Search Results (261)

Objective: Pain response scores were evaluated by associating pain biomarkers with several parameters affecting radiotherapy (RT)-induced pain response in patients with bone metastases. Methods: A newly developed ‘revised pain and response scale’ based on standardized scales was used for pain scoring. TRPV1, β-endorphin (bEP), neurotensin (NT), and orexin A (OXA) biomarkers were determined by ELISA before and after RT. Results: Pain response rates were 44.75% (n = 47) poor response, 10.5% (n = 11) moderate response, 44.75% (n = 47) good response. NLR before RT was higher in patients with poor response than those with good response (4.0 (1.3–36.7) vs. 2.6 (1.2–11.4), respectively (p = 0.036). NLR after RT was lower in patients with good response than in patients with poor response (3.1 (1.2–10.8) and 3.9 (0.8–37.2), respectively (p = 0.047). There was a significant correlation between response scores and NT, bEP, and TRPV1. In patients with good response, NT and bEP decreased, while TRPV1 increased, both of which were significant. Pre-RT and post-RT values were, respectively, NT: 631.4 (39.7–2863.0) vs. 400.3 (79.1–1479.0) p = 0.006) and bEP: 92.1 (18.7–228.8) vs. 49.1 (13.3–135.6) p ≤ 0.001). TRPV1 values: 321.7 (48.1–1100.7) vs. 352.8 (119.3–1510.9) p ≤ 0.001). Conclusions: The study found no difference in pain response scores between the different fractionation treatments. Significant changes in NT, bEP, and TRPV1 levels were seen in patients with a ‘good response’. Pain response ratings were potentially least affected by OXA. Changes in NT, TRPV1, and bEP levels represent RT’s pain response efficacy and patients’ pain perception. These pain biomarkers may be included in guidelines as part of pain response monitoring strategies in the future. Full article

Cholangiocarcinoma (CCA) is an aggressive malignancy originating from the epithelial lining of the intrahepatic or extrahepatic bile ducts. Although rare globally, its mortality closely mirrors incidence due to late-stage presentation of the disease and limited curative options. While surgical resection and liver transplantation remain the cornerstone treatments for those with resectable disease, endoscopic techniques have emerged as versatile tools for diagnosis, therapy, and palliation. In recent years, there have been major advancements in endoscopic therapies, including radiofrequency ablation (RFA), intraluminal brachytherapy (ILBT), and photodynamic therapy (PDT). The current narrative review serves to provide an overview of current and emerging endoscopic strategies for CCA, emphasizing diagnostic capabilities, therapeutic approaches, palliative interventions, and future directions. Full article

With increasing life expectancy, the number of older people living with comorbid diabetes and frailty is increasing. The development of frailty accelerates diabetes-related adverse outcomes. Frailty is a multidimensional syndrome with physical, mental and social aspects which is associated with increased risk of hypoglycaemia, dementia and hospitalisation. Therefore, regular screening for all aspects of frailty should be an integrated part of the care plans of older people with diabetes. In addition, every effort should be made for prevention, which includes adequate nutrition combined with regular resistance exercise training. In already frail older people with diabetes, metabolic targets should be relaxed and hypoglycaemic agents should be of low hypoglycaemic risk potential. Furthermore, the metabolic phenotype of frailty should be considered when choosing hypoglycaemic agents and determining targets. With increasing severity of frailty, proactive chronological plans of de-escalation, palliation and end-of-life care should be considered. These plans should be undertaken in a shared decision-making manner which involves patients and their families. This ensures that patients’ views, wishes and preferences are in the heart of these plans. Full article

