Oncogene-induced senescence in meningiomas-an immunohistochemical study.

PURPOSE: Meningiomas are tumours originating from meningothelial cells, the majority belonging to grade 1 according to the World Health Organization classification of the tumours of the Central Nervous System. Factors contributing to the progression to the higher grades (grades 2 and 3) have not been elucidated yet. Senescence has been proposed as a potential mechanism constraining the malignant transformation of tumours. Senescence-associated beta-galactosidase (SA-ß-GAL) and inhibitors of cyclin-dependent kinases p16 and p21 have been suggested as senescence markers. METHODS: We analysed 318 meningiomas of total 343 (178 grade 1, 133 grade 2 and 7 grade 3). Tissue microarrays were constructed and stained immunohistochemically, using antibodies for SA-ß-GAL, p16 and p21. RESULTS: The positive correlation of the tumour grade with the expression of p16 (p = 0.016) and SA-ß-GAL (p = 0.002) was observed. The expression of p16 and SA-ß-GAL was significantly higher in meningiomas grade 2 compared to meningiomas grade 1 (p = 0.006 and p = 0.004, respectively). SA-ß-GAL positivity positively correlated with p16 and p21 in the whole cohort. In grade 2 meningiomas, a positive correlation was only between SA-ß-GAL and p16. Correlations of senescence markers in meningiomas grade 2 were not present. CONCLUSION: Our findings suggest the senescence activation in meningiomas grade 2 as a potential mechanism for the restraining of tumour growth and give hope for applying of promising senolytic therapy.

Comprehensive Evaluation of Quality of Life following Upper Eyelid Blepharoplasty: A Prospective Analysis.

Background and Objectives: Upper eyelid blepharoplasty is a surgical procedure that addresses both aesthetic and functional concerns, offering transformative potential for patients' overall well-being. This study systematically evaluates the comprehensive impact of upper eyelid blepharoplasty on patients' quality of life, employing rigorous methodologies and standardized assessment protocols. Materials and Methods: A prospective, randomized controlled trial was conducted, involving 348 patients aged 49 to 87 years. Patients were randomly assigned to receive either continuous or intradermal sutures following upper eyelid surgery. Validated FACE-Q questionnaires were used to assess various outcomes, including early-life impact, expectations, satisfaction with eyes, overall face satisfaction, satisfaction with the outcome, psychological function, social function, and adverse effects. Results: Results indicate significant improvements in multiple domains of patient-reported outcomes following upper eyelid blepharoplasty, including satisfaction with eyes, overall face satisfaction, satisfaction with the outcome, psychological function, and social function. Notably, no significant differences were observed between suturing techniques regarding patient satisfaction and well-being. Adverse effects were minimal and improved over time. Conclusions: The study underscores the transformative nature of upper eyelid blepharoplasty in enhancing patients' quality of life, addressing both cosmetic and functional concerns. Utilizing standardized assessment tools like the FACE-Q questionnaire facilitates a comprehensive understanding of treatment outcomes and enables patient-centered care. Overall, this research contributes to the growing evidence supporting the positive impact of upper eyelid blepharoplasty on patients' well-being, emphasizing the importance of continued research and standardized assessment protocols in advancing patient care in cosmetic surgery.

Buffered Versus Nonbuffered Local Anesthetics and Local Pain Scores in Upper Eyelid Blepharoplasty: Randomized Controlled Trial.

