Search Results (9,379)

Background/Objective: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting adverse effect of various chemotherapeutic agents. Previous work demonstrated that cannabis alleviates symptoms of oxaliplatin-induced CIPN. To evaluate the effects of cannabis components, cannabidiol (CBD) and tetrahydrocannabinol (THC), on CIPN-related symptoms. Methods: We reviewed a patient-reported outcomes dataset from “Tikun Olam,” a major medical cannabis provider. Of 1493 patients, 802 reported at least one CIPN symptom at baseline, including a burning sensation, cold sensation, paresthesia (prickling) and numbness, and 751 of them met the study inclusion criteria. Patients were categorized into THC-high/CBD-low and CBD-high/THC-low groups. Symptom changes after six months of cannabis use were analyzed using K-means clustering and logistic regression, incorporating interactions between baseline symptoms and THC and CBD doses. Linear regression assessed changes in activities of daily living (ADL) and quality of life (QOL). Results: Both groups reported symptom improvement. The THC-high group showed significantly greater improvement in burning sensation and cold sensation (p = 0.024 and p = 0.008). Improvements in ADL and QOL were also significantly higher in the THC group (p = 0.029 and p = 0.006). A significant interaction between THC and CBD was observed for symptom improvement (p < 0.0001). Conclusion: Cannabis effectively reduces CIPN symptoms and improves QOL and ADL. Higher THC doses were more effective than lower doses, with combined CBD and THC doses yielding greater symptom relief. Full article

Telomeres are protective DNA sequences located at chromosome ends, essential to maintaining genomic stability. This narrative review examines how maternal lifestyle factors during pregnancy influence fetal telomere length (TL). Positive associations have been identified between offspring’s TL and maternal consumption of nutrients such as vitamins C and D, folate, and magnesium. Additionally, adherence to a Mediterranean diet and regular physical activity during pregnancy are correlated with increased placental TL, supporting fetal genomic integrity. Conversely, maternal dietary patterns high in carbohydrates, fats, or alcohol, as well as exposure to triclosan and sleep-disordered breathing, negatively correlate with offspring’s TL. Maternal infections may also shorten TL through heightened inflammation and oxidative stress. However, evidence regarding the impact of other lifestyle factors—including maternal stress, smoking, caffeine intake, polyunsaturated fatty acid consumption, obesity, and sleep quality—remains inconsistent. Given that shorter telomere length has been associated with cardiovascular, pulmonary, and neurodegenerative diseases, as well as certain types of cancer, these findings highlight the vital importance of maternal health during pregnancy in order to prevent potential adverse effects on the fetus. Further studies are required to elucidate the precise timing, intensity, and interplay of these influences, enabling targeted prenatal interventions to enhance offspring health outcomes. Full article

Background: Skin and soft tissue infections (SSTIs) are a major cause of emergency room (ER) visits and hospitalizations. Long-acting lipoglycopeptides (LALs), such as dalbavancin and oritavancin, offer potential for early discharge and outpatient management, especially in patients at risk for methicillin-resistant Staphylococcus aureus (MRSA) or with comorbidities. Methods: We conducted a retrospective observational cohort study from March to December 2024 in an Italian tertiary-care hospital. Adult patients treated in the ER with a single dose of dalbavancin (1500 mg) or oritavancin (1200 mg) for SSTIs were included. Demographic, clinical, and laboratory data were collected. Follow-up evaluations were performed at 14 and 30 days post-treatment to assess outcomes. Results: Nineteen patients were enrolled (median age 59 years; 53% female). Most had lower limb involvement and elevated inflammatory markers. Three patients (16%) were septic. Fourteen patients (74%) were discharged without hospital admission; hospitalization in the remaining cases was due to comorbidities rather than SSTI severity. No adverse drug reactions were observed. At 14 days, 84% of patients had clinical resolution; only 10% had recurrence by day 30, with no mortality nor readmission reported. Conclusions: LALs appear effective and well-tolerated in the ER setting, supporting early discharge and reducing healthcare burden. Broader use may require structured care pathways and multidisciplinary coordination. Full article

