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.

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.

Analysis of Lower Extremity Amputations from the SerbVasc Registry.

BACKGROUND: Peripheral arterial disease (PAD) and diabetes are the major causes of lower extremity amputations (LEAs) worldwide. Morbidity and mortality in patients with LEAs are high with an associated significant burden on the global health system. The aim of this article is to report the overall morbidity and mortality rates after major and minor LEAs from the Serbian Vascular Registry (SerbVasc), with an analysis of predictive factors that influenced adverse outcomes. MATERIALS AND METHODS: SerbVasc was created in 2019 as a part of the Vascunet collaboration that is aiming to include all vascular procedures from 21 hospitals in Serbia. Prevalence of diabetes among patients with LEAs, previous revascularization procedures, the degree and the type of foot infection and tissue loss, and overall morbidity and mortality rates were analyzed, with a special reference to mortality predictors. RESULTS: In the period from January 2020 to December 2022, data on 702 patients with LEAs were extracted from the SerbVasc registry, mean age of 69.06±10.63 years. Major LEAs were performed in 59%, while minor LEAs in 41% of patients. Diabetes was seen in 65.1% of the patients, with 44% of them being on insulin therapy. Before LEA, only 20.3% of patients had previous peripheral revascularization. Soft tissue infection, irreversible acute ischemia, and Fontaine III and IV grade ischemia were the most common causes of above-the-knee amputations while diabetic foot was the most common cause of transphalangeal and toe amputations. The infection rate was 3.7%, the re-amputation rate was 5.7%, and the overall mortality rate was 6.9%, with intrahospital mortality in patients with above-the-knee amputation of 11.1%. The most significant intrahospital mortality predictors were age >65 years (p<0.001), chronic kidney disease (CKD) (p<0.001), ischemic heart disease (IHD) (p=0.001), previous myocardial revascularization (p=0.017), emergency type of admission (p<0.001), not using aspirin (p=0.041), using previous anticoagulation therapy (p=0.003), and postoperative complications (p<0.001). CONCLUSIONS: The main predictors of increased mortality after LEAs from the SerbVasc registry are age >65 years, CKD, IHD, previous myocardial revascularization, emergency type of admission, not using aspirin, using previous anticoagulation therapy, and postoperative complications. Taking into account high mortality rates after LEAs and a small proportion of previous peripheral revascularization, the work should be done on early diagnosis and timely treatment of PAD hopefully leading to decreased number of LEAs and overall mortality. CLINICAL IMPACT: Mortality after lower limb amputation from the SerbVasc register is high. A small number of previously revascularized patients is of particular clinical importance, bearing in mind that the main reasons for above-the-knee amputations were irreversible ischemia, Fontaine III and Fontaine IV grade ischemia. Lack of diagnostics procedures and late recognition of patients with PAD, led to subsequent threating limb ischemia and increased amputation rates. The work should be done on early diagnosis and timely treatment of PAD in Serbia, hopefully leading to an increased number of PAD procedures, decreased number of LEAs, and lower overall mortality.

Crushing riluzole tablets: evaluation of loss of powder and active principle in a home-simulation experiment.

Objective: Swallowing difficulties cause patients with amyotrophic lateral sclerosis (ALS) to crush oral medications, falling outside the labeling instructions and entailing some risks. To date, there is no evidence about consequences of crushing riluzole tablets in a home setting. This simulation experiment evaluated the loss of powder and active principle ingredient (API) mimicking the home setting with two alternative crushing methods (A and B). Methods: The tests were carried out by 15 volunteers without experience in the preparation of medication. Each volunteer manually crushed 5 tablets with a meat tenderizer (method A) or two spoons pressed against each other (method B). Riluzole was weighed before (W1) and after crushing (W2). Then, a subsample of crushed tablets was analyzed by HPLC to measure API content. The loss of powder was calculated as a percentage of the intact tablet weight, and the loss of API as a percentage of the labeled API content. Results: The quantitative analysis showed a mean percentage loss of 6.27% corresponding to a mean (SD) loss of powder of 13(±13) mg. The API loss was directly related to the powder loss: overall the mean percentage of API loss was 8.53% (corresponding to a mean API loss of 4.27 ± 4.50 mg). The difference in powder and API loss was highly statistically significant. Conclusion: Crushing riluzole tablets in a simulated home setting determined a significant loss of powder and API. These results support neurologists to evaluate formulations that minimize the need to alter the product and can improve ALS patient journey.

