access sheath (FV-UAS) versus extracorporeal shock wave lithotripsy (ESWL) for the management of 1–2 cm lower pole renal calculi (LPC) in obese patients.Patients and methodsThis prospective, randomized study included 149 obese patients with 1–2 cm LPC. Patients were allocated into two groups: 76 patients underwent RIRS with FV-UAS, and 73 patients received ESWL. The parameters assessed included stone-free rate (SFR), retreatment rate, complications, operative time, and pain intensity measured by the visual analog scale (VAS). Stone-free status was defined as the absence of stones on computed tomography or residual fragments smaller than 4 mm at 4 weeks post-procedure.ResultsThe baseline characteristics of the two groups were comparable. The SFR was significantly higher in the RIRS group, reaching 86.8%, compared to 63.0% in the ESWL group (p = 0.034). Furthermore, the retreatment rate was significantly lower in the RIRS group, at 5.2%, versus 24.7% in the ESWL group (p < 0.001). The average operative time for RIRS was notably longer, at 65.3 ± 6.4 min, compared to 25.3 ± 7.8 min for ESWL (p < 0.001). The complication rates were 9.2% for the RIRS group and 6.8% for the ESWL group, with no statistically significant difference (p = 0.326). All complications were classified as Grade I or II according to the modified Clavien classification system. No significant differences were observed between the two groups regarding pain VAS scores and the composition of the stones.ConclusionRIRS with FV-UAS demonstrated superior efficacy, evidenced by a higher SFR and reduced retreatment rates compared to ESWL, despite a longer operative duration. Both treatment modalities showed comparable safety profiles. RIRS with FV-UAS emerges as a viable, effective, and reproducible intervention for managing 1–2 cm LPC in obese patients, providing significant clinical advantages.

Ultrasound-guided Double-point Versus Single-point Serratus Anterior Plane Block for Modified Radical Mastectomy: A Randomized Controlled Trial.

The double-point serratus anterior plane block(SAPB) covers more area, including the axilla, than the single-point approach, potentially offering better pain relief after Modified radical mastectomy(MRM). Sixty women were randomly assigned to double or single-point groups. Double-point received SAPB at the third and fifth ribs, single-point at the fifth rib. Primary outcome: pain numeric rating scale (NRS) at rest and movement 24 hours post-surgery. Secondary outcomes: axilla comfort NRS, recovery quality, and adverse events. At 24 hours post-surgery, the double-point group compared to the single-point group showed movement pain NRS of 3 (2-3) vs. 3 (3-4) (P = 0.011) and rest pain NRS of 1 (1-1) vs. 2 (1-3) (P = 0.037). The difference between them did not exceed the MCID. The axillary comfort NRS in the double-point group was lower than the single-point group at 6 and 12 hours post-surgery, at 1 (1-2) vs. 2 (2-4) (P=0.001) and 1 (1-2) vs. 2 (2-4) (P=0.01) respectively, but there was no difference at 24 and 48 hours post-surgery. At 48 hours post-surgery, pain scores and opioid use were similar in both groups. Recovery scores, rescue analgesia timing, adverse events, and hospital stay length were similar in both groups. Double-point SAPB offers wider anesthetic spread but shows no significant clinical advantage in pain or axillary comfort over single-point SAPB after MRM.

Dual-energy computed tomography: pediatric considerations.

Multidetector computed tomography (CT) has revolutionized medicine and is now a fundamental aspect of modern radiology. Hardware and software advancements have significantly improved CT accessibility, image quality, and acquisition times. While considerable attention has been directed towards the potential risks of ionizing radiation from CT scans in children, recent concerns regarding the possible short- and long-term risks related to magnetic resonance imaging (MRI) conducted under general anesthesia have generated fresh interest in novel pediatric CT applications and techniques that allow imaging of awake patients at low radiation doses. Among these novel techniques, dual-energy CT (DECT) stands out for its ability to provide enhanced diagnostic information, reduce radiation doses further, and facilitate faster scans, making it a highly promising tool in pediatric radiology. This manuscript explores the current role of DECT in pediatric imaging, emphasizing its technical foundations, hardware configurations, and various reconstruction techniques. We discuss advanced post-processing techniques, such as material decomposition algorithms and virtual monoenergetic imaging, highlighting their clinical advantages in improving diagnostic accuracy and patient outcomes. Furthermore, the paper reviews the clinical applications of DECT in evaluating pulmonary perfusion, cardiovascular assessments, and oncologic imaging in pediatric patients.