PURPOSE: This split-face study aimed to see whether different types of local anesthetics or their buffered/nonbuffered combinations produce lower pain scores in upper eyelid blepharoplasty. METHODS: The study involved 288 patients, randomly divided into 9 groups: 1) 2% lidocaine with epinephrine-Lid + Epi; 2) 2% lidocaine with epinephrine and 0.5% bupivacaine (1:1)-Lid + Epi + Bupi; 3) 2% lidocaine with 0.5% bupivacaine (1:1)-Lid + Bupi; 4) 0.5% bupivacaine-Bupi; 5) 2% lidocaine-Lid; 6) 4% articaine hydrochloride with epinephrine-Art + Epi; 7) buffered 2% lidocaine/epinephrine with sodium bicarbonate (SB) in a 3:1 ratio-Lid + Epi + SB; 8) buffered 2% lidocaine with SB in a 3:1 ratio-Lid + SB; 9) buffered 4% articaine hydrochloride/epinephrine with SB in a 3:1 ratio-Art + Epi + SB. Following the injection of the first eyelid and a 5-minute period of soft pressure on the injection site, patients were asked to rate their pain level on the Wong-Baker Face Pain Rating Visual Analogue Scale. Rating of the pain level was repeated 15 and 30 minutes following anesthetic administration. RESULTS: The lowest pain scores at the first time point were observed in Lid + SB when compared with all of the other groups ( p < 0.05). At the final time point, significantly lower scores were also observed in Lid + SB, Lid + Epi + SB, and Art + Epi + SB when compared with the Lid + Epi group ( p < 0.05). CONCLUSION: These findings could help surgeons select an appropriate combination of local anesthetics, particularly in patients with lower pain threshold and tolerance because buffered combinations of local anesthetics produce significantly lower pain scores compared with nonbuffered solutions.

Methicillin-resistant Staphylococcus aureus biofilm formation on dacryocystorhinostomy silicone tubes depends on the genetic lineage.

PURPOSE: The aim of this study was to investigate biofilm formation on silicone tubes by genetically diverse methicillin-resistant Staphylococcus aureus (MRSA) strains. METHODS: Capacity of biofilm formation on dacryocystorhinostomy silicone tubes was tested on 30 MRSA strains. Identification and methicillin resistance were confirmed by PCR for nuc and mecA genes. Strains were genotypically characterised (SCCmec, agr and spa typing). Biofilm formation was tested in microtiter plate and on silicone tubes. RESULTS: Tested MRSA strains were classified into SCCmec type I (33.3%), II (3.3%), III (20.0%), IV (26.7%) and V (16.7%), agr type I (56.7%), II (36.7%) and III (6.6%), and eight spa clonal complexes (CCs). All tested MRSA strains showed ability to form biofilm on microtiter plate. Capacity of biofilm formation on silicone tubes was as follows: 33.3% of strains belonged to the category of low biofilm producers, and 66.7% to moderate biofilm producers. There was statistically significant correlation between spa CC and the category of biofilm production on silicone tubes (p = 0.01): CC5 and CC45 with moderate amount of biofilm, and CC8 with low amount of biofilm. A moderate amount of biofilm formed on silicone tubes correlated with agr type II MRSA strains (p = 0.008). CONCLUSIONS: Biofilm formation by MRSA on silicone tubes is highly dependent on genetic characteristics of the strains. Therefore, MRSA genotyping may aid the determination of the possibility of biofilm-related ocular device infections. Genotyping and biofilm quantification may be helpful in determining when decolonisation and cohort isolation are required to prevent device-related infections.

Plurihormonal Pituitary Neuroendocrine Tumours - A Single Centre Experience.

Introduction. Plurihormonal pituitary neuroendocrine tumours (PitNET)/adenomas are pituitary neuroendocrine tumours composed of monomorphous cell populations expressing anterior pituitary transcription factors and/or hormones belonging to more than one cell lineage. Studies dedicated to plurihormonal tumours are rare and quite heterogenous with their results, bearing in mind changes in diagnostic criteria and inconsistent use of antibodies for anterior pituitary transcription factors in the diagnostic immunohistochemical panel. Material and Methods. We retrospectively analysed all patients surgically treated for PitNETs from 2016 to July 2022 in a tertiary healthcare institution. All tumours previously diagnosed PitNETs with the word "plurihormonal" were re-examined and potentially re-classified, according to 2022 WHO classification of endocrine tumours. Results. Among 721 patients surgically treated for PitNET in 5.5 years period, the diagnosis of plurihormonal PitNET was established in 11 tumours (1.3%). All tumours showed diffuse and intensive positivity for anterior pituitary transcription factors PIT1 and SF1. Clinically, all patients presented with acromegaly. Conclusions. Retrospective studies related to newly defined plurihormonal PitNETs with a reassessment of diagnoses are necessary due to their rarity and ambition to investigate their origin and biological behaviour. The fact that the majority of plurihormonal PitNETs are clinically presented with acromegaly and show simultaneous positivity to PIT1 and SF1 transcription factors deserve special attention and need for further research in larger cohorts of these exceptional tumours.