COVID-19 infection and vaccination against SARS-CoV-2 in myasthenia gravis.

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction which is typically presented with muscle weakness and excessive fatigability. Majority of MG patients require long-term immune suppression. Our aim was to analyze the frequency and severity of COVID-19 infection in MG patients, as well as the frequency of vaccinated MG patients against SARS-CoV-2. METHODS: We included 125 MG patients from the central Belgrade municipalities-60% females, age at MG onset 50.1 ± 19.7 years, age at testing 61.7 ± 16.8 years, anti-acetylcholine receptor (anti-AChR) positive 78% and muscle specific tyrosine kinase (MuSK) positive 8.6%. RESULTS: One-third of our MG patients had a COVID-19 infection and they were younger compared to those without verified COVID-19. Severe COVID-19 infection was registered in 28% of MG patients, mostly in elder subjects with comorbidities such as cardiac diseases and malignancies. MG worsening was noted in 21% of patients during/after COVID-19 and 42% had COVID-19 sequelae. Majority of MG patients were vaccinated against SARS-CoV-2 (almost 70%). Vaccination was more common among MG patients with diabetes and in those with a milder form of MG. The most common types of vaccines were Sinopharm (42%) and Pfizer-BioNTech (25.6%). Adverse events were observed in 36% of vaccinated patients, with flu-like symptoms (77%) and local reactions (13%) being the most common ones. MG worsening was noticed in 5 (5.8%) patients after vaccination. CONCLUSION: COVID-19 has placed a significant new burden for MG patients. Elder MG patients and patients with comorbidities are in higher risk of having adverse outcome following SARS-CoV-2 infection. Percentage of vaccinated MG patients was higher than in general Serbian population.

Age- and Gender-Related Differences in the Hemodynamic Status of Patients with Mild or Moderate Hypertension.

Purpose: The aim of this study was to use non-invasive impedance cardiography (ICG) to determine the hemodynamic status of patients with grade 1 and grade 2 hypertension in relation to gender and age. Patients and Methods: We analyse prospectively collected data of 158 patients with grade 1 or grade 2 arterial hypertension. Patients were grouped according to age: 1) <50 years and 2) ≥50 years. Hemodynamic status of patients was assessed by using non-invasive ICG. For the purpose of this study two hemodynamic parameters were used: a) systemic vascular resistance index (SVRI) and b) left cardiac work index (LCWI). The primary endpoint was the hemodynamic status of patients. The secondary endpoint was hypertension-mediated organ damage. Results: Increased SVRI was assessed in 80% of patients, more common in the ≥50 years group than in the <50 years group (88.5% vs 64.8%; p < 0.01). The occurrence of increased systemic vascular resistance correlates hierarchically with increasing age. Elevated LCWI (hypervolemia and/or hyperinotropy) was present in 63% of patients, more often in males than females (70.3% vs 57.1%; p < 0.05) as well in those <50 years than in older patients (70.4% vs 59.6%; p < 0.05). Patients with diabetes were less likely to have hypervolemia/hyperinotropy than those without diabetes (46.7% vs 67.2%; p < 0.01). Hypervolemia/hyperinotropy (46.7%) and hypovolemia/hypoinotropy (43.3%) were present in a similar percentage of diabetic patients. Left ventricular hypertrophy was found in 30 patients (19%). Patients with left ventricular hypertrophy were more commonly male (66.7% vs 42.2%; p = 0.016) and had increased systemic vascular resistance (96.7% vs 77.3%; p = 0.015) compared to the patients without left ventricular hypertrophy. Hypertensive retinopathy grade III was found in 14 patients (8.9%). Elevated daytime systolic pressure, diabetes and increased age are independent predictors of grade III hypertensive retinopathy. Patients with reduced renal function had higher mean systolic blood pressure (p < 0.05), were more commonly male (p < 0.01) and older (p < 0.01) than those without reduced renal function. Conclusion: Although there are certain correlations between hemodynamic disorders and age and gender, specific hemodynamic status of an individual patient with hypertension cannot reliably be predicted on the basis of age and gender. The measurement of hemodynamic parameters by ICG can guide the clinician to select appropriate antihypertensive therapy to the patients' hemodynamic pathophysiologic condition.

