Search Results (645)

In this work, we provide a promising way to alleviate the Hubble tension within the framework of Myrzakulov $f(R,T)$ gravity. The latter incorporates both curvature and torsion under a non-special connection. We consider the $f(R,T)=R+\alpha R^2$ class, which leads to modified Friedmann equations and an effective dark energy sector. Within this class, we make specific connection choices in order to obtain a Hubble function that coincides with that of $\Lambda$CDM at early times while yielding higher $H_0$ values at late times. The reason behind this behavior is that the dark energy equation of state exhibits phantom behavior, which is known to be a sufficient mechanism for alleviating the $H_0$ tension. A full observational comparison with various datasets, including the Cosmic Microwave Background (CMB), is required to test the viability of this scenario. Strictly speaking, the present work does not provide a complete solution to the Hubble tension but rather proposes a promising way to alleviate it. Full article

Background/Objectives: Immune checkpoint inhibitors have significantly transformed the treatment paradigm of advanced melanoma, leading to substantial improvements in survival outcomes. However, this therapeutic success is accompanied by a spectrum of treatment-related adverse events, some of which are increasingly recognised as enduring and non-reversible. Whilst early-onset immune-related toxicities have been well characterized, late-onset toxicities, often emerging in patients with long-term disease control, remain understudied and are frequently overlooked. Methods: To address this knowledge gap, we conducted a retrospective multicentre study in three UK tertiary referral centres, exploring immune-related adverse events in 246 patients with melanoma who received immune checkpoint inhibitors in the advanced setting. We defined late-onset immune-related adverse events as those occurring at least 3 months after the last cycle of immune checkpoint inhibitors. Results: Although most patients experienced early-onset toxicity, almost 15% of patients developed late-onset immune-related adverse events, including skin rash, colitis, hepatitis, and arthritis, among others. These were often challenging to manage and necessitated the use of systemic steroids. Up to 2% of patients presented ultra-late-onset toxicities, defined as those events occurring at least 12 months after treatment completion. Conclusions: This study provides valuable insights into the characteristics of late-onset immune-related adverse events. To further advance our understanding of these late-onset toxicities, dedicated prospective studies are needed to assess risk factors associated with their development and their impact on quality of life. Additionally, translational research focused on finding predictive biomarkers is essential to identify patients at a higher risk of developing delayed adverse events and to understand how best to manage them. Full article

Background: Cow’s milk allergy (CMA) is the most common food allergy in children, typically resolving by adolescence. In contrast, the clinical spectrum of allergies to non-cow mammalian milk and their patterns of IgE cross-reactivity are less well documented. Nutritional differences between various mammalian milks may also impact dietary management in milk-allergic patients. Objectives: To characterize clinical features, onset age, and IgE cross-reactivity patterns of non-cow mammalian milk allergies in adult patients seen at a tertiary allergy center, and to compare these findings with published cases. Methods: A retrospective analysis of patients included in the “Extended Laboratory Investigation for Rare Causes of Anaphylaxis study” with mammalian milk allergy was performed using clinical history, skin testing, and serum-specific IgE measurements. Cross-reactivity patterns were assessed in selected cases using immunoblotting, specific IgE inhibition, and basophil activation testing, and compared with published reports of non-cow mammalian milk allergy. Results: In our case series of 22 patients with mammalian milk allergy and 10 healthy control subjects, 3 patients were identified with isolated adult-onset non-cow mammalian milk allergy (n = 1 buffalo milk; n = 2 mare milk), confirmed via immunoblotting and basophil activation testing. Streptavidin-based specific IgE measurement for buffalo cheese was positive in the buffalo milk allergic patient. The literature review identified 82 cases of non-cow mammalian milk allergy. These cases typically showed late onset (mean age 8.6 years; range 1–70 years), severe reactions (CoFAR (Consortium for Food Allergy Research) grade 3 or 4 in 66%, and one fatality), and selective sensitization (affecting sheep and/or goat, camel, mare, buffalo, donkey, or combinations thereof in 56, 10, 5, 5, 4, and 2 cases, respectively). Conclusions: Non-cow mammalian milk allergies are rare but generally present later in life with selective IgE cross-reactivity, differing from the broader cross-reactivity observed in CMA. This selectivity may allow for safe dietary alternatives. These findings underscore the need for improved diagnostics and personalized dietary management in this patient population. Full article

