Treatment Outcomes In Patients Research Articles

Dual pathway inhibition in patients with atherosclerosis with and without heart failure: insights from the XATOA Registry

Abstract Introduction Patients with atherosclerotic cardiovascular disease (ASCVD) are at a high-risk of experiencing a major adverse cardiovascular event, with 1 in 10 individuals experiencing an event within four years (1). To address this risk of secondary cardiovascular events, there have been renewed efforts to enhance secondary prevention therapies through the application of guideline-directed medical therapy. One secondary prevention strategy is the use of dual pathway inhibition (DPI) therapy with aspirin and vascular-dose rivaroxaban (2.5mg twice daily), which simultaneously targets both the platelet activation and thrombin generation pathways. Patients with concomitant ASCVD and heart failure (HF) are a subgroup with a higher risk for ischemic events, but have not been adequately represented in recent clinical trials. Purpose To explore the risks and benefits of DPI therapy in a generalizable population of patients with concomitant ASCVD and HF. Methods The Xarelto plus Acetylsalicylic acid Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA) registry is a prospective, multicentre registry of patients with either coronary artery or peripheral artery disease that were initiated on DPI (2). The primary endpoint was a composite of cardiovascular death, myocardial infarction or stroke and the safety outcome was major bleeding. Multivariable logistic regression was performed to assess the association of HF status and ejection fraction (EF) on the outcomes of interest. Results Of 5532 participants, 4022 (72.7%) had documentation of HF status. Of those 873 (21.5%) had a history of heart failure (EF >40% - 461; EF ≤40% - 181, EF unknown – 231). Over a median follow-up of 465 days (IQR – 372-576), the primary outcome occurred in 4.9% of participants with HF compared to 2.4% in those without HF (aHR 1.57 95% CI 1.02-2.41). The safety outcome was similar in patients with and without HF (0.9% versus 1.11%; aHR 0.7 95% CI 0.31-1.67). Among patients with HF, those with an EF of ≤40% demonstrated a non-significant trend towards higher rates of adverse events including MACE (8.8% versus 3.5%; aHR 1.38; 95% CI 0.59-3.22) compared to those with an EF of > 40%. Conclusion In a generalizable cohort of patients with atherosclerotic disease and HF, the use of DPI is associated with similar outcomes to those observed in recent randomised controlled clinical trials.Table 1 - Demographics by HF statusFigure 1 - MACE by HF status

Demographic characteristics, clinical manifestations, and treatment outcomes of May-Thurner Syndrome: a five-year retrospective analysis using computed tomography venography in a Chinese population

Objective This study aimed to analyze the demographic characteristics, symptoms, and treatment outcomes of patients diagnosed with May-Thurner syndrome (MTS) using computed tomography venography (CTV). Methods Medical records of patients diagnosed with MTS through CTV at Hebei General Hospital of China between April 1, 2017, and May 31, 2022, were reviewed. The data collected included: (1) gender, age, body mass index (BMI), and smoking and drinking habits; (2) time of onset and symptoms of MTS, as well as other accompanying symptoms; (3) additional diagnoses, length of hospital stay (days), treatment methods, treatment success, and the occurrence of post-treatment bleeding or recurrence. Descriptive statistics were used, with mean ± standard deviation and median values reported. The t-test/u-test and Chi-square test (including the exact probability method) were used to compare means and rates, respectively, with a significance level set at α = 0.05. Results Out of 402 patients (233 males, 169 females), 118 (29.4%) were diagnosed with MTS, with 47 (21.1%) males and 71 (39.7%) females. The incidence of MTS was significantly higher in females than males (χ2 proportion = 16.545, χ2 composition = 9.763, p < 0.05). The average ages of male and female MTS patients were 56.4 and 59.9 years, respectively, with mean BMIs of 27.05 and 27.09 kg/m2. Among male patients, 27.7% (13) were smokers, and 17.0% (8) consumed alcohol. Inferior vena cava (IVC) thrombosis was notable in 59.3% of MTS patients, with a significantly higher proportion in females (70.4%) than in males (42.6%) (χ2 = 9.102, p < 0.05). Lower limb swelling without pain was reported by 70.3% of patients, with 53.4% (44.7% male, 59.2% female) experiencing swelling on the left side only, which was significantly more common than swelling on the right side only or both sides (χ2 = 44.554, p < 0.05). Additionally, 12.7% of patients reported both swelling and pain, with left-side symptoms being more prevalent than right-side or both sides. The average ages at symptom onset were 51.3 ± 17.1 years in males and 57.1 ± 13.2 years in females. All treatments for MTS were successful without bleeding or recurrence. The most common treatment method was balloon dilation combined with stent placement (57.6%). Conclusion CTV is highly effective in detecting and facilitating the successful treatment of MTS. It should be fully utilized to promote early diagnosis and treatment of MTS. Female MTS patients need more medical resources for diagnosis and treatment.

