Treatment Outcomes Research Articles

Perception of parents on barriers and facilitators of treatment outcomes among children and adolescents attending psychotherapy services in a primary health care centre in Belize

Background: The study assessed the perception of parents on barriers and facilitators treatment outcomes among children and adolescents attending psychotherapy services in a primary health care centre. Methods: A cross sectional descriptive study using both quantitative and qualitative methods. The quantitative method used retrospective review of records of 65 children and adolescent clients who accessed psychotherapy services between January 2022 and December 2023 at Port Loyola Health Centre in Belize city. The qualitative method used in-depth interviews of twenty parents of the patients randomly selected from the clinic registers. Univariate and bivariate analyses was used for the quantitative data while thematic analysis was used for the qualitative data. Results: 25 (38.5%) of the patients completed their treatment and 34 (52.3%) dropped out, with half dropped out after the first visit. The identified parental perceived barriers and facilitators are organized into four main themes. The first theme was related to knowledge and understanding of mental health problems by the parents which showed that respondents had good knowledge about mental health problems. The second theme identified attitudes towards treatment as a major factor to completion of treatment. The third theme was related to structural factors like transportation cost and parents’ work schedule identified as key barriers. The fourth theme was related to inconvenient appointment time and lack of flexibility in the scheduling of appointment at the clinic. Conclusions: The study highlights key areas of interventions to minimize barriers to completion of treatment among children accessing mental health services.

Investigating the Antibacterial Ability of Sodium Hypochlorite Solution Activated with PUI and XPF File Against Enterococcus faecalis Using CFU, RT-PCR, and SEM

Eradication of microorganisms present in the root canal system during endodontic therapy is one of the critical factors affecting the final outcome of endodontic treatment. However, even adequate technique of the root canal treatment and use of irrigants according to the established protocol does not lead to the complete elimination of microorganisms during endodontic treatment. The presence of Enterococcus (E.) faecalis inside the root canal system may be an important factor contributing to the failure of the treatment. Introducing agitation techniques in irrigation, such as passive ultrasonic irrigation (PUI) and the use of the activating instrument XP-endo Finisher (XPF), contribute to a better debridement and disinfection of the root canal. This study was conducted on 42 root canals experimentally inoculated with E. faecalis and exposed to three irrigation protocols. These have included a standard irrigation protocol using a syringe and needle, passive ultrasonic irrigation, and activation of the irrigant using an XPF instrument. The reduction in microorganisms was evaluated using the quantitative polymerase chain reaction in real-time (RT-PCR) as well as via the method of determining the number of colony forming units on nutrient medium (CFUs). The results of this study showed that the use of supplementary irrigation protocols, PUI, and XPF led to a significant decrease in the number of microorganisms inside the root canal of experimental teeth. These findings indicate a significant positive impact of these procedures on the disinfection of the root canal system.

Sex-related differences in demographics, diagnosis and management of patients with chronic coronary syndromes.

The impact of sex-related factors on current clinical management and outcomes of chronic coronary syndromes (CCS) are unclear. All patients belonging to the prospective, nationwide START registry were included. Their baseline characteristics, diagnostic workup, revascularization strategy, pharmacological treatment and 1-year clinical outcomes were compared with respect to sex overall and in age tertiles. A total of 5070 consecutive patients were included. Most patients were males (80.1%). As expected, the prevalence of females increased with age. Distribution of risk factors and history of cardiovascular disease were different depending on sex, as well as diagnostic workup, with lower use of exercise stress testing in women (25.1% vs. 36.7%, P < 0.0001). The use of coronary angiography was similar in the two groups. Women had lower rates of multivessel coronary artery disease (CAD) (33.0% vs. 40.6% P < 0.0001) and higher rates of nonobstructive CAD (18.3% vs. 11.3%, P < 0.0001). Rates of myocardial revascularization were similar, but women were more likely to receive percutaneous coronary intervention than men (84.3% vs. 77.8%, P < 0.0001) and less likely to receive surgical/hybrid revascularization (10.0% vs. 15.1%, P < 0.0001). At 12-month follow-up, no differences were observed for the combined endpoint of all-cause mortality, re-hospitalization for myocardial infarction, heart failure, stroke or myocardial revascularization between males and females; however, a significantly worse perceived quality of life was observed in women. In a large nationwide cohort of patients with CCS, clinical outcomes were not different depending on sex. However, several differences in the diagnostic work-up, treatment strategies and quality of life were found between sexes.

