Search Results (228)

The precipitation of cryoglobulins, serum immunoglobulins, below 37 °C defines the clinical cryoglobulinemic syndrome, a systemic vasculitis usually characterized by purpura, weakness, and arthralgia. In most cases, this condition is associated with chronic infection by the hepatitis C virus (HCV) and can evolve into B-cell dysregulation and malignancies. The current literature on non-HCV-associated cryoglobulinemia is very limited, and little is known about the immunological and serological profile of affected patients. The cryoglobulinemic syndrome not associated with HCV infection is often found concomitantly with other infections, autoimmune diseases, and B-cell lymphoproliferative disorders. The cryoprecipitation of fibrinogen has been described as a rare disorder, perhaps underestimated and not fully understood, causing thrombotic occlusion and ischemia in different rheumatic disorders. Cold temperature plays a pathogenetic role in autoimmune hemolytic anemias, in which the presence of cold agglutinins produced by B cells at the lymphoplasmacytic cell stage may promote agglutination of red blood cells in the coldest parts of the circulation, even at mild room temperatures, undergoing hemolysis. Laboratory methods for the detection and quantification of cryoproteins are downright critical, and their concurrent detection is pivotal for the diagnosis. In this review, we summarize the clinical involvement of cryoglobulins, cryofibrinogen, and cold agglutinins in non-HCV autoimmune diseases, underlining the crucial steps of the most employed analytic methods. Full article

Objectives: This study aimed to evaluate the ability of three-dimensional (3D) speckle tracking echocardiography (STE) to detect acute coronary occlusions in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and its potential diagnostic advantage over two-dimensional (2D) STE. Methods: Fifty-six patients with NSTE-ACS (mean age 64 ± 11 years; 80% male) underwent 2D and 3D transthoracic echocardiography prior to coronary angiography. Global longitudinal strain (GLS), global circumferential strain (GCS), and 3D ejection fraction (EF) were analyzed. Acute coronary occlusion was defined as TIMI flow 0–1 in the presumed culprit artery. Results: Acute coronary occlusion was present in 16 patients (29%). Patients with occlusion had significantly more impaired strain compared to those without: 3D GLS (−12.5 ± 2.7% vs. −15.5 ± 2.1%, p < 0.001), 2D GLS (−12.6 ± 2.8% vs. −15.6 ± 2.0%, p < 0.001), 3D GCS (−24.8 ± 4.4% vs. −27.8 ± 4.3%, p = 0.02), and 2D GCS (−18.1 ± 5.5% vs. −22.9 ± 4.7%, p = 0.002). In contrast, 3D EF did not differ significantly between groups (52.5 ± 4.7% vs. 54.7 ± 5.7%, p = 0.16). Receiver operating characteristic analysis showed that 3D and 2D GLS had the highest diagnostic performance (AUCs 0.81 and 0.78), while 3D EF had the lowest (AUC 0.61). Feasibility was lower for 3D STE (86%) than for 2D longitudinal strain (95%, p = 0.03). Conclusions: Both 3D and 2D GLS showed higher diagnostic accuracy than 3D EF in identifying acute coronary occlusion in NSTE-ACS patients. While 3D STE enables simultaneous assessment of multiple parameters, it did not offer incremental diagnostic value over 2D STE and had lower feasibility. Full article

This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications of various oculoplastic procedures used in their management. A narrative review was performed based on expert-guided selection of relevant studies retrieved from PubMed, Scopus, and Web of Science. Relevant keywords included “ocular surface disease”, “dry eye syndrome”, “exposure keratopathy”, “thyroid eye disease (TED)”, “neurotrophic keratopathy (NK)”, “Stevens-Johnson syndrome”, “toxic epidermal necrolysis”, “punctal occlusion”, “tarsorrhaphy”, “botulinum toxin”, “eyelid loading”, “retractor weakening”, “corneal neurotization (CN)”, “amniotic membrane transplantation (AMT)”, “conjunctival flap”, “ocular graft versus host disease”, and “salivary gland transplantation (SGT)”. Studies addressing surgical approaches for OSDs were included. In conclusion, surgical options for OSDs offer significant benefits when non-invasive treatments fail. Surgical techniques such as punctal occlusion, eyelid fissure narrowing, AMT, and conjunctival flap procedures help stabilize the ocular surface and alleviate symptoms. Advanced methods like CN and SGT target the underlying pathology in refractory cases such as oGVHD. The outcomes vary depending on the disease severity and surgical approach. Each procedure carries specific risks and requires individualized patient selection. Therefore, a tailored approach based on clinical condition, anatomical involvement, and patient factors is essential to achieve optimal results. Ongoing innovations in reconstructive surgery and regenerative medicine are expected to further improve outcomes for patients with OSDs. Full article

