Treatment Options Research Articles

Stress Maneuver for Basilar Invagination Reduction: A Technical Report

BackgroundBasilar invagination (BI) is a prolapse of the odontoid process cranially and posteriorly towards the foramen magnum. Several surgical treatment options are available for this condition. Herein, we describe a stress maneuver technique for BI reduction using a single-stage posterior approach. MethodsWe described the case of a 56-year-old male diagnosed with type A BI and brainstem compression, who was treated with posterior fossa decompression and occipitocervical fusion. The BI was reduced intraoperatively using a stress maneuver, and cranial traction or atlantoaxial joint distraction was not necessary. ResultsPostoperative imaging revealed a reduction of the odontoid process and adequate brainstem decompression. The patient showed progressive improvement of his symptoms. ConclusionIn selected cases, stress maneuvers for BI reduction can be a less morbid, easier, and replicable option within the already existing technical arsenal.

Combination Dornase and Alteplase for Intra-abdominal Drain, Abscess, and Hematoma Clearance: A Retrospective Case Series

Background: Since the advent of the MIST2 trial, the combined instillation of dornase and alteplase has become an effective nonsurgical treatment option for empyema and pleural fluid collection. Percutaneous drainage of abdominal abscesses and fluid collections, rather than open surgical treatment, also has become commonplace. The are several case reports and studies on the use of fibrinolytics to drain abdominal fluid collections but no literature reporting use of both alteplase and dornase for abdominal administration. Objective: We present a case series from an academic medical center where dornase therapy was added to fibrinolytic therapy to treat intra-abdominal fluid collections, hematoma, and abdominal drainage catheters with low output. Methods: This is an institutional review board-approved retrospective case series of 13 patients who underwent combination use of alteplase and dornase via intra-abdominal route. The primary objective was to assess for increased drain output, reduction in size of the fluid collection, and adverse events. Results: Many patients had improved drain output after dornase-alteplase therapy. One patient had significant bleeding complications. Conclusions: All patients were discharged alive from the hospital. Clinical success was difficult to define due to variable goals of therapy. Further data are needed to establish the safety and efficacy of this practice, especially compared with intra-abdominal alteplase alone. Patients in our series generally received larger doses of alteplase than in prior studies due to use of dosing modeled on the MIST2 trial. Based on the limited experience of our study, we recommend holding therapeutic anticoagulation during the administration of intra-abdominal dornase-alteplase.

Characterization of bi-segmented and tri-segmented recombinant Pichinde virus particles.

Mammarenaviruses include several highly virulent pathogens (e.g., Lassa virus) capable of causing severe hemorrhagic fever diseases for which there are no approved vaccines and limited treatment options. Mammarenaviruses are enveloped, bi-segmented ambisense RNA viruses. There is limited knowledge about cellular proteins incorporated into progeny virion particles and their potential biological roles in viral infection. Pichinde virus (PICV) is a prototypic arenavirus used to characterize mammarenavirus replication and pathogenesis. We have developed a recombinant PICV with a tri-segmented RNA genome as a viral vector platform. Whether the tri-segmented virion differs from the wild-type bi-segmented one in viral particle morphology and protein composition has not been addressed. In this study, recombinant PICV (rPICV) virions with a bi-segmented (rP18bi) and a tri-segmented (rP18tri) genome were purified by density-gradient ultracentrifugation and analyzed by cryo-electron microscopy and mass spectrometry. Both virion types are pleomorphic with spherical morphology and have no significant difference in size despite rP18tri having denser particles. Both virion types also contain similar sets of cellular proteins. Among the highly enriched virion-associated cellular proteins are components of the endosomal sorting complex required for transport pathway and vesicle trafficking, such as ALIX, Tsg101, VPS, CHMP, and Ras-associated binding proteins, which have known functions in virus assembly and budding. Other enriched cellular proteins include peripheral and transmembrane proteins, chaperone proteins, and ribosomal proteins; their biological roles in viral infection warrant further analysis. Our study provides important insights into mammarenavirus particle formation and aids in the future development of viral vectors and antiviral discovery.IMPORTANCEMammarenaviruses, such as Lassa virus, are enveloped RNA viruses that can cause severe hemorrhagic fever diseases (Lassa fever) with no approved vaccine and limited therapeutic options. Cellular proteins incorporated into progeny virion particles and their biological roles in mammarenavirus infection have not been well characterized. Pichinde virus (PICV) is a prototypic mammarenavirus used as a surrogate model for Lassa fever. We used cryo-electron microscopy and proteomic analysis to characterize the morphology and protein contents of the purified PICV particles that package either two (bi-segmented) or three (tri-segmented) genomic RNA segments. Our results demonstrate a similar virion morphology but different particle density for the bi- and tri-segmented viral particles and reveal major virion-associated cellular proteins. This study provides important insights into the virus-host interactions that can be used for antiviral development and optimizing arenavirus-based vaccine vectors.

