Search Results (566)

Cardiac sarcoidosis (CS) is a critical and frequently underdiagnosed phenotype of sarcoidosis, characterized by non-caseating granulomatous infiltration of the myocardium. This review synthesizes current knowledge regarding the pathogenesis, diagnosis, and management of CS. The disease manifests with a heterogeneous clinical spectrum ranging from asymptomatic conduction abnormalities to life-threatening ventricular arrhythmias and heart failure. Diagnosis remains challenging due to the patchy distribution of granulomas, which limits the sensitivity of endomyocardial biopsy. Consequently, a multimodal diagnostic approach is essential, integrating advanced imaging modalities such as cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET). These tools not only facilitate detection but also enable the differentiation of active inflammation from chronic fibrosis. Histopathological assessment, supported by specific immunophenotyping and electron microscopy, remains the gold standard for confirming diagnosis and excluding mimics like giant cell myocarditis or infectious granulomatous diseases. Management requires a multidisciplinary strategy combining immunosuppressive therapy, primarily corticosteroids and steroid-sparing agents, with guideline-directed cardiac care, including implantable cardioverter-defibrillators for arrhythmia risk stratification. Emerging biomarkers and artificial intelligence-driven imaging analysis promise to further refine risk stratification and therapeutic monitoring, advancing precision medicine in this complex disorder. Full article

The number of confiscated CITES-listed animals has increased dramatically worldwide, creating significant health, logistical, and resource challenges for responsible authorities. Rescue centers represent a scientific and humanitarian response to this challenge, providing solutions through rehabilitation, research, and environmental education. This postmortem survey provides information on disease and mortality during a four-year period, in confiscated CITES-listed birds and reptiles housed in an authorized rescue center. A total of 29 animals (17 birds and 12 reptiles) were examined by necropsy and histopathology. Infectious disease accounted for the mortality of 58.8% of birds and 49.8% of reptiles, with overrepresentation of bacterial disease in both groups. Lesions consisted mainly of granulomas in multiple organs. Suspected viral disease occurred in 23.3% of birds, and protozoal infections were found in 17.3% of birds. Systemic disease caused by an unknown haemosporozoan was the cause of death in a Lonchura oryzivora. An unknown infectious agent was associated with renal disease in a Ctenosaura sp. Gout secondary to dehydration was overrepresented in reptiles (33.3%). This study highlights the complexity of disease processes affecting confiscated birds and reptiles in CITES rescue settings and provides invaluable information for other rescue centers that may impact the success of conservation strategies. Full article

Background: Plasma cell granuloma is generally considered a pseudotumor formed by reactive, polyclonal plasma cells. Although most cases can show polyclonal gammaglobulin production, quite a minority may exhibit monoclonal gammopathy, which mimics plasma cell neoplasms such as multiple myeloma or plasmacytoma. Because of this overlap, distinguishing reactive monoclonal proliferation from true malignancy is clinically essential. Case report: A 79-year-old man was presented with an anterior chest wall mass that had grown during investigation for fever of unknown origin. ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed a sternal bone mass (SUVmax 9.04), aortic uptake of bifurcation (SUVmax 7.08), and Th7/8 soft tissue mass (SUVmax 5.32). Results from the FDG-PET revealed infectious reactions. A chest wall biopsy revealed high degree proliferation of plasma cells. Hematologists suspected plasmacytoma. The pathologist did not diagnose plasmacytoma; thus, there remains a possibility of reactive granuloma lesion. Lastly, the patient’s vertebral soft tissue mass culture yielded Staphylococcus aureus. The patient was treated with antimicrobials and responded well. Discussion: In the presented case, FDG-PET revealed an aortic mass with an aortic aneurysm, a sternal mass, and a vertebral mass, as multiple lesions. The abscess lesions that initially resembled multiple plasmacytomas were identified as plasma cell granuloma. The final diagnosis required demonstrating biopsy and definitive monoclonality. Light-chain restriction or monoclonal protein should be considered in the clinical context. Ultimately, this case highlights the diagnostic value of FDG-PET and the importance of differentiating reactive plasma cell granuloma from true plasma cell neoplasm to guide appropriate management. In conclusion, a reactive plasma cell granuloma associated with infectious aortitis can exhibit monoclonal gammopathy, mimicking plasma cell neoplasm. Careful pathological and clinical evaluation is essential to avoid misdiagnosis and ensure proper treatment. Full article