Defibrotide, which is approved for treating hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), exhibits pleiotropic anti-inflammatory, anti-thrombotic, and fibrinolytic properties, conferring broad endothelial protective effects. Given these mechanisms, defibrotide has potential utility in various conditions involving endothelial injury or activation. In this review we outline the endothelial-protective mechanisms of defibrotide and comprehensively summarize current evidence supporting its applications in hematologic malignancies, including the prevention and treatment of hepatic VOD/SOS, graft-versus-host disease, and transplant-associated thrombotic microangiopathy. Additionally, we discuss its role in mitigating key toxicities linked to chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We also explore emerging evidence on defibrotide’s potential in SARS-CoV-2 infection-associated endotheliopathies, including acute COVID-19 and post-acute sequelae of SARS-CoV-2 infection (“long-COVID”), and the endothelial protective activity of defibrotide in these settings. Finally, we highlight potential future applications of defibrotide in hematologic malignancies and viral infections, emphasizing its multimodal mechanism of action. Full article

Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease (SOS/VOD) is a severe complication of hematopoietic cell transplantation (HCT). Furthermore, emerging evidence suggests the potential role of complement activation and endothelial injury in SOS/VOD pathogenesis. In this study, we aimed to identify potential distinct pathogenic genetic variants between SOS/VOD and other endothelial injury syndromes following HCT, such as transplant-associated thrombotic microangiopathy (TA-TMA). For this aim, genomic DNA from 30 SOS/VOD patients and 30 controls with TA-TMA was analyzed. Using Next-Generation Sequencing (NGS), variants in complement-related genes (CFH, CFI, CFB, CFD, C3, CD55, C5, CD46, and thrombomodulin/THBD) and ADAMTS13 were examined. Out of 426 detected variants, 20 were classified as pathogenic. In SOS/VOD patients, variants were identified in ADAMTS13 (4), CFH (3), C3 (2), and CFB (1) genes. One of the variants has been recognized as the strongest genetic predictor of ADAMTS13 activity. Controls exhibited more variants in complement-related genes, particularly CFH, CFI, and C3. The genetic differences between SOS/VOD and TA-TMA highlight different pathogenic mechanisms, offering the potential for targeted risk assessment and therapy in HCT recipients. Full article

In 2023, the VAS international working group on Buerger’s Disease (BD) recommended two diagnostic criteria based on a prior Delphi study: “definitive” and “suspected”. The “definitive” criteria are history of smoking, typical angiography, and typical histopathological features. All three features are mandatory to confirm a “definitive” diagnosis of BD. The conundrum is—what features should be considered typical of BD angiography? According to this review, segmental occlusion of infrapopliteal arteries, corkscrew collaterals that appear to continue the occluded arterial segment (Martorell’s sign) or bypass the segmental occlusion, absence of atherosclerotic plaque or aneurysm could differentiate BD from ASO. Hence, for “typical” BD angiography, these manifestations should certainly be considered. However, data for differentiating angiography patterns of BD from the small- and medium-sized vasculitis including Behcet’s disease, scleroderma, hepatitis associated vasculitis, and anti-phospholipid syndrome are limited. Further studies for investigating the angiography pattern in BD patients in early and late presentation of BD, particularly in the patients with long-term follow up, are highly recommended. Full article

