Search Results (558)

Background: Pleuroparenchymal fibroelastosis (PPFE) is a rare fibroelastotic lung disease characterized histologically by dense pleural and subpleural fibrosis with upper-lobe predominance. In clinical practice, diagnosis often relies on characteristic radiologic findings, as surgical lung biopsy is rarely feasible. Unlike idiopathic pulmonary fibrosis, robust radiologic criteria validated against biopsy-proven cohorts remain limited, and the diagnostic performance of imaging alone is incompletely defined. Although initially described as idiopathic, PPFE is increasingly recognized in secondary settings, including connective tissue disease-associated interstitial lung disease (CTD-ILD), where it frequently overlaps with more common fibrotic patterns. Methods: We conducted a focused narrative review of the literature on PPFE in CTD-ILD, synthesizing evidence on morphology, epidemiology, clinical course, prognostic implications, and proposed pathobiological mechanisms, with emphasis on distinguishing true PPFE from PPFE-like lesions. Results: CTD-associated PPFE is associated with accelerated lung function decline, increased risk of pneumothorax, and poorer outcomes, particularly in systemic sclerosis and rheumatoid arthritis. However, distinguishing true PPFE from radiologic mimics remains challenging, and diagnostic approaches rely heavily on imaging without robust histopathologic validation. Proposed mechanisms include epithelial injury, immune dysregulation, and vascular or lymphatic abnormalities, although causal links remain unproven. Significant gaps persist regarding natural history and therapeutic responsiveness. Conclusions: Earlier identification of PPFE in CTD-ILD is important, as misclassification may delay risk stratification and management. Longitudinal imaging, multidisciplinary evaluation, and standardized diagnostic criteria are needed to improve clinical care and guide future research. Full article

Surgery continues to represent the central curative modality for melanoma despite major advances in systemic immunotherapy and targeted treatments. Contemporary surgical strategies aim to maintain oncologic safety while minimizing functional and aesthetic morbidity through optimized excision margins, highly selective use of sentinel lymph node biopsy (SLNB), and the omission of routine completion lymph node dissection (CLND). Rapid integration of neoadjuvant and adjuvant immunotherapies has begun to redefine surgical indications, timing, and extent—particularly for intermediate-stage and locoregionally advanced disease. Parallel innovations in Mohs micrographic surgery, reconstructive flap design, lymphatic reconstruction, and minimally invasive techniques further broaden the possibilities for individualized intervention. This expanded review synthesizes current evidence, ongoing controversies, and emerging trends that are shaping the future of melanoma surgery, highlighting how precision oncology, immunologic profiling, and technological advances are transforming the surgeon’s role and enabling more tailored, less invasive, and outcome-focused management. Full article

Background/Objectives: Testicular germ cell tumors, particularly seminoma, represent the leading cause of cancer in men aged 15–40 years. The decision about adjuvant therapy relies on histological features with uncertain prognostic value. The Pituitary-Tumor-Transforming Gene 1 (PTTG1), which encodes the securin protein, is crucial in sister chromatid separation. Our previous in vitro studies demonstrated that PTTG1 nuclear expression promotes invasiveness, dedifferentiation, and neolymphangiogenesis in testicular seminoma. Methods: We conducted a hypothesis-generating retrospective observational study on 51 patients (aged 23–68) with testicular seminoma, with (43%) or without (57%) lymph node involvement, evaluating potential correlations between PTTG1 and currently known prognostic factors. Clinical and pathological data were collected, including lymph node involvement, recurrence, necrosis, rete testis invasion, vascular invasion, and adipose tissue invasion. An immunohistochemical scoring system assessing intranuclear PTTG1 expression was developed. Results: The PTTG1 score was related to lymph node metastasis and adipose tissue invasion. ROC curve analysis showed that the PTTG1 immunohistochemical score showed good discriminatory ability in identifying lymph node involvement (AUC = 0.939); the optimal cut-off was 4.0 (sensitivity 90.5%; specificity 57.1%), while the ROC curve for adipose tissue invasion was inadequate. Lymph node metastasis also correlated with necrosis; however, logistic regression confirmed that PTTG1 score was independently associated with nodal involvement (p = 0.002), regardless of tumor size and necrosis. Conclusions: Our findings suggest a correlation between PTTG1 expression and lymphadenopathy at diagnosis, independent of tumor size and T stage. It may reflect biological features associated with lymphatic dissemination and requires further investigation in larger prospective studies. Full article