Long-term clinical outcomes of acute myocardial infarction based on a center's experience with IVUS in the contemporary drug-eluting stent era

Abstract Introduction Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) is recognized for improving patient prognosis. However, how a center's experience with IVUS affects clinical outcomes remains unclear. Purpose This study aims to elucidate the impact of a center's expertise in IVUS on clinical outcomes, emphasizing the value of institutional experience. Methods In this retrospective cohort study from the Korean AMI Registry (KAMIR), we analyzed 9,752 patients diagnosed with acute myocardial infarction (AMI) who underwent intervention with second-generation drug-eluting stents. The primary outcome was major adverse cardiovascular events (MACE) at 3 years, defined as the composite of all-cause deaths, any myocardial infarction, and any coronary revascularization. The secondary outcome was target-lesion failure (TLF), defined as the composite endpoint of all cardiac deaths, target vessel myocardial infarction, and ischemia-driven target lesion revascularization at 3 years. Results In this study, the median frequency of IVUS usage across 20 institutions was 10.3%. Hospitals were categorized as centers with extensive experience in IVUS or those with limited experience, based on the median frequency of IVUS usage. In centers with extensive experience in IVUS, IVUS-guided PCI consistently showed a reduction in MACE (18.5% vs. 15.3%, p=0.016) and TLF (8.3% vs. 6.3%, p=0.039) within propensity-score matched populations. Furthermore, multivariate Cox regression analysis revealed that IVUS-guided PCI was associated with decreased risks of MACE (HR 0.80, 95% CI [0.69-0.93], p=0.003) and TLF (HR 0.75, 95% CI [0.59-0.95], p=0.01). However, from propensity matched population in centers with limited experience in IVUS, there were no significant reductions in the incidences of MACE (18.6% versus 15.7%, p=0.422) and TLF (10.4% versus 8.9%, p=0.644). Conclusion This comprehensive, nationwide cohort study shows that outcomes of IVUS-guided PCI are more favorable in centers with extensive IVUS experience compared to those with limited experience. These results indicate that the clinical advantages of IVUS-guided PCI are more pronounced in centers with extensive experience than in those with limited experience.

Electrical performance of a novel extravascular temporary pacing lead system

Abstract Background An investigational extravascular (EV) cardiac temporary pacing system has been developed that includes a parasternally-positioned temporary pacing lead within the anterior mediastinum. The pacing lead is inserted using a custom delivery tool through a parasternal skin incision. This novel system may provide clinical advantages over existing device alternatives that require intravascular, endocardial, or epicardial contact. Objective The purpose of this study was to evaluate electrical performance of an EV temporary pacing lead over 48 hours. Methods In this single-center study, patients who underwent a transvenous (TV) permanent pacemaker implant or replacement were simultaneously implanted with the investigational EV temporary pacing lead. Electrical performance was evaluated through analysis of capture thresholds, impedance, and R-wave amplitudes during multiple times on the day of the procedure and on the subsequent 2 days of follow-up. Results Lead insertions with acute capture were successful in all 8 patients (40% female, 71 ± 8 years, BMI 27 ± 3 kg/m2). Mean acute measurements for pacing capture threshold at 1.5 ms, impedance and R-wave amplitude were 6.2 mA, 1396 Ω, 5.4 mV, respectively. Pacing capture was maintained in 100% of assessments conducted over 3 days (Figure 1). There were no serious complications during insertion, removal or chronic use of the lead. Conclusions Results support that the investigational EV temporary pacing lead is capable of safely providing temporary pacing with thresholds typically well below the maximum output of temporary pacemakers.

Systematic Review: Comparative Efficacy and Safety of Losartan vs. Candesartan for the Treatment of Hypertension

Hypertension is one of the most significant modifiable risk factors for cardiovascular disease (CVD) and remains a leading cause of morbidity and mortality globally. Effective management of hypertension is essential for preventing comp lications such as stroke, myocardial infarction, and heart failure. Angiotensin II receptor blockers (ARBs) like losartan and candesartan are well-established therapeutic options for blood pressure (BP) control and are widely prescribed due to their favorable side-effect profiles and organ-protective properties. Despite being members of the same drug class, these ARBs differ in their pharmacokinetics, receptor binding affinity, and clinical efficacy. This systematic review aims to provide a detailed comparison of the efficacy and safety of losartan versus candesartan in managing hypertension. We conducted a comprehensive search of the PubMed, Embase, and Cochrane databases, retrieving studies published from 2000 to 2024 that compared the two ARBs directly in hypertensive populations. A total of 25 randomized controlled trials (RCTs) and observational studies, comprising more than 12,000 participants, were included in the analysis. The primary outcomes evaluated were the reduction in systolic and diastolic blood pressure, cardiovascular event prevention, and adverse event profiles. The results suggest that both losartan and candesartan effectively lower BP, but candesartan consistently demonstrated greater reductions in both systolic and diastolic BP compared to losartan. Candesartan also appeared to have superior cardiovascular outcomes, with a lower incidence of major cardiovascular events such as stroke, myocardial infarction, and heart failure hospitalizations. The safety profiles of both drugs were comparable, though losartan was associated with a slightly higher incidence of cough and discontinuation due to adverse events. Overall, candesartan may offer a slight clinical advantage over losartan, particularly in patients requiring more potent or sustained BP control. However, both drugs remain valuable options in the management of hypertension. Further long-term studies are recommended to confirm these findings and to investigate the potential benefits of each drug in specific patient subgroups.