Malignant gastric outlet obstruction (MGOO) is a serious complication arising from advanced gastric or pancreatic head cancer, significantly impairing patients’ quality of life by disrupting oral intake and inducing severe gastrointestinal symptoms. With benign causes such as peptic ulcer disease on the decline, malignancies now account for 50–80% of gastric outlet obstruction (GOO) cases globally. This review outlines the pathophysiology, evolving epidemiology, and treatment modalities for MGOO. Therapeutic approaches include conservative management, endoscopic stenting, surgical gastrojejunostomy (GJ), stomach partitioning gastrojejunostomy (SPGJ), and endoscopic ultrasound-guided gastroenterostomy (EUS-GE). While endoscopic stenting offers rapid symptom relief with minimal invasiveness, it has higher rates of re-obstruction. Surgical options like GJ and SPGJ provide more durable palliation, especially for patients with longer expected survival. SPGJ, a modified surgical technique, demonstrates reduced incidence of delayed gastric emptying and may improve postoperative oral intake and survival compared to conventional GJ. EUS-GE represents a promising, minimally invasive alternative that combines surgical durability with endoscopic efficiency, although long-term data remain limited. Treatment selection should consider patient performance status, tumor characteristics, prognosis, and institutional resources. This comprehensive review underscores the need for individualized, multidisciplinary decision-making to optimize symptom relief, nutritional status, and overall outcomes in patients with MGOO. Full article

Osteoarthritis (OA) remains a major contributor to pain and disability; however, the current management is largely reactive, focusing on symptoms rather than preventing irreversible cartilage loss. This review first examines the mechanistic foundations for pharmacological chondroprotection—illustrating how conventional agents, such as glucosamine sulfate and chondroitin sulfate, can potentially restore extracellular matrix (ECM) components, may attenuate catabolic enzyme activity, and might enhance joint lubrication—and explores the delivery challenges posed by avascular cartilage and synovial diffusion barriers. Subsequently, a practical “What–How–When” framework is introduced to guide community pharmacists in risk screening, DMOAD selection, chronotherapeutic dosing, safety monitoring, and lifestyle integration, as exemplified by the CHONDROMOVING infographic brochure designed for diverse health literacy levels. Building on these strategies, the P4–4P Chondroprotection Framework is proposed, integrating predictive risk profiling (physicians), preventive pharmacokinetic and chronotherapy optimization (pharmacists), personalized biomechanical interventions (physiotherapists), and participatory self-management (patients) into a unified, feedback-driven OA care model. To translate this framework into routine practice, I recommend the development of DMOAD-specific clinical guidelines, incorporation of chondroprotective chronotherapy and interprofessional collaboration into health-professional curricula, and establishment of multidisciplinary OA management pathways—supported by appropriate reimbursement structures, to support preventive, team-based management, and prioritization of large-scale randomized trials and real-world evidence studies to validate the long-term structural, functional, and quality of life benefits of synchronized DMOAD and exercise-timed interventions. This comprehensive, precision-driven paradigm aims to shift OA care from reactive palliation to true disease modification, preserving cartilage integrity and improving the quality of life for millions worldwide. Full article

Pancreatic cancer is an aggressive malignancy, with a current 5-year survival rate in the United States of approximately 13.3%. Although the current standard for resectable pancreatic cancer most commonly includes neoadjuvant chemotherapy prior to a curative resection, surgery, in the majority of patients, has historically been palliative. The latter interventions include open or laparoscopic bypass of the bile duct or stomach in cases of obstructive jaundice or gastric outlet obstruction, respectively. Non-surgical interventional therapies started with percutaneous transhepatic biliary drainage (PTBD), both as a palliative maneuver in unresectable patients with obstructive jaundice and to improve liver function in patients whose surgery was delayed. Likewise, interventional radiologic techniques included the placement of plastic and ultimately self-expandable metal stents (SEMSs) through PTBD tracts in patients with unresectable cancer as well as percutaneous cholecystostomy in patients who developed cholecystitis in the context of malignant obstructive jaundice. Endoscopic retrograde cholangiopancreatography (ERCP) and stent placement (plastic/SEMS) were subsequently used both preoperatively and palliatively, and this was followed by, or undertaken in conjunction with, endoscopic gastro-duodenal SEMS placement for gastric outlet obstruction. Although endoscopic ultrasound (EUS) was initially used to cytologically diagnose and stage pancreatic cancer, early palliation included celiac block or ablation for intractable pain. However, it took the development of lumen-apposing metal stents (LAMSs) to facilitate a myriad of palliative procedures: cholecystoduodenal, choledochoduodenal, gastrohepatic, and gastroenteric anastomoses for cholecystitis, obstructive jaundice, and gastric outlet obstruction, respectively. In this review, we outline these procedures, which have variably supplanted surgery for the palliation of pancreatic cancer in this rapidly evolving field. Full article

