Abstract: Atrial fibrillation (AF) significantly increases stroke and mortality risk, and while high-sensitivity Troponin I (hs-TnI) is associated with AF in the general population, its predictive value in high-risk groups is unclear. This study investigated whether baseline hs-TnI predicts new-onset AF in patients with pre-existing non-AF arrhythmias. This prospective, single-center, observational study involved 232 patients without a prior history of AF, who were followed for a median of 12 months. Baseline hs-TnI levels were measured, and a multivariate Cox proportional hazards regression model was used to identify independent predictors of new-onset AF/Atrial Flutter (AFL). During fol-low-up, 16 cases (6.9%) of new-onset AF/AFL occurred. Although Kaplan-Meier analy-sis showed a trend, hs-TnI was not found to be an independent predictor in the multi-variate model (HR=1.000, p=0.844). Conversely, the risk of new-onset AF was strongly and independently predicted by Left Atrial (LA) size (HR=1.27, p< 0.001), a history of Diabetes Mellitus (HR=5.99, p=0.006), and a history of Stroke (HR=10.18, p=0.032). In conclusion, baseline hs-TnI does not independently predict the development of new-onset AF in patients with non-AF arrhythmias. Risk stratification in this vulnerable population should instead prioritize established structural changes (LA size) and major systemic comorbidities (Diabetes Mellitus and prior Stroke).

Abstract: Background: Folliculitis is a common inflammatory condition for which non-antibiotic topical options remain limited. This pilot study evaluated the performance and safety of a medical device gel containing hyaluronic acid and hydrogen peroxide, already in use in dermatologic practice. The study generated preliminary efficacy outcomes and assessed the viability for a future comparative trial on folliculitis.Methods: This open-label, non-comparative, post-marketing clinical follow-up study enrolled adults (aged 18–45 years) diagnosed with folliculitis. Patients applied the gel at home for eight weeks following the device’s instructions for use. Efficacy was assessed by the number of lesions, Total Severity Score (TSS), Investigator Global Assessment of Performance (IGAP), patient satisfaction, and Dermatology Life Quality Index (DLQI). Safety was evaluated by recording adverse events (AEs).Results: Thirteen patients (mean age 30.1 ± 7.72) were included. The duration of enrollment and its rate met the assumptions for carrying out the future comparative trial. The mean number of lesions decreased three-fold from baseline to week 8 (p = 0.005), while TSS improved by 66.6% (p = 0.002). All participants reported high or very high treatment satisfaction. The mean IGAP at week 8 was 1.39 ± 0.65, and DLQI scores indicated a marked improvement in quality of life. Two mild, transient site effects were recorded.Conclusions: This pilot study confirmed favorable safety and performance outcomes for the hyaluronic acid/hydrogen peroxide gel in patients with folliculitis. The findings support its use in daily dermatologic practice and provide feasibility data for a future randomized comparative trial.

Abstract:

Background: Takotsubo syndrome (TTS) often mimics anterior ST-elevation myocardial infarction (STEMI) caused by left anterior descending (LAD) occlusion, yet the two entities differ fundamentally in pathophysiology and mechanical behavior. Two-dimensional speckle-tracking echocardiography (2D-STE) enables detailed assessment of left ventricular (LV) deformation beyond conventional ejection fraction (LVEF). This meta-analysis compared global and regional LV strain patterns in TTS versus LAD-related anterior STEMI during the acute phase. Methods: A systematic search of PubMed, Embase, and Scopus through October 2025 identified observational case–control studies directly comparing TTS and angiographically confirmed anterior STEMI, with LV mechanics assessed by 2D-STE. Random-effects models were used to pool standardized mean differences (SMDs) for LVEF; global longitudinal strain (GLS); apical, mid-ventricular, and basal longitudinal strain (ALS, MLS, BLS); and global radial strain (GRS). Heterogeneity (I²), publication bias (funnel plots, Egger’s test), meta-regression, and leave-one-out sensitivity analyses were performed. Results: Six studies comprising 221 TTS and 290 anterior STEMI patients met the inclusion criteria. TTS patients were older, predominantly female, and had fewer metabolic risk factors, while LV size was comparable. LVEF was significantly lower in TTS (SMD −1.15; 95% CI −2.20 to −0.10; p = 0.032), with stable findings across sensitivity analyses and no evidence of publication bias. GLS, ALS, MLS, and BLS tended to be more impaired in TTS, although differences were not statistically significant due to marked inter-study heterogeneity. In contrast, GRS was significantly and consistently more reduced in TTS (SMD −1.28; 95% CI −1.59 to −0.98; p < 0.001), indicating more profound global radial dysfunction. Meta-regression showed no significant influence of demographic factors or vendor-specific software on LVEF or GLS differences. Conclusions: Compared with LAD-related anterior STEMI, TTS is characterized by more severely depressed LVEF and markedly impaired radial strain, with a consistent trend toward greater longitudinal dysfunction. This mechanical profile supports the concept of diffuse, stress-induced myocardial stunning in TTS and underscores the value of 2D-STE in differentiating stress cardiomyopathy from ischemic infarction in the acute setting.

Abstract:

This study investigates potential associations between aluminum-adjuvanted childhood vaccines and inflammatory conditions using population-level data from the National Survey of Children's Health (NSCH) 2020-2023 and the CDC National Immunization Survey (NIS) 2011-2017. By joining datasets across 50 U.S. states and the District of Columbia for birth years 2011-2017, we analyzed vaccine uptake probabilities as proxies for aluminum exposure and prevalences of autism (3.7%), allergies (26.1%), ADHD (8.1%), asthma (8.4%), epilepsy (0.94%), obesity (4.9%), and Tourette’s syndrome (0.21%), with blood disorders (0.46%) as a negative control.Methods involved calculating disease prevalence, disease correlations, and linear regressions between vaccine likelihoods (DTaP, HepB, Hib, PCV, Polio) across age windows (0-36 months) and outcomes.Results revealed strong positive correlations among inflammatory conditions (r=0.19-0.62, p<0.001) but none with blood disorders. Aluminum exposure proxies during 6-12 months forecasted higher disease prevalence (p<0.05), with nonlinear patterns including sign reversals across time periods, consistent with NLRP3 inflammasome's two-step activation threshold.These findings suggest aluminum adjuvants may contribute to NLRP3-mediated inflammation in susceptible populations, warranting further mechanistic and prospective studies to optimize vaccination strategies and explore inflammasome-targeted therapies for reducing chronic childhood disease burdens.

Abstract:

Background: The Right Ventricular Free Wall Longitudinal Strain/Pulmonary Arterial Systolic Pressure (RVFWLS/PASP) ratio is a novel echocardiographic parameter for assessing right ventricular–pulmonary artery (RV-PA) coupling. Its prognostic role in patients with pulmonary arterial hypertension (PAH) remains poorly defined. This study aimed to explore the prognostic value of RVFWLS/PASP in PAH. Methods: A retrospective cohort study was conducted involving patients with PAH at Shanghai Pulmonary Hospital and Nanyang Second People's Hospital from December 2009 to October 2024.The RVFWLS/PASP ratio is calculated, where the numerator (RVFWLS) is derived using speckle tracking echocardiography, and the denominator (PASP) is estimated based on the tricuspid regurgitation velocity. The primary endpoint was event-free survival, with events defined as all-cause mortality, lung transplantation, rehospitalization for right heart failure, or escalation of targeted therapy due to clinical deterioration. Cox regression analysis was used to identify and validate RVFWLS/PASP characteristics in patients with different outcomes. Kaplan-Meier survival analysis was employed to evaluate the additive value of RVFWLS/PASP to previously established risk models. Results: A total of 216 adult PAH patients were enrolled. The median follow-up time was 31 months. The survival rate of patients in the lower RVFWLS/PASP group was significantly worse than those in the higher RVFWLS/PASP group (Log-rank P <0.05). Multivariate Cox regression demonstrated that after adjusting for other prognostic factors,RVFWLS/PASP ratio (HR = 0.20, 95% CI: 0.04-0.92, p = 0.039) and CTD-PH diagnosis (HR = 2.09, 95% CI: 1.36-3.22, p < 0.001) remained independent predictors of adverse clinical events. RVFWLS/PASP enabled further risk stratification of patients classified as low-risk by established models. Conclusion: The echocardiographic parameter RVFWLS/PASP serves as an independent determinant of long-term prognosis in patients with PAH, indicating that improved RV-PA coupling is significantly associated with better clinical outcomes. RVFWLS/PASP provides incremental value for risk stratification and may demonstrate heterogeneous utility across different clinical subgroups.