The discovery of the glymphatic system (GS) transformed understanding of central nervous system homeostasis by revealing a brain-wide network that facilitates cerebrospinal and interstitial fluid exchange along perivascular pathways. This system clears metabolic waste and maintains the precise ionic environment required for neuronal function through the coordinated action of astrocytic aquaporin-4 channels and intact perivascular architecture. Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, alters physiological barriers through pathological angiogenesis, compression of perivascular spaces, depolarization of aquaporin-4 at astrocytic endfeet, and obstruction of venous and lymphatic drainage. This narrative review synthesizes current experimental and clinical literature identified through targeted searches of PubMed and Scopus to examine interactions between glioblastoma, glymphatic system dysfunction, and tumor microenvironmental changes. To minimize selection bias, studies were categorized according to evidence source and experimental design. Evidence from rodent models and advanced imaging demonstrates as tumor growth impairs glymphatic function, the resulting dysfunction promotes tumor progression by enabling accumulation of pro-tumorigenic growth factors, inflammatory mediators, and acidic metabolites, while elevated interstitial fluid pressure limits drug delivery. Impaired antigen drainage further diminishes immune surveillance, contributing to the immunosuppressive microenvironment that limits immunotherapy efficacy. A critical evaluation of these mechanisms highlights how the glymphatic system influences disease progression and suggests novel avenues for diagnostic imaging and therapeutic intervention. Although significant challenges remain in modeling human fluid dynamics, understanding these hidden networks offers a promising frontier for strategies aimed at restoring cerebral clearance and improving clinical outcomes. Full article

Monkeypox (Mpox) disease, caused by the Monkeypox virus (Mpox virus), emerged as a significant global health threat during the 2022 outbreak, prompting the World Health Organisation (WHO) to declare it a Public Health Emergency of International Concern (PHEIC). Rapid evolution through genomic modifications enhanced its outbreak potential. Zoonotic transmission occurs through close contact with infected rodents or primates; human-to-human transmission occurs via close contact or homosexual intercourse. The virus disseminates via the lymphatic system, causing symptoms ranging from mild skin lesions to severe multi-system complications or even death. Diagnosis incorporates clinical symptoms as well as advanced molecular and immunological methods. Currently, no specific antiviral medications or vaccines are available for Mpox, necessitating reliance on conventional therapeutic supports and treatments developed for smallpox. Raising awareness, promoting protective practices, implementing surveillance, enabling rapid diagnosis, ensuring timely treatment, and promoting mass vaccination are crucial to curb Mpox transmission. This narrative review provides a comprehensive overview of the current knowledge on epidemiology, evolution, transmission, pathogenesis, clinical signs, diagnosis, treatment, vaccination, and prevention strategies for Mpox. Full article

Type 2 Diabetes (T2D) is characterized by the toxic aggregation of human islet amyloid polypeptide (hIAPP or amylin) within pancreatic β-cells. IAPP is also a neuropancreatic hormone that plays a significant role in Alzheimer’s disease (AD) by co-depositing with amyloid-beta (Aβ) and Tau, supporting the Type 3 Diabetes (T3D) hypothesis. Soluble IAPP accelerates Aβ aggregation through cross-seeding and causes neurotoxicity by impairing the blood–brain barrier and activating neuroinflammation. Melatonin inhibits these processes by disrupting hydrophobic interactions in both hIAPP and Aβ, preventing the formation of toxic β-sheet structures. Furthermore, melatonin promotes amyloid clearance via the glymphatic and lymphatic systems, protects neurons from oxidative damage, and reduces Tau hyperphosphorylation. This suggests that melatonin serves as a promising multitarget therapeutic agent for both metabolic and neurodegenerative disorders by modulating structural protein transformations. Full article