The role and designation of emergency choledochoscopy in the laparoscopic treatment of patients with complicated choledocholithiasis

Background. The management of patients with cholelithiasis (gallstone disease) and choledocholithiasis who require removal of the gallbladder remains debatable and require urgent actions of the surgeon, especially in cases with concomitant mechanical jaundice. Laparoscopic choledochoscopy is an effective method of examining the bile ducts that allows for the complete removal of calculi, but in the meanwhile, there is not enough information about its effectiveness and sensitivity as part of surgical technology. Purpose: to improve the outcomes of treatment in patients with choledocholithiasis using laparoscopic choledocholithoextraction and choledochoscopy, as well as to assess the diagnostic value of laparoscopic choledochoscopy in bile duct examination and its significance as a component of surgical technology in laparoscopic choledocholithoextraction in patients with gallstone disease. Materials and methods. Between 2018 and 2024, we conducted an analysis of treatment outcomes in 139 patients with gallstone disease and choledocholithiasis, 51 males (36.7 %) and 88 females (63.3 %). The mean age of patients aged 17 to 86 years was 59.5 ± 1.7 years: males — 56.9 ± 1.7 years, females — 62.1 ± 1.7 years. All participants underwent laparoscopic choledocholithoextraction with choledochoscopy. In 29 (20.8 %) patients, choledocholithoextraction and choledochoscopy were performed through the cystic duct, the remaining 110 (79.1 %) people underwent choledocholithotomy with lithoextraction via choledochoscopy. Surgical intervention (laparoscopic choledocholithoextraction and choledochoscopy) was performed using a choledochofiberscope Olympus CHF-V with a diameter of 5 mm and a Karl Storz with a diameter of 3 mm; lithoextraction was done via choledochotomy access with the use of Dormia-type baskets (FG-55D, FG-55D Olympus). Results. All patients underwent bile duct examination via choledochoscopy with mechanical choledocholithoextraction. The first group included 110 (79.1 %) participants who had laparoscopic choledocholithotomy, lithoextraction and choledochoscopy. The second group comprised 29 (20.8 %) patients who underwent choledocholithoextraction and choledochoscopy through the cystic duct. In the first group, on average 3.4 ± 0.4 stones (from 1 to 24) were removed, in the second group — 2.6 ± 0.5 (from 0 to 6). During laparoscopic choledochoscopy with lithoextraction in the first group, bile duct clearance rate amounted to 108 (98.1 %), in the second group — 27 (93.0 %). Bile leakage through the drainage was recorded in 4 (4.5 %) patients from the first group. Endoscopic papillosphincterotomy with lithoextraction was performed in 2 (1.8 %) patients from the first group and 2 (6.8 %) from the second group, due to wedged stones that could not be removed. There were no fatal cases observed. Conclusions. Urgent laparoscopic choledocholithoextraction with choledochoscopy should be applied as one of the technologies for the treatment of gallstone disease and choledocholithiasis, which makes it possible to perform choledocholithoextraction, choledochoscopy with cholecystectomy in one step, while preserving the autonomy of the hepatopancreatobiliary zone and avoiding complications typical for transpapillary interventions.

Sodium bicarbonate use in the treatment of idiopathic intracranial hypertension.

This retrospective case-control study from 2008 to 2022 aimed to determine the effect of adjunctive sodium bicarbonate (NaHCO3) on treatment outcomes of and side effects of acetazolamide (ACZ) for the treatment of idiopathic intracranial hypertension (IIH). Retrospective data was collected via chart review. 288 eyes of 144 patients with IIH, including those taking ACZ alone (control group, n = 89) vs. ACZ and NaHCO3 (treatment group, n = 56). The primary outcome measure was time to IIH resolution. Secondary outcomes included retinal nerve fibre layer thickness (RNFL), visual field mean deviation (VFMD), visual acuity (VA), discontinuation ACZ, and patient-reported side effects of ACZ. Cox proportional hazards model for the primary outcome yielded a hazard ratio of 0.800, which was statistically insignificant (95% CI, 0.57-1.13; p = 0.200). There was no significant difference between groups when comparing RNFL, VFMD, VA, surgical intervention, or discontinuation of ACZ. The treatment group was more likely to experience side effects from ACZ prior to starting sodium bicarbonate therapy (p < 0.001). Among the treatment group, 92.7% remained on NaHCO3 until IIH resolution, and 9 of 12 (75%) subjects reported significant improvement in ACZ-related side effects. Sodium bicarbonate does not appear to impact treatment outcomes in patients taking acetazolamide for IIH. Sodium bicarbonate may represent a reasonable adjunctive medication to help mitigate acetazolamide-related side effects in this group of patients.