Gender-Related Differences in Dry Eye Symptoms Following Involutional Ectropion and Entropion Surgery.

This prospective case-control study investigated gender-related differences in dry eye symptoms following surgery for involutional ectropion and entropion. A total of 109 patients, aged between 65 and 89, were categorized by eyelid condition and gender. Postoperative assessments included the Tear Film Break-Up Time (TBUT) test, Schirmer I test results, corneal and conjunctival staining, eyelid margin characteristics, and scores from the Ocular Surface Disease Index (OSDI) questionnaire. The analysis revealed notable gender-related differences in dry eye manifestations. Initially, men exhibited lower TBUT scores but higher Schirmer test readings compared to women; however, these disparities diminished over time. No significant gender differences were detected in corneal and conjunctival staining, indicating similar levels of ocular surface damage across genders. Males showed significantly higher values in several eyelid margin characteristics (LMI, LMT) at various postoperative time points. According to the OSDI questionnaire, women experienced more severe symptoms of dry eye both pre- and post-operatively, suggesting a greater subjective symptom burden. When comparing surgical outcomes for ectropion and entropion, both conditions showed improvement in eyelid positioning and dry eye symptoms post-surgery. Despite these improvements, women with either condition reported more severe dry eye symptoms compared to men throughout the postoperative period. This study highlights the gender-specific variations in dry eye symptoms following eyelid malformation surgery and emphasizes the importance of adopting gender-sensitive approaches in postoperative care to improve outcomes and ocular health.

Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover.

Diabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury in diabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascular changes in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visual cycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were divided into the following groups: 1. control; 2. diabetic group (DM) treated with streptozotocin (100 mg/kg); 3. group exposed to light/dark cycle 6/18 h (6/18); 4. diabetic group exposed to light/dark cycle 6/18 h (DM+6/18). Retinal vascular abnormalities were estimated based on lectin staining, while the expression of genes involved in the visual cycle, cholesterol metabolism, and inflammation was determined by qRT-PCR. Reduced light exposure alleviated vasculopathy, gliosis and the expression of IL-1 and TNF-α in the retina with increased perivascular Aqp4 expression. The expression of genes involved in visual cycle and cholesterol metabolism was significantly up-regulated in RPE in DM+6/18 vs. DM group. In the retina only the expression of APOE was significantly higher in DM+6/18 vs. DM group. Reduced light exposure mitigates vascular changes and gliosis in DM via its anti-inflammatory effect, increased retinal cholesterol turnover and perivascular Aqp4 expression.

Comparison of postoperative pain and satisfaction after dacryocystorhinostomy in patients operated on under local and general anesthesia.

BACKGROUND: There has been only 1 study on postoperative pain after external dacryocystorhinostomy (DCR) that compared pain between 2 groups of patients; 1 group received local anesthesia and the other received general anesthesia. To further characterize the relationship between these 2 types of anesthesia and postoperative pain, we designed a study in which a single patient received these 2 different anesthesia modalities for a short interval on 2 different sides. MATERIAL/METHODS: There were 50 participants in this study. External DCR was performed on the same participant on both sides using local anesthesia on 1 side and general anesthesia on the other. Postoperative pain was measured using the visual analogue scale (VAS), and localization and timing of pain were reported by the participants. Postoperative nausea and vomiting (PONV) were documented if present. RESULTS: Pain levels were significantly higher with general anesthesia 3 hours post-surgery, and 6 hours post-surgery the pain remains higher following general anesthesia but is borderline insignificant (p=0.051). However, 12 hours post-surgery, there is no significant difference in the pain level (p=0.240). There was no significant difference in the localization of pain with local and general anesthesia. Postoperative nausea is significantly more frequent after general anesthesia, and vomiting only occurs with general anesthesia. Local anesthesia was preferred by 94% of the participants (47 out of 50). CONCLUSIONS: The vast majority of patients in our study who have undergone both GA and LA DCR would choose LA again, providing a compelling case for use of the LA technique.

It is still not for the old iron: adjuvant effects of carbonyl iron in experimental autoimmune encephalomyelitis induction.