Purpose/Objective(s): Peritoneal carcinosis can occur in several gastrointestinal or gynecological malignancies and its prognosis is usually poor. With the advent of more effective systemic agents, the overall survival of metastatic patients has been revolutionized and isolated peritoneal or abdominal wall metastases might benefit from local treatments; Stereotactic Body Radiotherapy (SBRT) might be considered in selected patients with oligometastatic presentation. Materials/Methods: Oligometastases were defined according to recent ESTRO/EORTC consensus. Inclusion criteria were as follows: ECOG PS ≤ 2, written informed consent, up to five lesions to be treated at the same time, patients treated with radiotherapy schedules applying minimum 6 Gy per fraction. The primary endpoint of the study was local control (LC); acute and late toxicity, distant progression-free survival (DPFS), time-to-next systemic treatment (TNST), polymetastatic-free survival (PMFS) and overall survival (OS) were secondary endpoints. Toxicity was assessed according to CTCAE criteria v5.0. Statistical associations between clinical variables and outcomes were assessed using Fisher’s exact test, and Kruskal–Wallis test, as appropriate. Survival outcomes were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: Between April 2020 and September 2024 a total of 26 oligometastatic lesions located in the peritoneum or in the abdominal wall detected in 20 patients received SBRT with Helical Tomotherapy. All cases have been assessed by a multidisciplinary team. Only in three patients out of twenty did more than one lesion receive SBRT: two lesions in two patients, and five lesions in a single case of colorectal cancer with ongoing third-line systemic treatment. Median total dose was 30 Gy (27–35 Gy) in five fractions (3–5). The most frequent primary neoplasm was ovarian cancer in 14/20, endometrial in 2/20, while the remaining were colorectal, vaginal, pancreatic and non-small cell lung cancer. Four lesions were located in the abdominal wall, while the remaining twenty-two were located in the peritoneum. Concurrent systemic therapy was administered in 18/20 patients. With a median follow-up of 15 months (range, 6–59), our 1-year LC was 100%, while 1-year DPFS, PMFS, TNTS and OS rates were 54%, 69%, 61% and 83%, respectively. Abdominal wall location and treatment of a subsequent oligometastatic recurrence with a second course of SBRT were both significantly associated with improved OS (p = 0.03 and p = 0.04, respectively). No G ≥ 3 adverse events occurred. Conclusion: Our preliminary data support the use of SBRT in selected cases of oligometastatic disease located in the peritoneum or in the abdominal wall with excellent results in terms of tolerability and promising clinical outcomes. Full article

(1) Background: Oral cancer (OC) is one of the most frequently diagnosed human cancers and remains a challenge for biologists and clinicians. More than 90% of OC cases are squamous cell carcinomas (OSCCs). Despite the use of modern diagnostic and prognostic methods, the 5-year survival rate remains unsatisfactory due to the late diagnosis of the neoplastic process and its resistance to treatment. This comprehensive review aims to present the latest literature data on the use and effectiveness of saliva as a non-invasive biomarker in patients with oral cancer. (2) Methods: The article reviews the current literature on the use of salivary omics biomarkers as an effective method in diagnosing and modifying treatment in patients with OSCC; the research corpus was acquired from the PubMed/Google/Scopus/Cochrane Library/Web of Science databases in accordance with the Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA 2020) guidelines. (3) Results: The identification of salivary omics biomarkers involved in carcinogenesis and neoplastic transformation may be a potential alternative to traditional invasive diagnostic methods. Saliva, being both an abundant reservoir of organic and inorganic components derived from epithelial cells as well as a cell-free environment, is becoming an interesting diagnostic material for studies in the field of proteomics, genomics, metagenomics, and metabolomics. (4) Conclusions: Saliva-based analysis is a modern and promising method for the early diagnosis and improvement of treatment outcomes in patients with OSCC and oral potentially malignant disorders (OPMDs), with high diagnostic, therapeutic, and prognostic potential. Full article