Outcome of Endometriosis Treatment In Infertile Patients In A Tertiary Level Hospital

Introduction: Prevalence of endometriosis is 6-10% in reproductive-age females. Around 25-35% of infertile women may be affected by endometriosis. Modalities of treatment for infertile patients depends on the stage of the disease. It starts from ovulation inducing drug to advanced ART. The objective of this study was to assess the outcome of surgical treatment in infertile, endometriosis patients. Materials and Methods: It was an observational study, which was conducted at Reproductive Endocrinology and infertility Unit, Dhaka Medical College. Total 144 patients were included during July 2018 to July 2021, aged 20-40 yrs. All the demographic variables, clinical and sonographic findings, and hormonal assessment were done. Then, staging was done by clinical pelvic assessment, and ultrasonographic findings. Patients who had ovarian endometrioma, more than 4 cm, were selected for laparoscopic surgery. In patients whose endometrioma was less than 4 cm, or had no ovarian endometrioma, were selected for ovulation induction with or without prior GnRH agonist therapy. Further infertility management were planned according to ovarian reserve, tubal patency, and male factor. Result: Mean age of the patients were 28.30±4.95 yrs. 75.0% patients had primary infertility. Dysmenorrhea was the most common symptom (86.96%), followed by chronic pelvic pain (81.16%). Bilaterality of endometrioma was associated with decreased serum AMH. Laparoscopic surgery was the mainstay of treatment, Cystectomy was done in 58% patients. Conservative treatment was done in remaining patients. Fertility enhancing treatment was done by ovulation inducing drug -letrozole, GnRH agonist, followed by controlled ovarian stimulation and followed by IUI. IVF was advised for fertility management in 26patients (18.06%). Conclusion: Endometriosis is not only associated with decreased ovarian reserve but also responsible for diminished response to ovarian stimulation. So, it is a great challenge to obtain successful fertility treatment for this group of patients. J Dhaka Med Coll. 2023; 32(1) : 9-15

Synergistic signal amplification for HER2 biosensing using tetrahedral DNA nanostructures and 2D transition metal carbon/nitride@Au composites via ARGET ATRP

The rising incidence of breast cancer underscores the critical need for accurate and early detection methods, particularly for key biomarkers like human epidermal growth factor receptor 2 (HER2). Here, a synergistic signal amplification electrochemical biosensor was developed for HER2 detection that utilizes tetrahedral DNA nanostructures (TDN), 2D transition metal carbon/nitride@Au (MXene@Au) composites, and activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). Specifically, TDN serves as the substrate, with the aptamer anchored by the MXene@Au composite support matrix. This design facilitates the generation of electrochemical currents through the ARGET ATRP signal amplification strategy. The robustness and high affinity of TDN minimize surface effects on the electrode and enhance target binding. Additionally, the high conductivity of the MXene@Au composites improves the detection sensitivity of the biosensor. The use of the ARGET ATRP strategy further enhances detection sensitivity. The biosensor exhibits a wide detection range from 10 pg·mL−1 to 10 µg·mL−1 with a remarkable detection limit of 0.39 pg·mL−1, verified under optimal experimental conditions. The designed biosensor offers a significant advancement in the field of oncological diagnostics, providing a highly sensitive, low-cost, and simple method for early HER2 detection, thereby potentially improving treatment outcomes for breast cancer patients.

