Optimal Treatment Strategy Research Articles

Precision Cancer Therapy Enabled Anti-Epidermal Growth Factor Receptor-Conjugated Manganese Core Phthalocyanine Bismuth Nanocomposite for Dual Imaging-Guided Breast Cancer Treatment.

Cancer remains a formidable global health challenge, demanding the exploration of innovative treatment modalities with minimized side effects. One promising avenue involves the synergistic integration of targeted photothermal/photodynamic therapy (PTT/PDT), utilizing specially designed functional nanomaterials for precise cancer diagnosis and treatment. This study introduces a composite biomaterial, anti-epidermal growth factor receptor-conjugated manganese core phthalocyanine bismuth (anti-EGFR-MPB), synthesized for precise cancer imaging and treatment. The biomaterial, synthesized via a solvothermal process, effectively treats and images breast cancer in mouse models. Its biomimetic design targets cancer cells precisely, with dual imaging for real-time monitoring. The biomimetic design of the composite enables precise targeting of cancer cells, whereas the dual imaging allows for real-time visualization and monitoring of the treatment. Invivo examinations confirm substantial damage to tumor tissues with no recurrence following 808-nm laser irradiation. The composite shows strong fluorescence/photoacoustic imaging (PAI) contrast, aiding malignancy detection. Biological assays and histological analyses confirmed the efficacy of the nanocomposite in inducing apoptosis in cancer cells. The integrated targeted dual image-guided phototherapy offered by this composite substantially enhances the precision and efficacy of cancer therapy, achieving an impressive photothermal efficiency of ~33.8%. Our findings demonstrate the utility of the anti-EGFR-MPB nanocomposite for both invitro and invivo photoacoustic image-guided PTT and PDT. The optimal treatment strategy for triple-negative breast cancer is found to be the use of 250 μg/ml of nanocomposite irradiated with 1.0 W/cm2 808-nm laser for 7 min.

Enhancing fixation stability in proximal humerus fractures: screw orientation optimization in PHILOS plates through finite element analysis and biomechanical testing

The optimal treatment strategy for proximal humerus fractures (PHFs) is debatable owing to the relatively high failure rate of locking plates. Optimizing implants may enhance the fixation stability of PHFs and reduce the rate of mechanical failures. We developed a finite element (FE) model to simulate the treatment of PHFs with Proximal Humerus Internal Locking System (PHILOS) plates. The model evaluated the average bone strain around the screw tips under vertical loading (as an alternative to the risk of cyclic screw cutout failure verified through biomechanical testing) to minimize this strain and maximize predicted fixation stability. After determining the optimal screw configuration, further FE analysis and in vitro biomechanical testing were conducted on both standard and optimized PHILOS screw orientation to assess whether the optimized plates have biomechanical advantages over the standard plates. The FE-based optimized configuration exhibited significantly lower bone strain around the implant than the standard PHILOS screw orientation (− 17.24%, p < 0.001). In both FE analysis and in vitro biomechanical testing, the optimized PHILOS plates achieved significantly lower average bone strain around the screws (p < 0.05), more uniform stress distribution, and greater structural stiffness (p < 0.05) than the standard PHILOS screw orientation. Our results show that biomechanical performance of the PHILOS plates can be improved by altering the orientation of the locking screws. This approach may be useful for future patient-specific design optimization of implants for other fractures.

Assessment of Optimal Treatment Strategies and Their Outcomes in T3N1 Rectal Cancers.