Abstract: Glioblastoma is known as the most aggressive primary brain tumor in adults and it is still largely not curable, with a median survival of approximately 15 months when standard multimodal therapy is applied. The standard treatment nowadays is maximal safe surgical resection, associated with radiotherapy and temozolomide. Treatment effectiveness is limited not only by an impassable blood–brain barrier (BBB) to drug delivery to the brain, but also by the heterogeneity of the tumors and by intrinsic or gained drug resistance – resulting in a certain and inescapable tumor relapse. Therefore, novel drug delivery systems are being designed to overcome the BBB and improve therapeutic efficacy. These approaches include nanoparticle-mediated delivery systems, convection-enhanced intratumoral infusion, implantable drug-releasing devices, and noninvasive focused ultrasound technology induced transient disruption of the BBB. These approaches are designed to enhance local drug exposure and to reduce systemic toxicity with promising preclinical and early clinical results. However, many clinical and technical challenges remain, especially the need for safety, homogeneous drug delivery, and translation of these advances into effective clinical therapies. Current glioblastoma treatment landscape and opportunities include maturing delivery systems, novel therapeutic approaches including targeted molecular therapies and immunotherapy, as well as personalized regimens. This multidisciplinary modality may have the capacity to help not only GBM patients but others as well through a multimodal approach of targeted drug delivery and innovative therapy in the long run in order to improve clinical outcomes of GBM in patients.

Abstract: BACKGROUND: to evaluate the anatomical and functional outcomes associated with temporal arcuate relaxing retinotomy technique for persistent full-thickness macular hole (FTMH) repair. METHODS: a retrospective, single-center, interventional study of temporal relaxing retinotomy in eyes with persistent FTMHs following one or more standard repair procedures with pars plana vitrectomy and internal limiting membrane peeling. Patients received an additional pars plana vitrectomy and temporal arcuate relaxing retinotomy, followed by fluid-air and air-gas exchange. Key postoperative outcomes included the achievement of FTMH closure and changes in visual acuity from baseline. RESULTS: nine patients with persistent FTMHs were included, with a median age of 70 years (range, 58-76 years). The diameter of the 9 FTMHs ranged from 412 to 1037 µm (median, 613 µm). Vitrectomy and temporal relaxing retinotomy were performed in all 9 eyes. Successful FTMH closure was achieved in 7 of 9 eyes (closure rate, 78%), with an average postoperative follow up of 10.4 months (range: 2 to 20 months). 8 of 9 eyes (89%) achieved BCVA improvement during postoperative follow-up, including the long-standing FTMHs. Overall, mean BCVA (± SD) improved significantly from 1.26 ± 0.51 logMAR at baseline to 0.56 ± 0.27 logMAR during postoperative follow-up (P = 0,002). CONCLUSIONS: Temporal arcuate relaxing retinotomy may be an effective method to promote anatomical closure and to improve vision outcomes in patients with persistent FTMHs.