Cohort Profile: VZNKUL–NMIBC Quality Indicators Program: A Flemish Prospective Cohort to Evaluate the Quality Indicators in the Treatment of Non-Muscle-Invasive Bladder Cancer

Purpose: Bladder cancer (BC) is a heterogeneous disease with varying outcomes, influenced by disease heterogeneity and variability in treatment and follow-up. Risk groups have been established for non–muscle-invasive BC (NMIBC) to standardize therapy, and several quality control indicators (QCIs) monitor adherence to these risk group-based guidelines. However, controversial results had been obtained regarding the oncological benefits of these QCIs until recent high-quality studies from large registries showed their usefulness. To improve adherence to the European Association of Urology (EAU) Guidelines and benchmark current care in Flemish hospitals within Vlaams Ziekenhuisnetwerk–KU Leuven (VZNKUL), a QCI program for NMIBC was initiated in 2013. This study aims to describe the demographic, clinical, and treatment data of patients enrolled in this program. Participants: The VZNKUL–NMIBC Quality Indicators Program Registry is a prospective cohort including patients treated and followed up with at seven academic and non-academic Flemish hospitals since June 2013. Data collection includes patient characteristics, tumor data, treatment, and oncological outcomes. Findings to date: From June 2013 to December 2020, 4744 transurethral resections of bladder tumors (TURBTs) from 2237 unique patients were analyzed. Most patients (80%) were men with a median age of 73. The median time from diagnosis to TURBT was 19 days. A single tumor was detected in 37% of TURBTs. Tumors larger than 3 cm were found in 20.8% of cases. In 46% of TURBTs, a reTURBT was scheduled according to guidelines. The complication rates were 7.5% and 2.4% for bladder perforation and bleeding, respectively. Postoperative single intravesical instillation of chemotherapy (SIVIC) was administered to 56.9% of 1533 indicated patients with a median time to administration of 4.7 h. Among the cohort, 60.4% had NMIBC, and 9.3% had muscle-invasive BC. Of 972 high-risk patients, 60.7% received adequate BCG induction, while 39.4% received adequate maintenance. After BCG induction ± maintenance, 39.7% were tumor-free, with 17.7% recurrence and 4% progression to muscle-invasive BC. BCG treatment was terminated early for 17% of patients due to intolerance. Early cystectomy was performed for 2.4% of the BCG-naïve patients, and 27.7% of patients with BCG failure underwent a BCG rechallenge. For intermediate-risk patients, 2.1% received adequate BCG, and 23% received intravesical chemotherapy. The median follow-up was 57 months. Five-year recurrence-free, progression-free, cancer-free, overall, and cancer-specific survival rates were 53%, 91.6%, 89%, 70.6%, and 95.6%, respectively, for the NMIBC patients. Of 400 non-metastatic MIBC patients, 217 (54.3%) underwent radical cystectomy (RC), of whom 46% received neoadjuvant chemotherapy, while 18 (4.5%) refused RC, and 74 (18.5%) were considered unfit for the surgery. Future plans: The VZNKUL–NMIBC Quality Indicators Program Registry will continue collecting data to evaluate QCIs and monitor treatment quality, enabling hospitals to benchmark their performance and improve patient care. Additionally, the registry’s real-world data can support research and international collaboration. Trial registration: The study was registered on ClinicalTrials.gov (NCT04167332).

MiR-3065-5p and miR-26a-5p as Clinical Biomarkers in Colorectal Cancer: A Translational Study