Amniotic bladder therapy: study of micronized amnion/chorion for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) at 6months.

Intravesical application of birth tissue has been reported to inhibit inflammation, alleviate collagen fiber accumulation, and enhance bladder tissue generation. We have previously reported that intra-detrusor micronized amnion monolayer (AM) injections provide short-term clinical improvement in refractory IC/BPS patients. Herein, we evaluate the therapeutic responses and adverse events of micronized amnion/chorion bilayer (AC) in patients with refractory IC/BPS with 6months follow-up. Fifteen patients affected by IC/BPS who failed conventional therapy received 100mg of reconstituted micronized AC was injected intra-detrusor via cystoscopy under general anesthesia, using a 23-gauge needle. Twenty 0.5-mL injections were administered into the lateral and posterior bladder walls, avoiding the dome and trigone. Changes in interstitial cystitis symptom index (ICSI), Interstitial cystitis problem index (ICPI), Bladder pain/ interstitial cystitis symptom score (BPIC-SS) and Overactive Bladder Assessment Tool (OAB), from baseline to 6months post-injection were evaluated retrospectively.The safety of injections was analyzed. Fifteen total refractory IC/BPS patients with an average age of 41.1 ± 14.5years were included in the study, receiving intra-detrusor injections of 100mg of micronized AC. One month after injections, significant improvement in IC/BPS symptom scores was noted in all patients. All patients maintained a sustained clinical response at 6months post-injection. No product-related adverse events were observed. Our findings indicate that the AC formulation significantly reduces time to symptom relief in patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS) and maintains a sustained response up to 6months post-injection. These results suggest a promising clinical benefit of using an amnion/chorion bilayer product for treating IC/BPS. Further research is needed to confirm these findings and assess the long-term durability of this treatment approach. This study represents the first evidence supporting the clinical advantages of an amnion/chorion bilayer product in managing IC/BPS.

Autogenous platelet concentrates for treatment of intrabony defects-A systematic review with meta-analysis.

To provide an overview of the use of autogenous platelet concentrates (APCs) in periodontal regeneration and to conduct a systematic review (SR) of the treatment outcomes of periodontal intrabony defects by using platelet-rich fibrin (PRF) compared with other commonly utilized modalities. The eligibility criteria comprised randomized controlled trials (RCTs) comparing the clinical outcomes of PRF with that of other modalities. Studies were classified into 21 categories and into five different groups as follows: Group I (1) open flap debridement (OFD) alone versus OFD/PRF, (2) OFD versus Titanium-PRF (T-PRF) Group II, (3) Comparative PRF protocols (PRF vs. T-PRF), Group III (Comparative Studies to PRF): (4) OFD/PRP versus OFD/PRF, (5) OFD/bone graft(BG)/PRGF versus OFD/BG/PRF, (6) OFD/EMD versus OFD/PRF, (7) OFD/BG/EMD versus OFD/BG/PRF, (8) OFD/collagen membrane (CM) versus OFD/PRF, (9) OFD/BG/BM versus OFD/BG/PRF, (10) OFD/BG versus OFD/PRF, Group IV (Addition of PRF to treatment groups) (11) OFD/BG versus OFD/BG/PRF, (12) OFD/GTR versus OFD/GTR + PRF (13) OFD/EMD versus OFD/EMD/PRF (14) OFD/BG/BM versus OFD/BG/BM/PRF, Group V (Addition of Biomaterial/Biomolecule to PRF): OFD/PRF versus … (15) OFD/PRF/BG, (16) OFD/PRF/antibiotic, (17) OFD/PRF/Metformin, (18) OFD/PRF/Bisphosphonates, (19) OFD/PRF/Statins, (20) OFD/BG/PRF versus OFD/BG/PRF/Statins, and (21) OFD/PRF/low-level laser therapy (LLLT). Weighted means and forest plots were calculated for probing pocket depth (PPD), clinical attachment level (CAL), and radiographic bone fill (RBF). From 596 records identified, 55 RCTs were included. Group I: The use of OFD/PRF statistically significantly reduced PPD and improved CAL and RBF when compared to OFD. Group II: A significant difference between various PRF protocols was only observed for PPD. Group III: No significant advantage was found when comparing OFD/PRF to the following groups: OFD/PRP, OFD/EMD, OFD/BM, or OFD/BG. Group IV: The addition of PRF to OFD/BG led to significant improvements in PPD, CAL and RBF compared with OFD/BG alone. Group V: The addition of either a BG as well as three of the following biomolecules (metformin, bisphosphonates, and statins) to OFD/PRF led to statistically significant improvements in PPD, CAL, and/or RBF when compared to OFD/PRF alone. The use of PRF significantly improved clinical outcomes in intrabony defects when compared to OFD alone. Similar results were observed when OFD/PRF was compared with OFD/BG, OFD/EMD, OFD/PRP, and OFD/BM. The addition of PRF to a bone grafting material as well as the addition of various small biomolecules to PRF may offer additional clinical advantages, thus warranting further investigations. Future research investigating various protocols of PRF, longer-term outcomes, as well as PRF at the human histological level remains needed.