Abstract: Redox (reduction-oxidation) processes underlie all forms of life and are a universal regulatory mechanism that maintains homeostasis and adapts the organism to changes in the internal and external environments. From capturing solar energy in photosynthesis and oxygen generation to fine-tuning cellular metabolism, redox reactions are key determinants of life activity. Proteins containing sulfur- and selenium-containing amino acid residues play a crucial role in redox regulation. Their reversible oxidation by physiological oxidants, such as hydrogen peroxide (H₂O₂), plays the role of molecular switches that control enzymatic activity, protein structure, and signaling cascades. This enables rapid and flexible cellular responses to a wide range of stimuli—from growth factors and nutrient signals to toxins and stressors. Mitochondria, the main energy organelles and also the major sources of reactive oxygen species (ROS), play a special role in redox balance. On the one hand, mitochondrial ROS function as signaling molecules, regulating cellular processes, including proliferation, apoptosis, and immune response, while, on the other hand, their excessive accumulation leads to oxidative stress, damage to biomolecules, and the development of pathological processes. So, mitochondria act not only as a "generator" of redox signals but also as a central link in maintaining cellular and systemic redox homeostasis. Redox signaling forms a multi-layered cybernetic system, which includes signal perception, activation of signaling pathways, the initiation of physiological responses, and feedback regulatory mechanisms. At the molecular level, this is manifested by changes in the activity of redox-regulated proteins of which the redox proteome consists, thereby affecting the epigenetic landscape and gene expression. Physiological processes at all levels of biological organization—from subcellular to systemic—are controlled by redox mechanisms. Studying these processes opens a way to understanding the universal principles of life activity and identifying the biochemical mechanisms whose disruption causes the occurrence and development of pathological reactions. It is important to emphasize that new approaches to redox balance modulation are now actively developed, ranging from antioxidant therapy and targeted intervention on mitochondria to pharmacological and nutraceutical regulation of signaling pathways. This article analyzes the pivotal role of redox balance and its regulation at various levels of living organisms—from molecular and cellular to tissue, organ, and organismal levels—with a special emphasis on the role of mitochondria and modern strategies for influencing redox homeostasis.

Abstract: The drug delivery system of today is made up of heap of innovations like lipid-based nanocarriers, controlled-release technologies, and rapidly developing oral dosage forms. The present article is the first to provide an exhaustive coverage of the latest methods along with their benefits that include greater therapeutic effectiveness, better patient compliance, and flexibility in formulation. One of these methods is the use of lipid nanoparticles: liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and other vesicular systems which are responsible for the better solubility, permeability and stability of difficult bioactive molecules. Their compatibility with oral dosage forms has resulted in improving gastrointestinal absorption, targeted delivery, and sustained exposure.The controlled-release systems have come a long way too, offering the most sophisticated modulation of drug release through diffusion, erosion, osmotic, and swelling mechanisms. The systems yield predictable pharmacokinetic profiles and reduce dosing frequency, while oral controlled-release strategies' innovations open the door for an application in various therapeutic categories. In the meantime, oral dosage technologies such as fast-dissolving tablets, effervescent systems, QbD-based solid dosage forms, and 3D-printed tablets are signs of the growing patient-centric and customizable therapeutic design themes.The amalgamation of nanocarriers with state-of-the-art oral and controlled-release systems leads to the formation of synergistic platforms that are capable of delivering drugs with very high bioavailability and targeted delivery. Future directions indicate the pathways of transporter-mediated absorption, AI-assisted formulation optimization, and new capsule-based inventions as revolutionary players of drug delivery in the next generation. The advances mentioned above form a united pattern for future pharmaceutical development that is based on creative ideas, accuracy, and improved efficiency in therapy.

