Search Results (33)

Background and Objectives: Gallbladder cancer (GBC) is a biologically aggressive malignancy characterised by poor survival outcomes often attributed to delayed diagnosis due to nonspecific clinical presentations. Paraneoplastic syndromes (PNSs), atypical symptoms caused by cancer itself, may serve as valuable indicators for timely diagnosis, particularly in malignancies with nonspecific features. Understanding the manifestations of PNSs in GBC is, therefore, critical. This systematic review collates case studies documenting the association of PNS with GBC, including subsequent management and clinical outcomes. Materials and Methods: A comprehensive search of PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases yielded 49 relevant articles. Upon searching other information sources, two more relevant articles were identified via citation sources. Results: The paraneoplastic syndromes were classified according to haematological (leukocytosis), dermatological (inflammatory myositis like dermatomyositis and polymyositis, acanthosis nigricans, Sweet’s syndrome, exfoliative dermatitis), neurological, metabolic (hypercalcemia, hyponatremia), and others (chorea). The analysis included the age, sex, and country of origin of the patient, as well as the time of PNS diagnosis relative to GBC diagnosis. Furthermore, common presenting complaints, investigations, and effectiveness of treatment modalities using survival time were assessed. Conclusions: While PNS management can offer some benefits, oncologic outcomes of GBC are largely poor. The majority of PNS in GBC are reported in advanced stages, and, hence, PNS has a minimal role in early diagnosis. PNS management can improve a patient’s quality of life, and thus recognition and treatment are important considerations in the holistic management of GBC patients. Full article

Pseudoexfoliation syndrome (PE), which is often unilateral in 60% of cases, is a risk for exfoliation glaucoma (EXG) with elevated inflammatory cytokines. This study aimed to clarify the dynamics of these cytokines in unilateral PE (u-PE) patients. This study included 20 eyes from 10 u-PE patients (PE+ eyes and fellow PE− eyes) and 20 eyes from 10 cataract patients without PE (control group). Clinical parameters, including age, visual acuity, and intraocular pressure, were assessed. Anterior chamber aqueous humor cytokine levels (IL-8, SAA, ET-1, VEGF) were measured and compared among groups. SAA was elevated in PE+ eyes compared to PE− and control eyes. IL-8 and ET-1 were elevated in both PE+ and PE− eyes compared to controls. IL-8 was associated with worsening visual acuity, while ET-1 correlated inversely. Our findings suggest that SAA is associated with the manifest disease while IL-8 and ET-1 could be early biomarkers for PE and therapeutic targets to prevent glaucomatous damage, as these markers appear in the aqueous humor even before pseudoexfoliation material becomes clinically evident. These results may enable earlier diagnosis and therapeutic intervention before the clinical onset of PE in patients with risk factors. Full article

Pseudoexfoliation syndrome (PXS) is an age-related fibrillopathy where fibrillar exfoliation material accumulates and deposits in ocular and extra-ocular tissue. Within the eye, this substance accumulates on the ocular surface and in the anterior segment of the eye, impacting ocular structures such as the conjunctiva, Tenon’s capsule, sclera, cornea, iris, ciliary body, trabecular meshwork, and lens. This review aims to collate the current literature on how each anatomical part of the eye is affected by PXS, with a strong focus on molecular changes. We also summarise the current understanding of the key genetic factors influencing the development of PXS. Full article

Objectives: The objective of this systematic review and meta-analysis is to evaluate the existing evidence and estimate the impact of phacoemulsification and intraocular lens implantation on the intraocular pressure (IOP) of subjects with exfoliation syndrome (XFS) or exfoliative glaucoma (XFG). Methods: In July 2024, an in-depth literature review across three databases was undertaken. This study focused only on adult patients with exfoliation who had not undergone previous ocular surgery. The primary outcome of interest was the mean IOP reduction at 6 and 12 months after uncomplicated phacoemulsification surgery. Results: This meta-analysis included one randomized controlled trial and eight observational studies, comprising 220 patients at 6 months and 430 patients at the 12-month time point, respectively. The mean IOP reduction after surgery was 3.43 mmHg (95% CI: −4.77 to −2.09) after 6 months and 2.75 mmHg (95% CI: −4.24 to −1.26) after 12 months. In both time points, there was no heterogeneity (I² = 0), but the certainty of evidence following the GRADE evaluation was very low. Conclusions: The present meta-analysis demonstrates that phacoemulsification can significantly reduce IOP in exfoliation subjects 6 and 12 months after surgery. Nevertheless, significant limitations in included studies do not allow a precise and certain estimate of the magnitude of postoperative IOP lowering in exfoliation patients. Additional research is needed to confirm these results. Full article