Effect of Timing of Third Molar Extraction on the Rate of Mandibular En Masse Distalization Using Buccal Shelf Implants – A Randomized Controlled Trial

This randomized controlled trial evaluates the impact of the timing of third molar extractions on the rate of mandibular en masse distalization and second molar angulation in orthodontic treatment, using buccal shelf implants in borderline Class III malocclusion patients. Late third molar extractions performed less than two weeks before distalization were compared to early extractions, performed six months prior, to investigate the effect of Regional Acceleratory Phenomenon (RAP) on tooth movement. The study also assessed second molar angulation changes, examining distal tipping differences between groups. Results showed a significantly faster rate of distalization in Group II (late extraction) at 0.637 ± 0.098 mm/month, compared to Group I (early extraction) at 0.422 ± 0.075 mm/month. Additionally, Group I experienced significantly greater second molar distal tipping (9.14°) than Group II (3.47°). These findings suggest that the timing of third molar extractions affects both distalization rates and second molar angulation, with early extraction offering a clinical advantage by leveraging RAP and minimizing undesirable tipping.

Research progress in repair and reconstruction of tumor-related bone defects in proximal femur

To review the repair and reconstruction methods for large segmental femoral proximal bone defects caused by tumors, and to explore their clinical application effects, advantages, and disadvantages, and future research directions. A comprehensive search of Chinese and foreign databases was conducted to select basic and clinical research literature related to the repair and reconstruction of femoral proximal bone defects caused by tumors. The studies were classified and analyzed based on two main strategies: hip-preserving reconstruction and non-hip-preserving reconstruction. In hip-preserving reconstruction, traditional methods such as allograft transplantation and vascularized autograft transplantation are common but have risks of poor bone integration and bone resorption. The clinical application of inactivated tumor segment reimplantation and distraction osteogenesis techniques is limited. In recent years, three-dimensional printing technology has become increasingly mature, with personalized prostheses and precise surgeries becoming development trends. Non-hip-preserving reconstruction primarily includes allograft prosthesis composite and total femoral replacement. The former focuses on improving the survival rate and bone integration efficiency of the allograft, while the latter requires the simultaneous reconstruction of hip and knee joint stability. Significant progress has been made in repairing and reconstructing proximal femoral bone defects caused by tumors, but many challenges remain. The integration of three-dimensional printing technology and digital design offers potential for precise bone defect repair. Future efforts should focus on new concepts, technologies, and materials through multidisciplinary approaches to provide personalized and precise solutions, thereby improving patient quality of life.