Mechanisms and salvage treatments in patients with multiple myeloma relapsed post-BCMA CAR-T cell therapy

Chimeric antigen receptor T-cell (CAR-T) therapy has ushered in a new era for the treatment of multiple myeloma (MM). Numerous clinical studies, especially those involving B-cell maturation antigen (BCMA)-directed CAR-T, have shown remarkable efficacy in patients with relapsed or refractory multiple myeloma (R/R MM). However, a considerable number of patients still experience disease recurrence or progression after BCMA CAR-T treatment, which is attributed to various factors, including antigen escape, CAR-T manufacturing factors, T cell exhaustion, inhibitory effects of tumor microenvironment and impact of prior treatments. The scarcity of effective treatment options following post-CAR-T disease recurrence, coupled with the lack of well-established salvage regimens, leaves patients who do relapse facing a bleak prognosis. In recent years, some academic institutions have achieved certain results in salvage treatments of patients with relapse after BCMA CAR-T treatment through secondary infusion of BCMA CAR-T, changing to non-BCMA-directed CAR-T, double-target CAR-T, bispecific antibodies or other novel therapies. This review summarizes the mechanisms of resistance or relapse after BCMA CAR-T administration and the available data on current salvage treatments, hoping to provide ideas for optimizing clinical salvage therapies.

Comparison of Surgical and Non-Surgical Treatments for Proximal Humerus Fractures: A Cross-Sectional Study

Background: The proximal humerus fracture (PHF) is one of the most common fractures of the upper limbs. PHF is more common in older people, usually following a fall, whereas in younger people this form of fracture is typically caused by high-energy trauma. There are several treatment options for PHFs, including surgical and non-surgical procedures. Our aim was to compare the outcomes of surgical and non-surgical treatment methods in Iranian patients with PHFs. Methods: Sixty patients with PHFs participated in this single-center cross-sectional study. Medical records were reviewed and evaluated according to demographic characteristics, underlying diseases, type of treatment, complications, need for reintervention, and Constant score. Results: The mean age of the patients was 45.65 years. Among those older than 50 years, women significantly outnumbered men (66.7%, P = 0.009). Thirty-one patients received surgical treatment, while 29 patients received non surgical care. The Constant scores of patients who underwent surgery were considerably higher than those of non-surgical patients [mean ± standard deviation (SD): 80.41 ± 1.89 versus 69.82 ± 1.82, P = 0.009]. This significant relationship was observed only in the age group of 18 to 49 years. Conclusion: Overall, the complications arising from both surgical and nonsurgical treatments were not statistically significant; however, patients under the age of 50 and men had higher Constant scores, indicating better clinical outcomes.

Exploring the use of point-of-care ultrasound by pelvic health physiotherapists in the UK

