The impact of obesity on thyroidectomy outcomes: a case-matched study.

Obesity is a well-known public health concern in Western World. Accordingly, an elevated number of obese patients undergo thyroidectomy every year. We aim to assess the impact of obesity on intraoperative and postoperative outcomes of patients who undergo thyroidectomy. 1228 patients underwent thyroidectomy at our department between January 2021 and September 2021. We divided patients into two groups according to body mass index (BMI): non-obese (BMI < 30 kg/m2) and obese (BMI ≥ 30 kg/m2). A propensity score approach was performed to create 1:1 matched pairs (matching according to age, gender, diagnosis, nodule size and type of operation). After matching, the final population included 522 patients, equally divided between each group: non-obese group (Group A; n = 261) and obese group (Group B; n = 261). The primary endpoint of the study was the overall rate of postoperative complications; secondary endpoints of the study were operative time, use of energy device and length of hospital stay. The duration of hospital stay resulted longer in Group B (p = 0.002). No statistically significant differences were documented in terms of operative time (p = 0.206), use of energy devices (p = 0.855) and surgical complications (p = 0.429). Moreover, no statistically significant differences were documented considering each specific complication: transient and permanent hypocalcemia (p = 0.336; p = 0.813, respectively), transient and permanent recurrent laryngeal nerve palsy (p = 0.483; p = 0.523, respectively), hematoma (p = 0.779), bleeding (p = 0.178), wound infection (p = 0.313) and cheloid formation (p = 0.412). Thyroidectomy can safely be performed in obese patients. Outcomes resulted comparable; nonetheless, obesity correlates to longer hospital stay.

Anti-vascular endothelial growth factor monotherapy or combined with verteporfin photodynamic therapy for retinal angiomatous proliferation: a systematic review with meta-analysis.

Purpose: To assess functional and anatomical outcomes of intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) monotherapy versus combined with verteporfin Photodynamic Therapy (PDT) for Retinal Angiomatous Proliferation (RAP). Methods: Studies reporting outcomes of intravitreal anti-VEGF monotherapy and/or in combination with verteporfin PDT in RAP eyes with a follow-up ≥ 12 months were searched. The primary outcome was the mean change in best corrected visual acuity (BCVA) at 12 months. Mean change in central macular thickness (CMT) and mean number of injections were considered as secondary outcomes. The mean difference (MD) between pre- and post-treatment values was calculated along with 95% Confidence Interval (95% CI). Meta-regressions were performed to assess the influence of anti-VEGF number of injections on BCVA and CMT outcomes. Results: Thirty-four studies were included. A mean gain of 5.16 letters (95% CI = 3.30-7.01) and 10.38 letters (95% CI = 8.02-12.75) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.01). A mean CMT reduction of 132.45 µm (95% CI = from -154.99 to -109.90) and 213.93 µm (95% CI = from -280.04 to -147.83) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.02). A mean of 4.9 injections (95% CI = 4.2-5.6) and 2.8 injections (95% CI = 1.3-4.4) were administered over a 12-month period in the anti-VEGF group and combined group, respectively. Meta-regression analyses showed no influence of injection number on visual and CMT outcomes. High heterogeneity was found across studies for both functional and anatomical outcomes. Conclusion: A combined approach with anti-VEGF and PDT could provide better functional and anatomical outcomes in RAP eyes compared with anti-VEGF monotherapy.

Combined Topography-Guided Trans-Epithelial PRK and PTK for Recalcitrant Recurrent Corneal Erosions in Lattice Corneal Dystrophy.

Purpose: To report morphologic and functional changes after topography-guided trans-epithelial photorefractive keratectomy (PRK) combined with phototherapeutic keratectomy (PTK) for recalcitrant recurrent corneal erosions in Lattice Corneal Dystrophy (LCD). Methods: One case report. Results: A 78-year-old man presented us with decreased visual acuity [20/100 in right eye (RE), and 20/400 in left eye (LE)], and redness with foreign body sensation in both eyes. Clinical examination revealed epithelial erosions, and linear stromal opacities involving the center of the cornea in both eyes, supporting the diagnosis of LCD. Several medical approaches including autologous serum, amniotic membrane extract, and nerve growth factor eye drops allowed a temporary improvement in symptoms. A single-step topography-guided trans-epithelial PRK combined with PTK (CIPTA®2 software, iVis Technologies) was performed in both eyes. After surface ablation using PRK, PTK was performed using masking agents (1% hydroxy-methylcellulose) to smooth the ablated surface. Subsequently, 0.02% Mitomycin C was applied over the ablated surface. At the 3-month follow-up, a resolution of corneal erosions, and stromal opacities were observed in both eyes, with a visual improvement to 20/25 in the RE and 20/50 in the LE. Furthermore, spherical equivalent, keratometric astigmatism, and corneal morphological irregularity index improved. Conclusion: Recalcitrant corneal erosions and stromal opacities in LCD may be successfully treated using combined topography-guided trans-epithelial PRK and PTK.