Choice Between Free Combination of Antihypertensive Agents and Fixed Dosed Combinations in the Treatment of Arterial Hypertension

Most patients with arterial hypertension require more than one antihypertensive drug for blood pressure target achievement. Some patients are recommended for a multi-pill antihypertensive regimen, others — treatment with fixed dosed combinations in one tablet. Analysis of elibrary and PubMed publications in the period mostly from 2014 to 2024 concerning the choice of two-component combined antihypertensive agents containing renin-angiotensin system inhibitor and diuretic or calcium channel blocker, revealed that fixed-dose combinations (FDC) use and taking one tablet once a day improves adherence to treatment and facilitates blood pressure control. Although the cost of FDC containing the renin-angiotensin-aldosterone system inhibitor and a thiazide/thiazide-like diuretic or calcium channel blocker is in most cases higher than the same drugs taken separately, the use of fixed combinations, increasing patient adherence to therapy, has clinical advantage in terms of the effectiveness of lowering blood pressure, which confirms their economic feasibility. On the other hand, the use of free combination therapy in two different tablets, when taken separately during the day, can sometimes provide a more sustained antihypertensive effect over 24 hours. Evidence of the effectiveness of blood pressure control for FDCs is often extrapolated from data on free combinations. In addition, FDCs are characterized by less detection of possible ineffectiveness of one of the components. The range of FDCs and the dosage ratios of the components presented in them is gradually expanding, but the choice among free combinations is still wider. In addition, the list of vital and essential drugs (VED) for 2024 does not contain FDCs for antihypertensive drugs, which excludes the possibility of free receiving them on a preferential basis and gives the opportunity for the manufacturer to set prices for them. Despite the fact that recently the scientific community has recommended the use of FDC antihypertensive drugs as initial therapy due to better compliance with the regimen, and therefore clinical effectiveness and economic feasibility, it cannot be said that there is no space left for free combinations of antihypertensive drugs in the treatment of arterial hypertension. The choice of doctor, frequency of prescription, share of purchases of the FDCs in the Russian Federation, review of their consumption requires further analysis.

New linear stapled semimechanical esophagogastric anastomosis with invagination

Objective. Development and implementation esophagogastric linear stapled semimechanical anastomosis with invagination. Material and methods. Seromuscular stitches are applied over 4 cm on both sides to the lateral surfaces of the esophagus posterior wall and gastric graft posterior wall, towards their edges. The posterior wall of the anastomosis is sutured and cutted with a linear stapler on 30–40 mm deep. The anterior wall sutured with a linear stapler. The next layer of sutures on the anastomosis anterior wall invaginates the anastomos and the esophageal stump into the gastric graft. Results. There was no early postoperative mortality. Average I. Lewis minimally invasive esophagectomy time was 353 minutes (245–470 minutes). The average volume of blood loss was 114 mL (50–200 mL). No patient faced an anastomotic leak. Anastomotic stricture occurred in 5 patients (19.2%) during 21 days to 6 months of follow-up. There were no anastomosis-related complications above Clavien-Dindo grade II. Conclusions. Linear stapled semimechanical anastomosis with invagination has proven both clinical and technical advantages of its use.

From Bank Preparation to Clinical Use of Homologous Skin Allografts in Wound Healing: A Sustainable Approach.

Given progressive population ageing and the increase in the number of patients with comorbidities, the management of chronic and/or hard-to-heal wounds (HHWs) nowadays represents a common problem in many clinical settings. In these cases, standard strategies may not be sufficient. Autologous grafting represent the gold standard for permanent wound closure, but is almost never realized when the skin loss is extensive/the patient is young. The grafting of homologous skin/dermal tissue procured from cadaver donors (i.e., allografting) represents the best alternative, especially when the dermal component is lost. This request supports the activities of skin bank establishments (including donor screening, skin procurement, processing, storage, and distribution) that are regulated by specific guidelines and need to continuously meet quality standard requirements. The aim of this work is to both give specific insights of all the procedures implied in allograft preparation as well as an overview of their practical application in the treatment of different HHWs. The particular characteristics of each skin/dermal allograft released by Siena Skin Bank (cryopreserved/glycerol-preserved skin/de-epidermized dermis, acellular lyophilized de-epidermized dermis/reticular dermis) are also discussed. The exemplificative series of HHWs managed in the Dermatology Department of Siena were classified according their etiology into post-traumatic, vascular (arterial/venous/mixed/lymphatic), inflammatory, surgical, and heat/chemical burns. Globally, the clinical advantages obtained include: acceleration of healing process, pain sparing, resistance to bacterial contamination, dermal regeneration (instead of scarring), and better aesthetic-functional outcome.

Evaluating Surgical Accuracy in Bimaxillary Surgery: A Systematic Review and Meta-Analysis of Mandible-First versus Maxilla-First Approaches.