Experimental autoimmune encephalomyelitis (EAE) is a model of multiple sclerosis. Dark Agouti rats immunized with spinal cord homogenate (SCH) and carbonyl iron (CI), as an adjuvant, develop severe hyperacute form of EAE. They succumb to EAE earlier and have higher clinical scores and lethality rate in comparison to counterparts immunized with SCH + complete Freund's adjuvant. There is no difference in the number of cells or in histological presentation of the CNS infiltrates of rats immunized with the two adjuvants. However, there are more granulocytes, NK and NKT cells, and less CD4(+) T cells in the spinal cord infiltrates of SCH + CI-immunized animals. Nitric oxide (NO)-generating enzyme inducible NO synthase have higher expression in spinal cord of SCH + CI-immunized rats, and this corresponds to more intensive nitrotyrosine formation in the CNS tissue of these rats. Abundant infiltration of granulocytes and NK cells into the CNS and excessive generation of peroxynitrite within the CNS of SCH + CI-immunized rats might account for the severe neurological deficits induced by immunization with CI. These factors should be closely examined in the fulminant forms of multiple sclerosis and acute disseminated encephalomyelitis, as they could represent a promising targets for therapy.

Pain during external dacryocystorhinostomy with local anesthesia.

BACKGROUND: External dacryocystorhinostomy (DCR) is often performed under local anesthesia (LA) without adequate knowledge of the pain experienced by the patient. MATERIAL/METHODS: We subdivided our surgical technique into stages easily understood by the patients (introducing cotton tipped applicators, performing parabulbar injection, creating the incision, bone cracking (opening the ostium), manipulating the nose, intubating, closing the wound, and packing with gauze). A total of 50 patients ranging in age from 31 to 83 years of age (63.64±9.64) underwent external DCR. Each patient was asked 30 minutes after surgery to indicate the intensity of pain experienced at each stage of the surgery and during intramuscular (i.m.) injection of an antibiotic using a visual analog scale (VAS). RESULTS: Analysis of the VAS-based pain scores indicated 3 statistically equal occurrences of pain coinciding with the opening of the ostium, and receiving both parabulbar anesthetic and i.m. antibiotic injections. CONCLUSIONS: The level of pain experienced during the most unpleasant stage of external DCR (ostium opening) was similar to the pain experienced from an i.m. injection. Patients can be informed that pain during external DCR with local anesthesia is comparable to receiving an i.m. gluteal injection.

A case of an unilateral tonsillar hypertrophy caused by actinomycosis.

The purpose of this report was to present an unusual case of an unilateral tonsillar hypertophy caused by actinomycosis. It is an infrequent bacterial infection nowadays. Only five such cases have been reported up to now. Diagnosis is difficult, because there are not specific diagnostic procedures. Medical treatment consists of surgical excision of tonsils and postoperative antibiotic therapy.

Clinical significance of routine lacrimal sac biopsy during dacryocystorhinostomy: A comprehensive review of literature.

The main purpose of this paper is to provide the information about the incidence and types of pathology of secondary acquired obstructions of the lacrimal excretory outflow system caused by primary lacrimal sac non-neoplastic and neoplastic lesions. After a thorough literature search, 17 case-control studies were found and selected, data were extracted and categorized, to evaluate specific lacrimal sac pathology mimicking inflammation. A total of 3865 histopathologically examined lacrimal sac wall biopsy specimens from 3662 patients, taken during dacryocystorhinostomy for clinically presumed primary chronic dacryocystitis, were analyzed. The most common reported histopathological finding was non-specific chronic inflammation with or without fibrosis (94.15% of cases). Lacrimal sac-specific pathologies were present in 226 (5.85%) cases. Unsuspected lacrimal sac-specific pathologies were present in 55/226 (24.34%) cases. Almost 45% of primary lacrimal sac malignant neoplasms were not suspected, preoperatively and intraoperatively. Tumor-like lesions of the lacrimal sac were the most common pathology found: (1) lacrimal stones-dacryoliths, (2) pyogenic granuloma, (3) granulation tissues, (4) reactive lymphoid hyperplasia, and (5) lacrimal sac-specific inflammation (Wegener's granulomatosis and sarcoidosis). Neoplastic pathology was found in 55/3865 (1.42%) lacrimal sac wall biopsy specimens; of those, malignant cases were 2.24 times more frequent than benign. Lymphoma was the most common preoperatively unsuspected or intraoperatively unexpected neoplastic pathology. This analysis of the relevant literature highlights the value of routine lacrimal sac biopsy during surgery for clinically presumed primary acquired nasolacrimal duct obstruction.