National and international surveys have highlighted point-of-care ultrasound (PoCUS) as an emergent technology that is being utilized by physiotherapists across a variety of clinical specialities. It confers advantages beyond traditional physiotherapy assessment and increases treatment options for patients with pelvic health conditions. What is not known is how pelvic health physiotherapists are routinely using PoCUS, or the barriers and enablers to its use that exist specifically within this population. The aim of this service evaluation was to explore the current use of PoCUS by pelvic health physiotherapists who are part of the POGP professional network to identify barriers and enablers to wider use within clinical practice across the UK. An online survey with both multiple-choice and free-text responses was shared. Questions covered four domains of interest: (1) demographic and professional characteristics; (2) current use of PoCUS; (3) perceived barriers and enablers; and (4) training. One hundred and two pelvic health physiotherapists with varied levels of experience responded from different sectors and areas of the UK. Only 30.4% reported routine use of PoCUS in their clinical practice despite consensus that PoCUS is an important tool for the rehabilitation of pelvic health conditions. Most barriers to the use of PoCUS identified could be linked to resource limitations, training or lack of support, and were also reflected in suggestions for enablers. Most users had formal training and felt that this had been sufficient to be competent in using PoCUS in their service. Physiotherapists recognize the advantages that PoCUS offers for rehabilitation in pelvic health populations, but are often unable to access the equipment or training required. Ongoing support after training is needed to ensure that users maintain confidence and competence, especially as many work as independent practitioners and are without a direct peer network. Updates to national recommendations or guidelines to include PoCUS as a recommended tool within rehabilitation may provide the impetus needed to support its adoption across more public healthcare settings.

Effects of Balance-Based Recreational Therapy on Postural Stability in Those Diagnosed with Parkinson’s Disease

Individuals diagnosed with Parkinson’s disease (PD) have reported increased incidence rates of falling in compari-son to undiagnosed peers. Falls in this population have been found to be related to increasing symptom intensity as well as decreases in overall quality of life. The follow-ing examines the effectiveness of balance-based Recre-ational Therapy within the community setting as part of a multidiscipline treatment team known as the Stillwater Communication, Arts, Nutrition, & Exercise program. A combination of previous data analysis from this longitudinal study have found that participants improved or main-tained their physical functioning and reported less occurrences of falling. Treatment protocol focused on strength, balance, and gait-utilizing modalities such as exercise, obstacle courses, boxing training, and tai chi. Data collection of postural stability, or static balance, occurred throughout the 8-month treatment period on a monthly ba-sis and the month 1 and month 8 mean differences were analyzed for statistical and clinical significance. Assessments revealed the successful increase and/or maintenance of overall postural stability through the 8-month treatment period. Results were not statistically significant, yet provide clinical evidence to the effectiveness of RT com-munity-based balance training for individuals diagnosed with PD. The following study builds upon previous evidence that recreational therapy can be an effective treatment option for those who have been diagnosed with PD and potentially others who are ex-periencing issues with their balance. Implications for future studies and current prac-tice are provided.

Conversion surgery for esophageal and esophagogastric junction cancer.

As a result of the recent advances in first-line treatment including chemotherapy, radiation therapy, targeted therapy, and immune checkpoint inhibitor immunotherapy (ICI) for locally advanced/metastatic initially unresectable esophageal and esophagogastric junction cancer, surgery aiming at cure after initial treatment, so-called "conversion surgery" has become more common in this field. Several studies have indicated encouraging survival outcomes for patients after conversion surgery with R0 resection. However, various issues, such the utility and the safety of conversion surgery remain unclear. In this review, we will focus on the surgical treatment for initially unresectable esophageal and esophagogastric junction cancer after first- or later- line treatment and review recent evidence regarding the safety and the efficacy of conversion surgery. Multidisciplinary treatment including surgery may serve as a novel treatment strategy for esophageal and esophagogastric junction cancer, thus provide a curative treatment option and potentially contribute to better prognosis for initially untreatable diseases.

First-in-Human Evaluation of Safety, Pharmacokinetics and Muscle Glycogen Lowering of a Novel Glycogen Synthase 1 Inhibitor for the Treatment of Pompe Disease.