Background: Coronary heart disease (CHD) remains the most prevalent pathology within the circulatory system. Among its chronic complications, ischemic mitral valve regurgitation (IMR) is observed in approximately 15% of patients with sustained myocardial ischemia. The presence of this complex valvular defect significantly increases both overall mortality and the incidence of adverse cardiovascular events. Notably, the presence of moderate to severe mitral regurgitation in patients undergoing surgical revascularization has been shown to double the risk of death. Despite the well-established etiology of IMR, data regarding the efficacy of surgical interventions and the determinants of postoperative outcomes remain inconclusive. Methods: The objective of the present study was to evaluate both early and long-term outcomes of surgical treatment of mitral regurgitation in patients undergoing coronary artery bypass grafting (CABG) due to ischemic heart disease. Particular attention was given to the influence of the severity of regurgitation, left ventricular ejection fraction (LVEF), and the dimensions of the left atrium (LA) and left ventricle (LV) on the postoperative prognosis. An additional aim was to identify preoperative risk factors associated with increased postoperative mortality and morbidity. A retrospective analysis was conducted on 421 patients diagnosed with ischemic mitral regurgitation who underwent concomitant mitral valve surgery and CABG. Exclusion criteria included emergent and urgent procedures as well as non-ischemic etiologies of mitral valve dysfunction. Results: The study cohort comprised 34.9% women and 65.1% men, with the mean age of 65.7 years (±7.57). A substantial proportion (76.7%) of patients were aged over 60 years. More than half (51.5%) presented with severe heart failure symptoms, classified as NYHA class III or IV, while over 70% were categorized as CCS class II or III. Among the surgical procedures performed, 344 patients underwent mitral valve repair, and 77 patients required mitral valve replacement. Additionally, 119 individuals underwent concomitant tricuspid valve repair. Short-term survival was significantly affected by the presence of hypertension, prior cerebrovascular events, and chronic kidney disease. In contrast, hypertension and chronic obstructive pulmonary disease were identified as significant predictors of adverse late-term outcomes. Conclusions: Interestingly, neither the preoperative severity of mitral regurgitation nor the echocardiographic measurements of LA and LV dimensions were found to significantly influence surgical outcomes. The perioperative risk, as assessed by the EuroSCORE II (average score: 10.0%), corresponded closely with observed mortality rates following mitral valve repair (9.9%) and replacement (10.4%). Notably, the need for concomitant tricuspid valve surgery was associated with an elevated mortality rate (12.4%). Furthermore, the preoperative echocardiographic evaluation of LA regurgitation severity, as well as LA and LV dimensions, did not exhibit a statistically significant impact on either early or long-term surgical outcomes. However, a reduced LVEF was correlated with increased long-term mortality. The presence of advanced clinical symptoms and the necessity for tricuspid valve repair were independently associated with a poorer late-term prognosis. Importantly, the annual mortality rate observed in the late-term follow-up of patients who underwent surgical treatment of ischemic mitral regurgitation was lower than rates reported in the literature for patients managed conservatively. The EuroSCORE II scale proved to be a reliable and precise tool in predicting surgical risk and outcomes in this patient population. Full article

Open reduction and internal fixation (ORIF) is widely regarded as the primary treatment for acetabular fractures, but limitations arise in complex cases, leading to non-anatomical reductions and increased risk of post-traumatic osteoarthritis. Given the high incidence of secondary arthritis (12–57%) following ORIF, total hip arthroplasty (THA) is often necessitated, particularly in scenarios unsuitable for ORIF, such as extensive comminution or combined femoral head and neck fractures. The surgical landscape has shifted from a traditional “fix or replace” to a more integrated “fix and replace” approach, especially beneficial in managing elderly patients with osteoporotic bones. THA is applied across various timelines, including acute (0–3 weeks), delayed (3 weeks to 3 months), and late (beyond 3 months), each presenting distinct challenges and requiring specific strategies to optimize outcomes. The importance of precise bone defect classifications and the role of dual mobility cups in reducing dislocation risks are highlighted, alongside the use of modern surgical and fixation techniques to improve stability and patient outcomes. Enhanced recovery protocols and meticulous postoperative management are critical to addressing complications, such as infections and hardware interference, tailoring treatment approaches to each patient’s needs, and advancing care for complex acetabular fractures. Full article