Bilateral ocular panadnexal mass as initial presentation of systemic blastoid variant of mantle-cell lymphoma.

A 66-year-old man developed a slowly enlarging, bilateral, painless, periorbital, and orbital swelling with ptosis, nonaxial proptosis, chemosis, exposure keratopathy, and decreased vision in both eyes. He had fever, night sweats, and weight loss (B-symptoms), along with lymphadenopathy and elevated serum lactate dehydrogenase, with no prior history of lymphoma. A transpalpebral incisional biopsy revealed a rare case of mantle-cell lymphoma of blastoid variant, stage IVB. The main immunophenotype characteristics were cyclin D1+, CD5+, CD10-, CD23-, Bcl-6-/+, and a high (up to 80%) Ki-67 proliferation index. Following an excellent response to the immune-chemotherapy treatment plan, all ocular adnexal lymphoma manifestations disappeared completely; however, 13 months after the initial presentation, there was a recurrence of the disease with rapid worsening and death. The blastoid variant of mantle cell lymphoma, a rare subtype of mantle-cell lymphoma, is a highly aggressive neoplasm, ultimately having a fatal outcome. As the initial manifestation of the disease, ocular adnexal region blastoid variant of mantle-cell lymphoma is an exceptional event, with only one previous case reported.

Surgical Treatment of Rhinogenic Contact Point Headache: An Experience from a Tertiary Care Hospital.

Introduction Even in the absence of inflammatory disease, facial pain often results from pressure of two opposing nasal mucosa surfaces. Objectives The objective of this study is to assess the efficacy of surgical treatment of contact point headache. Methods Our study enrolled patients with unilateral facial pain and without nasal/paranasal sinus disease. We confirmed the presence of mucosal contact by nasal endoscopy and by computed tomography. Forty-two subjects with the three most common anatomical variations underwent complete evaluation: 17 with concha bullosa (CB), 11 with septal deviation (SD), and 14 with septal spur (SS). All participants were treated by topical corticosteroid, adrenomimetic, and antihistamine. The patients without improvement were treated surgically. We assessed the severity of pain using a Visual Analogue Score (VAS) before surgical treatment and one, six, twelve, and twenty-four months after. Results The patients with SS had more severe facial pain in comparison with patients with CB (p = 0.049) and SD (p = 0.000). The subjects with CB had higher degree of facial pain than the ones with SD (p = 0.001). After an unsuccessful medical treatment and surgical removal of mucosal contacts, the decrease of headache severity was more intense in patients with CB and SS (p = 0.000) than in the patients with SD (p = 0.01). Conclusion Our results suggest that topical medications have no effects and that surgical removal of mucosal contacts could be effective in the treatment of contact point headache. The results of surgical treatment were better in cases of facial pain caused by SS and CB, than in those caused by SD.

Orbital lymphoma with isolated occult bilateral adrenal involvement: report of an extremely rare case.

Orbital lymphoma is very rare malignant neoplasm, usually diagnosed in early stage of disease as primary lymphoma, but dissemination occurs in approximately 33% of cases. Isolated bilateral adrenal lymphomatous involvement is extremely rare, described in 0.83% of cases. We present autopsy case of a 63-year-old man with bilateral orbital diffuse large cell lymphoma, clinical stage IEA, successfully treated by one cycle of chemo- and radiotherapy, but after administration of the second cycle, the patient developed signs of gastrointestinal hemorrhage and died two months after the diagnosis. Autopsy findings exclude lymphoma involvement of any organ except histopathological infiltration of both adrenal glands without evidence of a mass lesion.

Primary Merkel Cell Carcinoma of the Eyelid-- Clinical, Histopathological, Immunohistochemical and Electron Microscopical Features: A Case Report.