Delayed-type hypersensitivity (DTH) to Mycobacterium tuberculosis (MTb) antigens is a crucial component of the cellular immune response presented during tuberculosis infection. This reaction is driven primarily by T lymphocytes, which recognize mycobacterial antigens and trigger a focused inflammatory cascade. Cytokines produced by T lymphocytes stimulate the formation of granulomas, organized structures that help contain the bacteria and prevent their spread. DTH is essential for controlling the infection and forms the basis of diagnostic tools, including the still widely practiced tuberculin skin test despite its limitations. This immunological mechanism is also used as an important therapeutic target in the treatment of tuberculosis by modulating the cellular response. These approaches include immunomodulatory agents, therapeutic vaccines and host-directed treatment. Ongoing research offers promising opportunities for future interventions aimed at decreasing the global mortality associated with tuberculosis. Full article

Aesthetic medicine has progressed from the early 2000s fascination with bio-stimulation to the current dominance of hyaluronic acid (HA) fillers, prized for immediate, predictable, and reversible volumizing effects. Recently, demand for more natural results, stronger emphasis on skin quality, and increased post-pandemic self-scrutiny have renewed interest in regenerative strategies, sometimes called the “second wave of bio-stimulation.” This trend highlights the need for clearer terminology and a cautious, evidence-based reading of proposed biological mechanisms. This narrative review proposes a framework in which bio-regeneration denotes a hypothesized, controlled induction of physiological processes, fibroblast activation, collagen and elastin synthesis, extracellular matrix remodeling, and immune modulation, potentially producing sustained improvements in dermal structure and function beyond simple filling. Among emerging technologies, polyethylene glycol diglycidyl ether (PEGDE) cross-linking is reported to create a stable, flexible HA scaffold with homogeneous tissue integration, favorable rheology, thermal stability, and a reduced inflammatory profile, supporting safer multimodal use with energy-based devices. The framework is illustrated with PEGDE-crosslinked HA combined with low-concentration calcium hydroxyapatite (CaHA), exemplified by a PEGDE-HA filler containing CaHA microspheres plus glycine and L-proline. These formulations aim to deliver immediate correction via HA and delayed stimulatory effects possibly driven by gradual CaHA exposure and macrophage-associated signaling. Available clinical, imaging, and histological observations, including prospective ultrasound and biopsy assessments, suggest progressive dermal thickening and predominant type I collagen expression, without pathological inflammation or granuloma formation. Although evidence remains preliminary and largely non-comparative, findings are compatible with controlled remodeling and resolving inflammation; however, the underlying mechanism and any ‘regenerative’ versus ‘reparative’ classification require controlled comparative studies. Full article

Background and Clinical Significance: Sarcoidosis is a systemic inflammatory disorder characterized by noncaseating granulomas. While pulmonary involvement is common, isolated renal involvement is rare and diagnostically challenging. We report a case emphasizing the utility of urinary tubular markers for early detection. Case Presentation: A 60-year-old woman with a history of suspected ocular sarcoidosis presented with progressive renal impairment and constitutional symptoms. Initial workup for systemic sarcoidosis was negative, leading to a misdiagnosis of chronic fatigue syndrome. Her rising serum creatinine was initially attributed to dehydration. However, a marked elevation in urinary β2-microglobulin (33,736 μg/L) prompted a renal biopsy, which revealed granulomatous tubulointerstitial nephritis. Following prednisolone therapy, her renal function improved, and her fatigue resolved completely. Conclusions: This case demonstrates that the kidney can be the primary site for histological diagnosis in the absence of pulmonary lesions. Incorporating urinary β2-microglobulin into routine monitoring may facilitate the early detection of renal sarcoidosis, preventing diagnostic delays. Full article