Mandible-first surgery (MdFS) has gained attention as an alternative to the traditional maxilla-first surgery (MxFS) in bimaxillary procedures. Given the distinct sequence of operations between these approaches, evaluating the clinical advantages of MdFS compared to MxFS is crucial for optimizing surgical decision-making. This systematic review and meta-analysis examine intraoperative achievability and postoperative stability between these two surgical approaches. A thorough literature search was performed using PubMed, Embase, Web of Science, and MEDLINE, covering articles published from 2013 to 2023. Studies included were retrospective, prospective, and randomized trials that compared the accuracy and/or stability of MdFS with MxFS. The primary endpoint for the meta-analysis was the standardized mean difference in surgical accuracy for translational movements, with a secondary focus on rotational accuracy. A total of 11 studies encompassing 712 patients met the inclusion criteria. The analysis suggested that MdFS might reduce accuracy in the sagittal dimension (CI, 0.05 to 0.74) but offered greater achievability in the vertical direction (CI, - 0.47 to - 0.07). Additionally, MdFS was associated with a relatively posterior (CI, - 1.18 to - 0.60) and inferior (CI, - 0.64 to - 0.07) positioning of the maxillomandibular complex. Despite certain limitations, our findings indicate that MdFS can achieve clinical outcomes similar to MxFS in terms of both accuracy and stability. However, further researches with larger sample sizes and more rigorous study designs are necessary to validate these conclusions. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of contents or the online Instructions to Authors www.springer.com/00266 .

Identification of a senescence-related transcriptional signature to uncover molecular subtypes and key genes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a cancer caused by abnormal cell growth due to faulty signal transduction. Cells secrete tumor suppressor factors in response to potential carcinogenic signals, inducing cellular senescence (CS) as a countermeasure. However, accurately measuring CS levels in different types of tumors is challenging due to tumor heterogeneity and the lack of universal and specific CS markers. Machine learning has revealed unique molecular traits in HCC patients, leading to clinical advantages. More research is needed to understand senescence-related molecular features in these patients. In this study, the gene expression profile features of patients with HCC were analyzed by integrating single-cell RNA sequencing and bulk RNA-seq datasets from HCC samples. The analysis identified the senescence-related pathways exhibiting HCC specificity. Subsequently, genes from these pathways were used to identify senescence-related molecular subtypes in HCC, showing significant variations in biological and clinical attributes. An HCC-specific CS risk model developed in this study revealed substantial associations between the patients' CS scores and prognosis grouping, clinical staging, immune infiltration levels, immunotherapy response, and drug sensitivity levels. Within the constructed model, G6PD was identified as a key gene, potentially serving as a senescence-related target in liver cancer. Molecular biology experiments demonstrated that overexpression of G6PD effectively promotes the proliferative, invasive, and migration capacities of HepG2 and SK-HEP-1 cells. In conclusion, this analysis offers a valuable framework for understanding senescence in HCC and introduces a new biomarker. These findings improve our understanding of senescence in HCC and have potential for future research.

Clinical trial design for novel targeted agents in neuro-oncology.

Biomarker-based clinical trials investigating targeted treatments for brain tumors have surged due to better access to biomarker testing and a deeper grasp of the molecular basis of tumor development. The design of clinical trials is crucial for evaluating safety, confirming effectiveness, and affirming the clinical advantage of novel agents, with the goal of approval by regulatory authorities to expand patient treatment options. Given some challenges unique to brain tumors, early-stage clinical trials for novel targeted agents must integrate pharmacokinetics and tissue-based pharmacodynamic assessments to establish timely go-no-go decisions for larger studies. Surgical window-of-opportunity trials can allow for the comparison of treated and untreated tumor samples, verifying target engagement and its modulatory effects for evidence of biological activity. Due to the challenges of achieving the required sample sizes to power efficacy analyses, later-stage trials of targeted therapies can include basket trials which test one drug on multiple tumor types, while umbrella trials evaluate several biomarkers within a single histology. Platform trials can also be leveraged to investigate multiple biomarker-driven hypotheses within a unified protocol and can incorporate Bayesian algorithms for adaptive randomization. Selecting appropriate endpoints, such as progression-free survival or overall response rate, is crucial and novel response assessment criteria need to be considered in the context of the tumor and therapy being investigated. Lastly, inclusivity in trials is essential to address health disparities and engage diverse patient populations to ensure real-world impact. Future trials should build upon the knowledge gained from both initial achievements and past setbacks in the field.