Objective: To investigate any relationships between exfoliation syndrome or exfoliation glaucoma and age-related macular degeneration utilizing the Utah population database. Design: This was a retrospective, case–control cohort study. Subjects, Participants, and/or Controls: We identified 3405 patients diagnosed with exfoliation syndrome (XFS) or exfoliation glaucoma (XFG) during a dilated eye exam within the UHealth system from 1996 to 2021, whose dry or wet age-related macular degeneration (AMD) status was assessed. A population-based control pool of 257,714 UHealth patients with no XFS/XFG diagnosis and a dilated eye exam history from 1996 to 2021 was compiled, with its patients randomly selected and individually matched 3:1 to cases based on sex and age at index diagnosis of their respective case. Methods: A covariate analysis was performed of characteristics and risk factors associated with XFS/XFG, which included race/ethnicity, residence location, partner/marital status, and family history of XFS/XFG, obesity, tobacco use, alcohol use, osteoporosis/vitamin D deficiency, primary/essential hypertension, ocular hypertension, and cataract surgery. Main Outcome Measure: We studied the trends of non-exudative (dry) or exudative (wet) AMD in a large Utah population study of XFS/XFG patients and controls. Results: Of 3396 XFS/XFG patients, as well as 10,179 individually matched 3:1 control patients, 64% were female and the average age of XFS onset was 74.3 yrs. In a univariate model, we observed a very modest increased risk of wet AMD in XFS/XFG patients (odds ratio, OR = 1.14, 95% confidence interval (CI) 0.99–1.32), which did not achieve statistical significance (p = 0.07). After adjusting for the main effects of potential confounders, there was no greater presentation of AMD in XFS/XFG patients when compared with controls (dry AMD: OR = 0.94, 95% CI 0.85–1.05, p = 031; wet AMD: OR = 0.98, 95% CI 0.83–1.14, p = 0.76). In XFS/XFG patients compared to controls, the risk of having cataract surgery was elevated (OR = 2.39, 95% CI 2.18–2.62). However, after accounting for an interaction with AMD, XFS/XFG patients who underwent cataract surgery did not exhibit an increased risk of either dry or wet AMD (dry AMD: OR = 0.91, 95% CI 0.80–1.03; wet AMD: OR = 0.89, 95% CI 0.75–1.07). The risk of AMD in XFS/XFG patients vs. controls showed no association with osteoporosis/vitamin D deficiency for dry (OR 0.78 95% CI 0.66–0.92 p = 0.004) or wet AMD (OR = 0.72 95% CI 0.56–0.92 p = 0.01), while we found a borderline positive association with both dry and wet AMD if they had osteoporosis/vitamin D deficiency. Conclusion: Using the Utah Population Database, we found that a cataract surgery history significantly impacts the association between AMD and XFS, and that vitamin D deficiency/osteoporosis is a significant confounder of the association. However, no direct association between XFS and AMD was found in this study. Full article

(1) Background: The present review aims to identify risk factors with predictive value for differentiating between pseudoexfoliation patients at risk of developing intra- or postoperative complications and those without operative risk during cataract surgery. (2) Methods: The review protocol was registered at PROSPERO, registration no. CRD42023417721. The following databases were searched for studies between 2000 and 2023: PubMed/Medline, Scopus, Springer, Science Direct, Web of Science, Cochrane Database of Systematic Reviews, TRIP database, LILACS, Clinical Trials, and reference lists of articles. We included analytical studies of any design examining cataract surgery complications in pseudoexfoliation patients across two population groups, one who underwent uneventful cataract surgery and the other who experienced intra- or postoperative complications. The paper will follow PRISMA 2020 criteria for reporting. Effect measure was assessed using odds ratios (ORs) and corresponding 95% confidence interval (CI) for qualitative variables and means with their respective standard deviation (SD) for quantitative variables. The risk of bias was assessed using the method presented in the Cochrane Handbook for Systematic Reviews. The GRADE scale was used for quality of evidence and certainty. (3) Results: The initial search of published and gray literature databases retrieved 1435 articles, six of which were included in this report. A total of 156 intra- or postoperative incidents were reported in 999 eyes with pseudoexfoliation. The identified predictive factors were a shallow anterior chamber, cataract grade, neutrophil-to-lymphocyte ratio, preoperative intraocular pressure, and symmetry of the exfoliation material. Limitations include heterogeneity of data and limited number of studies identified in our search. (4) Conclusions: These findings suggest the potential to refine risk stratification protocols in clinical settings and assist surgeons in personalized decision-making among individuals with pseudoexfoliation syndrome. Full article