Mid-term safety and effectiveness of macular peeling one month after intravitreal dexamethasone implant for tractional diabetic macular edema.

Macular peeling combined or followed by intravitreal dexamethasone implant (DEX-i) was recommended as an efficacy approach for tractional diabetic macular edema (tDME). Knowing the synergistic effect of cataract surgery and DEX-i one month earlier in eyes with DME, we compared Epiretinal Membrane/Inner Limiting Membrane (ERM/ILM) peeling preceded by DEX-i one month before versus ERM/ILM peeling alone for the treatment of tDME. A retrospective study on patients affected by tDME who underwent ERM/ILM peeling one month after DEX-i (n = 11; Group A) or ERM/ILM peeling alone (n = 10; Group B) was performed. Longitudinal comparison of best-correct visual acuity (BCVA), central retinal thickness (CRT), and intraocular pressure (IOP) between the time of surgery (T0) and each time point (months 1,3,5,6) within and among the groups were assessed. To evaluate the repeated measurements of BCVA, CRT, and IOP, a linear mixed-effects model was used. In Group A, DEX-i significantly improved mean BCVA and CRT (P < 0.001) just after 1 month (T0). After ERM/ILM peeling, mean BCVA and CRT significantly improved from month 1 in Group A and month 3 in Group B. Mixed model revealed a significant difference in BCVA (P ≤ 0.0001) and CRT (P ≤ 0.02) at different time-points among the groups with better results in Group A. Neither complications nor uncontrolled IOP increase was detected. ERM/ILM peeling confirmed its effectiveness in treating tDME. DEX-i performed one month before surgery seemed to be a safe approach and ensured a greater and faster recovery considering functional and tomographic parameters.

An adrenal cortical adenoma with neuroendocrine-type granules mimicking pheochromocytoma.

Clinical and biochemical presentation of adrenal tumors may rarely conflict with their histologic features. In the present report, we describe a rare case of adrenal neoplasm clinically and biochemically labeled as pheochromocytoma which at histologic examination resulted adrenal cortical tumor. The neoplasm was examined with the electron microscope which revealed the presence of electron-dense neuroendocrine-type granules next to intracytoplasmic lipid droplets. The patient underwent laparoscopic left adrenalectomy which leads to normalization of 24 h urinary metanephrine and normetanephrine. This exceptional entity should be taken into consideration when the clinical and laboratory features conflict with the histological examination. The pathologist can clarify the mixed nature of the tumor by means of the identification of neuroendocrine granules at the electron microscope examination.

Associations and Prognostic Significance of Fluctuations in Diabetic Retinopathy Severity in Eyes Treated for Diabetic Macular Edema.

INTRODUCTION: The aim of our study was to investigate factors associated with diabetic retinopathy (DR) severity fluctuations in patients undergoing intravitreal injections for diabetic macular edema and to explore risk factors for proliferative DR (PDR). METHODS: We graded ultra-widefield fundus photography imaging at each visit using the Early Treatment Diabetic Retinopathy Study Severity Scale (DRSS). We calculated the deviation from the mode (DM) of DRSS values as a proxy of DR severity fluctuations, and we analyzed its clinical associations with linear models. We computed risk factors for PDR with Cox hazard models. We included the DRSS area-under-the-curve (AUC) of DRSS scores as a covariate in all analyses. RESULTS: We included 111 eyes with a median follow-up of 44 months. Higher DRSS-AUC values (ß = +0.03 DRSS DM for unitary DRSS/month increase, p = 0.01) and a higher number of anti-VEGF injections (ß = +0.07 DRSS DM for injection, p = 0.045) were associated with wider DR severity fluctuations. Higher DRSS-AUC values (HR = 1.45 for unitary DRSS/month increase, p = 0.001) and wider DR severity fluctuations (HR = 22.35 4th quartile vs. 1st-3rd quartile of DRSS DM, p = 0.01) were risk factors for PDR. CONCLUSION: Patients with larger DR variability in response to intravitreal injections may be at higher risk of DR progression. We advocate attentive follow-up in these patients to recognize PDR early.

Intravitreal Dexamethasone Implant at the Time of Silicon Oil Removal to Treat Persistent Macular Edema after Rhegmatogenous Retinal Detachment Repair.