Background: Cutaneous squamous cell carcinoma (SCC) is the most common primary malignant tumor of the hand, and its aggressive nature can lead to significant morbidity, particularly when affecting critical structures like the thumb. SCC in this location may arise in the periungual area or the pulp and frequently presents with non-specific symptoms such as swelling, nail deformity, or discharge, features that closely mimic common benign conditions. Methods: A retrospective study analyzed patients with neglected or misdiagnosed SCC of the thumb treated at the Hand and Microsurgery Unit of the Jewish Hospital, Rome, between 2015 and 2025. Patient demographics, duration from symptom onset to diagnosis, initial misdiagnoses, and imaging findings (X-rays, MRI, CT scans, lymph node sonography) were reviewed. Surgical interventions, histopathological grading, and postoperative management were documented, with long-term follow-up focusing on disease progression and patient survival. Results: Sixteen patients were included in the study. The mean age at surgery was 73.6 years (range: 55–93 years), with a mean delay of 8.2 months from symptom onset to diagnosis in 87.5% of cases. Initial misdiagnoses included verruca vulgaris, onychomycosis, paronychia, and osteomyelitis. Imaging consistently revealed soft tissue involvement, bony invasion, and occasional metastasis. Surgical approaches ranged from wide resection to amputation, with thumb reconstruction in selected cases and hand amputation in severe presentations. Long-term follow-up (mean 4.6 years) showed high morbidity, a reduction in hand function and QoL, and a 50% mortality rate, with two cases due to metastatic disease (12.5%). Conclusions: Thumb SCC presents diagnostic and therapeutic challenges, exacerbated by late diagnosis and initial misdiagnoses. Multidisciplinary management involving early recognition, comprehensive imaging, appropriate surgical interventions, and vigilant follow-up is crucial for optimizing outcomes. Full article

A two-dimensional time-dependent model is presented for upward-propagating internal gravity waves generated by an imposed thermal forcing in a layer of fluid with uniform background velocity and stable stratification under the anelastic approximation. The configuration studied is representative of a situation with deep or shallow latent heating in the lower atmosphere where the amplitude of the waves is small enough to allow linearization of the model equations. Approximate asymptotic time-dependent solutions, valid for late time, are obtained for the linearized equations in the form of an infinite series of terms involving Bessel functions. The asymptotic solution approaches a steady-amplitude state in the limit of infinite time. A weakly nonlinear analysis gives a description of the temporal evolution of the zonal mean flow velocity and temperature resulting from nonlinear interaction with the waves. The linear solutions show that there is a vertical variation of the wave amplitude which depends on the relative depth of the heating to the scale height of the atmosphere. This means that, from a weakly nonlinear perspective, there is a non-zero divergence of vertical momentum flux, and hence, a non-zero drag force, even in the absence of vertical shear in the background flow. Full article

Background/Objectives: Population aging and the rise in chronic diseases challenge healthcare systems to adopt person-centered approaches, especially in palliative care (PC), where symptom management remains limited. Physiotherapy plays a key role in alleviating discomfort but faces inconsistent integration in Portugal due to lack of recognition. Variations in intervention methods hinder uniform care delivery, limiting timely patient access to comfort-focused treatments and knowledge. This study aims to deepen the understanding of physiotherapy’s role in Portuguese PC to improve its integration into teams and enhance patient access to comfort care. Methods: This study used a descriptive qualitative approach with online focus groups (FG), guided by Krueger and Casey’s methodology and adhering to the COREQ checklist. A non-probabilistic convenience sample of physiotherapists working in palliative care across mainland Portugal and the islands was selected based on inclusion criteria. Three FGs were planned with up to ten participants each. However, due to availability and attendance issues, only 15 physiotherapists participated: 5 in FG1 (in-hospital PC units), 6 in FG2 (inpatient units), and 4 in FG3, the minimum appropriate number from community-based units. Results: Physiotherapy plays a crucial yet underrecognized role in PC, emphasizing the need for its full integration into care teams rather than reliance on late, on-call referrals. Techniques such as positioning, mobilization, pain and dyspnea relief, adapted exercises, massage, music therapy, and emotional support are employed. Conventional physiotherapy tools are used and personalized according to the patient’s context, duration, setting, dosage, and individual needs. Conclusions: Physiotherapy should be recognized as a fundamental part of PC, contributing not only to the prolongation of life but also to ensuring comfort and dignity for patients and their families. To achieve this, its role within multidisciplinary teams must be strengthened and supported by regulations that guarantee access and the formal integration of physiotherapists. However, a significant gap remains in patients’ regular access to comfort-focused interventions at the appropriate time, perhaps due to the considerable variation in physiotherapy practices depending on the patient and care setting, which presents a challenge for knowledge development both in Portugal and globally. Full article