Background:This study compares the outcomes of a surgery first vs a neoadjuvant treatment strategy in T3N1M0 rectal cancers. Methods:This was a single-centre retrospective cohort study of patients admitted for curative treatment of T3N1 rectal cancer. Patients with pre-treatment T3N1 and pathological T3N1 disease were included in the study. Patients were divided into two groups depending on whether they had surgery or neoadjuvant therapy as their initial phase of treatment. Primary outcome measures were local recurrence and distant recurrence. Secondary outcomes were disease-free survival (DFS) and overall survival (OS). Tabulated results were analyzed with appropriate statistical tests. Results:One hundred and ten patients were initially selected. Fourty-eight were finally included after excluding patients who did not meet the staging criteria or were not eligible for curative treatment. Twenty-nine patients underwent surgery, and 19 patients with neoadjuvant therapy as their first treatment. No local recurrence was noted in either group, with a distant recurrence noted in group 2 (6.9%) and group 1 (5.26%) cases among the surgery-first and neoadjuvant-first groups, respectively. Disease-free survival and overall survival were 29.5 and 30 months for the surgery-first group and 22 and 22 months for the neo-adjuvant group, respectively. Conclusions:Outcomes in the surgery-first group were non-inferior to that of the neoadjuvant group. A threatened circumferential resection margin (CRM) on pretreatment staging warrants neoadjuvant therapy to ensure an R0 resection. Extramural vascular invasion (EMVI), being a negative prognostic factor, doesn't preclude a surgery-first approach.

Protective effects of long term antiplatelet and anticoagulant therapy in hospitalized patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD), with its rising prevalence rates is associated with an increased risk of cardiovascular and thromboembolic events. Antiplatelets and/or anticoagulants agents are often prescribed but the literature on the impact of long-term anticoagulation and/or antiplatelet use among patients hospitalized with IBD is scarce. The aim of this study is to assess the outcomes of patients hospitalized with IBD on antiplatelet and/or anticoagulant agents. To investigate the effects of long-term use of antiplatelets/anticoagulants on clinical outcomes in patients hospitalized with IBD. We conducted a retrospective cohort study using the Nationwide Inpatient Sample database, including all adult IBD patients hospitalized in the United States from 2016 to 2019. Patient cohorts were stratified based on antiplatelet/anticoagulant therapy status. Multivariate regression analysis was done to assess outcomes, adjusting for potential confounders. The primary outcome was mortality, whereas length of stay (LOS), total parenteral nutrition, acute kidney injury, sepsis, shock, gastrointestinal bleeding, need for colonoscopy/sigmoidoscopy, abdominal surgery and total hospitalization charges were secondary outcomes. Among 374744 hospitalized IBD patients, antiplatelet or anticoagulant therapy alone was associated with significantly lower in-hospital mortality and reduced healthcare utilization, including shorter LOS and decreased hospitalization costs. Combined therapy was associated with a protective effect on mortality, but did not reach statistical significance. Notably, therapy did not exacerbate disease severity or complications, although higher odds of gastrointestinal bleeding were observed. Our study highlights the potential benefits of long-term anticoagulation/antiplatelet therapy in hospitalized IBD patients, with improved mortality outcomes and healthcare utilization. While concerns regarding gastrointestinal bleeding exist, the overall safety profile suggests a role for these agents in mitigating thromboembolic risks without exacerbating disease severity. Further research is needed to look at optimal treatment strategies and addressing limitations to guide clinical decision-making in this population.

Leveraging mathematical modeling framework to guide regimen strategy for phage therapy

Bacteriophage (phage) cocktail therapy has been relied upon more and more to treat antibiotic-resistant infections. Understanding of the complex kinetics between phages, target bacteria, and the emergence of phage resistance remain hurdles to successful clinical outcomes. Building upon previous mathematical concepts, we develop biologically-motivated nonlinear ordinary differential equation models to explore single, cocktail, and sequential phage treatment modalities. While the optimal pairwise phage treatment strategy was the double simultaneous administration of two highly potent and asymmetrically binding phage strains, it appears unable to prevent the evolution of resistance. This treatment regimen did have a greater lysis efficiency, promoted higher phage population sizes, reduced bacterial density the most, and suppressed the evolution of resistance the longest compared to all other treatments strategies tested. Conversely, the combination of phages with polar potencies allows the more efficiently replicating phages to monopolize susceptible host cells, thereby quickly negating the intended compounding effect of cocktails. Together, we demonstrate that a biologically-motivated modeling-based framework can be leveraged to quantify the effects of each phage’s properties to more precisely predict treatment responses.

An Innovative Telomere-associated Prognosis Model in AML: Predicting Immune Infiltration and Treatment Responsiveness.