Estimation of the latent therapeutic demand for immunoglobulin therapies in autoimmune neuropathies in the United States.

BACKGROUND AND OBJECTIVES: The use of immunoglobulin (IG) solutions as an immunomodulatory therapy in certain neurological conditions has become an established modality and represents a significant proportion of total IG use. The estimation of the evidence-based potential demand designated as the latent therapeutic demand (LTD) for IG in these diseases is required for adequate planning of the plasma supply required to manufacture the product. MATERIALS AND METHODS: The diseases studied included chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain-Barré syndrome (GBS) and multifocal motor neuropathy (MMN). The LTD for IG was assessed using a decision analysis model, using Microsoft Excel. The model analysed the epidemiological and clinical factors contributing to IG usage. One-way sensitivity analysis and probabilistic sensitivity analysis derived the LTD in grams per 1000 inhabitants. The key variables included the treatment schedule and the prevalence of the disease. RESULTS: The model estimates that an average annual IG demand and standard deviation for CIDP, GBS and MMN in the United States is 83.05 ± 24.5, 6.1 ± 3.2 and 36.1 ± 25.5 g/1000 inhabitants, respectively. CONCLUSION: Together with previous work on the LTD for IG in immunodeficiencies, these results indicate that current IG usage reflects the estimated LTD for the main indications for IG in the United States The wide range of LTD found in all these studies emphasizes the need for more precise assessment of the underlying variables, particularly disease prevalence and dosage. Further studies on other indications such as secondary immunodeficiencies will augment these results and will assist in guiding demand planning for IG use and plasma collection in the United States and inform blood policy in other countries.

Efficacy of Safinamide and Gender Differences During Routine Clinical Practice.

Background: There is increasing evidence of gender differences in the epidemiology and clinical manifestation of both motor and non-motor symptoms of Parkinson's disease (PD). Nevertheless, few data are available on gender differences in the response to antiparkinsonian drugs. Safinamide is a multimodal drug with positive effects on motor and non-motor fluctuations that might improve patients' care and quality of life. Objective: To analyze gender differences on clinical effects of safinamide in PD patients treated in real-life conditions during the SYNAPSES trial. Methods: SYNAPSES was a multinational, multicenter, observational study. At baseline, patients with PD diagnosis received safinamide as an add-on to levodopa and were followed up for 12 months, with visits performed every 4 months. A new statistical analysis was performed to describe the efficacy of safinamide in men and women on motor complications, motor symptoms, and adverse events. Results: Six hundred and sixteen (38%) out of 1,610 patients enrolled in the SYNAPSES study were women and 994 (62%) men. Safinamide improved motor symptoms and motor complications (fluctuations and dyskinesia) in both genders, with a good safety profile and without requiring any change in the concomitant dopaminergic therapy. Clinically significant improvements, according to the criteria developed by Shulman et al., were seen in 46% of male and female patients for the UPDRS motor score and 43.5% of men vs. 39.1% of women for the UPDRS total score. Conclusions: Safinamide was effective in improving motor fluctuations and dyskinesia and proved to be safe in both male and female patients with PD. Further prospective studies, specifically addressing potential gender differences in response to PD therapies, are needed to develop tailored management strategies.

The clinical features in patients with newly diagnosed pseudoexfoliative glaucoma in Serbia.