8614 Low Dose Sublingual Estradiol Decreases Protein S, Generating a Potentially Pro-thrombotic Profile: Interim Results of a Controlled Prospective Pilot Study of Treatment-Naïve Trans Women

Abstract Disclosure: S. Bar On: None. I. Yaish: None. M. Barzilai: None. Y. Greenman: None. G. Gindis: None. Y. Moshe: None. K.M. Tordjman: None. Background: Sublingual estradiol (SLE) for gender-affirming hormone therapy (GAHT) of transgender women (TW) might obviate the need for an anti-androgen, and mitigate pro-coagulant changes. We recently showed that 2 mg E, divided into 4 daily sublingual doses, offers no clinical advantage over the same dose given orally in combination with cyproterone acetate (CPA)1. Furthermore, we showed that after each sublingual administration, serum estradiol (sE2) peaked to levels, the likes of which are achieved only during induction of ovulation with gonadotrophins. Hypothesis and Aim: Given the exceedingly high peak sE2 measured under SLE-GAHT, we hypothesized it could lead to partial acquired Protein S deficiency, a recognized pro-thrombotic state and risk factor for venous thromboembolic events (VTE). Our aim was to assess the hemostatic system under SLE in comparison with the standard combined oral (CO) approach. Design and Methods: In this ongoing open label study, treatment-naïve TW are assigned in a 1:1 ratio (15 in each arm) to either standard CO (2 mg E2 with 10 mg CPA once daily), or to SLE with 2 mg sublingual estradiol divided into 4 daily dose for 6 months (6M). An extensive battery of hemostatic biomarkers, including free Protein S antigen (fPS), are assessed at baseline (BL) and at 6M. Results: We herein report on 27 subjects (15 CO/12 SLE) who initiated treatment, 17 of whom have already completed it. The median age of the cohort is 20 y (IQR 19-27; range 18-42]. There were no BL differences between the groups. At 6M, none of the hemostatic markers differed between the groups except for fPS, which was significantly lower in the SLE group 79.7%±11.6% vs. 104.6%±5.6%, P=0.039. By paired comparisons for the entire group, fPS decreased from 104%.2±5.2% at BL to 95.8%±5.9% at 6M, P=0.003. This was entirely accounted for by the change in the SLE group, in which fPS went down from 95.7%±10.3% to 79.7%±11.6%, P<0.001; with some values reaching the fPS deficiency range. In contrast, fPS, remained unchanged under CO 108.9%±5.7% and 104.5%±5.2%, at BL and 6M respectively, P=0.153. Conclusions: The most notable interim finding was a clinically significant decrease in fPS under low dose SLE. Given the extreme peaks of sE2 we previously reported with this protocol, an acquired deficiency of this natural anti-coagulant was expected. These preliminary findings support our hypothesis, and raise the concern that GAHT of TW with chronic SLE might carry an increased long-term risk for VTE. 1 Yaish I, Gindis G, Greenman Y, et al. Sublingual Estradiol Offers no Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. Transgend Health. 2023;8(6):485-493. Published 2023 Dec 13. doi:10.1089/trgh.2023.0022 Presentation: 6/2/2024

8614 Low Dose Sublingual Estradiol Decreases Protein S, Generating a Potentially Pro-thrombotic Profile: Interim Results of a Controlled Prospective Pilot Study of Treatment-Naïve Trans Women

Abstract Disclosure: S. Bar On: None. I. Yaish: None. M. Barzilai: None. Y. Greenman: None. G. Gindis: None. Y. Moshe: None. K.M. Tordjman: None. Background: Sublingual estradiol (SLE) for gender-affirming hormone therapy (GAHT) of transgender women (TW) might obviate the need for an anti-androgen, and mitigate pro-coagulant changes. We recently showed that 2 mg E, divided into 4 daily sublingual doses, offers no clinical advantage over the same dose given orally in combination with cyproterone acetate (CPA)[1]. Furthermore, we showed that after each sublingual administration, serum estradiol (sE2) peaked to levels, the likes of which are achieved only during induction of ovulation with gonadotrophins. Hypothesis and Aim: Given the exceedingly high peak sE2 measured under SLE-GAHT, we hypothesized it could lead to partial acquired Protein S deficiency, a recognized pro-thrombotic state and risk factor for venous thromboembolic events (VTE). Our aim was to assess the hemostatic system under SLE in comparison with the standard combined oral (CO) approach. Design and Methods: In this ongoing open label study, treatment-naïve TW are assigned in a 1:1 ratio (15 in each arm) to either standard CO (2 mg E2 with 10 mg CPA once daily), or to SLE with 2 mg sublingual estradiol divided into 4 daily dose for 6 months (6M). An extensive battery of hemostatic biomarkers, including free Protein S antigen (fPS), are assessed at baseline (BL) and at 6M. Results: We herein report on 27 subjects (15 CO/12 SLE) who initiated treatment, 17 of whom have already completed it. The median age of the cohort is 20 y (IQR 19-27; range 18-42]. There were no BL differences between the groups. At 6M, none of the hemostatic markers differed between the groups except for fPS, which was significantly lower in the SLE group 79.7%±11.6% vs. 104.6%±5.6%, P=0.039. By paired comparisons for the entire group, fPS decreased from 104%.2±5.2% at BL to 95.8%±5.9% at 6M, P=0.003. This was entirely accounted for by the change in the SLE group, in which fPS went down from 95.7%±10.3% to 79.7%±11.6%, P<0.001; with some values reaching the fPS deficiency range. In contrast, fPS, remained unchanged under CO 108.9%±5.7% and 104.5%±5.2%, at BL and 6M respectively, P=0.153. Conclusions: The most notable interim finding was a clinically significant decrease in fPS under low dose SLE. Given the extreme peaks of sE2 we previously reported with this protocol, an acquired deficiency of this natural anti-coagulant was expected. These preliminary findings support our hypothesis, and raise the concern that GAHT of TW with chronic SLE might carry an increased long-term risk for VTE. [1] Yaish I, Gindis G, Greenman Y, et al. Sublingual Estradiol Offers no Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. Transgend Health. 2023;8(6): 485-493. Published 2023 Dec 13. doi:10.1089/trgh.2023.0022 Presentation: 6/2/2024