Background and Objectives: Effective myocardial protection is essential for successful cardiac surgery outcomes, especially in complex and prolonged procedures. To this end, Del Nido (DN) and histidine-tryptophan-ketoglutarate (HTK) cardioplegia solutions are widely used; however, their comparative efficacy in adult surgeries with prolonged aortic cross-clamp (ACC) times remains unclear. This study aimed to compare the efficacy and safety of DN and HTK for myocardial protection during prolonged ACC times in adult cardiac surgery and to define clinically relevant thresholds. Materials and Methods: This retrospective study included a total of 320 adult patients who underwent cardiac surgery under cardiopulmonary bypass (CPB) with an aortic cross-clamp time ≥ 90 min. Data were collected from the medical records of elective adult cardiac surgery cases performed at a single center between 2019 and 2025. Patients were categorized into two groups based on the type of cardioplegia received: Del Nido (n = 160) and HTK (n = 160). The groups were compared using 1:1 propensity score matching. Clinical and biochemical outcomes—including troponin I (TnI), CK-MB, lactate levels, incidence of low cardiac output syndrome (LCOS), and need for mechanical circulatory support—were analyzed between the two cardioplegia groups. Subgroup analyses were performed according to ACC duration (90–120, 120–150, 150–180 and >180 min). The predictive threshold of ACC duration for each complication was determined by ROC analysis, followed by the analysis of independent predictors of each endpoint by multivariate logistic regression. Results: Intraoperative cardioplegia volume and transfusion requirements were lower in the DN group (p < 0.05). HTK was associated with lower TnI levels and less intra-aortic balloon pump (IABP) requirement at ACC times exceeding 180 min. Markers of myocardial injury were lower in patients with an ACC duration of 120–150 min in favor of HTK. The propensity for ventricular fibrillation after ACC was significantly lower in the DN group. Significantly lower postoperative sodium levels were observed in the HTK group. Prolonged ACC duration was an independent risk factor for LCOS (odds ratio [OR]: 1.023, p < 0.001), VIS > 15 (OR, 1.015; p < 0.001), IABP requirement (OR: 1.020, p = 0.002), and early mortality (OR: 1.016, p = 0.048). Postoperative ejection fraction (EF), troponin I, and CK-MB levels were associated with the development of LCOS and a VIS > 15. Furthermore, according to ROC analysis, HTK cardioplegia was able to tolerate ACC for up to a longer duration in terms of certain complications, suggesting a higher physiological tolerance to ischemia. Conclusions: ACC duration is a strong predictor of major adverse outcomes in adult cardiac surgeries. Although DN cardioplegia is effective and economically advantageous for shorter procedures, HTK may provide superior myocardial protection in operations with long ACC duration. This study supports the need to individualize cardioplegia choice according to ACC duration. Further prospective studies are needed to establish standard dosing protocols and to optimize cardioplegia selection according to surgical duration and complexity. 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

In today’s oncology, immunotherapy arises as a potent complement for conventional cancer treatment, allowing for obtaining better patient outcomes. B7-H3 (CD276) is a member of the B7 protein family, which emerged as an attractive target for the treatment of various tumors. The molecule modulates anti-cancer immune responses, acting through diverse signaling pathways and cell populations. It has been implicated in the pathogenesis of numerous malignancies, including melanoma, gliomas, lung cancer, gynecological cancers, renal cancer, gastrointestinal tumors, and others, fostering the immunosuppressive environment and marking worse prognosis for the patients. B7-H3 targeting therapies, such as monoclonal antibodies, antibody–drug conjugates, and CAR T-cells, present promising results in preclinical studies and are the subject of ongoing clinical trials. CAR-T therapies against B7-H3 have demonstrated utility in malignancies such as melanoma, glioblastoma, prostate cancer, and RCC. Moreover, ADCs targeting B7-H3 exerted cytotoxic effects on glioblastoma, neuroblastoma cells, prostate cancer, and craniopharyngioma models. B7-H3-targeting also delivers promising results in combined therapies, enhancing the response to other immune checkpoint inhibitors and giving hope for the development of approaches with minimized adverse effects. However, the strategies of B7-H3 blocking deliver substantial challenges, such as poorly understood molecular mechanisms behind B7-H3 protumor properties or therapy toxicity. In this review, we discuss B7-H3’s role in modulating immune responses, its significance for various malignancies, and clinical trials evaluating anti-B7-H3 immunotherapeutic strategies, focusing on the clinical potential of the molecule. Full article