Evaluation of relationship between clinical, paraclinical characteristics and treatment outcomes in patients with infective endocarditis at Ha Noi Heart Hospital

Background: Globally, infective endocarditis (IE) patients exhibit a positive blood culture rate of 80-90%, while in Vietnam, this rate is lower at 68-70%. Hanoi Heart Hospital lacks previous evaluations of microbiological outcomes and their correlation with IE treatment. Objective: “Survey of clinical and paraclinical characteristics, microbiological results and treatment outcomes; relationship with clinical outcomes in patients with infective endocarditis”. Methods: A prospective, descriptive, cross-sectional study with longitudinal follow-up was conducted on IE patients diagnosed using the modified Duke criteria between May 2022 and October 2023. Results: Among 63 patients (mean age: 51.03 ± 15.92 years), 63.5% had NYHA class 2, and 93.7% had echocardiographic vegetations. Positive blood cultures were found in 36.5%, with Streptococcus, Staphylococcus, and Enterococcus faecalis being the predominant pathogens. Treatment included medical therapy (31.7%), emergency surgery (7.9%), and scheduled surgery (60.3%). Recurrence occurred in 12.7%, and mortality was 9.5%; C-reactive protein (CRP) was significantly associated with clinical outcomes (OR: 1.017, p = 0.003); AUC = 0.731 of negative blood cultures on admission to clinical outcomes. Conclusion: Transthoracic echocardiography effectively detects vegetations, and while positive blood culture rates are lower, overall outcomes are favorable. Elevated CRP and negative blood cultures at admission are significant predictors of clinical outcomes in IE patients.

Clinical outcomes of post-surgery osteoporosis treatment in elderly intertrochanteric fracture patients: a prospective study

Background: This study aims to evaluate the clinical and functional outcomes of administering zoledronic acid in elderly patients undergoing surgical management of hip fractures. The goal is to assess the impact on mortality, postoperative complications, and functional recovery as measured by the modified Harris hip score. Methods: A prospective study was conducted over 18 months at a tertiary care center in New Delhi, India, involving 42 patients aged 60 and above with intertrochanteric femur fractures. Patients received surgical fixation and standard postoperative care. Zoledronic acid (5 mg) was administered intravenously three months post-surgery. Data on demographics, injury-to-surgery interval, fracture type, DEXA score, and functional outcomes were collected at follow-ups of 6 weeks, 3 months, 6 months, and 12 months. Results: The mean age of participants was 72.67 years. Zoledronic acid administration was associated with a 9.5% mortality rate. Functional outcomes, measured by the modified Harris hip score, significantly improved from a mean of 42.14 at 6 weeks to 77.68 at 12 months (p&lt;0.001). Younger patients (&lt;70 years) had significantly better scores at 3 months compared to older patients (&gt;80 years). However, no significant differences were observed at 6 and 12 months. The mean modified Harris hip scores did not differ significantly between patients with osteopenia and osteoporosis at any time point. Additionally, the type of surgical fixation (intramedullary versus extramedullary) showed no significant impact on functional outcomes. Conclusions: Zoledronic acid administration in elderly hip fracture patients may reduce mortality and enhance functional recovery. The study supports its use in postoperative care to improve outcomes, although larger, randomized controlled studies are needed to confirm these findings. The results suggest that zoledronic acid can be an effective adjunct therapy in managing osteoporosis-related hip fractures in the geriatric population.

Investigation of Blood Count-Based Inflammatory Biomarkers as Predictors of Response to Dupilumab Treatment in Patients with Chronic Rhinosinusitis with Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease often resistant to standard treatments. Dupilumab, a monoclonal antibody targeting the IL-4α receptor, has shown efficacy in CRSwNP, but a significant subset of patients do not respond to this therapy. This study aims to investigate pretreatment complete blood count (CBC)-based inflammatory biomarkers as predictors of response to dupilumab in patients with CRSwNP. This mono-centric, retrospective, single-arm longitudinal cohort study included 80 patients with uncontrolled CRSwNP who received dupilumab treatment at the Medical University of Graz. Patients were classified into responder and non-responder groups based on a reduction of >1 in nasal polyp score (NPS) and a sinonasal outcome test-22 (SNOT-22) score <40 points at six months. Pretreatment CBC-derived biomarkers, including eosinophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation indices including the aggregate inflammation systemic index (AISI), systemic inflammation index (SII), and systemic inflammation response index (SIRI), were analyzed for their predictive value. Of the 80 patients, 72.5% were classified as responders, while 27.5% were non-responders. A significant positive correlation was found between baseline eosinophil count and NPS reduction (p = 0.027), suggesting that higher eosinophil levels may predict higher NPS reduction in dupilumab treatment. However, no significant associations were observed between NLR, PLR, and systemic inflammation indices with treatment outcomes. Pretreatment eosinophil count may serve as a potential biomarker for predicting nasal polyp reduction in dupilumab treatment of CRSwNP. Other CBC-based inflammatory markers did not show significant predictive value. Further prospective studies are needed to validate these findings and explore additional, reliable biomarkers to optimize treatment outcomes for CRSwNP patients.