Background: Patients with single right ventricular morphology (SRV) may exhibit impaired function with increased morbidity, mortality, and need for cardiac transplant due to progressive SRV failure after the Fontan procedure. The aim of the study was to longitudinally characterize the cardiac mechanics and trajectory of disease evolution of SRV failure in Fontan patients. Methods: We performed a case-controlled longitudinal study of 52 patients who underwent extracardiac Fontan palliation for SRV between 1994 and 2015 and compared echocardiographic measures of right ventricular (RV) function, RV-systemic vascular coupling and ventricular remodeling between patients who required heart transplants due to SRV failure (study group, n = 26) and those who did not (control group, n = 26). To define the trajectory, measurements were obtained at four matching time points equivalent in duration from Fontan. Results: RV circumferential shortening function declined in both groups over the time period, but was significantly lower (p < 0.01) in the study group farther from the Fontan. RV-systemic vascular coupling, assessed by systolic time interval measures and RV work, was preserved in the control group, but significantly altered (p < 0.001) in the study group. Relative wall thickness decreased, and the minor/major-axis ratio, as an index of ventricular geometry, increased in the study group, but both remained stable in the control group. Conclusions: This study suggests that positive ventricular remodeling with enhanced circumferential systolic function, and preserved RV-vascular coupling, appear to be adaptive and protective mechanisms against RV failure in Fontan with SRV. These indices of cardiac mechanics may serve as clinically relevant quantifiable markers of disease evolution, and early indicators for therapeutic intervention. Full article

Background/Objectives: Colorectal cancer (CRC) is the most common gastrointestinal (GI) malignancy, the second leading cause of cancer-related mortality, and the third most prevalent tumor. Around 20% of cases are metastatic or inoperable at diagnosis, often requiring palliative treatment, which may not be feasible in frail patients. Calcium-electroporation, a less invasive alternative, induces cell death via apoptosis, necrosis, and pyroptosis. This study is the first in the United Kingdom to evaluate the efficacy and safety of endoscopic calcium-electroporation in palliating distal CRC. Methods: Frail patients with inoperable left-sided CRC were included. The diagnosis and staging followed standard guidelines, while frailty was assessed using the performance status (PFS), Charlson comorbidity index (CCI), and American Society of Anesthesiologists (ASA) score. Calcium electroporation was performed via a flexible endoscopy usually under sedation, with symptom relief, quality of life (QoL), survival, and adverse events (AE) monitored. Results: Sixteen patients (median age 84.5) underwent 36 treatments with electroporation over 28 months (November 2022 to March 2025). The incidence of common symptoms was rectal bleeding (75%), constipation (25%), and pain (75%). Nine patients had metastases and three had failed conventional treatments. Symptomatic relief and an improved QoL occurred in 86.7%, with transfusion/iron infusion needs reduced by 91.7%. The median cancer-specific survival was 10 months, with a 94% survival rate. No device-related AE was recorded. One patient died after 11 months due to disease progression while two patients passed away from other medical conditions. Conclusions: Endoscopic calcium electroporation is a safe, palliative option effective for tumor reduction and symptomatic relief in frail CRC patients unfit for conventional therapies. Full article