Abstract: Effective communication in critical care units, such as the CVICU, is vital for patient safety, but clinical notes from multiple professionals are often lengthy and complex. This study evaluated the Mistral Large Language Model for summarizing progress notes from the Cardiovascular Intensive Care Unit using the I-PASS framework for structured communication. A total of 385 progress notes were combined for each patient and summarized by the model. The readability was assessed using multiple metrics, including Flesch Reading Ease, Flesch-Kincaid Grade Level, Gunning-Fog Index, SMOG Index, Automated Readability Index, and Dale-Chall Score, and cosine similarity was used to measure alignment with the original notes. The AI summaries were harder to read, with a Flesch Reading Ease score of 29.25 compared to 56.89 for the original notes, and required a higher reading level—Grade 15.24 for the summaries versus Grade 8.98 for the original notes. A cosine similarity of 0.6 showed moderate alignment, retaining key details but losing some context in the generated summaries. Mistral effectively condensed the notes, but readability suffered as a result. Future work will aim to improve clarity and preserve key clinical details through human-guided evaluation.

Abstract:

Background: Prosthesis patient mismatch (PPM) is associated with poor outcomes in literature. Prevention of mismatch is crucial in aortic valve replacement, yet there is no current consensus on preventative strategies. Objectives: This study introduces a novel clinical framework, nomenclature, and algorithm for contemporary Heart Team practice, providing a systematic approach for a tailored surgical strategy to anticipate and prevent mismatch. Methods: Single-centre observational study with descriptive analysis of an evolving practice on 100 consecutive patients operated for aortic valve stenosis between 2020 – 2024. A step-by-step No-Mismatch algorithm was designed for the Heart Team to triage, discuss and decide the surgical strategy prior to the procedure, identifying patients at risk of mismatch, and guiding the surgeon’s plan to prevent PPM and consider a lifetime valve strategy. Results: The algorithm identified 26% of patients at risk of mismatch requiring a No-Mismatch strategy, and 20% at risk of small valve implantation requiring a Lifetime Valve Strategy. This cohort included 51 urgent cases. Valve pathology included 35% congenital, 59% degenerative, 1% rheumatic, and 5% redo operations. Valve implant type: 82% biological, including 29% rapid deployment valve (RDV), 18% mechanical, and 20% of patients required aortic root enlargements (ARE). Pre, intra and post operative data presented. Mortality occurred at 1%. All degrees of mismatch were prevented. Conclusion: The surgeon was able to predict mismatch and elected either ARE, RDV, or a mechanical valve as required. Patient selection and a No-Mismatch Heart team approach are essential to provide a tailored strategy for aortic valve interventions.

Abstract: While essential for the ethical practice of veterinary medicine, euthanasia profoundly complicates research with a survival outcome. In particular, euthanasia can make it difficult to determine the extent to which a certain clinical sign, laboratory, or imaging finding is associated with poor prognosis since animals that die while receiving veterinary care are often euthanized rather than dying naturally. The reasons for euthanasia, however, could be dramatically different. Some are euthanized due to perceived poor prognosis, others due to client financial limitations, and others for multifactorial reasons. In addition, when a clinician-scientist veterinarian believes a clinical finding is associated with poor survival, they might consciously or unconsciously influence clients to euthanize their animals. In effect, this could create – or artificially inflate the strength of – an association between that finding and animal survival. In this viewpoint, I will discuss the use of causal inference tools like directed acyclic graphs (DAGs) to identify the treating veterinarian’s belief about prognosis as a variable that mediates the effect of clinical findings on the probability of survival. Then, I briefly discuss some statistical methods already in use to account for euthanasia in veterinary research and their limitations. Lastly, I speculatively propose the use of expert elicitation to estimate counterfactual survival probability distributions (CSPD) for euthanized animals. By using these CSPDs to weight survival probability in euthanized animals and DAGs to identify and adjust for potential confounding, investigators might be able to estimate the direct causal effects of different clinical findings on probability of animal survival.