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare eyelid neoplasm which can cause significant diag- nostic and especially therapeutic challenges. CASE OUTLINE: This is the first documented report of the case of primary MCC of the eyelid in Serbia. CONCLUSION: The optimal therapy must be individualized in any given patient and, early diagnosis and meticulous follow-up are mandatory to achieve a long-term cure.

Breast cancer metastasis to the conjunctiva.

INTRODUCTION: Conjunctival metastasis is exceedingly rare, and it is, as a rule, a sign of advanced malignant disease with poor prognosis. We presented a female patient with breast cancer metastasis to the conjunctiva. CASE REPORT: A 45-year-old premenopausal female patient was presented with a solitary, yellowish, thin, demarcated lesion in the superior nasal quadrant of the bulbar conjunctiva of the left eye noted by chance a week earlier. There was no sign of irritation, and no pain, and no other functional or morphological problem in either eye or orbit. Five years before the appearance of conjunctival metastasis, breast carcinoma was diagnosed and the patient underwent chemotherapy, preoperative radiotherapy and radical mastectomy. Three years later, computed tomography scan showed metastasis in the left hepatic lobe with ascites and the patient underwent chemotherapy again. But, four months prior to the appearance of conjunctival lesion body scintigraphy showed multifocal sceletal lesions and nuclear magnetic resonance revealed diffuse hepatic metastases and bilateral ovarial tumors. Paliative radiotherapy and hormonal therapy (megestrol, 160 mg) were carried out. An excisional biopsy of the observed conjunctival lesion was performed under topical anesthesia and the material was subjected to histopathological (HP) examination. HP and immunohistochemical examinations established the presence of breast infiltrating lobular carcinoma metastatic to the conjunctiva. The patient showed rapid deterioration after intervention, and died after three weeks. CONCLUSION: A survival period less than one month after the appearance of conjunctival metastasis deserves attention because it is unexpected and has never been reported previously. It is not a rule that HP presentation of a metastatic lesion is so characteristic that it is possible to determine a primary tumor.

[Orbital decompression in Graves' orbitopathy].

INTRODUCTION: This paper was aimed at presenting our experience and results in the surgical management for proptosis in patients with Graves' orbitopathy. MATERIAL AND METHODS: This is a retrospective, interventional, non-comparative case series review. Seventeen eyes often patients underwent orbital decompression between 2008 and 2009. Depending on case, the surgery involved one to 3 orbital walls with or without fat removal, being approached through combined transcaruncular and lower fornix incision. RESULTS: All the operated patients were females, their mean age being 48, with proptosis ranging from 21 to 28 mm, and 18 to 22 mm three months after surgery. A mean reduction in proptosis of 4.59 +/- 1.58 mm was attained. Intra-operative course was uneventful and post-operatively transient infraorbital hypoesthesia was seen in twelve patients (70.57%). CONCLUSION: Orbital decompression proved to be a safe, reliable and effective way to reduce proptosis provided that the procedure is carefully planned and properly performed.

A 7-year prospective study of routine histopathological evaluation of the lacrimal sac wall incisional biopsy specimens obtained during external dacryocystorhinostomy in adults and a review of the literature.

The most common lacrimal sac pathology is chronic inflammation with or without occlusive fibrosis. However, a substantial number of lacrimal sac-specific pathologies were reported throughout the literature which may mimic chronic inflammation and be misdiagnosed. From a tertiary ophthalmic care centre in Serbia, in a single ophthalmic pathology laboratory, during a 7-year period (January 2004 to October 2010), a 599 consecutive lacrimal sac wall biopsy samples routinely obtained during external dacryocystorhinostomy in adult patients with clinically presumed primary acquired lacrimal drainage system obstruction were analysed. Although non-specific lacrimal sac pathology was present in the vast majority of cases (578 biopsy specimens; 96.49%), this report also reveals a relatively substantial number (21 biopsy specimens; 3.51%) of clinically non-suspected or intraoperatively unexpected primary lacrimal sac-specific pathology--among them, six lesions with malignant biological behaviour were identified: one microinvasive squamous cell carcinoma and five malignant lymhoproliferative lesions. Usefulness of routine lacrimal sac wall biopsy during surgery for primary acquired lacrimal drainage system obstruction is undoubtful and commensurate with the constant need for better understanding of the pathological processes that involve lacrimal drainage system.