Purpose: We present our single-institution experience of sarcomatous brain metastasis patients who underwent stereotactic radiosurgery (SRS) over the past 35 years. Methods: In total, 31 patients (16 males) who underwent SRS for sarcoma brain metastases were identified. Median age at presentation to SRS was 47 (range: 4–78) months. Common histopathologies included leiomyosarcoma (eight patients), osteosarcoma (six patients), alveolar sarcoma (three patients), Ewing sarcoma (three patients), and undifferentiated/unclassified sarcoma (three patients). The median Karnofsky Performance Score (KPS) was 90. Nine patients underwent pre-SRS craniotomy. The median dose prescribed was 18 Gy. The median cumulative tumor volume was 1.4 cc. Results: Median patient overall survival (OS) after SRS was 7 (range: 0–155) months. Local tumor control (LTC) was achieved in 105 out of 113 tumors, at a median time of 3 (range: 0–17) months between SRS and progression. LTC rates per patient and per tumor were 74.2% and 92.9%, respectively. Following SRS, 10 patients (32.3%) developed new tumors at a median time of 6 (range: 1–25) months. Four patients experienced adverse radiation effects (AREs). At the last follow-up, all patients died, one patient from intracranial progression, 27 from systemic disease progression, and the remaining from unrelated medical conditions. Conclusions: Given high LTC and low ARE rates, this suggests SRS as a strong candidate for the non-invasive management of sarcomatous brain metastases, which typically present late following initial presentation of the primary disease. Full article

Late ruptures of abdominal aortic aneurysms post-endovascular aneurysm repair present a significant risk, occurring in about 0.9% of cases. The typical timeframe leading to rupture is roughly 37 months, with the primary factors often linked to endoleaks, especially types I and III, which sustain pressure within the aneurysm sac. The approaches to managing late ruptures consist of endovascular approaches, open surgical interventions, and conservative care, each customised to the patient’s specific characteristics. When feasible endovascular repair is favoured, additional stent grafts are deployed to seal endoleaks and offer lower perioperative mortality rates compared to those for open surgery. Open repair is considered when endovascular solutions fail or are not feasible. Conservative management with active monitoring and supportive treatment can be considered for haemodynamically stable non-surgical patients. Endovascular repair methods like fenestrated/branched EVAR (F/BEVAR) and parallel grafting (PGEVAR) are effective for complicated anatomies and show high technical success with reduced morbidity compared to that with open repairs. Chimney techniques and physician-modified endografts may help regain and broaden the sealing zone. Limb extensions with or without embolisation, interposition endografting, and whole-body relining are helpful options for type IB and type 3–5 endoleaks. Open surgical repair carries a higher perioperative mortality but may be essential in preventing death due to rupture following failed EVAR. The choice depends on the patient’s clinical stability and fitness for surgery in the absence of a viable endovascular alternative. This article discusses the available options for treating late rupture after EVAR, emphasising the importance of individualised treatment plans and the need for rigorous postoperative surveillance to prevent such complications. Full article