The phenotypic similarities between exfoliation syndrome (XFS)/exfoliation glaucoma (XFG) and pigment dispersion syndrome (PDS)/pigmentary glaucoma (PG), particularly their association with material deposition in the eye’s anterior segment, have prompted investigations into genetic commonalities. This study focuses on the LOXL1 gene, conducting a comprehensive meta-analysis of three candidate gene association studies. We analyzed three single nucleotide polymorphisms (SNPs) of LOXL1: rs1048661, rs3825942, and rs2165241. Our results reveal nominal significance for the exonic SNPs rs1048661 and rs3825942 (p ≤ 0.01), but show no significant association for the intronic SNP rs2165241 (p = 0.83) with PDS/PG. There was homogeneity across study cohorts (I² = 0), and sensitivity analyses and funnel plots confirmed a lower likelihood of bias in our findings. The lack of a statistically significant association between LOXL1 variants and PDS/PG at p < 0.05 was attributable to the insufficient statistical power of the pooled data, which ranged from 5% to 37% for the three SNPs. This study suggests no association between LOXL1 variants and PDS/PG. Further validation and exploration of XFS/XFG-associated genes in larger and more diverse cohorts would be helpful to determine the genetic correlation or distinctiveness between these conditions. Full article

This study aimed to genotypic and phenotypic analyses of the enterotoxigenic potential of Staphylococcus spp. isolated from raw milk and raw milk cheeses. The presence of genes encoding staphylococcal enterotoxins (SEs), including the classical enterotoxins (sea-see), non-classical enterotoxins (seg-seu), exfoliative toxins (eta-etd) and toxic shock syndrome toxin-1 (tst-1) were investigated. Isolates positive for classical enterotoxin genes were then tested by SET-RPLA methods for toxin expression. Out of 75 Staphylococcus spp. (19 Staphylococcus aureus and 56 CoNS) isolates from raw milk (49/65.3%) and raw milk cheese samples (26/34.7%), the presence of enterotoxin genes was confirmed in 73 (97.3%) of them. Only one isolate from cheese sample (1.3%) was able to produce enterotoxin (SED). The presence of up to eight different genes encoding enterotoxins was determined simultaneously in the staphylococcal genome. The most common toxin gene combination was sek, eta present in fourteen isolates (18.7%). The tst-1 gene was present in each of the analyzed isolates from cheese samples (26/34.7%). Non-classical enterotoxins were much more frequently identified in the genome of staphylococcal isolates than classical SEs. The current research also showed that genes tagged in S. aureus were also identified in CoNS, and the total number of different genes detected in CoNS was seven times higher than in S. aureus. The obtained results indicate that, in many cases, the presence of a gene in Staphylococcus spp. is not synonymous with the ability of enterotoxins production. The differences in the number of isolates with genes encoding SEs and enterotoxin production may be mainly due to the limit of detection of the toxin production method used. This indicates the need to use high specificity and sensitivity methods for detecting enterotoxin in future studies. Full article

Staphylococcus aureus stands as one of the most pervasive pathogens given its morbidity and mortality worldwide due to its roles as an infectious agent that causes a wide variety of diseases ranging from moderately severe skin infections to fatal pneumonia and sepsis. S. aureus produces a variety of exotoxins that serve as important virulence factors in S. aureus-related infectious diseases and food poisoning in both humans and animals. For example, staphylococcal enterotoxins (SEs) produced by S. aureus induce staphylococcal foodborne poisoning; toxic shock syndrome toxin-1 (TSST-1), as a typical superantigen, induces toxic shock syndrome; hemolysins induce cell damage in erythrocytes and leukocytes; and exfoliative toxin induces staphylococcal skin scalded syndrome. Recently, Panton–Valentine leucocidin, a cytotoxin produced by community-associated methicillin-resistant S. aureus (CA-MRSA), has been reported, and new types of SEs and staphylococcal enterotoxin-like toxins (SEls) were discovered and reported successively. This review addresses the progress of and novel insights into the molecular structure, biological activities, and pathogenicity of both the classic and the newly identified exotoxins produced by S. aureus. Full article