Pompe disease is a rare glycogen storage disease caused by mutations in the enzyme acid α-glucosidase (GAA) resulting in pathological accumulation of glycogen in muscle tissues leading to progressive weakness and respiratory dysfunction. Enzyme replacement therapy (ERT) with GAA is currently the sole treatment option for patients with Pompe disease. ERT burdens patients with frequent intravenous infusions while insufficiently halting disease progression due to incomplete ERT skeletal muscle distribution. Glycogen synthase 1 (GYS1) has been proposed as a substrate reduction therapy (SRT) target for Pompe disease. Here, we report results from the first-in-human study of the orally available GYS1 inhibitor MZE001 in healthy subjects. In 88 participants, MZE001 was well-tolerated up to a single dose of 480 mg BID and multiple doses of 720 mg BID for 10 days. Noncompartmental analysis determined that the half-life and Ctrough concentrations of MZE001 could provide efficacious exposures with once or twice daily oral dosing. Change from baseline of peripheral blood mononuclear cell (PBMC) glycogen, which correlated with muscle glycogen levels in preclinical models, was significantly reduced dose-dependently following 10 days of MZE001 treatment in healthy subjects. A muscle biopsy sub-study demonstrated that 10 days of MZE001 (480 mg BID) dosing safely and substantially lowered muscle glycogen stores in healthy adults. This correlated with the PBMC exposure response and supports the use of PBMC glycogen reduction as a surrogate for muscle response, and MZE001 potential for development as the first oral substrate reduction therapy for patients with Pompe disease.

TRANscranial direct current stimulation for FOcal Refractory epilepsy in mitochondrial disease (TRANSFORM): delayed-start, randomised, double-blinded, placebo-controlled study

BackgroundFocal epilepsy is common in children and adults with mitochondrial disease. Seizures are often refractory to pharmacological treatment and, in this patient group, frequently evolve to refractory focal status epilepticus (also known as epilepsia partialis continua). Where this occurs, the long-term prognosis is poor. Transcranial DC stimulation (tDCS) is a promising, non-invasive, adjunctive treatment alternative to common surgical procedures. Limited recruitment of study participants with this rare disease and the ethical challenges of administering a treatment to one group and not another, while maintaining strict methodological rigour can pose challenges to the design of a clinical study.MethodWe designed the first delayed start, double-blinded, sham-controlled study to evaluate the efficacy of tDCS as an adjunctive treatment for focal epilepsy. We will include participants with a genetically confirmed diagnosis of mitochondrial disease with drug-resistant focal epilepsy aged ≥ 2 years, aiming to collect 30 episodes of focal status epilepticus, each treated for a maximum period of 14 days. The early start intervention arm will receive tDCS from day 1. The delayed start intervention arm will receive sham stimulation until crossover on day 3. Our primary endpoint is a greater than 50% reduction from baseline (on day 0) in seizure frequency assessed by 3x daily reporting, accelerometery, and video monitoring. Changes in the underlying epileptogenic focus within the brain related to the tDCS intervention will be assessed by magnetic resonance imaging (MRI) and/or electroencephalography (EEG).DiscussionStudy results in favour of treatment efficacy would support development of tDCS into a mainstream treatment option for focal epileptic seizures related to mitochondrial disease.Trials registrationISRCTN: 18,241,112; registered on 16/11/2021.

Cutting-Edge Technology Without Cutting: Treating Skin Cancer in This Era—A Case Series

Background: Traditional treatment methods for non-melanoma skin cancer (NMSC) include surgical excision with histological evaluation, yet advancements such as reflectance confocal microscopy (RCM) and superficial radiation therapy (SRT) offer non-invasive management alternatives. This study aims to evaluate the use of RCM for the evaluation of treatment outcomes after SRT in managing localized NMSC. Methods: A prospective interventional case series study was conducted on patients treated for NMSC with SRT between March 2020 and December 2023. Suspected NMSC lesions were initially evaluated with a handheld dermoscope and then imaged at multiple depths using a VivaScope 1500 RCM. Two dermatologists trained in RCM reviewed the images. Confirmed NMSC lesions were biopsied and treated with SRT, followed by RCM imaging at six months post-treatment to assess cancer clearance, scarring, and inflammation. Results: Of the 38 lesions (composed of SCC (24) and BCC (14)) treated affecting the 29 patients, all lesions showed no residual tumor activity upon conducting follow-up RCM (100% clearance). Scarring and mild erythema were noted clinically. Six lesions demonstrated moderate to severe inflammation at a 6-month follow-up. Conclusions: This study demonstrates successful non-invasive management of localized NMSC using RCM and SRT. RCM was able to non-invasively demonstrate complete tumor clearance achieved by SRT with minimal adverse effects. These findings support considering the use of RCM and SRT as primary diagnostic, monitoring, and treatment options for NMSC without the need for biopsies, especially for elderly patients or those unsuitable for surgery due to medical conditions.