Abstract:

Objective, We investigated the relationship between venous thromboembolism (VTE) and pelvic and para-aortic lymphadenectomy (LND) within the first 90 days post gynaecological cancer surgery. Methods, A retrospective cohort analysis was conducted on 1,021 patients who underwent gynecological cancer surgery between 2006 and 2019. Univariate and multivariate analysis was performed to assess the effects of LND and lymph node (LN) metastasis on VTE occurrence within 90 days post-surgery. Results, 41 patients developed VTE within 90 days post-surgery. Para-aortic LND, was significantly associated with VTE (P < 0.001), with the highest rates (14.6%) observed in patients who had >10 para-aortic LN removed. In patients with pelvic LN metastasis, 10 (7.5%) developed VTE; patients with > 5 pelvic nodes positive for metastasis had a HR =4.83 (95% CI: 0.99- 13.9) after adjustment for age, duration of hospital stay, and surgical approach. The highest VTE rates (27.3%) occurred in patients with >5 para-aortic LN positive for metastasis, HR=3.79 (95% CI 1.44-14.23) after adjustment for age, duration of hospital stay, and surgical approach (P = 0.011). Conclusion, Para-aortic LND significantly increases VTE risk within the first 90 days post-surgery. The risk is further amplified in cases with metastatic LN and persists even after adjustment for other risk factors for VTE. While extended thromboprophylaxis is standard for all cancer patients, our findings suggest that para-aortic LND—especially with nodal metastases—may help identify those who would benefit most from a more tailored, risk-based prophylaxis approach.

Abstract: Chronic kidney disease (CKD) is a growing global health burden for which there are no curative treatments; therefore, it is essential to implement preventive and kidney-protective strategies. The renal kallikrein-kinin system (KKS) is a vasodilator, anti-inflammatory, and antifibrotic pathway located in the distal nephron, whose decline contributes to hypertension and CKD progression. A thorough evaluation of both experimental and clinical data was undertaken to ascertain the interactions between dietary potassium, renal KKS activity, and kidney protection. A particular focus was placed on animal models of proteinuria, tubulointerstitial damage, and salt-sensitive hypertension, in conjunction with human studies on potassium intake and renal outcomes. Experimental models show that potassium-rich diets stimulate renal kallikrein synthesis, increase urinary kallikrein activity, and up-regulate kinin B₂ receptor expression, leading to reduced blood pressure, oxidative stress, apoptosis, inflammation, and fibrosis. These effects are lost with B₂ receptor blockade. In humans, higher potassium intake enhances kallikrein excretion and lowers cardiovascular and renal risk, independently of aldosterone, and low potassium intake has the potential to exacerbate CKD progression. Notwithstanding the concerns that have been raised regarding the potential necessity of increasing potassium intake in cases of advanced CKD, extant evidence would appear to indicate that potassium excretion persists until late disease stages. Activation and preservation of the renal KKS through a potassium-rich diet represents a rational, low-cost renoprotective strategy. Combined with sodium reduction and nutritional education, this approach could mitigate CKD progression and improve cardiovascular health on a population scale.

Abstract: Intervertebral disc (IVD), the largest avascular structure in the human body, contains nucleus pulposus (NP) cells that generate an abundant quantity of lactate from anaerobic glycolysis as an adaptation to hypoxia. Historically, IVD lactate was viewed as a metabolic toxic byproduct necessitating clearance to maintain IVD health. This is because accumulation of lactic acid, the protonated form of lactate, acidifies the IVD microenvironment, impairs cell viability, disrupts extracellular matrix integrity, and promotes degeneration. However, recent studies discovered that lactate serves as an important IVD biofuel in a process known as lactate-dependent metabolic symbiosis in which lactate produced by NP is shuttled into cells of the neighboring annulus fibrosus (AF), and cartilage endplate (CEP) to be metabolized via the tricarboxylic acid cycle and oxidative phosphorylation to generate ATP and amino acids to maintain IVD matrix homeostasis. Additionally, lactate is found to function as a signaling molecule and epigenetic regulator in IVD: it regulates transcription via histone lactylation that modulates ferroptosis and other cell fate decisions. Lactate also modulates senescence, apoptosis, and inflammatory responses through pathways such as Phosphatidylinositol 3-kinase/Protein kinase B (PI3K/Akt) in IVD and other organs. This review synthesizes current knowledge on lactate production, transport, and clearance in the IVD along with the emerging roles of lactate in IVD health and pathophysiology. The review also provides research perspectives and directions aimed at advancing our understanding of lactate biology and evaluating its potential as a therapeutic target for treating intervertebral disc degeneration.