PURPOSE: To evaluate the clinical characteristics of newly diagnosed pseudoexfoliative glaucoma and compare them with those pertaining to newly diagnosed primary open-angle glaucoma as well as pseudoexfoliation syndrome. METHODS: This case-control study involved 306 participants, including patients with newly diagnosed pseudoexfoliative glaucoma, age- and sex-matched normal controls, patients with newly diagnosed primary open-angle glaucoma, and subjects with pseudoexfoliation syndrome. The study was conducted at the Glaucoma Department of Clinic for Eye Diseases, Clinical Center of Serbia, as the referral center for glaucoma in Serbia. RESULTS: The mean age in the pseudoexfoliative glaucoma, primary open-angle glaucoma, pseudoexfoliation syndrome, and normal control groups was 73.61 ± 8.46, 65.50 ± 8.97, 74.81 ± 6.80, and 73.58 ± 9.34 years, respectively (pseudoexfoliative glaucoma vs primary open-angle glaucoma, p < 0.001). Unilateral pseudoexfoliative glaucoma was diagnosed in 35 patients (42.2%). The intraocular pressure was higher in the eyes affected by pseudoexfoliative glaucoma (32.0 ± 9.5 mmHg) than that in the primary open-angle glaucoma eyes (28.8 ± 5.9 mmHg) (p < 0.001). In pseudoexfoliative glaucoma and primary open-angle glaucoma eyes, glaucoma severity was determined via the vertical cup-to-disk ratio (C/D) 0.65 (0.45-1.0) versus 0.60 (0.45-1.0), p = 0.048 and visual field mean deviation -5.68 (-1.58 to -30.9) versus -4.70 (-1.39 to -31.0), p = 0.045. Alzheimer's was the only systemic disease associated with pseudoexfoliative glaucoma in the study sample, with an odds ratio of 0.021 (95% confidence interval = 0.00-21.52, p = 0.022). CONCLUSION: At the time of diagnosis, pseudoexfoliative glaucoma exhibits different clinical features compared with primary open-angle glaucoma. Higher intraocular pressure, narrow or occludable angle, increased trabecular pigmentation, phacodonesis, and poorer pupillary dilatation emerged as the factors associated with pseudoexfoliative glaucoma.

Nailfold capillary morphology and platelet function in patients with exfoliative glaucoma.

PURPOSE: The purpose of the present study was to evaluate the nailfold capillary morphological features in patients with exfoliative glaucoma (XFG) and compare them with those pertaining to primary open-angle glaucoma (POAG), normal controls and subjects with exfoliation syndrome (XFS). The second purpose was to investigate all parameters related to platelet function on the hemogram, including the platelet count (PLT), the mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) in patients with XFG. These parameters were subsequently compared with those belonging to normal controls, POAG and XFS subjects. METHODS: This case control study involved 152 consecutive patients that were examined at the Glaucoma Department of Clinic for Eye Diseases, Clinical Centre of Serbia, as the referral center for glaucoma in Serbia, between June 2016 and December 2017. RESULTS: Regarding capillaroscopic characteristics, statistically significant difference was found in capillary diameter and tortuosity between the XFG and POAG group (p = 0.050 and p = 0.035) and the XFG and NC group (p = 0.003 and p = 0.044), as well as in the distribution of capillary loops and avascular zones between the XFG and NC group (p = 0.014 and p = 0.004). The subjects with XFG had lower PLT values compared to POAG patients (p = 0.022). CONCLUSIONS: In conclusion, to the best of our knowledge, this study marks the first attempt to evaluate capillary morphology as well as to investigate all parameters related to platelet function on the hemogram, in patients with newly diagnosed XFG. Our findings revealed nailfold capillary morphological vascular changes in XFG patients. The subjects with XFG had lower PLT values and a higher MPV serum parameter compared to normal controls and patients with POAG. Further research in this field should therefore aim to evaluate the consequences of the aforementioned microvascular abnormalities in patients with XFG.