Autophagy is a cell’s evolutionary conserved process for degrading and recycling cellular proteins and removing damaged organelles. There has been an increasing interest in identifying the basic cellular mechanism of autophagy and its implications in health and illness during the last decade. Many proteinopathies such as Alzheimer’s and Huntington’s disease are reported to be associated with impaired autophagy. The functional significance of autophagy in exfoliation syndrome/exfoliation glaucoma (XFS/XFG), remains unknown though it is presumed to be impaired autophagy to be responsible for the aggregopathy characteristic of this disease. In the current study we have shown that autophagy or ATG5 is enhanced in response to TGF-β1 in human trabecular meshwork (HTM) cells and TGF-β1 induced autophagy is necessary for increased expression of profibrotic proteins and epithelial to mesenchymal (EMT) through Smad3 that lead to aggregopathy. Inhibition of ATG5 by siRNA mediated knockdown reduced profibrotic and EMT markers and increased protein aggregates in the presence of TGF-β1 stimulation. The miR-122-5p, which was increased upon TGF exposure, was also reduced upon ATG5 inhibition. We thus conclude that TGF-β1 induces autophagy in primary HTM cells and a positive feedback loop exists between TGF-β1 and ATG5 that regulated TGF downstream effects mainly mediated by Smad3 signaling with miR-122-5p also playing a role. Full article

Background and Objectives: Oral disorders, frequently observed in patients with primary Sjögren’s syndrome, can profoundly affect patients’ daily lives and well-being, as oral health represents a fundamental part of general health. Saliva plays an essential part in maintaining and protecting oral health, so the decrease in its quantity and quality leads to chronic oral discomfort alongside a broad spectrum of problems. The objective of the present study was to evaluate the oral health of patients with primary Sjögren’s syndrome and establish its effect on the different domains of their oral health-related quality of life (OHRQoL). Materials and Methods: The research was designed as an observational case–control study with prospective data collection. Eighty patients, divided into two groups based on their oral status, participated in the study. All subjects underwent a complete oral examination. The OHRQoL was assessed using the Oral Health Impact Profile-14 (OHIP-14). Results: The most prevalent oral manifestation was exfoliative cheilitis, while 30% of subjects complained of chewing and swallowing difficulties. The OHIP-14 summary score was significantly higher in the patients with oral lesions (26.0 (5.0) vs. 17.0 (4.0), respectively; p < 0.001). Oral manifestations, systemic involvement, medication, and periodontal indexes were significantly associated with OHIP-14 scores. Conclusions: Patients with oral alterations had a substantially decreased OHRQoL. These findings emphasize the importance of oral diseases for patients’ well-being. Therefore, it is essential for dentists to be included in the multidisciplinary teams managing primary Sjögren’s syndrome, as improving patients’ oral status would lead to better oral health and enhanced OHRQoL. Full article

As the prevalence of Staphylococcus aureus infections is of worldwide concern, phenotype and genotype in prevalent MRSA strains require longitudinal investigation. In this study, the antibiotic resistance, virulence gene acquisition, and molecular type were determined on a large scale of nosocomial S. aureus strains in Southern China during 2009–2015. Bacterial identification and antimicrobial susceptibility to 10 antibiotics were tested by Vitek-2. Virulence genes encoding staphylococcal enterotoxins (SEA, SEB, SEC, SED, and SEE), exfoliative toxins (ETA and ETB), Panton–Valentine leukocidin (PVL), and toxic shock syndrome toxin (TSST) were detected by PCR, with SCCmec typing also conducted by multiplex PCR strategy. Genotypes were discriminated by MLST and spaA typing. MLST was performed by amplification of the internal region of seven housekeeping genes. PCR amplification targeting the spa gene was performed for spa typing. No resistance to vancomycin, linezolid, or quinupristin and increase in the resistance to trimethoprim/sulfamethoxazole (55.5%) were identified. A total of nine SCCmec types and subtypes, thirteen STs clustered into thirteen spa types were identified, with ST239-SCCmec III-t037 presenting the predominant methicillin-resistant S. aureus (MRSA) clone. Typically, SCCmec type IX and ST546 were emergent types in China. Isolates positive for both pvl and tsst genes and for both eta and etb genes were also identified. Important findings in this study include: firstly, we have provided comprehensive knowledge on the molecular epidemiology of MRSA in Southern China which fills the gap since 2006 or 2010 from previous studies. Secondly, we have presented the correlation between virulence factors (four major groups) and genotypes (SCCmec, ST and spa types). Thirdly, we have shown evidence for earliest emergence of type I SCCmec from 2012, type VI from 2009 and type XI from 2012 in MRSA from Southern China. Full article