In this study, pharmacotherapies of abdominal compartment syndrome (ACS) and intra-abdominal hypertension (IAH) in animal studies were reviewed from the perspective of ACS/IAH as failed cytoprotection issues, as non-specific injuries, and from the point of view of the cytoprotection concept as resolution. Therefore, this review challenges the unresolved theoretical and practical issues of severe multiorgan failure, acknowledged significance in clinics, and resolving outcomes (i.e., open abdomen). Generally, the reported agents not aligned with cytoprotection align with current pharmacotherapy limitations and have (non-)confirmed effectiveness, mostly in only one organ, mild/moderate IAH, prophylactic application, and provide only a tentative resolution. Contrarily, stable gastric pentadecapeptide BPC 157 therapy, as a novel and relevant cytoprotective mediator having pleiotropic beneficial effects, simultaneously resolves many targets, resolving established disturbances, specifically compression/ischemia (grade III and grade IV), and decompression/advanced reperfusion. BPC 157 therapy rapidly activates collateral bypassing pathways, and, in ACS and IAH, and later, in reperfusion, there is a “bypassing key” (i.e., azygos vein direct blood flow delivery). This serves to counteract multiorgan and vessel failure, including lesions and hemorrhages in the brain, heart, lung, liver, kidney and gastrointestinal tract, thrombosis, peripherally and centrally, intracranial (superior sagittal sinus), portal and caval hypertension and aortal hypotension, occlusion/occlusion-like syndrome, advanced Virchow triad circumstances, and free radical formation acting as a membrane stabilizer and free radical scavenger. Likewise, not only in ACS/IAH resolving, but also in other occlusion/occlusion-like syndromes, this “bypassing key” could be an effect of the essential endothelial cytoprotective capacity of BPC 157 and a particular modulatory effect on the NO-system, and a rescuing impact on vasomotor tone. Full article

Background and Clinical Significance: Carotid stump syndrome (CSS) is a rare and unexpected cause of recurrent ischemic ipsilateral events in the carotid vascular territory despite the demonstrated occlusion of the internal carotid artery (ICA). It is believed to be caused by microemboli due to turbulent blood flow in the patent stump of the occluded ICA that passes through anastomotic channels and retrograde flow into the middle cerebral artery circulation. Case Presentation: We describe the case of a 65-year-old male patient who suffered multiple concurrent transient ischemic attacks (TIAs) with a totally occluded ipsilateral ICA revealed by computed tomography angiography (CTA). He was diagnosed with CSS, which required the safest therapeutic approach. A further investigation with digital subtraction angiography (DSA) was performed, and a trickle of blood flow was observed in the reportedly occluded ICA. The diagnosis of a true ICA occlusion was withdrawn, and a diagnosis of pseudo-occlusion was established, affecting the final treatment strategy. Therefore, the patient underwent an ipsilateral carotid endarterectomy (CEA), and he has remained asymptomatic since then. Conclusions: The differentiation between a pseudo-occlusion and a true ICA occlusion is essential in promptly managing acute recurrent ipsilateral ischemic strokes in the carotid vascular territory. A further investigation with DSA in cases with a totally occluded ICA using CTA is essential for excluding pseudo-occlusions in ipsilaterally symptomatic patients. Full article

Background: Postoperative fluid collections (POFCs) after abdominal surgeries, particularly pancreatic surgeries, are associated with high morbidity and mortality rates and were historically managed with surgical re-exploration and drainage. In particular, postoperative pancreatic fluid collections (PPFCs) are the most common complications after pancreatic surgery resulting from pancreatic leaks. They occur in up to 50% of cases, and approximately 10% of them need to be drained to avoid further sequelae. Endoscopic ultrasonography (EUS)-guided drainage of PPFCs represents the first-line treatment nowadays, but many aspects are still debated. Methods: We describe a retrospective case series of patients from multiple Italian centers who underwent EUS-guided drainage (EUS-D) of POFCs, aiming to provide data on the efficacy and safety of this procedure, supported by a review of the existing literature on this topic. The primary outcomes were technical and clinical success, and the secondary outcomes were the type and rate of adverse events (AEs) and the rate of recurrence. Results: A total of 47 patients were included. The procedure demonstrated a technical success rate of 98% (46/47) and a clinical success rate of 96% (45/47). The rate of AEs was 11% (5/47), represented by bleeding (3/5), stent occlusion (1/5), and buried syndrome (1/5). Conclusions: Management of POFCs has shifted over time towards an endoscopic approach with optimal efficacy and safety. Full article