Safety and efficacy of DEB-TACE in combination with lenvatinib and camrelizumab for the treatment of unresectable hepatocellular carcinoma (uHCC): a two-centre retrospective study

ObjectivesThe purpose of this study was to compare the safety and efficacy of drug-eluting bead (DEB) transarterial chemoembolization combined with lenvatinib and camrelizumab (DEB-TACE-Len-C) and DEB-TACE-Len for the treatment of unresectable hepatocellular carcinoma (uHCC).MethodsThis retrospective study consecutively included uHCC patients who underwent DEB-TACE-Len-C or DEB-TACE-Len treatment at our hospital and Qujing Second People’s Hospital from April 2020 to April 2022. In total, 85 patients were enrolled. There were 42 patients in the DEB-TACE-Len-C group and 43 patients in the DEB-TACE-Len group. The disease control rate (DCR), objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups, and the factors influencing OS and PFS were analysed.ResultsThe ORR, DCR, PFS and OS were significantly greater in the DEB-TACE-Len-C group than in the DEB-TACE-Len group (ORR: 76.2% vs. 46.5%, P = 0.005; DCR: 88.1% vs. 67.8%, P = 0.039; PFS: 10 months vs. 6 months, P <0.0001; OS: 24 months vs. 16 months, P = 0.0038). Multivariate Cox proportional hazard regression analysis revealed that portal tumour thrombus (PVTT) and therapeutic approach were independent factors affecting PFS and OS. There were no statistically significant differences in the incidence of AEs between the two groups (P > 0.05).ConclusionCompared with DEB-TACE-Len, DEB-TACE-Len-C is an effective treatment option that can improve the tumour therapeutic response and prolong the OS and PFS in uHCC patients.

Role of Lipoprotein(a) Reduction in Cardiovascular Disease

Recent studies have shown that lipoprotein(a) (Lp(a)) is an important risk factor for a plethora of different cardiovascular diseases. It has been proven that Lp(a) levels are genetically determined and correlate with risk of cardiovascular disease, independent of lifestyle factors. As of yet, treatment options to reduce Lp(a) levels are limited, but new research into Lp(a) reduction yields promising results. This review delves into Lp(a)’s biochemistry and mechanism of effect, the association between Lp(a) and cardiovascular diseases, and possible therapies to minimise cardiovascular disease.

Multilevel analysis of the central-peripheral-target organ pathway: contributing to recovery after peripheral nerve injury.

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities. Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites, neglecting multilevel pathological analysis of the overall nervous system and target organs. This has led to restrictions on current therapeutic approaches. In this paper, we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective, covering the central nervous system, peripheral nervous system, and target organs. After peripheral nerve injury, the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves; changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord. The nerve will undergo axonal regeneration, activation of Schwann cells, inflammatory response, and vascular system regeneration at the injury site. Corresponding damage to target organs can occur, including skeletal muscle atrophy and sensory receptor disruption. We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury. The main current treatments are conducted passively and include physical factor rehabilitation, pharmacological treatments, cell-based therapies, and physical exercise. However, most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway. Therefore, we should further explore multilevel treatment options that produce effective, long-lasting results, perhaps requiring a combination of passive (traditional) and active (novel) treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

Biofilm Demolition by [AuIII(N^N)Cl(NHC)][PF6]2 Complexes Fastened with Bipyridine and Phenanthroline Ligands; Potent Antibacterial Agents Targeting Membrane Lipid.