Hematopoietic stem cell transplant (HSCT) recipients are at high risk for opportunistic infections due to profound immunosuppression and graft-versus-host disease (GvHD). Molds and nontuberculous mycobacteria (NTM) pose diagnostic and therapeutic challenges, especially when infections overlap. A 42-year-old woman with prior allogeneic HSCT for acute myeloid leukemia (AML) developed pulmonary infections with Microascus spp. and Mycobacterium chimaera, later complicated by Aspergillus calidoustus and RSV infection. Initial therapy included voriconazole, amphotericin B, and a macrolide-based multidrug regimen for NTM. Modifications were required for drug resistance and hepatotoxicity. Despite partial response, recurrent fungal infection necessitated prolonged antifungal therapy, including adjunctive inhaled amphotericin B and terbinafine. Ultimately, progressive bronchiolitis obliterans prompted bilateral lung transplantation. Explant pathology revealed necrotizing granulomas positive for NTM and Microascus spp. Post-transplant prophylaxis with voriconazole, rifabutin, azithromycin, and inhaled amikacin prevented recurrence, and the patient remained clinically stable at 6-month follow-up. This case illustrates the complexity of managing overlapping mold and NTM infections in HSCT recipients, highlighting the need for individualized, multidisciplinary care. Therapeutic drug monitoring, careful adjustment for drug–drug interactions, and the use of adjunctive inhaled antifungals were critical to achieving a favorable outcome. Full article

Background/Objectives: Conjunctival closure may influence early postoperative comfort and wound healing after pediatric strabismus surgery. We compared fibrin glue with absorbable sutures using anterior segment optical coherence tomography (AS-OCT)-based conjunctival thickness, serial clinical scores, ocular-surface screening, and operative time. Methods: We retrospectively reviewed 82 children (5–15 years) who underwent bilateral medial rectus recession. The conjunctiva was closed with 8-0 polyglactin 910 (Vicryl) (suture group, n = 40) or fibrin glue (fibrin group, n = 42) according to routine practice; right eyes were analyzed. Conjunctival thickness was measured by AS-OCT preoperatively and at week 6. The comfort questionnaire (CQ) score and inflammation score (IS) were recorded on postoperative day 1 and weeks 1, 2, and 6. Total operative time and closure time were obtained from surgical video recordings. Ocular Surface Disease Index-6 (OSDI-6) and non-invasive keratographic break-up time (NIKBUT) were assessed preoperatively and at week 6 in cooperative children (n = 62). Results: Conjunctival thickness increased in both groups and was slightly higher at week 6 with sutures (p < 0.001), with a slightly greater percentage increase (p = 0.001). CQ and IS were worse with sutures through week 2 (all p < 0.05) and converged by week 6 (both p > 0.05). Fibrin glue shortened total operative time (32.75 vs. 35.46 min; p < 0.05) and closure time (3.90 vs. 5.35 min; p < 0.001). In the ocular-surface subset, OSDI-6 and NIKBUT did not differ between groups at week 6. No infections or granulomas occurred; two early conjunctival wound gaps occurred in the fibrin group and one resolved with topical management, while the other met the dehiscence definition (≥2 mm) and required re-suturing, and both healed without sequelae. Conclusions: In pediatric strabismus surgery, fibrin glue demonstrated better early comfort with a modest difference in conjunctival thickness at week 6 along with slightly shorter operative time while clinical scores converged by week 6, and ocular-surface screening outcomes were similar. Full article

Background/Objectives: The precise elimination of Schistosoma japonicum eggs within host tissues poses a significant therapeutic obstacle due to the ineffectiveness of existing drugs in penetrating the eggs’ protective shields. This investigation sought to create a surface-modified magnetic nanoparticle (MNP) framework to surmount this hurdle and realize targeted theranostics for combating schistosomiasis. Methods: Fe₃O₄ MNPs, MNP-NH₂, and MNP-COOH were synthesized and characterized before systematically studying their interactions with parasites. The intrinsic autofluorescence of eggs and adult worms served as an optical background for the investigation. In vitro co-incubation assays, confocal microscopy, and Prussian blue staining were utilized to quantify both adsorption and internalization. The in vivo efficacy was assessed in a Schistosoma japonicum murine model following tail vein injection. Results: A pronounced surface chemistry-dependent interaction was noted. Fe₃O₄ MNP and MNP-NH₂ displayed remarkable adsorption and effective internalization into eggs in vitro, while MNP-COOH exhibited limited uptake. This varying effectiveness was similarly observed in vivo, with Fe₃O₄ MNP and MNP-NH₂ predominantly gathering in hepatic granulomas and effectively infiltrating deposited eggs. Within adult worms, Fe₃O₄ MNP and MNP-COOH exhibited distribution on the tegument and within adult worms. Conclusions: We developed a functional MNP platform in which surface charge governs parasiticidal targeting. Among the candidates investigated, MNP-NH₂ proved to be the most efficient for egg-targeted theranostics. This study introduces an innovative nanotechnology-based approach for accurate diagnosis and treatment of schistosomiasis by specifically tackling the challenge of impermeable eggs. Full article