Abstract: Sarcopenia is a progressive condition in older adults characterized by reduced muscle mass, strength, and function, increasing the risk of disability and mortality. Resistance training is the primary intervention, and creatine supplementation may enhance its ef-fects. This meta-analysis assessed the impact of creatine, alone or combined with re-sistance training, on muscle mass and strength in elderly individuals with sarcopenia. A systematic search was conducted in PubMed, Scopus, and Web of Science following PRISMA 2020 guidelines, identifying 14 eligible studies. Two primary outcomes were an-alyzed: lean mass gain and strength improvement measured by leg press. Creatine com-bined with resistance training significantly increased lean mass (p = 0.0034; I² = 0%), in-dicating consistent benefits, while no significant improvement was observed in leg press strength (MD = −0.66; p = 0.83; I² = 21%). Reported adverse effects were minimal and mainly gastrointestinal. These findings suggest creatine supplementation effectively im-proves muscle mass but does not enhance leg press performance, which may not ade-quately reflect functional recovery. Future research should incorporate comprehensive functional assessments, including balance and mobility tests, to better evaluate the clini-cal impact of creatine in sarcopenia.

Abstract: Background: Subcutaneous pertuzumab and trastuzumab with hyaluronidase (PHESGO®) shortens chair time versus intravenous dual HER2 blockade, but Asian real-world data are scarce. Methods: We retrospectively reviewed 47 Asian patients with HER2-positive breast cancer treated with PHESGO® (January 2024–July 2025) across neoadjuvant, adjuvant, and metastatic settings. The primary endpoint was pathological complete response (pCR) in the neoadjuvant cohort; secondary endpoints included sequencing, safety, and metastatic activity. Results: Median age was 65 years. In the neoadjuvant cohort (n=26), pCR was 65% (17/26). PHESGO®-first regimens achieved higher pCR than anthracycline-first regimens (85.7% vs 41.7%; p=0.038). Treatment was generally well tolerated: the most frequent events were dysgeusia (57%), diarrhea (38%), and rash (34%), mostly grade 1–2; one grade ≥3 event (thrombocytopenia) occurred, and no symptomatic cardiac dysfunction was observed. Adverse event profiles were broadly comparable in patients ≥70 versus &lt;70 years. In metastatic disease (n=10), objective response and disease control rates were 56% and 78%, respectively. Conclusions: In routine practice, PHESGO® showed substantial neoadjuvant activity, acceptable toxicity, and workflow advantages. Early use of subcutaneous dual HER2 blockade with taxane may enhance pCR and facilitate delivery; prospective validation is warranted.

Abstract:

Background: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, such as erenumab (ERE) are effective migraine preventive therapies for many patients. Identifying clinic and genetic factors associated with treatment failure is crucial for optimizing patients’ management. Methods: This multicenter, prospective observational study included patients with episodic or chronic migraine treated with ERE for 12 months. Demographics, migraine history, comorbidities, treatment outcomes and genetic variants in CGRP receptor-related genes (CALCRL and RAMP1) were evaluated for associations with non-response to ERE defined as <50% reduction in monthly migraine days. Results: Of 140 patients starting ERE, 11 were lost to follow up, 12 stopped ERE due to side effects; 18 patients were non-responders and were compared to 99 responders. Arterial hypertension (adjusted OR [aOR]: 7.77, p = 0.007), smoking (aOR: 4.98, p = 0.014), and insomnia requiring medication (aOR: 4.51, p = 0.027) were associated with non-responder status. Genetic analysis revealed an association between the RAMP1 rs6431564 polymorphism and non-responder status, with the G allele linked to reduced risk (aOR per G allele: 0.28, p = 0.025) and causing increased expression of RAMP1 in an allele-dose manner. Conclusion: Hypertension, smoking, insomnia requiring medication and RAMP1 rs6431564 polymorphism were associated with non-responder status to ERE in migraine patients. Further validation of the present results in larger cohorts is needed.