The development of new antibacterial drugs is essential for staying ahead of evolving antibiotic resistant bacterial (ARB) threats, ensuring effective treatment options for bacterial infections, and protecting public health. Herein, we successfully designed and synthesized two novel gold(III)- NHC complexes, [Au(1)(bpy)Cl][PF6]2 (2) and [Au(1)(phen)Cl][PF6]2 (3) based on the proligand pyridyl[1,2-a]{2-pyridylimidazol}-3-ylidene hexafluorophosphate (1•HPF6) [bpy= 2,2'-bipyridine; phen= 1,10-phenanthroline]. The synthesized complexes were characterized spectroscopically; their geometries and structural arrangements were confirmed by single crystal XRD analysis. Complexes 2 and 3 showed photoluminescence properties at room temperature and the time-resolved fluorescence decay confirmed the fluorescence lifetimes of 0.54 and 0.62 ns respectively; which were used to demonstrate their direct interaction with bacterial cells. Among the two complexes, complex 3 was found to be more potent against the bacterial strains (Staphylococcus aureus, Gram-positive and Pseudomonas aeruginosa, Gram-negative bacteria) with the MIC values of 8 µg.mL-1 and 16 µg.mL-1 respectively. Studies revealed the binding of the complexes with the fundamental phospholipids present in the cell membrane of bacteria, which was found to be the leading cause of bacterial cell death. Cytotoxicity was evaluated using an MTT assay on 293T cell lines; emphasizing the potential therapeutic uses of the Au(III)-NHC complexes to control bacterial infections.

Hip shelf acetabuloplasty in borderline dysplasia, an alternative between Periacetabular Osteotomy and arthroscopic procedures.

Surgical treatments for symptomatic borderline dysplastic hips (Lateral Center-Edge Angle: LCEA 18-25°) remain challenging, instability being the primary issue. Currently, treatment options include arthroscopic procedures or peri-acetabular osteotomy (PAO). Although the popularity of the acetabular shelf bone block has declined in favor of PAO, it may still be relevant as a hip joint stabilizer and coverage area, rather than for increasing coverage area by cartilage. We analyzed clinical and radiographic outcomes of 23 borderline hips after undergoing shelf procedure with a minimum follow-up of two years. This is a retrospective descriptive study. Clinical evaluations (modified Harris Hip Score: mHHS, Non-Arthritic Hip Score: NAHS, International Hip Outcome Tool: iHOT12) and radiographic assessments were performed before and after surgery. We collected data on revision surgery rates, associated surgical procedures (labrum, impingement), complications, arthrosis progression, and conversion to total hip replacement (THR). The mean LCEA was 21°, and the mean follow-up period was five years (2 to 14 years). Clinical scores showed significant improvement at the last follow-up, mHHS increasing from 47 to 72 (p < 0.001), NAHS from 42 to 68 (p < 0.001), iHOT12 from 28 to 52 (p < 0.001), and pain levels decreasing from 7 to 3. Revision surgery rate was 13%, and complication rate was 8%. No osteoarthritis beyond Tönnis grade 2, and no cases required conversion to THR. Arthroscopic procedures and PAO have shown promising results in the treatment of borderline hips. The hip shelf procedure appears to be a simple and effective treatment for stabilizing borderline hips, with favorable outcomes for 80% of patients and a low rate of arthritic progression. Shelf procedure could be a valuable addition to the therapeutic options for painful borderline dysplasia of the hip.

Ultrasound‐guided embolization for renal artery pseudoaneurysm in solitary kidney

IntroductionRenal artery pseudoaneurysm is a rare yet serious complication following percutaneous nephrolithotomy, especially in patients with solitary kidneys. Effective management is crucial to prevent further renal damage.Case presentationWe report a case of a 41‐year‐old male with a solitary kidney who experienced gross hematuria and renal insufficiency 3 months after percutaneous nephrolithotomy. Due to the patient's renal insufficiency and the risks associated with arterial catheterization, ultrasound‐guided embolization was chosen as the treatment approach. Initial angiographic attempts were impeded by renal vessel spasms, delaying intervention. However, successful direct percutaneous embolization was subsequently performed using ultrasound and digital subtraction angiography.ConclusionThe patient's recovery was uneventful, and follow‐up assessments showed no recurrence of renal artery pseudoaneurysm. This case highlights the effectiveness of ultrasound‐guided embolization as a viable treatment option for post‐percutaneous nephrolithotomy renal artery pseudoaneurysm, particularly in patients with solitary kidneys.