Background/Objectives: The prognosis of colorectal cancer (CRC) is mainly based on the clinical stage; however, CRC is considered a complex disease due to its molecular heterogeneity. The development of novel biomarkers to improve patients’ diagnosis and prognosis remains fundamental. Methods: A cohort of forty-nine CRC patients from the National Cancer Institute of Mexico was included to collect clinical and miRNA expression data. The expression of a group of miRNAs was compared between CRC and non-tumoral adjacent tissues. Prognosis assessment considering each miRNA expression was tested using Kaplan–Meier survival curves and Cox regressions. Statistical significance was defined as p ≤ 0.05. Trial registration: Retrospective study No.2021/046. Results: miR-3065-5p and miR-26a-5p expression differed between non-tumoral adjacent and tumoral tissues (p = 0.02). In terms of overall survival (OS), patients with low expression of miR-3065-5p had a median OS of 70 months, while patients with high levels did not reach the median OS (p = 0.041). Male patients with low expression of this miRNA had an OS of 70 months, whereas patients with high levels did not reach the median OS (p = 0.050). Under uni-multivariate analysis, clinical stage (HR: 1.30, CI 1.23–2.30; p: 0.001) and low levels of miR-3065-5p (HR: 1.30, CI 1.23–2.30; p: 0.001) were determined as predictor factors of OS. To this end, we designed the “Prognosis miRNAs assessment in cancer” (PROMIR-C) algorithm, which integrated clinical features with miR-3065-5p expression levels. Conclusions: These findings support the clinical utility of miR-26a-5p and miR-3065-5p in the diagnosis and prognosis of CRC. PROMIR-C is a fundamental tool for clinicians in treatment decision-making, prognosis assessment, and outcome of CRC.

Optimizing the Prediction of Depression Remission: A Longitudinal Machine Learning Approach.

Decisions about when to change antidepressant treatment are complex and benefit from accurate prediction of treatment outcome. Prognostic accuracy can be enhanced by incorporating repeated assessments of symptom severity collected during treatment. Participants (n = 714) from the Genome-Based Therapeutic Drugs for Depression study received escitalopram or nortriptyline over 12 weeks. Remission was defined as scoring ≤ 7 on the Hamilton Rating Scale. Predictors included demographic, clinical, and genetic variables (at 0 weeks) and measures of symptom severity (at 0, 2, 4, and 6 weeks). Longitudinal descriptors extracted with growth curves and topological data analysis were used to inform prediction of remission. Repeated assessments produced gradual and drug-specific improvements in predictive performance. By Week 4, models' discrimination in all samples reached levels that might usefully inform treatment decisions (area under the receiver operating curve (AUC) = 0.777 for nortriptyline; AUC = 0.807 for escitalopram; AUC = 0.794 for combined sample). Decisions around switching or modifying treatments for depression can be informed by repeated symptom assessments collected during treatment, but not until 4 weeks after the start of treatment.

Determining the Accuracy of Two Pelvic Ring Classification Systems: AO Tile and Young Burgess- A Systematic Review

Pelvic ring fractures (PRF) are high energy fractures with an incidence of 20/100,000 among all fractures and significant associated morbidity and mortality. PRF are often classified using Young-Burgess classification, and Tile AO classification. This project aims to review the literature comparing the two classification systems for reliability, clinical implications and guide for treatment plan. Google Scholar search was performed with the following words: “Young”, “Burgess”, “Tile”, “presentation”, “treatment”, “pelvic ring” in the Title/Abstract. After review of 828 results, 11 articles are included in this systematic review. Reliability of the classification systems positively correlated with an increase in years of experience. When comparing the reliability, Young-Burgess is shown to have moderate-to-substantial level of agreement for classifying pelvic fractures when accounting for expertise level, while Tile showed substantial agreement between specialists only. Young-Burgess better predicted mortality as compared to Tile, while another study found no significant difference. Tile B and LC fractures are found to have higher frequency of hemodynamic instability and undergo laparotomies more frequently. When comparing treatment options, there is a moderate level of agreement for the treatment option solely based on images. However, the question of how the classifications guide treatment outcomes remains unanswered. After review of current literature, it appears that Young-Burgess classification has slightly higher reliability and better prediction for mortality than Tile. However, there is a need for further research on how the classification systems can determine the treatment and outcomes to improve morbidity and mortality.

Leveraging Neural Crest-Derived Tumors to Identify NF1 Cancer Stem Cell Signatures

Neurofibromatosis type 1 (NF1) is a genetic disorder that predisposes individuals to develop benign and malignant tumors of the nerve sheath. Understanding the signatures of cancer stem cells (CSCs) for NF1-associated tumors may facilitate the early detection of tumor progression. Background: Neural crest cells, the cell of origin of NF1-associated tumors, can initiate multiple tumor types, including melanoma, neuroblastoma, and schwannoma. CSCs within these tumors have been reported; however, identifying and targeting CSC populations remains a challenge. Results: This study aims to leverage existing studies on neural crest-derived CSCs to explore markers pertinent to NF1 tumorigenesis. By focusing on the molecular and cellular dynamics within these tumors, we summarize CSC signatures in tumor maintenance, progression, and treatment resistance. Conclusion: A review of these signatures in the context of NF1 will provide insights into NF1 tumor biology and pave the way for developing targeted therapies and improving treatment outcomes for NF1 patients.