Update on the treatment of BRAFmut metastatic melanoma and future perspectives

Abstractv‐Raf murine sarcoma viral oncogene homolog B (BRAF) mutations were first identified in melanoma in 2002, leading to increased cell division and proliferation, and resultant tumour growth. The identification and characterisation of BRAF mutations (BRAFmut) led to the development of several highly specific, BRAF‐, then mitogen‐activated kinase enzyme (MEK)‐targeted therapies that have enabled rapid tumour responses and improved treatment outcomes in most patients with metastatic BRAFmut melanoma. The combination of these two drug classes (BRAF inhibitors and MEK inhibitors) has demonstrated improved response rates, progression‐free survival, and overall survival (OS), along with a more tolerable safety profile, compared with BRAF inhibition alone. In parallel, improved knowledge of the immune system has enabled the development of immune checkpoint inhibitors (ICIs), although immune‐related adverse events with ICIs may prove to be problematic in some patients and require careful management. While targeted therapy appears to provide rapid disease control in a relatively high proportion of patients, the development of secondary resistance may limit the overall duration of responses. Acquired resistance, along with primary resistance, has also been reported for ICIs, with a lower overall response rate to that with targeted therapy, although durable responses have been reported in some responding patients. A combination strategy of targeted therapy with ICIs has demonstrated modest increases in efficacy compared with targeted therapy combinations, although data significance varies across studies, there is increased risk of toxicity, and triple combination therapy has not yet received clinical approval in Europe. Thus, there is an ongoing need to establish optimal sequencing of these treatments in patients with advanced BRAFmut melanoma, and this has become the focus of current research. The aim of this narrative review was to provide an update on the treatment of BRAFmut metastatic melanoma, current guideline recommendations, and future clinical perspectives.

Time to Treatment and Outcomes of Hemorrhagic Stroke, Comparing Patients Entering Surgery before and after 120 Minutes Upon Arrival at the Emergency Department Pattani Hospital

Background: The duration between a patient’s hospital arrival and the point at which they enter surgery for hemorrhagic stroke affects survival, length of stay, health care costs, and outcome (Glasgow Outcome Scale). Therefore, a study to explore the effects of time on these outcomes is warranted. Objective: To compare treatment outcomes of patients with hemorrhagic stroke having entered surgery before and after 120 minutes upon arrival at the emergency department. Materials and Methods: A therapeutic and interventional study with a retrospective observational cohort design at Pattani Hospital in patients with hemorrhagic stroke who received treatment between October 2018 and April 2023. A retrospective review of medical records, which collected clinical characteristics and the time to treatment. Glasgow Outcome Scale was evaluated at 72 hours, two weeks, one month, and date of hospital discharge. Length of stay, health care costs, and survival status at date of hospital discharge were analyzed. Comparative analysis was performed by Fisher’s exact probability test and t-test, and prognostic analysis was performed by risk ratio. Results: Of all the patients in the present study, 49 and 182 received treatment before and after 120 minutes, respectively, upon arrival at the emergency department. Clinical characteristics of gender, age, underlying conditions, regular medications, and level of consciousness were not significantly different between the two groups. Patients who entered surgery within 120 minutes of arrival had more occurrences of basal ganglia hemorrhage compared with those who received surgery thereafter. Furthermore, patients who received surgery within 120 minutes had a 11.4% increased chance of survival. The number needed to treat (NNT) hemorrhagic stroke patients with a time to treatment of under 120 minutes is 9. However, there was an associated increase in complications, health care cost, and length of stay. The Glasgow Outcome Scale improvement was greater only in the two-week follow-up period. These results were similar when subarachnoid hemorrhage and anticoagulating medication used were excluded. Conclusion: Patients with hemorrhagic stroke who receive early surgical treatment have lower mortality rates. Adequate provision of personnel and facilities for delivering prompt care should be made available. Measures should be taken to reduce the complications of patients who receive surgical treatment after 120 minutes upon arrival at the emergency department.