Background: Axillary lymph node dissection (ALND) remains necessary for selected patients with breast cancer but is associated with lymphatic morbidity, including seroma formation and breast cancer-related lymphedema (BCRL). The Total Sealing Technique (TST) is a technique-centered operative concept that emphasizes systematic sealing of lymphatic and vascular structures during ALND. Methods: This review integrates mechanistic rationale and clinical evidence derived from comparative cohort studies evaluating TST (using advanced bipolar vessel-sealing systems) versus conventional electrocautery (CONV). Key perioperative and long-term outcomes are summarized quantitatively. Results: In a comparative cohort of total mastectomy with ALND, TST significantly reduced total drainage volume (360.5 ± 187.9 vs. 820.6 ± 661.6 mL; p < 0.001) and shortened time to drain removal (4.8 ± 1.3 vs. 6.8 ± 2.1 days; p < 0.001). Postoperative hospital stay was reduced by 3.7 days on average (5.9 ± 1.3 vs. 9.6 ± 3.4 days; p < 0.001). The incidence of seroma decreased from 65.9% to 28.6% (p = 0.001), with fewer aspiration procedures (1.8 vs. 4.6 per patient; p = 0.022). Importantly, long-term follow-up demonstrated a statistically significant reduction in BCRL incidence (2.9% vs. 22.2%; p = 0.028). Operative time and blood loss were not increased. Conclusions: Current single-center data indicate that TST is associated with substantial reductions in postoperative lymphatic morbidity and a statistically significant decrease in BCRL incidence. While independent multicenter validation is warranted, TST represents a reproducible technique-centered approach with meaningful clinical impact in ALND. Full article

Background/Objectives: Chronic venous disease (CVD) is a prevalent condition marked by valve dysfunction and increased pressure in lower limb veins. The trans-nodal veins in the inguinal region and Scarpa triangle, which connect the superficial and deep venous systems, provide new insight into venous insufficiency pathways. While they function normally in healthy individuals, they can become dilated in chronic venous disease or following surgery. The purpose of this study was to provide an ultrasonographic anatomical description of intranodal varicose veins and to assess possible changes in the stiffness of varicose, dilated inguinal lymph nodes. Methods: The study comprised 92 participants, including 69 women and 23 men, who underwent Doppler ultrasound examinations of the lower-limb venous system, focusing on the groin from both a descriptive morphological and an elastographic perspective. The diagnosis of lymph node varices was made according to established criteria, its severity was assessed using an original classification system, and shear-wave elastography (SWE) values were recorded. Results: More than 83% of patients with operated CVD had lymph node varicose veins. Patients with lymph node varicose veins had larger groin lymph node diameters than patients with CVD without lymph node varicose pathology. The mean shear wave elastography values were significantly lower in the group with lymph node varices compared to the group without (12.2 ± 1.1 kPa vs. 20.1 ± 2.3 kPa; p < 0.05). Elastographic values correlate with lymph node diameter (p = 0.039) and with varicose vein grade (p < 0.001). Conclusions: Intranodal varices may indicate disease progression. These vascular abnormalities impact SWE measurements by altering tissue mechanics. It is imperative to consider the interactions between the lymphatic and venous systems in the management of CVD to improve patient outcomes. Full article

Bone metastasis is a devastating complication of advanced osteotropic malignancies, notably breast, prostate, lung carcinomas, and malignant melanoma, and remains a primary driver of mortality. Historical paradigms have conceptualized skeletal dissemination almost exclusively as a hematogenous process wherein circulating tumor cells colonize receptive bone marrow niches. However, this model fails to reconcile why lymph node metastasis consistently serves as a potent predictor of bone involvement even though therapeutic lymphadenectomy rarely prevents distant spread. This discordance suggests that lymph nodes function not merely as passive reservoirs but as active ‘evolutionary gateways’ that sculpt bone-tropic metastatic clones. In this review, we introduce the Lymphatic–Bone Axis, a framework integrating lymphatic biology into models of bone metastasis. We synthesize emerging evidence elucidating how the lymph node microenvironment primes tumor cells through CCR7-CXCR4 switching, induction of osteomimicry programs, and metabolic reprogramming that favors survival within the bone marrow. We also discuss preclinical data demonstrating direct intranodal intravasation via high endothelial venules (HEVs), providing a rapid route into the systemic circulation that bypasses the thoracic duct. Beyond consolidating current knowledge, we outline a research agenda for dissecting this axis, including longitudinal single-cell transcriptomic mapping and functional assessments of lymph node-derived tumor cells. Finally, we consider translational implications, highlighting why bone-targeted agents alone may prove insufficient once cells are conditioned within lymphatic niches. By mechanistically linking lymphatic priming to skeletal colonization, this review informs the rational design of multimodal therapeutic approaches that jointly target lymphatic transit and the bone microenvironment. Full article