Blended Psychological Therapy for the Treatment of Psychological Disorders in Adult Patients: Systematic Review and Meta-Analysis.

Blended therapy (BT) combines digital with face-to-face psychological interventions. BT may improve access to treatment, therapy uptake, and adherence. However, research is scarce on the structure of BT models. We synthesized the literature to describe BT models used for the treatment of psychological disorders in adults. We investigated whether BT structure, content, and ratio affected treatment efficacy, uptake, and adherence. We also conducted meta-analyses to examine treatment efficacy in intervention-control dyads and associations between treatment outcomes versus BT model structure. PsycINFO, CINAHL, Embase, ProQuest, and MEDLINE databases were searched. Eligibility criteria included articles published in English till March 2023 that described digital and face-to-face elements as part of an intervention plan for treating psychological disorders in adult patients. We developed a coding framework to characterize the BT interventions. A meta-analysis was conducted to calculate effect size (ES; Cohen d and 95% CIs) regarding pre- and posttreatment outcomes in depression and anxiety versus BT structure. The review was registered with PROSPERO and followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Searches identified 8436 articles, and data were extracted from 29 studies. BT interventions were analyzed and classified according to mode of interaction between digital and face-to-face components (integrated vs sequential), role of the components (core vs supplementary), component delivery (alternate vs case-by-case), and digital materials assignment mode (standardized vs personalized). Most BT interventions (n=24) used a cognitive behavioral therapy approach for anxiety or depression treatment. Mean rates of uptake (91%) and adherence (81%) were reported across individual studies. BT interventions were more effective or noninferior to treatment as usual, with large spread in the data and a moderate to large ES in the treatment of depression (n=9; Cohen d=-1.1, 95% CI -0.6 to -1.6, P<.001, and z score=-4.3). A small, nonsignificant ES was found for anxiety outcomes (n=5; Cohen d=-0.1, 95% CI -0.3 to 0.05, P=.17, and z score=-1.4). Higher ESs were found in blended interventions with supplementary design (depression: n=11, Cohen d=-0.75, 95% CI -0.56 to -0.95; anxiety: n=8, Cohen d=-0.9, 95% CI -0.6 to -1.2); fewer (≤6) face-to-face sessions (depression: n=9, Cohen d=-0.7, 95% CI -0.5 to -0.9; anxiety: n=7, Cohen d=-0.8, 95% CI -0.3 to -1.3); and a lower ratio (≤50%) of face-to-face versus digital sessions (depression: n=5, Cohen d=-0.8, 95% CI -0.6 to -1.1; anxiety: n=4, Cohen d=-0.8, 95% CI 0.006 to -1.6). This study confirmed integrated BT models as feasible to deliver. We found BT to be effective in depression treatment, but anxiety treatment results were nonsignificant. Future studies assessing outcomes across different psychological disorders and therapeutic approaches are required. PROSPERO CRD42021258977; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=258977.

Surgical treatment strategies for gastroesophageal reflux after laparoscopic sleeve gastrectomy

Bariatric surgery has emerged as an effective therapeutic approach for combating obesity. As the most commonly performed bariatric surgery, laparoscopic sleeve gastrectomy (LSG) has a long-term and effective outcome in weight reduction. However, studies have reported an increased incidence of gastroesophageal reflux disease (GERD) among patients after LSG. For those who fail to respond to conventional oral acid-suppressing medication, surgical intervention comes into consideration. The most commonly performed revisional surgery for sleeve gastrectomy is the Roux-en-Y gastric bypass, which can effectively alleviate the symptoms of reflux in patients and also continues to promote weight loss in patients who have not achieved satisfactory results or have experienced weight regain. In addition to this established procedure, innovative techniques such as laparoscopic magnetic sphincter augmentation (MSA) are being explored. MSA is less invasive, has good reflux treatment outcomes, and its safety and efficacy are supported by the literature, making it a promising tool for the future treatment of gastroesophageal reflux. This article also explores the role of endoscopic interventions for GERD treatment of post-sleeve gastrectomy patients. Although these methods have shown some therapeutic effect, their efficacy still requires further study due to a lack of support from more clinical data. For patients with preoperative hiatal hernia or gastroesophageal reflux symptoms, some experts now consider performing LSG combined with hiatal hernia repair or fundoplication to alleviate or prevent postoperative reflux symptoms. Both of these surgical approaches have demonstrated favorable outcomes; however, the addition of fundoplication requires further investigation regarding its long-term effects and potential postoperative complications. This article gathers and examines the current laparoscopic and endoscopic treatments for refractory gastroesophageal reflux following LSG, as well as the concurrent treatment of LSG in patients with preoperative gastroesophageal reflux or hiatal hernia.