Dealing with the Verteporfin Shortage: Treatment Options and Outcomes in Patients with Chronic and Non-Resolving Central Serous Chorioretinopathy

Introduction: Half-dose photodynamic therapy (HD-PDT) with verteporfin is the mainstay treatment in central serous chorioretinopathy (CSC). Since 2021, there is a worldwide shortage of verteporfin. This called for adjustments of daily practice. Here, we provide a comprehensive evaluation of the adapted treatment methods and outcomes in patients with non-resolving and chronic CSC. Methods: In this retrospective cohort study, we compared patients referred in the year before the verteporfin shortage (group 1), with patients referred in the first year of verteporfin shortage (group 2). Treatment strategies, subretinal fluid (SRF) resolution, and visual acuity (VA) were evaluated during a follow-up period of at least 4 months. Results: Eighty-five eyes of 79 patients were analyzed, 36 eyes in group 1 and 49 in group 2. The treatment strategy at the first visit shifted from HD-PDT as the most performed treatment in group 1 to a more patient-tailored approach in group 2, with a wait-and-see policy in most cases. During follow-up, HD-PDT was performed significantly less in group 2 (89% vs. 45%; p < 0.001). At a mean follow-up time of 6.2 months, SRF resolved in 61% of the eyes in group 1 and in 55% in group 2 (p = 0.821). No difference in VA was observed between the groups at follow-up (p = 0.637). Conclusion: During the shortage of verteporfin, a different treatment strategy was applied, with HD-PDT being performed less frequently. By implementing a more patient-tailored approach, the VA and the resolution rate of SRF remained similar to the year before the shortage.

Predicting Treatment Outcomes in Patients with Drug-Resistant Tuberculosis and Human Immunodeficiency Virus Coinfection, Using Supervised Machine Learning Algorithm.

Drug-resistant tuberculosis (DR-TB) and HIV coinfection present a conundrum to public health globally and the achievement of the global END TB strategy in 2035. A descriptive, retrospective review of medical records of patients, who were diagnosed with DR-TB and received treatment, was conducted. Student's t-test was performed to assess differences between two means and ANOVA between groups. The Chi-square test with or without trend or Fischer's exact test was used to test the degree of association of categorical variables. Logistic regression was used to determine predictors of DR-TB treatment outcomes. A decision tree classifier, which is a supervised machine learning algorithm, was also used. Python version 3.8. and R version 4.1.1 software were used for data analysis. A p-value of 0.05 with a 95% confidence interval (CI) was used to determine statistical significance. A total of 456 DR-TB patients were included in the study, with more male patients (n = 256, 56.1%) than female patients (n = 200, 43.9%). The overall treatment success rate was 61.4%. There was a significant decrease in the % of patients cured during the COVID-19 pandemic compared to the pre-pandemic period. Our findings showed that machine learning can be used to predict TB patients' treatment outcomes.

Evaluation of Circulating Tumor DNA and Carcinoembryonic Antigen Levels and Relationship with Clinicopathological Risk Factors and Prognostic Indices in Colorectal Cancer Patients

Objective: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. ctDNA has emerged as a promising biomarker for CRC management, offering real-time insights into tumor burden and genetic mutations. This study investigates the correlation between CEA levels, ctDNA, clinicopathological factors, and treatment outcomes in early and advanced CRC patients. Methods: The study retrospectively analyzed data from CRC patients, including early-stage disease and metastatic disease. ctDNA levels, demographic data, and clinical parameters such as CEA, inflammatory indexes, and tumor characteristics were evaluated to determine correlations with treatment outcomes. Results: The study included 20 patients, with 60% diagnosed at the metastatic stage. The study found no statistically significant correlation between ctDNA levels and disease stage, recurrence, or overall survival. While CEA and ctDNA levels were measured, they did not demonstrate a significant relationship with treatment outcomes. Notably, ctDNA levels were higher in metastatic patients, though this was not statistically significant. Conclusion: Despite its potential, the integration of ctDNA as a routine biomarker in CRC care faces challenges, including variability in measurement techniques and cost-effectiveness. However, ctDNA's ability to guide personalized treatment strategies and monitor disease recurrence holds promise. The study's findings align with previous research, suggesting ctDNA as a poor prognostic indicator, though further research is needed. ctDNA represents a significant advance in CRC management, offering non-invasive, real-time insights into tumor dynamics. Ongoing research is expected to solidify its role in personalized treatment planning, potentially leading to more effective and tailored therapies for CRC patients.

PTPRZ1 dephosphorylates and stabilizes RNF26 to reduce the efficacy of TKIs and PD-1 blockade in ccRCC.

Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma, often exhibits resistance to tyrosine kinase inhibitors (TKIs) when used as monotherapy. However, the integration of PD-1 blockade with TKIs has significantly improved patient survival, making it a leading therapeutic strategy for ccRCC. Despite these advancements, the efficacy of this combined therapy remains suboptimal, necessitating a deeper understanding of the underlying regulatory mechanisms. Through comprehensive analyses, including mass spectrometry, RNA sequencing, lipidomic profiling, immunohistochemical staining, and ex vivo experiments, we explored the interaction between PTPRZ1 and RNF26 and its impact on ccRCC cell behavior. Our results revealed a unique interaction where PTPRZ1 stabilized RNF26 protein expression by dephosphorylating it at the Y432 site. The modulation of RNF26 levels by PTPRZ1 was found to be mediated through the proteasome pathway. Additionally, PTPRZ1, via its interaction with RNF26, activated the TNF/NF-κB signaling pathway, thereby promoting cell proliferation, angiogenesis, and lipid metabolism in ccRCC cells. Importantly, inhibiting PTPRZ1 enhanced the sensitivity of ccRCC to TKIs and PD-1 blockade, an effect that was attenuated when RNF26 was simultaneously knocked down. These findings highlight the critical role of the PTPRZ1-RNF26 axis in ccRCC and suggest that combining PTPRZ1 inhibitors with current TKIs and PD-1 blockade therapies could significantly improve treatment outcomes for ccRCC patients.

Companion Diagnostics (CDx) Based on Molecular Biology Techniques.

Molecular profiling based on genomic mutations provides clinically important diagnostic and prognostic information. Companion diagnostic (CDx) testing, which is based on targeted drug therapy, is being applied to a variety of molecular diagnostic techniques (e.g., fluorescent in situ hybridization-FISH; polymerase chain reaction-PCR; and next-generation sequencing-NGS) to diagnose complex etiologies using a minimal number of specimens, replacing immunohistochemical analysis, which may show bias at certain stages. The safety and effectiveness of CDx testing using molecular diagnostic technology in precision medicine is an important factor in determining the treatment outcome and prognosis of patients. Meeting minimum safety and effectiveness performance standards is essential for CDx testing, and a thorough understanding of regulatory considerations is necessary to plan and design the optimal product. In this review, we focus on the diagnostic field of precision medicine and discuss the safety and effectiveness that each molecular diagnostic technology must meet according to CDx testing diversity.

Reevaluating Pediatric Osteomyelitis with Osteoarticular Tuberculosis: Addressing Diagnostic Delays and Improving Treatment Outcomes.

Pediatric osteoarticular tuberculosis (TB) remains a significant global health challenge, particularly in resource-limited settings, where delayed diagnosis and treatment frequently lead to severe long-term complications. Despite advancements in TB control, skeletal TB in children is often misdiagnosed due to its non-specific clinical presentation, contributing to poor outcomes such as joint deformities, growth disturbances, and chronic pain. The complexity of diagnosing osteoarticular TB is further exacerbated by the limited sensitivity of conventional diagnostic tools and the overlap with other musculoskeletal conditions. This study seeks to evaluate the impact of early detection and multidisciplinary management on treatment outcomes in pediatric patients with osteoarticular TB. A retrospective review was conducted at the Pediatric Orthopedics Department of the "Grigore Alexandrescu" Children's Hospital in Romania from 2009 to 2023. Case data included clinical, imaging, and microbiological findings, and treatment outcomes in children aged 0-18 years diagnosed with tuberculous osteomyelitis. The study identified varied clinical presentations, with delayed diagnosis often linked to misinterpretation of symptoms as non-TB infections. Multimodal diagnostic approaches combining imaging, microbiological testing, and histopathology improved diagnostic accuracy. Early surgical intervention alongside anti-TB therapy proved effective in reducing long-term complications. Timely, accurate diagnosis and multidisciplinary treatment are critical to improving outcomes in pediatric osteoarticular TB. Vaccination status and comprehensive diagnostic tools significantly influence disease progression and treatment success. The study underscores the need for enhanced screening and diagnostic methods to prevent delays in treatment.

Intensification of upfront chemotherapy for patients with myeloid blast phase CML: a single center experience.

Outcomes for patients with myeloid blast phase chronic myeloid leukemia (CML-MBP) are dismal, and no preferred chemotherapy regimen has been identified. Recent studies have suggested a higher response rate with administration of timed-sequenced regimens (TSR) (purine analog, high-dose cytarabine, anthracycline) in high-risk acute myeloid leukemia patients. We retrospectively evaluated outcomes of newly diagnosed CML-MBP patients consecutively treated at our institution with a TSR or standard-dose cytarabine and an anthracycline ("7 + 3") combined with a tyrosine-kinase inhibitor (TKI) between 2011 and 2023. Endpoints of interest included hematologic response, clinically significant cytogenetic response (CSCR) defined as achieving at least a minor cytogenetic response (Ph + metaphases 0%-≤65%) after induction therapy, event-free survival (EFS), and overall survival (OS). A total of 18 patients with CML-MBP were included of whom 9 (50%) received a TSR and 9 (50%) received "7 + 3". Hematologic response (55.6% vs. 55.6%) and CSCR (25% vs. 37.5%) were similar between TSR- and "7 + 3" treated patients. Twelve patients (66.7%) experienced at least one grade ≥ 3 non-hematologic, end-organ toxicity with 33.3% and 11.1% of TSR- and 7 + 3-treated patients, respectively, experiencing at least two. Our data suggests that intensification of upfront chemotherapy does not appear to improve treatment outcomes in CML-MBP patients however, further studies are warranted to confirm these findings involving a larger cohort.