BACKGROUND: An intravitreal dexamethasone implant (DEX-I) was found to be effective and safe for the treatment of cystoid macular edema (CME) after vitrectomy for rhegmatogenous retinal detachment (RRD) and in silicone oil (SO)-filled eyes. We aimed to investigate the efficacy and safety of DEX-I at the time of SO removal for the treatment of recalcitrant CME after successful RRD repair. METHODS: A retrospective review of the medical records was performed on 24 consecutive patients (24 eyes) with recalcitrant CME after RRD repair who were treated with a single 0.7-mg DEX-I at the time of SO removal. The main outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT). A regression model was performed to assess the relationship between BCVA and CMT at 6 months and independent variables. RESULTS: In all 24 patients, CME occurred after RRD repair and remained despite topical therapy. The mean time of CME onset was 27.4 ± 7.7 days after vitrectomy. The mean time between vitrectomy and DEX-I was 106.8 ± 10.1 days. The mean CMT was significantly decreased from 429.6 ± 59.1 µm at baseline to 294 ± 46.4 µm at month 6 (p < 0.0001). The mean BCVA significantly improved from 0.99 ± 0.3 at baseline to 0.60 ± 0.3 at month 6 (p < 0.0001). An elevation of intraocular pressure was observed in one (4.1%) eye, which was medically managed. A univariate regression model revealed a relationship between month-6 BCVA after DEX-I and gender (ß = -0.27; p = 0.03) and macular status (ß = -0.45; p = 0.001) when RRD occurred. No relationship between month-6 CMT and independent variables was found. CONCLUSIONS: DEX-I at the time of SO removal had an acceptable safety profile and achieved favorable outcomes in eyes affected by recalcitrant CME that occurred after RRD repair. RRD-related macular status is significantly associated with visual acuity after DEX-I.

Microvascular Changes after Scleral Buckling for Rhegmatogenous Retinal Detachment: An Optical Coherence Tomography Angiography Study.

This retrospective study aimed to investigate macular microvascular alterations after successful scleral buckling (SB) for rhegmatogenous retinal detachment (RRD). Nineteen eyes with macula-on RRD and 18 eyes with macula-off RRD were included. In all cases, an encircling band was placed. Optical coherence tomography angiography (OCTA) was performed at baseline and postoperatively. Changes in the foveal avascular zone (FAZ) area and vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were the primary outcomes. Correlations between OCTA findings and clinical variables were considered secondary outcomes. In both the macula-on and macula-off groups, the FAZ area was comparable with controls. In the macula-on group, VD in the whole SCP was lower compared with controls at both baseline (p < 0.001) and 6 months (p = 0.03), but showed a significant increase after surgery (p = 0.004). In the macula-off group, postoperative VD in both whole SCP and whole DCP was lower compared with controls (p < 0.001). In the macula-on group, there was an inverse correlation between axial length increase and SCP VD change (r = −0.508; p = 0.03). These findings demonstrated microvascular alterations after SB for RRD. However, VD impairment seems to be mitigated after surgery. A greater increase in postoperative axial length was associated with a poorer VD outcome.

Polyhexamethylene biguanide hydrochloride (PHMB)-properties and application of an antiseptic agent. A narrative review.

The prevention and management of ocular surface infections is still one of the great challenges for ophthalmologists. The spread of antimicrobial resistance makes it necessary to use antiseptic substances with a broad antimicrobial spectrum. Polyhexamethylene biguanide hydrochloride (Polyhexanide, PHMB) is a broad-spectrum antiseptic with excellent tolerance and a low-risk profile. Its physicochemical action on the phospholipid membrane and DNA replication or repair mechanism, prevents or impedes the development of resistant bacterial strains. PHMB revealed its effective against numerous organisms like viruses, Gram-negative and Gram-positive bacteria, and fungi. Polyhexanide is commonly used as preservative in commercially available disinfecting solutions for contact lens care and in ophthalmic formulations at different concentrations ranging from 1 µg/ml to 50 µg/ml. The administration of 0.02% (200 µg/ml) PHMB is often the first-line therapy of Acanthamoeba keratitis. However, to date, only one close-out randomized controlled study tested the efficacy of 0.02% PHMB in Acanthamoeba keratitis and a phase III study is still ongoing. This paper reviews the antiseptic agent PHMB, focusing on biochemical mechanisms, safety profile and applications in ophthalmology.

ASSOCIATED FACTORS AND SURGICAL OUTCOMES OF MICROCYSTOID MACULAR EDEMA AND CONE BOUQUET ABNORMALITIES IN EYES WITH EPIRETINAL MEMBRANE.