To build an innovative telomere-associated scoring model to predict prognosis and treatment responsiveness in acute myeloid leukemia (AML). AML is a highly heterogeneous malignant hematologic disorder with a poor prognosis. While telomere maintenance is frequently observed in tumors, investigations into telomere-related genes (TRGs) in AML remain limited. This study aimed to identify prognostic TRGs using the least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression, evaluate their predictive value, explore the association between TRG scores and immune cell infiltration, and assess the sensitivity of high-scoring AML patients to chemotherapeutic agents. Univariate Cox regression analysis was conducted on the TCGA cohort to identify prognostic TRGs and to develop the TRG scoring model using LASSO-Cox and multivariate Cox regression. Validation was performed on the GSE37642 cohort. Immune cell infiltration patterns were assessed through computational analysis, and the sensitivity to chemotherapeutic agents was evaluated. Thirteen prognostic TRGs were identified, and a seven-TRG scoring model (including NOP10, OBFC1, PINX1, RPA2, SMG5, MAPKAPK5, and SMN1) was developed. Higher TRG scores were associated with a poorer prognosis, as confirmed in the GSE37642 cohort, and remained an independent prognostic factor even after adjusting for other clinical characteristics. The high-score group was characterized by elevated infiltration of B cells, T helper cells, natural killer cells, tumor-infiltrating lymphocytes, regulatory T (Treg) cells, M2 macrophages, neutrophils, and monocytes, along with reduced infiltration of gamma delta T cells, CD4- T cells, and resting mast cells. Moreover, high infiltration of M2 macrophages and Tregs was associated with poor overall survival compared to low infiltration. Notably, high-risk AML patients were resistant to Erlotinib, Parthenolide, and Nutlin-3a, but sensitive to AC220, Midostaurin, and Tipifarnib. Additionally, using RT-qPCR, we observed significantly higher expression of two model genes, OBFC1 and SMN1, in AML tissues compared to control tissues. This innovative TRG scoring model demonstrates considerable predictive value for AML patient prognosis, offering valuable insights for optimizing treatment strategies and personalized medicine approaches. The identified TRGs and associated scoring models could aid in risk stratification and guide tailored therapeutic interventions in AML patients.

Development and Validation of a Novel Classification System and Prognostic Model for Open Traumatic Brain Injury: A Multicenter Retrospective Study.

Open traumatic brain injury (OTBI) is associated with high mortality and morbidity; however, the classification of these injuries and the determination of patient prognosis remain uncertain, hindering the selection of optimal treatment strategies. This study aimed to develop and validate a novel OTBI classification system and a prognostic model for poor prognosis. This retrospective study included patients with isolated OTBI who received treatment at three large medical centersin China between January 2020 and June 2022 as the training set. Data on patients with OTBI collected at the Fuzong Clinical Medical College of Fujian Medical University between July 2022 and June 2023 were used as the validation set. Clinical parameters, including clinical data at admission, radiological and laboratory findings, details of surgical methods, and prognosis were collected. Prognosis was assessed through a dichotomized Glasgow Outcome Scale (GOS). A novel OTBI classification was proposed, categorizing patients based on a combination of intracranial hematoma and midline shift observed on imaging, and logistic regression analyses were performed to identify risk factors associated with poor prognosis and to investigate the association between the novel OTBI classification and prognosis. Finally, a nomogram suitable for clinical application was established and validated. Multivariable logistic regression analysis identified OTBI classification type C (p<0.001), a Glasgow Coma Scale score (GCS)≤8 (p<0.001), subarachnoid hemorrhage (SAH) (p=0.004), subdural hematoma (SDH) (p=0.011), and coagulopathy (p=0.020) as independent risk factors for poor prognosis. The addition of the OTBI classification to a model containing all the other identified prognostic factors improved the predictive ability of the model (Z=1.983; p=0.047). In the validation set, the model achieved an area under the curve (AUC) of 0.917 [95% confidence interval (CI)=0.864-0.970]. The calibration curve closely approximated the ideal curve, indicating strong predictive performance of the model. The implementation of our proposed OTBI classification system and its use alongside the other prognostic factors identified here may improve the prediction of patient prognosis and aid in the selection of the most suitable treatment strategies.