Spatial transcriptomics (ST) enables genome-wide gene expression profiling while preserving tissue architecture, bridging the gap between bulk, single-cell, and histological analyses. Originating in 2016 and rapidly evolving since, ST has transformed infectious disease research by mapping host–pathogen interactions directly within intact tissues. Current platforms fall into two categories: sequencing-based methods (Visium, GeoMx, Stereo-seq) offering whole-transcriptome coverage at modest resolution and imaging-based platforms (Xenium, CosMx, MERFISH) providing single-cell or subcellular detail with targeted gene panels. These technologies reveal spatially organized immune responses, local tissue remodeling, and pathogen niches across viruses, bacteria, and parasites. In viral infection, ST uncovered heterogeneity in COVID-19 lung microenvironments, spatial immune activation in lymphoid tissues, and variant-specific inflammatory patterns. In bacterial disease, ST delineated granuloma architecture in tuberculosis and mapped vaccine-induced lung responses in Shigella studies. Parasitic infection studies identified localized inflammatory hotspots and microenvironmental control of T-cell differentiation in malaria. Despite powerful insights, ST faces constraints including RNA quality limitations, tradeoffs between resolution and transcript breadth, high cost, and analytical complexity. Nonetheless, ST increasingly informs vaccine design by identifying tissue-specific immune programs and protective microenvironments and is poised to become a standard tool for infectious disease biology. Full article

Tuberculosis and coronavirus disease 2019, also known as COVID-19, remain major global health challenges that disproportionately affect individuals with metabolic disorders, chronic inflammation, and limited access to healthcare. Although these diseases are caused by different pathogens, they share important host-related determinants of severity, including immune dysfunction, oxidative stress, endothelial injury, and maladaptive inflammatory responses. Glutathione, the primary intracellular antioxidant and a key regulator of redox balance, has emerged as an important host factor connecting these processes across infectious diseases. This review integrates experimental, translational, and clinical evidence supporting the role of glutathione in regulating immune function, oxidative stress, and tissue damage in tuberculosis and COVID-19. In tuberculosis, glutathione deficiency compromises macrophage antimicrobial activity, disrupts granuloma structure, and alters T helper cell responses, leading to impaired immune containment and disease progression. In COVID-19, reduced glutathione levels are associated with redox imbalance, excessive cytokine signaling, endothelial dysfunction, and thromboinflammatory complications, especially in high-risk populations. In both diseases, glutathione depletion reduces host resilience and increases vulnerability to severe outcomes through shared immune and vascular pathways. By unifying disease-specific findings within a host-directed framework, this review highlights glutathione and redox signaling as common vulnerability pathways that help explain overlapping risk profiles for severe tuberculosis and COVID-19. It also places glutathione biology within the broader context of host-directed immunotherapy, emphasizing its potential role in prevention-focused and resilience-based strategies that complement pathogen-targeted treatments. Although current evidence does not support simple claims of disease prevention, it provides strong mechanistic justification for further investigation of glutathione as a modifiable host factor in high-risk populations. Full article

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency or inborn error of immunity (IEI) encountered in clinical practice. Characterized by a remarkably broad clinical spectrum, CVID presents with phenotypes spanning from “infection only” to significant non-infectious complications. The frequent overlap between these classifications underscores that their distinction is more accurately viewed as a continuous spectrum, rather than a binary categorization. CVID-associated liver disease is a significant source of morbidity, yet often poses diagnostic challenges due to its insidious and clinically silent nature, typically becoming apparent only upon the development of complications. Manifestations range from abnormal liver tests to irreversible organ damage, with reports including granulomas, autoimmune hepatitis, fibrosis, and porto-sinusoidal vascular disorder (PSVD). Regenerative nodular hyperplasia (RNH), commonly associated with PSVD, is a frequent histopathological finding. Management requires a multidisciplinary approach, including cause-directed immunosuppression and supportive treatment for non-cirrhotic portal hypertension. Despite significant advances in comprehending CVID-associated liver involvement, substantial gaps persist concerning its pathogenesis, its optimal management, and the correlation between histological findings and clinical outcomes. A heightened awareness of CVID-associated liver disease is paramount for multidisciplinary teams across IEI centers. Furthermore, given its prevalence, its insidious clinical phenotype until advanced complications, and the significant diagnostic delay and underdiagnosis, such awareness is critical across a broader range of medical specialties. In this paper, we aim to consolidate current knowledge regarding CVID-related liver disease, examining its clinical presentation, recent genetic and pathogenetic advancements along with current diagnostic methodologies, and therapeutic strategies. Full article