Glioblastoma (GBM, isocitrate dehydrogenase wild-type) is the most common primary malignant brain tumor in adults and is associated with a severely low survival rate. Treatments offer mere palliation and are ineffective, due, in part, to a lack of understanding of the intricate mechanisms underlying the disease, including the contribution of the tumor microenvironment (TME). Current GBM models continue to face challenges as they lack the critical components and properties required. To address this limitation, we developed innovative and practical three-dimensional (3D) GBM models with structural and mechanical biomimicry and tunability. These models allowed for more accurate emulation of the extracellular matrix (ECM) and vasculature characteristics of the native GBM TME. Additionally, 3D bioprinting was utilized to integrate these complexities, employing a hydrogel composite to mimic the native environment that is known to contribute to tumor cell growth. First, we examined the changes in physical properties that resulted from adjoining hydrogels at diverse concentrations using Fourier-Transform Infrared Spectroscopy (FTIR), compression testing, scanning electron microscopy (SEM), rheological analysis, and degradation analysis. Subsequently, we refined and optimized the embedded bioprinting processes. The resulting 3D GBM models were structurally reliable and reproducible, featuring integrated inner channels and possessing tunable properties to emulate the characteristics of the GBM ECM. Biocompatibility testing was performed via live/dead and AlamarBlue analyses using GBM cells (both commercial cell lines and patient-derived cell lines) encapsulated in the constructs, along with immunohistochemistry staining to understand how ECM properties altered the functions of GBM cells. The observed behavior of GBM cells indicated greater functionality in softer matrices, while the incorporation of hyaluronic acid (HA) into the gelatin methacryloyl (gelMA) matrix enhanced its biomimicry of the native GBM TME. The findings underscore the critical role of TME components, particularly ECM properties, in influencing GBM survival, proliferation, and molecular expression, laying the groundwork for further mechanistic studies. Additionally, the outcomes validate the potential of leveraging 3D bioprinting for GBM modeling, providing a fully controllable environment to explore specific pathways and therapeutic targets that are challenging to study in conventional model systems. Full article

Staged palliation with the creation of a Fontan circulation is the standard surgical approach in patients with a single ventricle. The Fontan circulation is a complex circuit that is associated with various complications that may present early or later in life and can limit life quality and expectancy. In this context, a good understanding of the Fontan physiology is important to improve outcomes for single-ventricle patients. Cardiovascular magnetic resonance (CMR) is recommended for the long-term follow-up of Fontan patients, as it provides functional and haemodynamic information. Four-dimensional (4D) Flow MRI is a time-resolved, three-dimensional, velocity-encoded cardiovascular magnetic resonance technique that is increasingly used in Fontan patients because it not only enables measuring blood flow within a three-dimensional (3D) volume, but also allows for assessing more advanced haemodynamic parameters that may help in understanding the Fontan physiology and pathophysiology. Furthermore, 4D Flow is used for image-based simulations using computational fluid dynamics. In this review, we provide an overview of the use of cardiovascular magnetic resonance flow assessment, with a focus on four-dimensional flow (‘4D Flow’). Full article

Background: Keratinocyte carcinomas, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), presents a growing concern. Electrochemotherapy (ECT), an emerging treatment modality, combines chemotherapy and electroporation to enhance drug delivery into cells. However, reviews evaluating ECT in keratinocyte carcinomas are lacking. Objectives: This study reviews the efficacy and toxicity of ECT in the treatment and palliation of keratinocyte carcinomas. Methods: A systematic search was conducted across PubMed, Cochrane, Embase, and Scopus databases. Patient, tumor, and treatment characteristics, tumor response, long-term disease outcomes, and toxicity data were extracted. Quality of studies was assessed using validated tools. Primary endpoints included tumor response; secondary endpoints included long-term disease outcomes and toxicity. Results: Twenty-one studies were included. Complete response (CR) rates ranged from 50 to 100% and from 10 to 100% for BCC and SCC, respectively. OS rates ranged from 95 (14 months) to 100 (1 year) % and from 64 (1 year) to 85.1 (8.6 months) % for BCC and SCC, respectively. One-year local disease-free survival (LDFS) rates were 89% and 87% for BCC and SCC, respectively. For BCC, local progression-free survival (LPFS) rates were 96% (1 year), 90% (2 year), and 70% (5 year). For SCC, 1-year LPFS rates were 80% on a per-patient basis and 49% on a per-lesion basis. Conclusions: ECT is effective and tolerable in the treatment and palliation of keratinocyte carcinomas. Future studies should focus on improving reporting quality, optimizing treatment protocols, and investigating long-term outcomes. Full article