Efficacy of subsequent treatment for unresectable locally-advanced non-small cell lung cancer after relapse of concurrent chemoradiotherapy with durvalumab consolidation therapy: a single-center retrospective study

ObjectivesThe current standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemoradiation therapy (CCRT) followed by durvalumab consolidation therapy. Although the trial revealed the survival benefit of adding an immune checkpoint inhibitor (ICI) to the population, the optimal treatment strategy and efficacy of subsequent treatment after relapse remain unclear. Materials and MethodsWe retrospectively collected data from patients with unresectable LA-NSCLC who completed platinum-based CCRT as first-line treatment. Patients who received molecular-targeted therapy for driver gene alterations or did not receive durvalumab as consolidation therapy following the approval were excluded. We assessed differences in regimen and efficacy of subsequent treatment in patients who underwent durvalumab consolidation therapy (D group) and those who did not (CR group). ResultsAmong the 62 eligible patients, 32 were assigned to the D group and 30 to the CR group. Patients in the CR group were more frequently treated with an immune checkpoint inhibitor (ICI)-containing regimen than those in the D group (57% vs. 13%, p < 0.001). The median overall survival from initiation of subsequent treatment was shorter in the D group than in the CR group (13.0 months vs. 26.7 months, hazard ratio 2.60; 95% confidence interval: 1.28–2.56, p=0.008). ConclusionsPatients with unresectable LA-NSCLC who relapsed after durvalumab consolidation therapy received an ICI-containing regimen less frequently, and the efficacy of the subsequent treatment was limited.

A Bullous Variant of Central Serous Chorioretinopathy Treated With Sclerotomy.

Bullous serous central chorioretinopathy (bCSCR) is an atypical form of CSCR characterized by large serous detachment. This variant presents significant diagnostic challenges, and optimal treatment strategies are not well defined. This report presents a case of a 31-year-old man with bCSRC treated with scleral thinning surgery in four quadrants with scleral windows created in the two inferior quadrants. The etiology, pathogenesis, and optimal treatment of bCSCR are not fully understood. Various therapeutic options, including photocoagulation and photodynamic therapy, have been employed with varying degrees of success. We describe a case of scleral thinning (sclerectomy) with two inferior sclerotomies without subretinal drainage, which resulted in a positive outcome.[Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Population Pharmacokinetic/Pharmacodynamic Study of Linezolid in Hospital-Acquired Pneumonia Patients with Renal Insufficiency.

The optimal treatment strategy in patients with hospital-acquired pneumonia (HAP) due to Gram-positive bacteria and renal insufficiency remains challenging. The objective of this study was to compare the outcomes of linezolid versus teicoplanin in HAP patients with renal insufficiency and to explore optimal dosage strategy for linezolid. The retrospective study enrolled adult patients treated with intravenous linezolid or teicoplanin at Suzhou Municipal Hospital between July 2018 and August 2023. For the comparative pharmacodynamic study, effectiveness, safety and target attainment of trough concentration (Cmin) for teicoplanin versus linezolid treatment in HAP patients with document Gram-positive bacteria and renal insufficiency were compared. For the population pharmacokinetics (PPK) analyses, linezolid concentrations collected exclusively from HAP patients with renal insufficiency were used and the optimal dosage strategy was investigated using Monte Carlo simulations. Linezolid-treated patients had a higher bacterial eradication rate than teicoplanin-treated patients (88.5% vs 63.4%, P < 0.001). A higher proportion of patients in the linezolid group experienced at least one adverse reaction (42.0% vs 25.0%, P = 0.025). Significantly more supratherapeutic Cmin, less therapeutic Cmin were achieved in the linezolid group (adjusted P < 0.05). A total of 207 linezolid concentrations from 166 patients with renal insufficiency were available for the PPK analysis. Age and creatinine clearance (CrCL) were identified as significant covariates that influenced clearance. Simulations show that 300 mg q12h provide the optimal exposure in patients with a CrCL of 60 or 45 mL/min, and 200 mg q12h was recommended for patients with a CrCL of 30 or 15 mL/min. Linezolid-treated patients with HAP and renal insufficiency had higher bacterial eradication rates, supratherapeutic exposure and adverse reactions than teicoplanin-treated patients. Linezolid dose reduction in patients with renal insufficiency improved the probability of achieving optimal exposure.