Aims: To compare retinal nerve fiber layer (RNFL) thickness and choroidal thickness in patients with exfoliation syndrome (XFS) and exfoliative glaucoma (XFG) for 1–5 years or 6–10 years compared to healthy volunteers. Methods and Material: Seventy-eight eyes of 78 patients with XFG, 78 eyes of 78 patients with XFS, and 83 eyes of 83 healthy individuals were included in this prospective study. SD-OCT data for choroid thickness and RNFL were recorded. Results: RNFL thickness was statistically significantly lower in eyes with XFG and XFS than in the control group (p < 0.001). Macular choroidal thickness decreased significantly in the XFG group compared to the XFS and control groups (p < 0.001). No significant difference was observed between the XFS and control groups (p > 0.05). In terms of choroidal and RNFL thicknesses by years in XFG and XFS patients, values were lower in the patients diagnosed 6–10 years previously than in those diagnosed 1–5 years previously. However, the difference was not statistically significant (p > 0.05). Conclusions: Thinning of both choroidal and RNLF thickness in XFG and XFS patients may mean that PEX material is an important risk factor for the progression of XFS to XFG. In addition, thinner choroid and RNLF thickness in the 6–10 years groups show the effect of PEX material and the importance of time. Full article

This study evaluates the cytomorphometric measures of cells obtained from the buccal mucosa of dental students to assess the fluctuation of the cellular characteristics among relatively normal subjects, with any potential correlations with demographic information, different habits, and hormonal disturbance. This prospective study included 100 dental students with no detectable oral alterations submitted to brush cytology. The smears were fixed with 95% ethyl alcohol and stained with hematoxylin and eosin stain. The stained section was observed under an image analyzer for cytomorphometric analysis. Cytopathological observations were recorded, including inflammation, microbial colonies, micronuclei, keratinization, overlapping, and hemorrhage. Chi-square tests were applied for non-parametric variables. One-way analysis of variance (ANOVA) was used to compare the cytometric parameters to habits and hormonal disturbances. A p-value < 0.05 was considered statistically significant. The results showed close proximity among subjects in the matter of cytomorphometric measures; no significant influence of sex, smoking, alcohol drinking habits, and menstruation was found on cytomorphometric diameters or cytopathological observation, and vice versa, while polycystic ovary syndrome impacted nuclear and nuclear-cytoplasmic ratio (p = 0.003, p = 0.02), respectively. Oral exfoliative cytology combined with cytomorphometric analysis for the studied normal individuals can be helpful in various investigations of oral and systemic diseases. Full article

Pseudoexfoliation glaucoma (XFG) is an aggressive form of secondary open angle glaucoma, characterised by the production of exfoliation material and is estimated to affect 30 million people worldwide. Activation of the TGF-β pathway by TGF-β1 has been implicated in the pathogenesis of pseudoexfoliation glaucoma. To further investigate the role of TGF-β1 in glaucomatous changes in the trabecular meshwork (TM), we used RNA-Seq to determine TGF-β1 induced changes in the transcriptome of normal human trabecular meshwork (HTM) cells. The main purpose of this study was to perform a hypothesis-independent RNA sequencing analysis to investigate genome-wide alterations in the transcriptome of normal HTMs stimulated with TGF-β1 and investigate possible pathophysiological mechanisms driving XFG. Our results identified multiple differentially expressed genes including several genes known to be present in exfoliation material. Significantly altered pathways, biological processes and molecular functions included extracellular matrix remodelling, Hippo and Wnt pathways, the unfolded protein response, oxidative stress, and the antioxidant system. This cellular model of pseudoexfoliation glaucoma can provide insight into disease pathogenesis and support the development of novel therapeutic interventions. Full article