Serum heparan sulfate and chondroitin sulfate concentrations in patients with newly diagnosed exfoliative glaucoma.

BACKGROUND: Exfoliative glaucoma (XFG) is typically classified as a high-pressure type of secondary open-angle glaucoma that develops as a consequence of exfoliation syndrome (XFS). Exfoliation syndrome is an age-related, generalized disorder of the extracellular matrix characterized by production and progressive accumulation of a fibrillar exfoliation material (XFM) in intra- and extraocular tissues. Exfoliation material represents complex glycoprotein/proteoglycan structure composed of a protein core surrounded by glycosaminoglycans such as heparan sulfate (HS) and chondroitin sulfate (CS). The purpose of the present study was to investigate HS and CS concentrations in serum samples of patients with newly diagnosed XFG and compare the obtained values with those pertaining to newly diagnosed primary open-angle glaucoma (POAG), normal controls (NC) and subjects with XFS. METHODS: This case-control study involved 165 subjects, including patients with newly diagnosed XFG, patients with newly diagnosed POAG, subjects with XFS and age- and sex-matched NC. The study was conducted at the Glaucoma Department of Clinic for Eye Diseases, Clinical Centre of Serbia, as the referral center for glaucoma in Serbia. RESULTS: The mean age in the XFG, POAG, XFS and NC groups was 73.3 ± 9.0, 66.3 ± 7.8, 75.5 ± 7.0 and 73.5 ± 9.5 years, respectively, XFG vs. POAG, p < 0.001. Mean serum HS concentrations in the XFG, POAG, NC and XFS groups were 3,189.0 ± 1,473.8 ng/mL, 2,091.5 ± 940.9 ng/mL, 2,543.1 ± 1,397.3 ng/mL and 2,658.2 ± 1,426.8 ng/mL respectively, XFG vs. POAG, p = 0.001 and XFG vs. NC, p = 0.032. Mean serum CS concentrations in the XFG, POAG, NC and XFS group were 43.9 ± 20.7 ng/mL, 38.5 ± 22.0 ng/mL, 35.8 ± 16.4 ng/mL and 43.3 ± 21.8 ng/mL, respectively, XFG vs. NC, p = 0.041. CONCLUSIONS: Our findings revealed greater HS and CS concentrations in XFG patients and XFS subjects compared to those without XFM. Implications of HS and CS in the pathophysiology of XFS and glaucoma should be studied further. Serum is easily accessible and should thus be explored as rich sources of potential biomarkers. Further research should aim to identify XFG biomarkers that could be utilized in routine blood analysis tests, aiding in timely disease diagnosis.

The evaluation of short- and long-term stability studies for brimonidine in aqueous humor by DPV/BDDE method-possible application for direct assay in native samples.

A novel voltammetric method was developed for brimonidine (BRIM) determination in deproteinized aqueous humor, simplifying preparation of biological samples for analysis for stability studies. The differential pulse voltammetric (DPV) method using boron doped diamond electrode (BDDE), based on characteristic oxidation peaks, was proposed and successfully applied. The linearity range was within 5.0 × 10-6 to 5.0 × 10-5 M of brimonidine, and limit of detection and limit of quantitation were 1.94 × 10-6 M and 6.46 × 10-6 M, respectively. Intra-day and inter-day precision and accuracy were evaluated and all results were in accordance with validation ICH guidelines. The best short-term stability study results were obtained for a concentration level of 3.0 × 10-5 M expressed by deviation of + 1.86% between initial and post storage concentrations. A long-term stability study was performed for two concentrations of 3.0 × 10-5 M and 5.0 × 10-5 M and resulted in deviations of + 1.63% and + 3.56%, respectively. A freeze and thaw stability study indicated that samples might be frozen only once. The enhancement of DPV/BDDE method sensitivity gained by modification, for the analysis of immeasurable BRIM quantities in native, untreated aqueous humor, was reached for quantities of 6 or 12 nmol/0.1 mL aqueous humor with acceptable accuracy (up to + 7.5%). The nature of the process-the irreversible one electron oxidation voltammetric peak of BRIM-limited the sensitivity. Only electrochemical pre-treatment of the BDD electrode before each measurement significantly speeded up the whole procedure. The advantages of the proposed method are simplicity, short-time performance, and good specificity/selectivity, as well as satisfactory accuracy, and no chemical modification of BDDE was necessary.