Comparison of clinical characteristics, microvascular complications and inflammatory markers in type 2 diabetic patients under insulin versus metformin treatment: A cross-sectional study at Karbala Diabetic Center, Iraq.

Type 2 diabetes mellitus (T2DM) is a major global health issue associated with chronic inflammation, which contributes to both disease progression and its complications, including cardiovascular and microvascular disorders. Key inflammatory markers such as tumor necrosis factor-alpha, interleukin-6 (IL-6), E-selectin, and P-selectin are elevated in T2DM patients and are implicated in the development of these complications. Understanding how treatments such as insulin and metformin affect these markers is crucial for improving therapeutic strategies in T2DM. This study investigated the effects of insulin and metformin on these inflammatory markers in T2DM patients. This was a cross-sectional study involving patients with diabetes on insulin (group A), metformin only (group B), and healthy controls (group C). Participants were enrolled from the Diabetic Center in Karbala, Iraq and underwent clinical assessments including ophthalmologic examinations. Fasting blood glucose, HbA1c and lipids levels were assessed. The levels of inflammatory markers (IL-6 and TNF-α), and adhesion molecules (sE-selectin and sP-selectin) were measured using Enzyme-Linked Immunosorbent Assay (ELISA). The study included 522 patients with diabetes: 356 receiving insulin (group A), 70 receiving metformin (group B) and 96 healthy controls (group C). T2DM patients treated with insulin exhibited significantly more microvascular complications than those treated with metformin. Higher rates of retinopathy (64.3% vs 11.4%) and neuropathy (69.9% vs 11.4%) were observed in the insulin group, whereas the incidence of nephropathy did not differ significantly (14.6% vs 11.4%). Inflammatory markers were lower in the insulin group: TNF-α levels were 3-fold lower and IL-6 levels were 8-fold lower. Conversely, sE-selectin levels were 1.5-fold higher in the insulin group, and sP-selectin levels were 1.4-fold higher in the metformin group. This study highlights distinct differences in inflammatory markers and systemic complications between T2DM patients treated with insulin and those treated with metformin alone. Further research is needed to explore the mechanisms underlying these observations and optimize treatment strategies for T2DM patients.

Maintenance immunosuppressive therapy in liver transplantation: results from CESIT study, an Italian retrospective cohort study

ObjectivesTo investigate the use of maintenance immunosuppressive treatments following liver transplantation and to compare their risk–benefit profiles in clinical practice.DesignRetrospective multicentrer cohort study.SettingFour Italian regions (Lombardy, Veneto, Lazio, Sardinia).MethodsData were...

Patient-specific responses to SMN2 splice-modifying treatments in spinal muscular atrophy fibroblasts

The availability of three therapies for the neuromuscular disease spinal muscular atrophy (SMA) highlights the need to match patients to the optimal treatment. Two of these treatments (nusinersen and risdiplam) target splicing of SMN2, but treatment outcomes vary from patient to patient. An incomplete understanding of the complex interactions between SMA genetics, SMN protein and mRNA levels, and gene-targeting treatments, limits our ability to explain this variability and identify optimal treatment strategies for individual patients. To address this, we analyzed responses to nusinersen and risdiplam in 45 primary fibroblast cell lines. Pre-treatment SMN2-FL, SMN2Δ7 mRNA, and SMN protein levels were influenced by SMN2 copy number, age, and sex. After treatment, SMN and mRNA levels were more heterogeneous. In 43% of patients, response to both therapies was similar, but in 57% one treatment led to a significantly higher SMN increase than the other treatment. Younger age, higher SMN2 copy number, and higher SMN levels before treatment predicted better in vitro efficacy. These findings showcase patient-derived fibroblasts as a tool for identifying molecular predictors for personalized treatment.