Etrasimod is an oral selective sphingosine-1 phosphate receptor modulator, and its anti-inflammatory mechanism of action in inflammatory bowel diseases is not completely understood. It targets pro-inflammatory immune cells expressing sphingosine-1-phosphate receptors during their migration from the lymphatic system to the circulation and intestinal mucosa. Reductions in certain lymphocyte subsets in the peripheral blood have been reported, but its effects in lymph nodes remain unknown. This study investigated changes in leukocyte subpopulations in peripheral lymph nodes and blood in Crohn’s disease patients treated with etrasimod. Moderate-to-severe Crohn’s disease patients participated in this randomized, double-blind study, within the phase 2 CULTIVATE clinical trial. At baseline and after 14 weeks of etrasimod treatment, peripheral blood and inguinal lymph node biopsies were obtained. Isolated peripheral blood mononuclear cells and lymph node leukocyte populations were analyzed at single cell level using mass cytometry at both timepoints. The immunophenotyping revealed 15 innate and adaptive major immune cell populations, as well as 14 subpopulations of CD4+ and CD8+ T-cells. In peripheral lymph nodes, etrasimod resulted in significant accumulation of naïve, central memory, and effector memory CD4+ T-cells (+10.7%, +4.2%, and +2.3%, respectively; all p = 0.03), as well as naïve CD8+ T-cells (+4.2%; p = 0.03). Conversely, these subsets were reduced in peripheral blood (−6.2%, −6.0%, −2.0%, and −2.2%, respectively; all p = 0.03). Naïve and memory B-cells decreased in the circulation (−1.7%, p = 0.057; −0.6%, p = 0.03, respectively) but were unchanged in the lymph nodes. Innate immune cell populations remained mostly unaffected in both compartments. Our data indicate that etrasimod’s pharmacodynamic effect is related primarily with the attenuation of the T-cell mediated inflammation with minor changes in B-cells. However, additional follow-up studies are needed for the validation of these observations in the context of Crohn’s disease. Full article

Background: Acalabrutinib is a selective Bruton tyrosine kinase inhibitor widely used for chronic lymphocytic leukemia and mantle cell lymphoma. Real-world safety evidence from Latin America remains limited, which restricts local benchmarking and pharmacovigilance planning. In this study we aimed to assess exposure-adjusted adverse events in routine care in Mexico. Methods: We analyzed postmarketing surveillance datasets and spontaneous reports from March 2020 to August 2024, classifying events with MedDRA and summarizing seriousness, severity, and incidence per 100 patient-years. Results: A total of 266 patients were registered; 193 had evaluable exposure and safety data, contributing 242.73 patient-years. The overall adverse event incidence was 24.71 per 100 patient-years. Twenty-eight individual case safety reports documented 60 events. Forty-four events were serious. Among 33 events with reported severity, 14 were severe, 14 moderate, and five mild. Frequently affected system organ classes were blood and lymphatic, vascular, and infections. Seven deaths were reported; most were associated with COVID-19 complications or disease progression. Conclusions: The adverse event profile observed aligns with published trial experience and supports the tolerability of acalabrutinib in Mexican practice. These country-level, exposure-adjusted estimates provide actionable context for clinicians, institutional pharmacists and pharmacovigilance teams and point to the value of strengthening report completeness to improve signal detection in routine oncology care. Full article

Lymphatic filariasis (LF) is a mosquito-borne neglected tropical disease that causes substantial morbidity and social exclusion. Global efforts under the World Health Organization’s Global Programme to Eliminate Lymphatic Filariasis have markedly reduced prevalence, and several Pacific Island Countries and Territories (PICTs) have achieved elimination of the disease as a public health problem. However, post-validation surveillance (PVS), essential for detecting resurgence and enabling early response, has rarely been implemented, and barriers to its delivery remain poorly understood. We used two complementary qualitative approaches to identify systemic barriers and enablers to LF PVS in PICTs. First, we conducted a Nominal Group Technique followed by a structured expert elicitation involving program managers and technical staff. Data were analysed thematically and triangulated across sources. Participants identified 70 challenges which were consolidated into ten thematic domains. Pertinent barriers relate to limited leadership understanding of LF and surveillance options, inconsistent technical and financial support, and a lack of context-appropriate operational guidance. Additional challenges included limited field-ready diagnostics, procurement delays, the absence of formal mandates, and low community engagement. Enablers included embedding PVS within existing health services, leveraging trusted community networks, strengthening regional frameworks, and co-developing practical tools with countries. Sustaining LF elimination in the Pacific will require political commitment, regional collaboration, and integrated, programmatic approaches informed by recent PVS experience. Full article