Proventricular dilatation disease (PDD) is a neurologic syndrome of birds caused by the infectious agent Psittacine Bornavirus (PaBV). Clinical disease may be based on the T-cell-mediated immune response to PaBV within the central and peripheral nervous system, similar to Borna disease virus, a closely related mammalian virus. Lymphoplasmacytic infiltrations may occur in ganglia, nerve plexuses, peripheral nerves and the central nervous system of the infected bird. Clinical disease may result in multiple neurologic disorders and life-threatening morbidity. Treatment of PDD with antivirals and non-steroidal anti-inflammatories has thus far been non-curative and unsuccessful long-term. Cyclosporine is an immunosuppressant drug that decreases cell-mediated immune responses by inhibiting T-cell proliferation and decreasing cytokine production. In avian species, cyclosporine is a potent immunosuppressant with T-cell-specific action. A pilot study performed in PaBV-infected cockatiels showed increased weight gain and a lack of morbidity or mortality following experimental PaBV infection and cyclosporine treatment at 10 mg/kg orally every 12 h. In this case series of six psittacine birds affected by PDD, cyclosporine at this dose alleviated or reduced clinical signs in multiple birds without severe sequelae. Itraconazole was used concurrently in these cases to prevent secondary fungal infections during immunosuppression but may have had a synergetic effect when used in combination with cyclosporine. Further prospective research is indicated to better evaluate cyclosporine use in birds with PDD. However, these preliminary clinical findings suggest that cyclosporine and itraconazole administration is a treatment option for palliation of PDD in psittacine patients, especially those refractory to other treatments. Full article

Background: It is well known that supportive care clinics are vital in medical oncology practice. This study aims to present a portrait of the supportive care clinic of a tertiary cancer center in a low-middle-income country. Methods: This study included patients admitted to our supportive care clinic between January 2019 and December 2023. This study included patients who attended the supportive care clinic. For patients who were readmitted more than once throughout the study period, only the first readmission was included in the analysis. The primary outcome of this study was a better understanding of the risk factors associated with hospital readmissions in cancer patients, which could lead to improved patient outcomes. In addition, the secondary objective was to identify the characteristics of patients and clinical decisions regarding follow-ups as inpatients or outpatients referred to the supportive care clinic. Results: This study included 477 patients; 300 (62.9%) were directed to oncology inpatient care, while 177 (37.1%) were treated as outpatients. The most common diagnoses were lung cancer (20.5%), colorectal cancer (13.6%), and breast cancer (8.4%). Most patients (71.5%) were evaluated for symptom palliation. In multivariate analysis, metastatic disease (OR: 2.52 95% CI 1.48–4.29 p = 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (OR: 1.58 95% CI 1.04–2.42 p = 0.034), and a decrease in albumin levels (OR: 0.42 95% CI 0.29–0.61 < 0.001) were significantly related to hospitalization. In univariate analyses, albumin level (p < 0.001), disease stage (p = 0.007), and ECOG performance status (p = 0.025) were statistically associated with unplanned hospital readmission. Among these factors, a decrease in albumin levels was significantly associated with the outcome, with an odds ratio of 0.54 (95% CI 0.39–0.75, p < 0.001), indicating a protective effect of higher albumin levels. In univariate analyses, sex (p = 0.016), cancer treatment type (p = 0.010), albumin level (p < 0.001), disease stage (p < 0.001), unplanned hospital readmission (p < 0.001), ECOG performance status (p < 0.001), and hemoglobin (p = 0.008) were statistically related to overall survival. Among these factors, sex (HR: 1.28 95% CI 1.03–1.59 p = 0.025), a decrease in albumin levels (HR: 0.67 95% CI 0.56–0.82 p < 0.001), disease stage (HR: 1.52 95% CI 1.11–2.09 p = 0.008), unplanned hospital readmission (HR: 1.30 95% CI 1.03–1.63 p = 0.027), and ECOG performance status (HR: 3.45 95% CI 2.68–4.45 p < 0.001) remained significant in the multivariate analysis. Conclusions: This study shows that supportive care clinics are a key element of patient care. Early evaluation of patients in supportive care clinics may aid clinicians in identifying high-risk patients who may require closer follow-up or inpatient care. Several factors were identified as predisposing to hospitalization, unplanned hospital readmission, and overall survival. Further prospective studies are needed to determine the risk factors associated with hospitalization, readmission, and overall survival. Full article