RCHOP plus BTK Inhibitor Improves Clinical Outcomes in Double Expressor Diffuse Large B-Cell Lymphoma, Unlike RCHOP plus Lenalidomide

BackgroundDouble-expressor diffuse large B-cell lymphoma (DE-DLBCL) has a poor prognosis, and optimal treatment strategies remain unclear. This study evaluates the efficacy and safety of RCHOP, R2-CHOP (RCHOP plus lenalidomide), and RCHOP plus Bruton's Tyrosine Kinase inhibitors (BTKi) in DE-DLBCL treatment. MethodsData from 213 DE-DLBCL patients treated from January 2019 and February 2024. Among them, 112 received R-CHOP, 65 received R2-CHOP, and 36 received R-CHOP plus BTKi. We evaluated clinical characteristics, overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) for each groups. ResultsBaseline characteristics were comparable across groups. ORRs were 95.5% for R-CHOP, 96.9% for R2-CHOP, and 97.2% for R-CHOP plus BTKi, with CR rates of 76.5%, 80%, and 75%, respectively. BTKi significantly improved PFS (p=0.033) but not affect OS (p=0.165). Lenalidomide showed no benefit in PFS (p=0.153) or OS (p=0.351). With median follow-up times of 20.6 months for R-CHOP, 23.5 months for R2-CHOP, and 17.6 months for R-CHOP plus BTKi, the 1-year PFS rates were 73.6%, 82.2%, and 93.3%, and the 1-year OS rates were 96.2%, 93.2%, and 100%, respectively. Grade 3-4 adverse events included leukopenia, neutropenia, and anemia, and thrombocytopenia, with no significant differences among groups. ConclusionThe addition of BTK inhibitor enhances progression-free survival in DE-DLBCL, especially in advanced-stage patients, without introducing new severe adverse reactions. In contract, adding lenalidomide dose not does not offer additional efficacy or survival benefits.

Research Progress of PD 1/PD L1 Inhibitors in the Treatment of Urological Tumors.

Immune checkpoint inhibitors (ICIs) offer significant advantages for the treatment of urologic tumors, enhancing the immune function of anti-tumor T cells by inhibiting PD-1 and PDL1 binding. They have been shown to be well tolerated and remarkably effective in clinical practice, offering hope to many patients who are not well treated with conventional drugs. Clinical trials in recent years have shown that anti-PD-1 and PD-L1 antibodies have good efficacy and safety in the treatment of urologic tumors. These antibodies can be applied to a variety of urologic tumors, such as bladder cancer, renal cell carcinoma, and prostate cancer. They have been approved for the first-line treatment or as an option for follow-up therapy. By blocking the PD-1/PD-L1 signaling pathway, ICIs can release immune functions that are suppressed by tumor cells and enhance T-cell killing, thereby inhibiting tumor growth and metastasis. This therapeutic approach has achieved encouraging efficacy and improved survival for many patients. Although ICIs have shown remarkable results in the treatment of urologic tumors, some problems remain, such as drug resistance and adverse effects in some patients. Therefore, further studies remain important to optimize treatment strategies and improve clinical response in patients. In conclusion, PD-1/PD-L1 signaling pathway blockers have important research advances for the treatment of urologic tumors. Their emergence brings new hope for patients who have poor outcomes with traditional drug therapy and provides new options for immunotherapy of urologic tumors. The purpose of this article is to review the research progress of PD-1 and PD-L1 signaling pathway blockers in urologic tumors in recent years.

Burden of atherogenic lipids and association with cardiac allograft vasculopathy in heart transplant recipients.

Cardiac Allograft Vasculopathy (CAV) is a leading cause of morbidity and mortality after heart transplantation. There are limited contemporary studies examining post-transplant lipid management and cardiometabolic health. We study the burden of cardiometabolic derangements post transplantation and its impact on CAV in a modern cohort of heart transplant recipients. All heart transplant (HTx) recipients between January 2019 and December 2020, with two lipid assessments and angiographic surveillance were included. Logistic regression was used to assess association of lipid levels with cardiovascular outcomes and CAV. Among 87 HTx recipients, atherogenic lipids were significantly elevated after Htx. Median LDL-C increased from a baseline level of 69.5 mg/dL to 86.5 mg/dL, p = 0.002, non-HDL-C 91.5 mg/dL to 118 mg/dL, p < 0.001, triglycerides 94.5 mg/dL to 133 mg/dL, p < 0.001, and remnant cholesterol 19 mg/dL to 27 mg/dL, p < 0.001. Increases in non-HDL-C, triglycerides, and remnant cholesterol were significantly associated with increased risk of CAV (Stanford Grade 4 and intimal thickness). Increases in triglycerides and remnant-C were associated with increased risk of composite major adverse cardiovascular events. We demonstrate a significant increase in atherogenic lipids two years following transplantation with low use (20 %) of high-intensity statin. Increase in atherogenic lipids was associated with increased risk of CAV and increase in triglycerides and remnant cholesterol with increased MACE. Future studies examining cardiometabolic consequences of heart transplantation and optimal treatment strategies to reduce risk of CAV and MACE are needed.