This study addresses the coupled influence of the threshold pressure gradient and stress sensitivity during the seepage process in low-permeability reservoirs. By integrating Laplace transform, perturbation transform, the image principle, and the superposition principle, a non-steady-state seepage model for segmented-fractured horizontal wells considering both effects is established for the first time. The analytical solution of the point source function including the threshold pressure gradient ($\lambda$) and stress sensitivity effect (permeability modulus $\alpha$) is innovatively derived and extended to closed-boundary reservoirs. The model accuracy is verified by CMG numerical simulation (with an error of only 1.02%). Based on this, the seepage process is divided into four stages: I linear flow (pressure derivative slope of 0.5), II fracture radial flow (slope of 0), III dual radial flow (slope of 0.36), and IV pseudo-radial flow (slope of 0). Sensitivity analysis indicates the following: (1) The threshold pressure gradient significantly increases the seepage resistance in the late stage (the pressure curve shows a significant upward curvature when $\lambda$ = 0.1 MPa/m); (2) Stress sensitivity dominates the energy dissipation in the middle and late stages (a closed-boundary-like feature is presented when $\alpha$ > 0.1 MPa⁻¹); (3) The half-length of fractures dominates the early flow (a 100 m fracture reduces the pressure drop by 40% compared to a 20 m fracture). This model resolves the accuracy deficiency of traditional single-effect models and provides theoretical support for the development effect evaluation and well test interpretation of fractured horizontal wells in low-permeability reservoirs. Full article

The global impact of HIV is especially significant when diagnoses are made in advanced stages. While strategies exist to mitigate late presentations, Ecuador’s 2018–2022 strategic plan has not yet been evaluated. This study assesses the prevalence and implications of late and advanced HIV presentations in Ecuador, using data from a reference hospital in Quito. A cross-sectional analysis of 436 medical records of people living with HIV from the “Hospital de Especialidades Eugenio Espejo” was conducted between November 2015 and February 2020. The data were divided into “Pre-Plan” and “Post-Plan” periods for comparative analysis. The mean CD4 T count showed a non-statistically significant increase in the post-plan period (January 2018–February 2020). Notably, 65.1% of patients presented late, and 39.4% had advanced disease. Demographic data indicated that 89.9% were men, and 54.1% were under 30 years of age. No characteristics were identified that were associated with advanced late presentation of HIV infection. Sexual orientation data revealed that 69.1% identified as homosexual or bisexual. A predominance of late and advanced presenters was identified in the post-plan period, associated with being employed (p < 0.05) and being drug users (p < 0.001). There was also a greater incidence of late presenters among immigrants in the post-plan period (p = 0.045). Despite the implementation of Ecuador’s 2018–2022 strategic plan for HIV, substantial challenges in reducing late presentations remain. This study suggests that early diagnoses have not significantly improved. Employed patients and drug users were more likely to present late, with drug users also accounting for many advanced cases. This study highlights the need for more focused and targeted strategies to supplement the existing plan. Full article

Background/Objectives: Worldwide, glaucomas are the leading cause of irreversible blindness in adults. On the ocular level, they are fairly well understood; however, the functional and structural changes that occur in the brain have become a subject of great interest lately, mostly owing to improved accessibility and effectiveness of functional magnetic resonance imaging (fMRI). This, coupled with the non-invasive nature of the methodology, has contributed to an ever-growing body of research published on the topic. In this systematic review, we gather, systematize, and compare the results and methodologies reported in the literature, as pertaining to resting-state fMRI brain changes in primary open-angle glaucoma (POAG). Methods: A systematic search in PubMed, Scopus, and Web of Science was carried out, resulting in a total of 290 records identified, with 67 assessed for eligibility and 24 selected for inclusion. Results: The main findings include worse functional parameters in the early visual centers in POAG across all methodologies, reduced functional connectivity between V1 and other parts of the visual cortex, functional aberrations in higher levels of the visual system, predominantly in the ventral stream and in extravisual networks, among others. Moreover, the majority of these changes are shown to be correlated with ophthalmological measurements. Conclusions: Although studies on this matter tend to suffer from a limited sample size and a lack of methodological standardization, we nevertheless manage to present common results and conclusions regarding the effects of POAG on brain function. Full article