Clinical, Radiological Features and Treatment Outcomes of Tuberculosis in Patients Aged 75 Years and Older.

Tuberculosis (TB) is a significant contributor to morbidity and mortality. With a progressively aging population, TB is increasingly encountered in older adults. Understanding the clinical presentation and optimal treatment strategies for TB in this population is essential. Clinical, radiological features, treatment, and outcome of patients aged 75 and above who were diagnosed with tuberculosis at King Abdulaziz Medical City in Riyadh in the period between January 2015 to December 2021wereevaluated retrospectively. Among 92 elderly tuberculosis patients, most were male (76.1%) with a mean age of 82.5 years. Pulmonary TB was diagnosed in 52.2% of patients, Extra Pulmonary TB in 32.6%, and Disseminated TB in 15.2%. Comorbidities included Diabetes Mellitus (59.8%) and Congestive Heart Failure (41.3%). The most common presentation symptoms included cough (51.1%), fever (43.5%), dyspnea (39.1%), and weight loss (31.5%). Delay of TB diagnosis for up to 3 months was observed in 31.5% of patients. Weight loss and male gender were significant predictors of delayed diagnosis. Laboratory findings varied among TB types, with disseminated TB showing higher eosinophilia and thrombocytopenia. Completion of an initial RIPE treatment protocol was achieved in 67.6% of patients. Mortality during treatment occurred in 23.9% of patients. Pulmonary TB was associated with higher mortality compared to extrapulmonary TB (p = 0.007). Tuberculosis is associated with high mortality in patients above the age of 75. There is still a substantial delay in TB diagnosis in the elderly. RIPE regimen is frequently changed due to side effects. Alternative regimen choices were quite variable. More studies on tuberculosis in this patient's population are needed to define the most effective therapeutic approach.

Exploring the Synergy of Immunotherapy and Conventional Treatments in Cancer Therapy

Immunotherapy (cancer immunotherapy) is a promising approach to cancer treatment that recognizes and destroys cancer cells by employing immune-related components or by directing the immune system. Between 2017 and 2020, the R&amp;D pipeline for cancer immunotherapies increased by 233%. Immunotherapy can be broadly divided into five broad categories and is suitable for 20 different types of cancer. With the introduction of immune checkpoint inhibitors and CAR-T cell therapies, this approach has revolutionized the way of cancer treatment, even treating some patients with advanced cancers, while not all cancer types respond well to this approach. The effectiveness of immunotherapy as a stand-alone treatment is often constrained by tumor heterogeneity, immune evasion, and resistance mechanisms. To address these issues, immunotherapy is being investigated in combination with other traditional treatment modalities such as radiotherapy, chemotherapy and targeted drugs as a way to improve treatment outcomes. This review explores the rationale behind these combination therapies and discusses the potential of these combined therapies to improve patient survival and quality of life.

Targeting CDK2 to combat drug resistance in cancer therapy.

Drug resistance remains a major obstacle in cancer treatment, leading to treatment failures and high mortality rates. Despite advancements in therapies, overcoming resistance requires a deeper understanding of its mechanisms. This review highlights CDK2's pivotal role in both intrinsic and acquired resistance, and its potential as a therapeutic target. Cyclin E upregulation, which partners with CDK2, is linked to poor prognosis and resistance across various cancers. Specifically, amplifications of CCNE1/CCNE2 are associated with resistance to targeted therapies, immunotherapy, endocrine therapies and chemo/radiotherapy. Given CDK2's involvement in resistance mechanisms, investigating its role presents promising opportunities for developing novel strategies to combat resistance and improve treatment outcomes.