Comparative Cardiovascular Risks of Radical Prostatectomy and External Beam Radiation Therapy in Early-Stage Prostate Cancer: A Comprehensive Retrospective Analysis.

The risk of cardiac disease mortality has recently become a focal point of concern within the medical community for patients with prostate cancer (PCa). Given that radical prostatectomy (RP) and external beam radiation therapy (EBRT) are the main treatment modalities for localized PCa, their specific impact on cardiovascular-specific mortality (CSM) remains unclear. This study explored the specific effects of RP and EBRT on CSM risk to guide clinical treatment decisions. Data from patients aged 45-74years, who were diagnosed with T1-2N0M0 stage PCa from the SEER database (2010-2015), were used. Multivariate statistical methods, including propensity score matching (PSM), competing risk regression, COX regression analysis, and Fine-Gray testing, were applied to assess the impact of RP and EBRT on CSM risk. Among 146,082 T1-2 stage PCa patients, cardiac disease emerged as the primary cause of death, surpassing PCa itself. Multifactorial COX regression and competing risk regression analyses indicated that local treatments do not increase CSM risk. Further analysis revealed a significant increase in CSM risk for patients undergoing only EBRT compared with those undergoing only RP (hazard ratio [HR] = 2.71, 95% confidence interval [CI] 1.96-3.74, P < 0.001), with subsequent PSM adjustment, further confirming a significantly reduced risk in the RP treatment group (HR 0.23, 95% CI 0.13-0.40, P < 0.001). T1-2 stage PCa patients face a significant risk of CSM, with RP offering a potential advantage over EBRT in reducing this risk. These findings encourage clinicians to comprehensively consider the potential impact on cardiac health when formulating treatment plans, providing crucial guidance for optimizing treatment strategies.

The Optimal Radiotherapy Strategy for Patients With Small Cell Lung Cancer and Brain Metastasis: A Retrospective Analysis.

Extensive-stage small cell lung cancer (ES-SCLC) is a notoriously aggressive malignancy frequently associated with brain metastases (BMs), presenting substantial therapeutic challenges. This study delves into the effectiveness of immunotherapy combined with diverse radiotherapy, especially the influence of brain radiotherapy (BRT) on survival outcomes in the immunotherapy era. ES-SCLC patients treated at Xiangya Hospital and Xiangya Boai Hospital from February 2020 to June 2024 were retrospectively included. The study focused on patients receiving immune checkpoint inhibitors (ICIs). Metrics included overall survival (OS) and progression-free survival (PFS), employing univariate and multivariate Cox regression models for statistical analysis. A total of 393 patients with ES-SCLC who received ICIs were included in the study. Within the entire cohort, the presence of baseline BMs did not statistically affect OS or PFS. However, thoracic radiotherapy (TRT) was identified as a favorable prognostic factor for both OS and PFS. BRT demonstrated a beneficial effect on OS across both the general cohort and the baseline_BMs subgroup. In patients from the baseline_BMs subgroup who had previously undergone TRT, ICIs plus BRT did not significantly improve OS compared to ICIs alone. Conversely, for patients who had not received prior TRT, adding BRT to ICIs significantly enhanced OS. Among the patients who underwent BRT, 71 received whole brain radiotherapy (WBRT) while 19 opted for stereotactic radiosurgery (SRS). No significant differences in OS and PFS were observed between the SRS and WBRT modalities. The sequence of ICIs relative to BRT was found to influence PFS adversely. Administering BRT before ICIs (RT-ICI) was associated with worse PFS compared to administering ICIs followed by BRT (ICI-RT). Additionally, no significant differences in OS and PFS were noted among the three subgroups defined by varying intervals between ICIs and BRT. For patients without baseline BMs, TRT and prophylactic cranial irradiation were associated with delayed onset of brain metastases. Our study underscores the importance of optimizing treatment strategies and considering the timing and integration of radiotherapy and immunotherapy to improve outcomes for patients with ES-SCLC, particularly those at risk of or presenting with BMs.