Autogenous Tooth Graft Biomaterial in Guided Bone Regeneration: A Comprehensive Review

Objective: This review evaluated the use of autogenous tooth as a bone graft material in guided bone regeneration (GBR). Moreover, it compared the results of GBR using autogenous demineralized dentin, partially demineralized dentin, and mineralized dentin with or without membrane to verify its clinical advantage, effectiveness, and safety. Methods: A search was conducted in PubMed/MEDLINE, Lilacs, Embase, Cochrane, and Scopus databases. Specific criteria were established for the inclusion and exclusion of studies, including types of studies considered, target population (clinical studies: humans), evaluated intervention (studies assessing and comparing autologous demineralized dentin, partially demineralized dentin, and mineralized dentin in GBR with or without resorbable membrane), and language and publication period of articles (English and published in the last 11 years). A detailed assessment of the methodological quality of the selected studies was conducted using the JBI critical appraisal tool. Results: Based on the analysis conducted, out of 174 potentially relevant articles obtained, only 19 publications met the inclusion criteria, with three papers showing medium quality/moderate risk of bias and the rest with high quality/low risk of bias. Comparison between groups revealed stability of the newly formed bone, low marginal bone loss, clinically acceptable primary and secondary implant stability quotient (ISQ) values, and high implant survival rates after using autogenous tooth biomaterial. Conclusions: The results of this review on the use of autogenous teeth as a bone graft material in guided bone regeneration indicated that the technique has the potential to be an effective and safe treatment option. Analysis of selected studies showed favorable evidence for the use of autogenous teeth in bone regeneration, suggesting clinical benefits, most for socket preservation. These results are relevant for guiding clinical practice and assisting dental professionals in having options for biomaterials for bone regeneration.

Clinical Effects of Laparoscopic Radical Colon Cancer Treatment with Complete Mesocolic Resection for Colon Cancer

Objective: This paper aims to evaluate the effect of laparoscopic complete mesocolic resection on the efficacy and survival of patients with colon cancer. Methods: 80 colon cancer patients were included in this study, 40 of whom were treated with traditional radical colon cancer surgery as the control group, and the other 40 were treated with laparoscopic complete mesocolic resection radical colon cancer surgery as the observation group. The study period lasted from April 2022 to April 2023, and the surgical indexes, postoperative recovery, quality of life, and the occurrence of complications of the two groups were monitored throughout the whole process and compared and analyzed. Results: The therapeutic effect of the observation group was better than that of the control group (P < 0.05). The operation time, bleeding volume and postoperative hospitalization time of the observation group were significantly lower than those of the control group, and the number of lymph node dissection was significantly higher than that of the control group, with highly significant differences (all P < 0.001). The postoperative recovery of the observation group (time of first anal defecation, time of first solid food intake, and time of wound healing) was significantly better than that of the control group (all P < 0.001). The quality of life of the observation group was significantly improved with a highly significant correlation (P < 0.001), and the complication rate was significantly lower than that of the control group (P < 0.05). Conclusion: Laparoscopic radical colon cancer surgery with complete mesocolic resection for colon cancer shows better clinical effects and advantages in the treatment of colon cancer, which is worth further promotion and application in clinical practice.