Research Progress of Chinese Medicine Monomers in Treatment of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocytes. However, it remains unclear about the pathogenesis of this carcinoma, which may be related to multiple factors. Currently, CCA is mainly treated by surgery, chemotherapy, and radiotherapy. Among them, surgery is the only potentially curative option for CCA. Nevertheless, the high malignancy and asymptomatic nature of CCA may lead to poor treatment outcomes. It has been demonstrated that Chinese medicine (CM) plays a significant role in various antitumor applications. Meanwhile, CM exhibits fewer side effects and high availability. Moreover, the in vitro application of CM monomers has been explored in many domestic and foreign studies. This article mainly reviews the signaling pathways and molecular mechanisms of CM monomers in the treatment of CCA in recent years. These findings are expected to provide new insights into the treatment of CCA.

Impact of systemic diseases on oral health and facial surgery outcomes

Systemic diseases have a profound influence on oral health and maxillofacial surgical outcomes, presenting challenges that require comprehensive management. Diabetes mellitus is a prominent example, with its impact on periodontal health and healing processes being well-established. Elevated blood glucose levels in diabetic patients impair immune response, reduce collagen synthesis, and delay wound healing, increasing the risk of periodontitis and postoperative complications following surgical interventions such as dental implants. Similarly, cardiovascular diseases exacerbate the inflammatory response linked to periodontal disease, potentially worsening both oral health and systemic conditions, thus complicating the recovery process after maxillofacial surgery. These patients often face heightened risks of infections and slower healing, partly due to the frequent use of anticoagulant medications, which can interfere with surgical procedures. Immunocompromised individuals, such as those with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) or undergoing chemotherapy, also experience significant oral health challenges, including higher susceptibility to oral infections and delayed tissue repair. Reduced immune function and mucosal integrity make it difficult for these patients to recover effectively after maxillofacial surgery, increasing the risk of complications such as infection and wound dehiscence. Moreover, osteoporosis, a systemic condition characterized by reduced bone density, affects the success of dental implants and bone grafting procedures. The decreased bone quality in osteoporotic patients compromises the ability to achieve stable osseointegration, leading to higher implant failure rates and additional surgical challenges. Addressing these complex interactions between systemic health and oral conditions requires an interdisciplinary approach, integrating medical and dental care to enhance treatment outcomes. Proper management of systemic diseases, along with individualized dental and surgical protocols, is essential to improving the prognosis for patients with concurrent systemic and oral health issues.

Unlocking Nitrofurantoin: Understanding Molecular Mechanisms of Action and Resistance in Enterobacterales.

Antimicrobial resistance (AMR) is a global health crisis that has already claimed millions of lives and is projected to affect millions more unless urgent action is taken. Effective control of AMR requires the correct choice and dosage of antibiotics, as well as robust surveillance and research. Understanding the mechanisms of antibiotic action and the emergence of resistance phenotypes along with their genotypes is essential. This knowledge, combined with insights into resistance prevalence and spread, empowers clinicians to propose alternative therapies. Nitrofurantoin, a 70-year-old antibiotic, remains effective for the treatment of uncomplicated lower UTIs. Preventing emergence and spread of nitrofurantoin resistant superbugs would preserve the efficacy of this antibiotic which is crucial for ongoing and future AMR efforts. Nitrofurantoin resistance evolves slowly, leading to low prevalence compared to other antibiotics. However, it is often linked with extensive drug resistance, complicating treatment outcomes. Even a minor percentage of nitrofurantoin-resistant bacteria can cause significant clinical challenges due to irreversible evolution. While detailed study of these mechanisms can guide the development of strategies to combat nitrofurantoin resistance, early detection of resistant infections is critical for saving lives. The current review aims to provide a comprehensive analysis of nitrofurantoin's mechanisms of action, resistance evolution, prevalence, and resistance prediction. Our goal is to offer valuable insights for researchers and clinicians to enhance nitrofurantoin use and address the challenges posed by AMR.

Platelets and circulating (and tumor) cells: partners in promoting metastatic cancer.