Sickle cell disease (SCD) is a group of recessive diseases caused by the β^S sickling mutation of HBB in homozygosity or in compound heterozygosity with other pathogenic HBB mutations. Patients with severe SCD typically experience painful vaso-occlusive crises and other pain-related phenomena, including acute chest syndrome, priapism, dactylitis, avascular necrosis, and splenic sequestration and infarction. High variability of pain-related phenomena per SCD genotype indicates genetic disease modifiers (GDMs) as pathology determinants and, thus, as critical to prognosis, treatment choice, and therapy development. Articles likely holding genetic information for SCD pain phenomena were identified in PubMed and SCOPUS for article quality assessment and extraction of corresponding GDMs and observations indicative of development areas in our understanding of SCD GDMs. This process led to the initial selection of 183 articles matching the search terms, which, after two-step selection, resulted in the inclusion of 100 articles for content analysis and of significant findings for GDMs from 37 articles. Published data point to gender effects and to 51 GDM SNVs, deletions, and regions, including globin genes and significant overrepresentation of gene ontology pathways related, e.g., to oxidative stress, hypoxia, and regulation of blood pressure. Analyzed articles further pointed to additional candidate GDMs affecting SCD VOC and pain phenomena and to potential confounding factors for GWAS analyses. We found that despite the critical importance of VOC and pain phenomena for SCD pathology, corresponding clinically relevant genetic insights are held back by a shortage of large-scale, systematic multi-ethnic efforts, as undertaken by the INHERENT Network. Full article

Background and Objectives: Thermography is a non-invasive diagnostic technique that measures skin surface temperatures to reflect normal or abnormal physiology. This review explores the clinical utility of thermography in diagnosing and monitoring stroke, with an emphasis on its clinical applications. Materials and Methods: This systematic review followed PRISMA guidelines, with a protocol published prior to analysis. Three databases were screened up to end of 2024. Article selection was conducted in two stages: title and abstract screening using Rayyan^®, followed by full-text eligibility assessment. Discrepancies were resolved through consensus. Risk of bias assessment was performed with ROBINS-I. Narrative synthesis was planned in addition to descriptive statistics. Results: A total of 20 studies were included after screening 277 records. Thermography emerged as a promising tool for stroke patients in both the acute and chronic phases. In the acute phase, it demonstrated potential in detecting early signs of carotid occlusive disease by identifying temperature differences in the forehead or neck regions. Additionally, thermography contributed to the differential diagnosis of Wallenberg syndrome. In the chronic phase, it exhibited clinical utility in monitoring rehabilitation progress. Conclusions: Thermography shows promise as a non-invasive tool for stroke assessment and monitoring. While preliminary studies suggest physiological relevance, its clinical utility remains investigational and requires further validation. Full article

Drug-coated balloons (DCBs) have emerged as a promising alternative therapeutic strategy to traditional drug-eluting stent (DES) implantation in various coronary artery lesion scenarios, aiming to minimize complications associated with permanent metallic scaffolds, such as chronic inflammation, delayed vessel healing, and stent thrombosis. This review systematically evaluates the current clinical evidence supporting the use of DCBs across diverse anatomical and clinical contexts, including small-vessel disease, in-stent restenosis, bifurcation lesions, diffuse coronary lesions, acute coronary syndromes, and chronic total occlusions, as well as in special patient populations such as individuals with diabetes mellitus or at high bleeding risk. The literature analysis incorporated recent randomized controlled trials, observational studies, and real-world registries, highlighting the clinical efficacy, safety profiles, and specific advantages of DCB angioplasty. The findings consistently demonstrated non-inferior clinical outcomes of DCBs compared to DESs across multiple lesion types, with particular benefits observed in special populations, including reduced restenosis rates and comparable major adverse cardiac events (MACEs). Nevertheless, clinical data gaps remain, emphasizing the need for larger, longer-term randomized trials to refine patient selection and procedural techniques. In conclusion, DCB angioplasty represents a viable and effective alternative to conventional stenting, particularly advantageous in complex lesions and specific patient subsets, pending further definitive evidence. Full article

Gorlin-Goltz syndrome (GGS) is also known as Nevoid basal cell carcinoma syndrome (NBCCS). In the most common manifestation, GGS is diagnosed based on multiple cysts in the jaw bones, namely OKCs (odontogenic keratocysts). Other features might include major and minor clinical and radiological criteria to confirm this syndrome. Quite commonly, BCCs (basal cell carcinomas), bifid ribs, palmar and plantar pits, and ectopic calcification of the falx cerebri can be found in the majority of patients. Currently, the mutation of the PTCH1 gene seems to be responsible for GGS occurrence, while the male-to-female ratio is 1:1. The following radiological study based on OPGs and CBCT confirmed multiple cystic lesions in jaw bones, confirmed to be OKCs in the histopathological evaluation with an occurrence of numerous skin BCC lesions. In cases of most oral OKC cystic lesions, either surgical removal, curettage, or enucleation with or without any bone grafting can be used with a good amount of success. Rarely, some stable bone osteosynthesis procedures have to be carried out to avoid pathological bone fractures after cyst removal. A special consideration should include the temporomandibular joint. TMJ surgery and the replacement of the joint with an alloplastic material can be performed to improve biting, chewing, proper mouth opening, and maintain good patient occlusion. The authors want to present how effective and simple a standard dental panoramic radiograph combined with CBCT is and how it is suitable for GGS detection. They also want to underline how a standard TMJ prosthesis can be used as an alternative to a custom-made prosthesis. Full article