Extrapulmonary tuberculosis (EPTB) is an infectious disease characterized by the invasion of Mycobacterium tuberculosis beyond the lungs. Diagnosis is frequently delayed due to nonspecific clinical presentations that vary by organ system, making diagnostic imaging essential for disease detection, characterization, and treatment monitoring. The objective of this review is to examine and summarize imaging-based approaches for the diagnostic evaluation of EPTB across multiple body systems, including the central nervous system, spine, cardiovascular system, lymphatic system, abdominal and hepatic organs, genitourinary tract, cutaneous and soft tissue, and other rare sites. While computed tomography, magnetic resonance imaging, positron emission tomography, and ultrasound are widely used in the evaluation of EPTB, their ability to provide a definitive diagnosis is often limited by nonspecific radiologic findings. Emerging techniques, including perfusion-weighted MRI, contrast-enhanced ultrasound, and machine learning, have been discussed, as they improve lesion characterization and EPTB differentiation. By organizing imaging findings according to affected organ systems, this review highlights both shared diagnostic challenges and site-specific patterns that can inform clinical suspicion. Together, these developments underscore the value of a multimodal, organ-specific imaging approach integrated with the clinical context to improve the recognition and management of EPTB. Full article

Immune checkpoint inhibitors have transformed the treatment landscape for advanced melanoma in the past 15 years, delivering unprecedented and durable survival benefits. This success has propelled the development of complementary immune-directed therapies, including cancer vaccines. Among these, synthetic long peptide (SLP) and mRNA vaccine platforms have emerged as highly promising. Advances in next-generation sequencing technology, alongside computational neoantigen algorithm predictions, have enabled patient-specific neoantigen identification to improve vaccine immunogenicity and enhance therapeutic efficacy. Off-the-shelf and personalised SLP and mRNA vaccines have demonstrated the ability to induce robust antigen-specific T-cell responses and modulate the tumour microenvironment. Mechanistically, cancer vaccines synergise with immune checkpoint inhibition. This review outlines the current clinical development of mRNA and peptide vaccines in melanoma, highlighting the significant promise to synergise with immune checkpoint inhibition to enhance efficacy without adding to the systemic toxicity profile. The neoadjuvant setting, characterised by intact tumour antigens and draining lymphatic architecture, offers a compelling biological context for leveraging cancer vaccines for enhanced immune priming and response assessment. Collectively, the rapid advances in technology and emerging clinical data position cancer vaccines as a promising therapy capable of improving immunotherapy in Stage III and IV melanoma. Full article

Background and Clinical Significance: CEUS enhances the visualization of vascular patterns within liver lesions, enabling differentiation between benign and malignant lesions, including hemangiomas, focal nodular hyperplasia, and hepatocellular carcinoma, with high accuracy. Lymphangiomas are rare benign lymphatic-system tumors, with intra-abdominal lymphangiomas accounting for approximately 5% of cases, most of which occur in the pediatric population. Intra-abdominal lymphangiomas commonly occur in multiple localizations due to lymphangiomatosis, but solitary lymphangiomas in adults are rare and easy to be misdiagnosed due to asymptomatic cases or non-specific symptoms. Case Presentation: A 65-year-old male with a history of left nephroadrenalectomy due to clear renal-cell carcinoma and paraaortic lymphadenectomy (staging pT3bN0M0V1R0) presented for a routine contrast-enhanced abdominal computer tomography examination. The scan showed several hypervascular structures that accumulate contrast in the arterial phase in the right liver lobe. Three years later, the patient developed complaints of abdominal pain and night sweats. Multiple MRI and CT examinations were performed, followed by a CEUS and a liver-core biopsy, which supported the diagnosis of hepatic lymphangioma. Conclusions: CEUS may be a more valuable evaluation method for follow-up examination than repeating CT and MRI scans. The real-time diagnostic possibility and tissue-perfusion data provide more profound information about the lesion of interest. Thus, it can be used as a primary diagnostic tool when a biopsy is performed. Although this method is relatively new, it can be applied in clinical settings with great value, and it saves time and resources. Full article