Background: Central airway obstruction (CAO) remains a major challenge in thoracic oncology, particularly in patients with advanced lung cancer. Despite advances in systemic therapies, interventional bronchoscopy, especially rigid bronchoscopy (RB), plays a critical role in managing CAO. Methods: Between June 2005 and December 2023, 416 patients with central airway obstructions were treated. The cohort included 213 males (51%) and 203 females (49%), with a mean age of 64.8 years. A retrospective review of patient data was conducted, and descriptive statistics were used to summarize demographics and procedural outcomes. Survival rates and complication data were analyzed using Kaplan–Meier survival curves. Multivariate analysis was performed to identify significant predictors of survival and complications, considering factors such as tumor stage, prior treatments, and comorbidities. The study also analyzed the impact of adjuvant therapies and stenting on patient outcomes. Results: Of the 416 patients, 86 (20.7%) had benign lesions, including 61 cases of post-tracheostomy stenosis or prolonged intubation, while the remaining 330 (79.3%) had malignant CAO. Patients receiving adjuvant therapies showed a significant survival advantage, with a median survival of 24 months compared to 15 months for those not receiving adjuvant therapies (p = 0.015). Stenting was performed in 141 cases, but no significant survival difference was found between patients with and without stents (p = 0.52). Complications were rare, with airway rupture observed in 1.9% and perioperative mortality in 0.25%. Symptom relief was achieved in the majority of patients, with significant improvements in quality of life, particularly in those with malignant obstructions. Conclusions: RB remains a cornerstone in the management of CAO, providing effective and durable symptom relief. It is particularly beneficial for advanced malignancies, offering a palliative approach that improves both survival and quality of life. Our study supports the guidelines endorsing RB for CAO management and highlights its role in providing significant symptom relief and stabilization in patients with severe airway obstruction. Full article

Background: Mild traumatic brain injury (mTBI) in the pediatric population is a significant public health concern, often associated with persistent post-concussion symptoms, including postural instability. Current tools for assessing postural control, such as the Balance Error Scoring System (BESS), lack integration with objective metrics. Incorporating force plate sensors into BESS assessments may enhance diagnostic accuracy and support return-to-play or sports decisions. This study evaluates postural performance in children with mTBI compared to controls using an instrumented BESS and examines recovery trajectories after mTBI. Methods: This prospective, longitudinal study included 31 children with mTBI (12.01 ± 3.28 years, 20 females) and 31 controls (12.31 ± 3.27 years, 18 females). Postural control was assessed using an instrumented BESS protocol during standing on a ground reaction force plate at three timepoints: within 72 h post injury (T1), at two weeks (T2), and three months after trauma (T3). Posturographic parameters derived from the displacement of the center of pressure included the ellipse area, path length, and mean velocity in the anterior–posterior and medio–lateral directions. Symptom burden was monitored using the Post-Concussion Symptom Inventory (PCSI). Results: The BESS total scores did not differ significantly between the groups at any timepoint. A significant reduction in BESS errors over time was observed exclusively in the two-legged stance on a soft surface (p = 0.047). The instrumented BESS revealed higher body swaying in the mTBI group compared to controls, particularly under demanding conditions. Significant between-group differences were most frequently observed in single-leg soft surface (38% of comparisons) and two-legged soft surface stances (29%). In those cases, path length and mean velocity differed between groups, respectively. Ellipse area did not show significant differences across conditions. Conclusions: An instrumented BESS has the potential to enhance the detection of subtle postural deficits in pediatric mTBI patients. Specifically, more demanding conditions with altered sensory-proprioceptive input and path length as an outcome measure should be focused on. This study underscores the need for tailored and age-appropriate objective and quantitative balance assessments to improve diagnostic precision in pediatric mTBI populations. Full article