The Effect of Androgen Deprivation Therapy on the Cardiovascular System in Advanced Prostate Cancer

Androgen deprivation therapy (ADT) is a mainstay treatment for metastatic prostate cancer, improving progression-free survival. ADT suppresses the production of testosterone and reduces circulating levels of the hormone. Luteinizing hormone-releasing hormone (LH-RH) agonists are the most commonly used ADT modality. They can be given alone or in combination with androgen synthesis inhibitors or androgen receptor antagonists. An estimated 40% of prostate cancer patients will receive ADT as part of their therapy during their lifetime. However, ADT has numerous adverse effects, including an increased cardiovascular risk that impacts quality of life. Relugolix is an alternative form of ADT. It is the only oral gonadotropin-releasing hormone antagonist, circumventing injection site reactions, making it easier for patients to take, and thus increasing compliance. Testosterone suppression with relugolix is excellent and testosterone recovery after discontinuation is rapid. This paper reviews the ADT and anti-androgen treatment options for men with prostate cancer and the cardiovascular effects of these therapies. There is accumulating evidence that cardiovascular risk with relugolix is lower than with other ADT medications and also lower than with androgen synthesis inhibitors and androgen receptor antagonists. This paper provides insight into the use of different ADT regimens based on the cardiovascular status and circumstances. It explores strategies to mitigate negative cardiovascular consequences and highlights the need for further study.

Inhibition of KDM4A restricts SQLE transcription and induces oxidative stress imbalance to suppress bladder cancer

In clinical practice, the limited efficacy of standard comprehensive therapy for advanced bladder cancer and the lack of targeted treatment options are well recognized. Targeting abnormal epigenetic modifications in tumors has shown considerable potential in cancer therapy. Through drug screening in tumor organoids, we identified that ML324, a histone lysine demethylase 4A (KDM4A) inhibitor, exhibits potent antitumor effects in both in vitro and in vivo cancer models. Mechanistically, Kdm4a demethylates H3K9me3, leading to chromatin opening and increased accessibility of Gabpa to the squalene epoxidase (Sqle) gene promoter, resulting in transcriptional activation. Inhibition of Kdm4a downregulates Sqle transcription, blocking cholesterol synthesis and causing squalene (SQA) accumulation. This process induces reactive oxygen species (ROS) clearance and suppresses JNK/c-Jun phosphorylation, ultimately inducing apoptosis. Furthermore, ML324 treatment significantly inhibited tumor growth in bladder cancer patient-derived xenograft (PDX) models. Our findings reveal the presence of a Kdm4a-Sqle-ROS-JNK/c-Jun signaling axis that regulates oxidative stress balance, offering a novel strategy for targeted therapy in bladder cancer.

Explainable 18F-FDG PET/CT radiomics model for predicting EGFR mutation status in lung adenocarcinoma: a two-center study

PurposeTo establish an explainable 18F-FDG PET/CT-derived prediction model to identify EGFR mutation status and subtypes (EGFR wild, EGFR-E19, and EGFR-E21) in lung adenocarcinoma (LUAD).MethodsBaseline 18F-FDG PET/CT images of 478 patients with LUAD from 2 hospitals were collected. Data from hospital A (n = 390) was randomly split into a training group (n = 312) and an internal test group (n = 78), with data from hospital B (n = 88) utilized for external test. Further, a total of 4,760 handcrafted radiomics features (HRFs) were extracted from PET/CT scans. Candidates for the prediction model were constructed by cross-combinations of 11 feature selection methods and 7 classifiers. The optimal model was determined by combining the results of cross-center data validation and model visualization (Yellowbrick). The predictive performance was assessed via receiver operating characteristic curve, confusion matrix and classification report. Four explainable artificial intelligence technologies were used for optimal model interpretation.ResultsSex and SUVmax were selected as clinical risk factors, which were then combined with 8 robust PET/CT HRFs to establish the models. The optimal performance was obtained by combining a light gradient boosting machine classifier with random forest feature selection method achieving an optimal performance with a macro-average AUC of 0.75 in the internal test group and 0.81 in the external test group.ConclusionThe explainable EGFR mutation status prediction model have certain clinical practicability and good generalization performance, which may help in the timely selection of treatment options and prognosis prediction in patients with LUAD.