Abstract: Background: While anti-shock therapy provided early after hemorrhage may be beneficial, the problem of delivery of potential therapeutics to ischemic tissue has not been well-appreciated. Polydatin (PD) and 5-aminoimidazole-4-carboxamide 1-β-D-ribonucleoside (AICAR) alleviate mitochondrial dysfunction and acute renal injury (AKI) following resuscitation, but it is unclear whether PD or AICAR are still effective before resuscitation when drug delivery can be still impeded. Because a low volume of polyethylene glycol (PEG) improves tissue perfusion in rats following hemorrhagic shock, we hypothesized that either PD or AICAR, when administered in combination with PEG, will be more effective on restoring hemodynamic function and mitochondrial function than when either drug is administered without PEG. Methods: Rats were randomized into 6 treatment groups (n=8/group): saline, PEG, PD, PD+PEG, AICAR, and AICAR+PEG. Extremity trauma was induced in anesthetized rats followed by pressure-controlled hemorrhage (mean arterial pressure (MAP) = 55 mmHg) for 45 minutes, at which point treatment was administered without fluid resuscitation. MAP, renal blood flow (RBF) and oxygen delivery (DO2), glomerular filtration rate (GFR), and sodium and potassium reabsorption were measured. Two hours after treatment, rats were euthanized to measure renal mitochondrial function. Results: Hemorrhage caused hyperlactatemia and decreased RBF, DO2, GFR, and urine flow; PEG, PD+PEG, and AICAR+PEG similarly improved these parameters, but neither PD nor AICAR alone showed any hemodynamic effects. However, preserved renal mitochondrial respiratory activities were only observed in PD+PEG and AICAR+PEG but not in PD, AICAR, or PEG alone groups. In addition, PD+PEG but not PD alone inhibited the tubular mitochondrial activity during shock as indicated by decreased renal sodium and potassium reabsorption. Conclusion: During hemorrhagic shock, PD or AICAR demonstrated preservation of mitochondrial function only when co-administered with PEG to alleviate tissue ischemia. This finding suggests a potential pharmacologic strategy to improve tissue delivery of therapeutics when resuscitation is limited.

Abstract: Docetaxel is a widely used chemotherapeutic agent effective against sol-id tumors, but its clinical use is limited by systemic toxicities, especially hepatotoxicity and nephrotoxicity. Curcuma longa, a phytochemical with antioxidant and anti-inflammatory properties, may offer organo-protective effects. Objective: To evaluate the protective effects of orally administered Curcuma longa against docetaxel-induced systemic toxicity in Wistar rats. Methods: Male Wistar rats were assigned to 5 subgroups (n=7/group) and treated for 7, 14, or 21 days with placebo, docetaxel (2.5 mg/kg, i.p.), or docetaxel combined with Curcuma longa (25, 50, or 500 mg/kg/day, oral). Serum biomarkers of hepatic function (Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT_, bilirubins) and renal function (urea, creatinine, electrolytes) were evaluated using summary measures, ANOVA, and Tukey’s post-hoc test, in addition to the relative weights of the liver, kidneys, heart, lungs, and small intes-tine. Results: Docetaxel induced significant elevations in hepatic and renal biomarkers and altered organ weights. Curcuma longa co-treatment attenuated these effects in a dose- and time-dependent man-ner. The 50 mg/kg dose consistently provided optimal protection. High-dose treatment was associated with marked splenic and intestinal hy-pertrophy. Conclusion: Curcuma longa demonstrates cytoprotective po-tential against docetaxel-induced toxicity, likely via Nrf2, NF-κB, and PI3K/Akt modulation. These findings support further translational re-search on Curcuma longa as an adjuvant in oncologic therapy.