Is the Use of Refrigerated Fixed Combination of Dorzolamide 2%-Timolol 0.5% (COSOPT) Associated with Less Ocular Discomfort: A Pilot Study.

PURPOSE: To test the hypothesis that the use of refrigerated fixed combination of dorzolamide 2% plus timolol 0.5% solution (COSOPT®) is associated with less ocular discomfort compared with the use of this solution kept at room temperature. METHODS: In this prospective comparative study, 30 primary open-angle patients and 30 healthy subjects filled in the questionnaire on symptoms (Ocular Surface Disease Index) and subjective stinging feeling scale (1-10), at the start of study and 30 days after continuous use of refrigerated fixed combination or placebo eye drops. Results were processed by applying the methods of descriptive (arithmetical mean, standard deviation) and analytical statistics for evaluation of significance of the difference (Student's t-test). RESULTS: Ocular discomfort parameters were significantly lower after the use of refrigerated fixed combination of dorzolamide 2% plus timolol 0.5% solution (t-test, P < 0.0001). Breakup time, Schirmer 1 test, and intraocular pressure values did not differ. CONCLUSIONS: The use of refrigerated fixed combination of dorzolamide 2% plus timolol 0.5% (COSOPT) solution is associated with less ocular discomfort than the use of the same fixed combination at room temperature.

High-dose intravenous immunoglobulins reduce nerve macrophage infiltration and the severity of bortezomib-induced peripheral neurotoxicity in rats.

BACKGROUND: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe adverse effect in patients receiving antitumor agents, and no effective treatment is available. Although the mechanisms responsible for the development of CIPN are poorly understood, recent findings make neuroinflammation an attractive target to be investigated, particularly when neuropathic pain is a prominent feature such as after bortezomib administration. The aim of our study was to evaluate the effect of intravenous immunoglobulins (IVIg) delivery in chronic CIPN. The related neuro-immune aspects were investigated in a well-characterized rat model of bortezomib-induced peripheral neurotoxicity (BIPN). METHODS: After determination of a suitable schedule based on a preliminary pharmacokinetic pilot study, female Wistar rats were treated with IVIg 1 g/kg every 2 weeks. IVIg treatment was started at the beginning of bortezomib administration ("preventive" schedule), or once BIPN was already ensued after 4 weeks of treatment ("therapeutic" schedule). Neurophysiological and behavioral studies were performed to assess the extent of painful peripheral neurotoxicity induced by bortezomib, and these functional assessments were completed by pathologic examination of peripheral nerves and intraepidermal nerve fiber quantification (IENF). The role of the innate immune response in BIPN was investigated by immunochemistry characterization of macrophage infiltration in peripheral nerves. RESULTS: Both schedules of IVIg administration were able to significantly reduce bortezomib-induced heat and mechanical allodynia. Although these changes were not evidenced at the neurophysiological examination of peripheral nerves, they behavioral effects were paralleled in the animals treated with the preventive schedule by reduced axonopathy in peripheral nerves and significant protection from loss of IENF. Moreover, IVIg administration was very effective in reducing infiltration in peripheral nerves of macrophages with the M1, pro-inflammatory phenotype. CONCLUSION: Our results suggest a prominent role of neuroinflammation in BIPN and that IVIg might be considered as a possible safe and effective therapeutic option preventing M1 macrophage infiltration. However, since neuropathic pain is frequent also in other CIPN types, it also indicates the need for further investigation in other forms of CIPN.

Unraveling ALS due to SOD1 mutation through the combination of brain and cervical cord MRI.