Biodegradable tracheal stents have been developed to overcome the limitations of metallic and removable stents in benign airway disease. This study evaluated the local and systemic inflammatory response induced by a biodegradable polydioxanone tracheal stent in a rabbit model. Twenty-one rabbits were assigned to three follow-up groups (30, 60, and 90 days). In each group, six animals received a tracheal stent, and one served as a sham control. Clinical status and respiratory symptoms were monitored, and serial peripheral blood interleukin-8 (IL-8) levels were measured. At the end of follow-up, tracheoscopy, IL-8 quantification in tracheal lavage, and necropsy were performed. No deaths or severe respiratory symptoms occurred. Tracheoscopic findings were significantly less severe after stent degradation, with reduced congestion (p = 0.030), inflammation (p = 0.003), and secretions (p = 0.030). Two granulomas and two cases of stenosis were identified. Mean IL-8 expression in tracheal lavage (relative quantification, RQ) was 14,129 ± 3007 when the stent was present and 426 ± 100 after degradation (p = 0.003). Blood IL-8 expression increased significantly on day 1 compared with baseline (p = 0.022) and subsequently decreased (p = 0.034). Inflammatory and structural alterations induced by a polydioxanone tracheal stent decrease after stent degradation. Full article

Intestinal emphysema is a rare pathological condition observed in humans and animals, characterized by the presence of multiple gas-filled cysts within the intestinal wall. In pigs, it is occasionally observed at slaughter, without affecting carcass suitability for human consumption or impairing farm profitability. Despite investigations, the etiology and pathogenesis of intestinal emphysema remain poorly understood. Therefore, this study aimed to provide further morphological insights into porcine intestinal emphysema through histopathological, histochemical and immunohistochemical methods. A total of ten slaughtered heavy pigs were examined, showing gross lesions consistent with intestinal emphysema. Gaseous cysts were predominantly located in the submucosal and mesenteric layers, at least partially lined by lymphatic endothelial cells. The cysts were separated by fibrous connective septa and were almost invariably associated with granulomas, consisting of epithelioid macrophages and multinucleated giant cells. Overall, the immunohistochemical patterns of porcine intestinal emphysema overlap with those described in humans and support the hypothesis that lesions likely originate within the lymphatic vessels. Full article

Background: Sarcoidosis is a multisystem inflammatory disorder characterized by non-caseating granulomas, most commonly affecting the lungs and intrathoracic lymph nodes. Angiotensin-converting enzyme (ACE) levels and calcium abnormalities are recognized biomarkers, while ^18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is increasingly used to assess disease activity. However, neither provides sufficient diagnostic accuracy alone. Therefore, this study aimed to investigate the relationship between FDG-PET/CT metabolic findings and serum ACE and calcium (Ca²⁺) levels as surrogate indicators of inflammatory metabolic intensity in sarcoidosis. Methods: In this retrospective single-center study, 127 patients with pulmonary sarcoidosis who underwent PET/CT at diagnosis were evaluated. Demographic and clinical data, ACE, and Ca²⁺ levels were recorded. FDG uptake in mediastinal, pulmonary, and extrapulmonary sites was analyzed, and correlations with biomarkers were assessed. Results: The cohort included 89 females (70.1%) and 38 males (29.9%), mean age 51.3 ± 11.9 years. FDG uptake was most frequent in mediastinal lymph nodes (84.3%) and lung parenchyma (40.9%). ACE levels correlated weakly with total SUVmax (r = 0.214, p = 0.019). Calcium levels correlated with extrapulmonary SUVmax (r = 0.327, p = 0.001) and were higher in patients with extrapulmonary involvement (p = 0.045). No associations were found between symptom presence and biomarkers or SUVmax values. Conclusions: FDG-PET/CT metabolic parameters, particularly total and extrapulmonary SUVmax, demonstrated modest yet statistically significant associations with ACE and calcium levels. These findings suggest that a combined biomarker-imaging approach may provide complementary information regarding inflammatory metabolic intensity and systemic involvement; however, the results should be interpreted as exploratory and require validation in prospective studies. Full article