Melatonin and vitamin D as potential synergistic adjuvants for cancer therapy (Review).

Significant advancements have been made in cancer therapy; however, limitations remain with some conventional approaches. Adjuvants are agents used alongside primary treatments to enhance their efficacy and the treatment outcomes of patients. Modern lifestyles contribute to deficiencies in melatonin and vitamin D. Limited sun exposure affects vitamin D synthesis, and artificial light at night suppresses melatonin production. Both melatonin and vitamin D possess anti‑inflammatory, immune‑boosting and anticancer properties, rendering them potential adjuvants of interest. Studies suggest melatonin and vitamin D supplementation may address antioxidant imbalances in lip, oral and pharyngeal cancers. Moreover, promising results from breast, head and neck, brain, and osteosarcoma research indicate potential for tumor growth inhibition, improved survival, and a better quality of life of patients with cancer. The radioprotective properties of melatonin and vitamin D are another exciting area of exploration, potentially enhancing radiotherapy effectiveness while reducing side effects. For its part, the sleep‑promoting effects of melatonin may indirectly benefit patients with cancer by influencing the immune system. Thus, the prevalence of vitamin D and melatonin deficiencies highlights the importance of supplementation, as lower levels can worsen side‑effects from cancer treatments. The present review explores the potential of combining melatonin and vitamin D as synergistic adjuvants for cancer therapy. These agents have shown promise individually in cancer prevention and treatment, and their combined effects warrant investigation. Therefore, large‑scale controlled trials are crucial to definitively determine the optimal dosage, safety and efficacy of this combination in improving the lives of patients with cancer.

Artificial intelligence-assisted delineation for postoperative radiotherapy in patients with lung cancer: a prospective, multi-center, cohort study.

Postoperative radiotherapy (PORT) is an important treatment for lung cancer patients with poor prognostic features, but accurate delineation of the clinical target volume (CTV) and organs at risk (OARs) is challenging and time-consuming. Recently, deep learning-based artificial intelligent (AI) algorithms have shown promise in automating this process. To evaluate the clinical utility of a deep learning-based auto-segmentation model for AI-assisted delineating CTV and OARs in patients undergoing PORT, and to compare its accuracy and efficiency with manual delineation by radiation oncology residents from different levels of medical institutions. We previously developed an AI auto-segmentation model in 664 patients and validated its contouring performance in 149 patients. In this multi-center, validation trial, we prospectively involved 55 patients and compared the accuracy and efficiency of 3 contouring methods: (i) unmodified AI auto-segmentation, (ii) fully manual delineation by junior radiation oncology residents from different medical centers, and (iii) manual modifications based on AI segmentation model (AI-assisted delineation). The ground truth of CTV and OARs was delineated by 3 senior radiation oncologists. Contouring accuracy was evaluated by Dice similarity coefficient (DSC), Hausdorff distance (HD), and mean distance of agreement (MDA). Inter-observer consistency was assessed by volume and coefficient of variation (CV). AI-assisted delineation achieved significantly higher accuracy compared to unmodified AI auto-contouring and fully manual delineation by radiation oncologists, with median HD, MDA, and DCS values of 20.03 vs. 21.55 mm, 2.57 vs. 3.06 mm, 0.745 vs. 0.703 (all P<0.05) for CTV, respectively. The results of OARs contours were similar. CV for OARs was reduced by approximately 50%. In addition to better contouring accuracy, the AI-assisted delineation significantly decreased the consuming time and improved the efficiency. AI-assisted CTV and OARs delineation for PORT significantly improves the accuracy and efficiency in the real-world setting, compared with pure AI auto-segmentation or fully manual delineation by junior oncologists. AI-assisted approach has promising clinical potential to enhance the quality of radiotherapy planning and further improve treatment outcomes of patients with lung cancer.