Despite being discovered decades ago, metastasis remains a formidable challenge in cancer treatment. During the intermediate phase of metastasis, tumor cells detach from primary tumor or metastatic sites and travel through the bloodstream and lymphatic system to distant tissues. These tumor cells in the circulation are known as circulating tumor cells (CTCs), and a higher number of CTCs has been linked to poor prognoses in various cancers. The blood is an inhospitable environment for any foreign cells, including CTCs, as they face numerous challenges, such as the shear stress within blood vessels and their interactions with blood and immune cells. However, the exact mechanisms by which CTCs survive the hostile conditions of the bloodstream remain enigmatic. Platelets have been studied for their interactions with tumor cells, promoting their survival, growth, and metastasis. This review explores the latest clinical methods for enumerating CTCs, recent findings on platelet-CTC crosstalk, and current research on antiplatelet therapy as a potential strategy to inhibit metastasis, offering new therapeutic insights. Laboratory and clinical data have provided insights into the role of platelets in promoting CTC survival, while clinical advancements in CTC enumeration offer improved prognostic tools. CTCs play a critical role in metastasis, and their interactions with platelets aid their survival in the hostile environment of the bloodstream. Understanding this crosstalk offers insights into potential therapeutic strategies, including antiplatelet therapy, to inhibit metastasis and improve cancer treatment outcomes.

From hurdles to high performance: overcoming day-to-day challenges for successful clinical trials at sites

Randomized clinical trials are fundamental in testing new drugs, medical devices and treatment protocols. They help to determine the efficacy and safety of new treatments, leading to medical innovations that can significantly improve treatment outcomes. Clinical trial sites are the engines that drive medical advancements, but they face numerous challenges in their day-to-day operations and impact the study outcome as well as data quality. Continuous improvement through research and innovation ensures that clinical trials are conducted more effectively, leading to better healthcare advancements and patient outcomes. Execution of clinical trial at the hospital site is a critical task and associated with the new challenges every day which may include patient recruitment, retention and compliance to the data collection. GCP compliance is a soul of clinical research and difficult task to comply with. GCP is a harmonized guideline accepted by most of the countries all across the globe.

Sequential Release of Ibuprofen and the Gasotransmitter Hydrogen sulfide using Oxanorbornane-Based Synthetic Lipids as Carriers.

After understanding the biological signaling roles of hydrogen sulfide and its involvement in various physiological processes, there has been enormous interest in exploring its therapeutic utility in areas such as cancer, inflammation, cardiovascular diseases, etc. There is also growing interest in using suitable H2S donors in combination with other drugs to improve the treatment outcome through the modulation of multiple pathways. The premature release of H2S from small molecule donors and the difficulty in controlling its spatio-temporal distribution are the major challenges during these efforts. Hence the development of appropriate carriers that can release this gasotransmitter along with the therapeutic entity of interest in a controlled manner has high significance. In this regard, this report presents a novel drug delivery system from oxanorbornane-based synthetic lipids that carries a H2S-releasing 1,2-dithiole-3-thione moiety as part of the head group. Nanoaggregates of the resulting conjugate are not only capable of efficiently entrapping a non-steroidal anti-inflammatory drug such as ibuprofen, but also release this drug and H2S in a controlled and sequential manner.

Cachexia and efficiency of trifluridine/thymidine phosphorylase inhibitor + bevacizumab in metastatic colorectal cancer

In later-line treatment of metastatic colorectal cancer (mCRC), there may be large differences in treatment efficacy depending on cancer cachexia. Recently, the cachexia index (CXI), which was calculated from the skeletal muscle mass index (SMI), serum albumin concentration, and neutrophil-to-lymphocyte ratio, was developed to evaluate cancer cachexia. We retrospectively examined the CXI of 80 patients who were treated with trifluridine/thymidine phosphorylase inhibitor (FTD/TPI) + bevacizumab (Bmab) therapy as a later-line treatment for mCRC, and assessed the impact of cancer cachexia on chemotherapeutic efficacy using CXI. Progression-free and overall survival rates were significantly worse in the low CXI group than in the high CXI group, although there were no marked differences in tumor factors, such as the number of metastatic organs or gene mutations, between the two groups. As the cross-sectional area of the iliopsoas muscle was significantly associated with that of the skeletal muscle, the accuracy of the CXI based on the psoas mass index (P-CXI), which is easier to calculate than the SMI, in predicting treatment outcomes was equivalent to that of the CXI based on the SMI (S-CXI). Cancer cachexia is an important factor related to treatment efficacy in later-line treatments, such as FTD/TPI + Bmab therapy.