Novel scoring system for predicting stone-free rate after flexible ureteroscopy lithotripsy.

This study aims to investigate the factors affecting the stone-free rate (SFR) of flexible ureteroscopy and laser lithotripsy (fURSL) for renal stones and establish predictive models by identifying their prognostic factors. We retrospectively examined 252 patients with renal stones who were treated with fURSL between July 2020 and April 2022. We analyzed the relationship between the patient's clinical data (sex, age, and body mass index), stone status (side, size, location, stone/transverse process pixel ratio [STPR], and the CT value of stone [SCTV]), and SFR to determine the relevant factors and analyze their influence. Additionally, a nomogram was constructed based on these prediction results. A total of 252 patients were enrolled based on the inclusion and exclusion criteria. They were reviewed 7, 30, and 90 days postoperatively, with 46, 23, and 10 patients failing to discharge stones, respectively. Univariate Cox proportional hazard regression results revealed that the SFR was correlated with stone location, diameter (D1, diameter of stone measured by computed tomography [CT]; D2, diameter of stone measured by kidney-ureter-bladder abdominal radiography), SCTV, STPR, and operation time. Multivariate Cox proportional hazard regression was used to develop 2 predictive models for the SFR. The influencing factors of model 1 included D1, location, and SCTV, whereas those of model 2 were D2, location, and STPR. The results are shown in the nomogram. Receiver operating characteristic curves showed no significant difference between models 1 and 2 (P = .498), indicating that the nomogram was highly predictive. After 1000 resamples and internal self-validation, the C-indices of models 1 and 2 were 0.924 and 0.895, respectively, showing that the stone clearance predicted by the nomogram matched the actual situation. Stone location, size, and density (SCTV and STPR) were significant predictors of SFR after fURSL. The scoring system based on these factors may be used to guide optimal treatment strategy selection.

The occurrence of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) after arthroplasty mimicking a periprosthetic joint infection: A case report and literature review.

As the elderly population grows, the number of joint arthroplasty surgeries is also increasing. Periprosthetic joint infection (PJI) is a postoperative complication that occurs in 1%-2% of the arthroplasties. Once it occurs, PJI is refractory to treatment. Similar symptoms of PJI, including joint synovitis and elevated body temperature, sometimes arise because of crystal arthritis, rheumatoid arthritis, or other inflammatory diseases. Precise diagnosis is essential for determining the optimal treatment strategy. An 81-year-old female patient with a history of bilateral knee arthroplasty presented with a high fever of 38 °C and was unable to walk due to swelling and pain in the bilateral lower extremities. Infectious conditions, such as cellulitis or PJI, were suspected. Imaging findings revealed bilateral knee joint synovitis with pitting edema around the lower extremities, and cultures of bilateral joint fluids were negative. No crystals were observed in the joint fluid. Laboratory data revealed highly elevated levels of inflammatory marker; however, antinuclear antibodies, including rheumatoid factor and cyclic citrullinated peptide, were not detected. Based on bilateral synovitis with pitting edema in the lower extremities, in addition to negative culture findings and normal antinuclear antibodies, the diagnosis of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) was made. Steroid therapy was performed. The dose was gradually reduced, with the improvement of the symptoms. The inflammatory reaction promptly decreased and then normalized. With improved inflammation, the symptoms of pitting edema, pain in the bilateral lower extremities, and fluid effusion of the knee joints were reduced. She was able to walk without a cane, and her activities of daily living fully recovered. High fever and synovitis after joint arthroplasty do not necessarily indicate an infectious condition. Clinicians should be familiar with the occurrence of RS3PE, regardless of whether arthroplasty is performed.