OBJECTIVE: To explore structural and functional changes of the brain and cervical cord in patients with amyotrophic lateral sclerosis (ALS) due to mutation in the superoxide dismutase (SOD1) gene compared with sporadic ALS. METHODS: Twenty patients with SOD1 ALS, 11 with sporadic ALS, and 33 healthy controls underwent clinical evaluation and brain MRI. Cortical thickness analysis, diffusion tensor MRI of the corticospinal tracts (CST) and corpus callosum, and resting-state functional connectivity were performed. Patients with ALS also underwent cervical cord MRI to evaluate cord cross-sectional area and magnetization transfer ratio (MTR). RESULTS: Patients with SOD1 ALS showed longer disease duration and slower rate of functional decline relative to those with sporadic ALS. No cortical thickness abnormalities were found in patients with ALS compared with controls. Fractional anisotropy showed that sporadic ALS patients had significant CST damage relative to both healthy controls (p = 0.001-0.02) and SOD1-related ALS (p = 0.05), although the latter showed alterations that were intermediate between controls and sporadic ALS. Functional hyperconnectivity of the motor cortex in the sensorimotor network was observed in patients with sporadic ALS relative to controls. Conversely, patients with SOD1 ALS showed lower cord cross-sectional area along the whole cervical cord relative to those with sporadic ALS (p < 0.001). No cord MTR differences were found between patient groups. CONCLUSIONS: Patients with SOD1 ALS showed cervical cord atrophy relative to those with sporadic ALS and a relative preservation of brain motor structural and functional networks. Neurodegeneration in SOD1 ALS is likely to occur primarily in the spinal cord. An objective and accurate estimate of spinal cord damage has potential in the future assessment of preventive SOD1 ALS therapies.

Comparison of the clinical and cognitive features of genetically positive ALS patients from the largest tertiary center in Serbia.

Discovering novel mutations in C9orf72, FUS, ANG, and TDP-43 genes in ALS patients arises necessities for better clinical characterizations of these subjects. The aim is to determine clinical and cognitive profile of genetically positive Serbian ALS patients. 241 ALS patients were included in the study (17 familiar and 224 apparently sporadic). The following genes were analyzed: SOD1, C9orf72, ANG, FUS, and TDP-43. An extensive battery of classic neuropsychological tests was used in 27 ALS patients (22 SOD1 positive and 5 SOD1 negative) and 82 healthy controls (HCs). Overall 37 (15.4%) of 241 ALS patients carried mutations in tested genes-among 17 familiar ALS patients 16 (94.1%) were positive and among 224 apparently sporadic 21 (9.4%) had causative mutation. Mutations in SOD1 gene were the most common, representing 27 (73.0%) of all genetically positive ALS patients. The main clinical characteristics of SOD1 positive patients were: spinal onset in lower extremities, common sphincter and sensitive disturbances, and dysexecutive syndrome. Within SOD1 positive patients, we noticed somewhat earlier onset in patients with A145G, sensory and sphincter disturbances were dominant in patients with L144F, while D90A patients had significant sensory involvement. SOD1 negative group consisted of ten (27.0%) patients (six C9orf72, two ANG, one TDP-43, and one patient baring triple FUS, C9orf72 expansion, and ANG variants). Bulbar involvement and more extensive neuropsychological impairment (including executive, visuospatial, and memory difficulties) were the main features of SOD1 negative cohort. Our results suggest that meaningful clinical suspicion of certain ALS genotype might be made based on thorough clinical evaluation of patients.