Background and Objectives: The neutrophil-percentage-to-albumin ratio (NPAR) has been recognized as an independent risk factor for cardiovascular diseases. In our study, we investigated whether the NPAR is associated with the formation of coronary collateral circulation (CCC) in patients with chronic coronary syndrome (CCS). Materials and Methods: A total of 681 patients with CCS were included in this study. Of these patients, 571 had chronic total occlusion in at least one major vessel and developed collateral vessels. In total, 110 patients were in the control group, who had CCS but did not have complete occlusion in a major vessel and did not develop collateral vessels. Patients with collateral vessels on coronary angiography were divided into two groups according to the Rentrop score: poor CCC (Rentrop 0–1) and good CCC (Rentrop 2–3). Blood samples were taken for the NPAR and other biochemical parameters in all patients during hospitalization. The NPAR was calculated as the neutrophil-percentage-to-albumin ratio. Results: The group of patients with poor CCC had a higher white blood count (WBC), neutrophil, C-reactive protein (CRP), neutrophil–lymphocyte ratio (NLR), CRP/albumin ratio (CAR), and NPAR values than patients with good CCC (p < 0.001, for all). Multivariate logistic regression analysis showed that high NPAR levels were an independent predictor of poor CCC (OR: 2.79, 95% CI:1.7–4.6, p < 0.001), accompanied by neutrophil, CRP, CAR, and NLR levels. In the receiver operator characteristic curve (ROC analysis), the cut-off value for the NPAR to indicate poor CCC was 1.78 with a sensitivity of 76.6% and specificity of 81.4% (area under ROC curve = 0.804 95% CI (0.753–0.854), p < 0.001). Conclusions: We demonstrated that the NPAR may be an independent predictor of poor CCC development in clinical practice. Full article

Background/Objectives: Retinal vein occlusion (RVO) represents a common ophthalmological disorder that, if untreated, often leads to severely impaired vision. The classic vascular risk factors, aging and glaucoma, represent the core pathogenic factors for RVO. However, antiphospholipid syndrome (APS) has been involved in a non-negligible number of patients with RVO. The main objective of the present study was to assess the performance of the new 2023 ACR/EULAR classification criteria for APS in a cohort of patients with RVO fulfilling the Sydney classification criteria. Methods: A prospective study of consecutive patients with RVO diagnosed with APS in a third-level university hospital. The new 2023 ACR/EULAR classification criteria for APS were applied to all patients. Vascular risk factors, the antiphospholipid antibody (aPL) profile, clinical management, and clinical outcomes were assessed and compared between those fulfilling the Sydney and the 2023 ACR/EULAR criteria. Results: Sixty-nine RVO-APS patients were included in the study. After applying the new classification criteria, 18 patients (26.1%) did not fulfill the new criteria for APS. Specifically, 17 (24.6%) were excluded due to the new Domain 8 (p < 0.001) as they presented only aPL IgM serology, and 1 patient (1.4%) was excluded due to having high venous thromboembolic risk (VTE) with a clinical domain score < 3. Interestingly enough, the presence of high arterial risk (45.1% vs. 50%; p = 0.72) was greater than the presence of high VTE (3.9% vs. 5.6%; p = 0.99); in both cases, the 51 RVO-APS patients were classified with the 2023 ACR/EULAR criteria, and the 18 cases were excluded according to the new classification criteria. Except for the expected differences in serological domains (Domain 7, p < 0.001, and Domain 8, p < 0.001), we did not find other significant differences in terms of prognosis or risk of recurrence between both groups of patients. Conclusions: The implementation of the new ACR/EULAR 2023 classification criteria for APS resulted in the exclusion of about one out of four previously diagnosed RVO-APS patients. The higher prevalence of manifestations of high arterial risk compared with high VTE among both newly classified and excluded APS patients highlights the importance of monitoring cardiovascular risk factors for both the prevention and the management of potential retinal and cardiovascular events. Full article