Background: Hip fractures represent a major clinical challenge, particularly in elderly and frail patients, where postoperative pain control must balance effective analgesia with motor preservation to facilitate early mobilization. Various regional anesthesia techniques are used in this setting, including the pericapsular nerve group (PENG) block, fascia iliaca compartment block (FICB), femoral nerve block (FNB), and quadratus lumborum block (QLB), yet optimal strategies remain debated. Objectives: To systematically review the efficacy, safety, and clinical applicability of major regional anesthesia techniques for pain management in hip fractures, including considerations of fracture type, surgical approach, and functional outcomes. Methods: A systematic literature search was conducted following PRISMA 2020 guidelines in PubMed, Scopus, Web of Science, and the virtual library of the Hospital Central de la Defensa “Gómez Ulla” up to March 2025. Inclusion criteria were RCTs, systematic reviews, and meta-analyses evaluating regional anesthesia for hip surgery in adults. Risk of bias in RCTs was assessed using RoB 2.0, and certainty of evidence was evaluated using the GRADE approach. Results: Twenty-nine studies were included, comprising RCTs, systematic reviews, and meta-analyses. PENG block demonstrated superior motor preservation and reduced opioid consumption compared to FICB and FNB, particularly in intracapsular fractures and anterior surgical approaches. FICB and combination strategies (PENG+LFCN or sciatic block) may provide broader analgesic coverage in extracapsular fractures or posterior approaches. The overall risk of bias across RCTs was predominantly low, and certainty of evidence ranged from moderate to high for key outcomes. No significant safety concerns were identified across techniques, although reporting of adverse events was inconsistent. Conclusions: PENG block appears to offer a favorable balance of analgesia and motor preservation in hip fracture surgery, particularly for intracapsular fractures. For extracapsular fractures or posterior approaches, combination strategies may enhance analgesic coverage. Selection of block technique should be tailored to fracture type, surgical approach, and patient-specific functional goals. Full article

Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice. Full article

Dose-dense chemotherapy shortens the interval between chemotherapy cycles and has shown improved outcomes in high-risk breast cancer patients. We retrospectively evaluated the efficacy and safety of dose-dense chemotherapy in 80 breast cancer patients treated at our hospital from 2020 to 2024. The regimen included epirubicin and cyclophosphamide followed by paclitaxel or docetaxel, with pegfilgrastim support. The overall treatment completion rate was 82.5%. Of the 80 patients, 55 underwent neoadjuvant chemotherapy, and the pathological complete response rate was significantly higher in triple-negative breast cancer (59.1%) compared to that in luminal-type cancer (9.1%). Common adverse events included anemia, liver dysfunction, myalgia, and peripheral neuropathy. Febrile neutropenia occurred in 8.8% of patients, with some cases linked to pegfilgrastim body pod use, particularly in individuals with low subcutaneous fat. Notably, two patients developed pneumocystis pneumonia, potentially associated with steroid administration. Despite these toxicities, most were manageable and resolved after treatment. Our findings support the efficacy of dose-dense chemotherapy, particularly in triple-negative breast cancer, while highlighting the importance of individualized supportive care and vigilance regarding hematologic and infectious complications. Full article

Anomalies of coronary artery origins are rare but significant conditions that can range from benign to life-threatening. Early detection through imaging is crucial in preventing adverse outcomes. The treatment strategy varies depending on the type and severity of the anomaly, ranging from pharmacological treatment to surgery. A 22-year-old male patient, after syncope, after excluding other causes, had an exercise drill test, which was clinically negative and ECG-positive. Angio-CT revealed an undeveloped left main coronary artery (LMCA), and the circulation was supplied through the right coronary artery (RCA). The RCA provides the left anterior descending artery (LAD), and the LAD retrogradely supplies the left circumflex artery (LCX). The myocardial perfusion scintigraphy showed a slight lack of perfusion in the anterior wall (6% of total perfusion). The patient was qualified for further observation. A 77-year-old female underwent cardiac CT due to stenocardia. CT showed a lack of LMCA. The initial segment of the RCA gave rise to the left coronary artery (LCA), which encircled the aortic bulb posteriorly and bifurcated into branches resembling the LCX and LAD. After the Heart Team consultation, the patient was deemed eligible for conservative treatment. Angio-CT is a valuable tool for detecting coronary artery anomalies. Full article

This comprehensive review examines the role of septoplasty in the pediatric population, emphasizing its therapeutic significance in relieving nasal obstruction and facilitating normal craniofacial growth. Despite the evident advantages of septoplasty, its application in young patients remains a subject of ongoing debate. This issue is primarily characterized by concerns regarding the still-developing immaturity of nasal cartilage, potential intraoperative and postoperative risks, and the current absence of robust data on long-term outcomes following septoplasty. Common complications such as bleeding, septal perforation, saddle nose deformity, and persistent nasal obstruction are reported in the literature; however, many studies lack long-term follow-up data on the incidence of these adverse events and revision rates, which may be higher compared to adult populations, often leading to the need for secondary surgical interventions. Strict inclusion criteria and comprehensive patient selection are paramount to maximize therapeutic success while minimizing complications. Current evidence suggests that appropriately indicated septoplasty can improve airway patency, support optimal facial development, and reduce the risk of secondary sinonasal pathology. There is a significant necessity for additional prospective, large-scale studies to establish standardized therapeutic guidelines and management strategies for this specific population, thereby ensuring effective and evidence-based pediatric otolaryngologic care. Full article