High-dose Ig VENA is well tolerated and efficacious in patients with multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) is a rare, chronic, motor neuropathy that progressively impairs physical functioning and quality of life. Randomised controlled trials have shown that high-dose intravenous immunoglobulin (IVIg) is superior to placebo in improving muscle strength and disability, but many patients require periodic infusions to maintain long-term improvement. This observational, multicentre, retrospective study investigated the efficacy and tolerability of human normal immunoglobulin (Ig VENA) at high intravenous infusion rates in 20 MMN patients (14 male, 6 female). Thirty days after the first infusion, there was an improvement of at least 1 point in two muscles compared to baseline on the Medical Research Council (MRC) scale and of 1 point in the ONLS (Overall Neuropathy Limitation Scale) scale in 15 patients (75%) and 10 patients (50%), respectively; 45% improved on both scales. At 6 months, 100% of 12 patients had improved on the MRC and 79% of 14 patients had improved on the ONLS scale; 83% improved on both scales. All reported adverse drug reactions (ADR) were mild, transient and possibly related to the study drug. Four patients (20%) reported ADRs, three reported headache and one fever. There were no serious or unexpected ADRs. By confirming that high-dose Ig VENA is efficacious and well tolerated, this study adds to the evidence base for IVIg in MMN and potentially increases clinicians' and patients' choice of therapy.

Acquired ectropion uveae and secondary glaucoma due to trauma: report of 3 cases.

PURPOSE: To investigate the possible association between acquired ectropion uveae and blunt trauma to the eye. We present 3 cases of acquired ectropion uveae that occurred after blunt trauma to the eye. There are no previously published data on possible association of these conditions. METHODS:: A retrospective review was conducted of patients with ectropion uveae and eye injury at University Eye Hospital over a 10-year period (2006-2016). We analyzed medical records and clinical findings. RESULTS:: Three eyes of 3 male patients with ocular trauma and ectropion uveae, ages 71, 68, and 5 years, were reviewed. The period between the eye injury and the diagnosis of ectropion uveae ranged from 10 to 36 months. All 3 eyes developed clinical evidence of secondary glaucoma with moderately to severely elevated intraocular pressure (IOP) (ranging from 29 to 48 mm Hg). Surgical treatment (trabeculectomy) was needed in 2 cases in order to control secondary glaucoma and conservative treatment was sufficient in 1 case. Mean patient follow-up was 19.3 ± 4.6 months. CONCLUSIONS:: Trauma can be considered as a cause of acquired ectropion uveae. Acquired ectropion uveae following eye trauma may be associated with significant increase in IOP. All patients in our series had secondary glaucoma and 2 of 3 required surgical treatment for IOP control.

Ocular pulse amplitude after panretinal photocoagulation in normotensive eyes with proliferative diabetic retinopathy.

PURPOSE: To assess the effect of panretinal laser photocoagulation on ocular pulse amplitude (OPA) in normotensive eyes with proliferative diabetic retinopathy. METHODS: Prospectively, we performed unilateral argon laser panretinal photocoagulation (PRP) in 30 patients with diabetes mellitus type II and previously untreated bilateral proliferative diabetic retinopathy. Before and 7 and 30 days after the treatment, OPA was measured using dynamic contour tonometer. RESULTS: Compared with the untreated contralateral eyes, laser photocoagulation led to a reduction of OPA. Ocular pulse amplitude did not significantly differ in photocoagulated eyes 7 days after the treatment, but there was a significant difference in OPA 30 days after the treatment. The decrease in OPA values was 15% 7 days after PRP and 40% 30 days after PRP. CONCLUSIONS: Ocular pulse amplitude reduction after PRP indirectly informs us about choriocapillary closure, already reported in previous studies.

Erythropoietin in the Evaluation of Treatment Outcomes in Patients with Polytrauma.

Polytrauma is a term describing patients with injuries involving multiple body regions that compromises function of the body and/or organ involved. The aim of the study was to evaluate the potential role of erythropoietin in predicting poorer outcome in trauma patients. This prospective study included 86 patients admitted to the Emergency Center of Serbia due to polytrauma assigned according to Injury Severity Score (ISS). The patients were further evaluated using the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores and erythropoietin levels. There was a significant difference among erythropoietin levels at admission, after 48 and 72 hours, and on day 7 of hospital stay, with significantly higher levels in patients with ISS values 49-75. Based on the results, ROC curves were used to identify cut-off levels to predict ISS score with critical clinical course. It was concluded that erythropoietin could be a good marker of injury severity. Further research has to be performed to determine the cut-off values of erythropoietin that are significant for injury severity.