This review aims to discuss how heat stress affects ovarian follicles and oocytes, steroidogenesis, and embryo development in ruminants. The literature shows that quiescent primordial follicles appear to be less susceptible to heat stress, but from the primary follicle stage onwards, they begin to suffer the consequences of heat stress. These adverse effects are exacerbated when the follicles are cultured in vitro. In antral follicles, heat stress reduces granulosa cell viability and proliferation in both in vivo and in vitro models. Oocyte maturation, both nuclear and cytoplasmic, is also compromised, and embryo quality declines under elevated thermal conditions. These effects are linked to intracellular disturbances, including oxidative imbalance, mitochondrial dysfunction, and altered hormonal signaling. The differences between in vivo and in vitro responses reflect the complexity of the biological impact of heat stress and emphasize the protective role of the physiological microenvironment. A better understanding of how heat stress alters the function of ovarian follicles, oocytes, and embryos is crucial. This knowledge is critical to devise effective strategies that mitigate damage, support fertility, and improve outcomes in assisted reproduction for livestock exposed to high environmental temperatures. Full article

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

Background: RSV remains a leading cause of infant hospitalization worldwide, and the recently approved nirsevimab could represent an effective and safe prophylactic strategy to prevent severe infections in the general neonatal population. Objectives: We conducted a retrospective observational monocentric pilot study in a mixed preterm/term birth cohort to add real-world evidence of the efficacy and safety of nirsevimab in preventing severe RSV infection. Methods: We included a total of 2035 consecutive infants admitted to the Neonatal Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy, from November 2024 to April 2025. We evaluated 30-day safety profiles and season-wide RSV infection rates, and the outcomes were also compared to newborns’ birth rate in the two previous seasons (2022–2023 and 2023–2024). Results: After the introduction of nirsevimab, a lower RSV infection rate was reported compared to previous seasons, and no adverse effects were observed. Compared to previous seasons, the clinical outcomes were more favorable, as only one unvaccinated neonate with RSV infection required invasive ventilation. Conclusions: In this real-world analysis, we demonstrated a good short-term safety profile of nirsevimab, as well as a potentially high efficacy in the general neonatal population with lower RSV infection incidence. However, future studies are needed to better assess its long-term safety and season-wide efficacy. Full article

Background and Objective: Adverse pathology to high-risk prostate cancer (PCa) after radical prostatectomy (upgrading) poses a threat to risk stratification and treatment planning. The impact on sexual function, urinary continence, and health-related quality of life (HRQOL) remains unclear. Methods: From 2004 to 2024, 4189 patients with preop low-/intermediate-risk PCa (Gleason score 6 or 7a, PSA ≤ 20 ng/mL) underwent radical prostatectomy at our department and were analyzed. Primary endpoint was HRQOL, erectile function, and urinary continence. Secondary endpoint was rate of salvage therapies and biochemical-free survival. Propensity score matching was performed using “operative time”, “robot-assisted surgery”, “blood loss”, “nerve-sparing surgery”, “age”, and “BMI” to represent comparable surgical approach. Median follow-up was 39 months (Interquartile-range (IQR) 15–60). Key Findings and Limitations: Patients who were upgraded to high-risk PCa showed a higher rate of postoperative radiotherapy and androgen-deprivation therapy compared to patients who were not upgraded (21% vs. 7%, p < 0.001; 9% vs. 3%, p = 0.002). Five-year biochemical recurrence-free survival was 68% in the upgrading group vs. 84% in the no-upgrading group (p < 0.001). We saw no difference in patient-reported HRQOL, urinary continence, or erectile function. Multivariable analysis showed that postoperative upgrading was a significant risk for not achieving good overall HRQOL (OR: 0.77, 95% CI: 0.61–0.97, p = 0.028) during the follow-up. Conclusions and Clinical Implications: Although postoperative upgrading to high-risk PCa leads to worse oncologic outcomes and higher salvage therapy rates, this study indicates that its impact on health-related quality of life is minimal and should not deter a cautious approach to radical prostatectomy. Full article