PURPOSE: To investigate the associated features and the surgical outcomes in eyes with microcystoid macular edema (MME) and cone bouquet abnormalities (CBA) undergoing epiretinal membrane peeling. METHODS: Retrospective study including patients who underwent pars plana vitrectomy for idiopathic epiretinal membrane. Factors associated with MME and CBA at baseline and their regression were identified with logistic regression models. Postoperative visual acuity was evaluated with linear mixed models from baseline to 12 months. Risk factors for new or worsened macular edema were explored with a Cox regression model. RESULTS: One hundred and eighty-seven eyes are included in this study; 30 eyes (16%) had MME and 53 eyes (28%) had CBA preoperatively. Microcystoid macular edema was associated with severe epiretinal membrane stage (odds ratio [95% confidence interval] = 3.6 [1.3-12.7], P = 0.02); CBA was inversely associated with ectopic inner foveal layer thickness (odds ratio [95% confidence interval] = 0.97 [0.97-0.99] for each 1- µ m EIFL increase, P = 0.006). Eyes with MME had worse visual acuity after epiretinal membrane peeling ( P = 0.01) and were at risk of macular edema worsening (hazard ratio [95% confidence interval] = 2.22 [1.01-5.16], P = 0.04). Older age was associated with MME persistence (odds ratio [95% confidence interval] = 2.46 [1.06-6.82] for each 10-year increase, P = 0.04). No significant associations were found for CBA. CONCLUSION: Although CBA had no prognostic consequences, MME was associated with suboptimal visual recovery and less efficient control of inflammation after surgery. Degeneration of Müller cells may have an alleged role, and further imaging and functional tests are warranted.

Assessment of Diabetic Choroidopathy Using Ultra-Widefield Optical Coherence Tomography.

Purpose: The purpose of this study was to investigate a confocal scanning laser ophthalmoscopy (cSLO) ultra-widefield (UWF) swept-source optical coherence tomography (S-SOCT) in assessment of diabetic choroidopathy and to evaluate the agreement of measurements with a spectral-domain OCT (SD-OCT) instrument. Methods: We conducted a cross-sectional study of patients with diabetes evaluating the choroidal vascularity index (CVI) in the nasal, temporal, and central macula segments of a UWF SS-OCT scan centered to the fovea. UWF pseudocolored fundus images were used for diabetic retinopathy (DR) severity staging. The CVI values were compared between different degrees of severity of DR and different posterior-pole sectors with linear mixed models. Central macula CVI measurements were repeated on SD-OCT scans; the interobserver intraclass coefficient (ICC) was calculated between SS-OCT and SD-OCT. Results: A total of 151 eyes of 85 patients were included. The CVI values decreased from nonproliferative DR to proliferative DR, with high-risk proliferative DR having significantly lower CVI values than moderate to severe nonproliferative DR (P = 0.03). The central macula region was the most evidently affected; the nasal sector was the least affected. The agreement between SS-OCT and SD-OCT was moderate (ICC = 0.50). Conclusions: Diabetic choroidopathy progresses with worsening of DR toward proliferative disease; choroidal depletion is more prominent in the macula. Caution is recommended in comparing CVI values between different devices. Translational Relevance: Choroidal vascularity informs about the severity of DR and its complications, such as macular edema. The agreement between readers and between instruments may be suboptimal in certain cases.

Epiretinal Membrane Vitrectomy With and Without Intraoperative Intravitreal Dexamethasone Implant: A Systematic Review With Meta-Analysis.

Purpose: To evaluate the efficacy of vitrectomy combined with intravitreal dexamethasone implant vs. vitrectomy without the implant in patients with epiretinal membrane (ERM) by conducting a systematic review and meta-analysis. Methods: Studies that compared ERM vitrectomy with and without intraoperative dexamethasone implant with a follow-up ≥3 months were included. The primary outcome was mean best corrected visual acuity (BCVA) change between eyes undergoing ERM vitrectomy combined with dexamethasone implant (DEX group) and eyes undergoing ERM vitrectomy alone (control group) at 3 months. Secondary outcomes included mean BCVA change at 6 months and mean optical coherence tomography central macular thickness (CMT) change at both 3-months and 6-months follow-up. Mean differences (MDs) with their 95% confidence interval (95%CI) were calculated. Meta-analyses were based either on random effect model or fixed effect model according to heterogeneity. Results: Four studies were included. At 3 months, ERM vitrectomy combined with dexamethasone implant yielded a greater visual gain compared to vitrectomy alone (MD = 9.7; 95%CI = 2.6-16.8; p = 0.01). However, significant heterogeneity was found. A sensitivity analysis excluding the only retrospective non-randomized study confirmed a greater visual gain in the DEX group (MD = 7.1; 95%CI = 2.7-11.6; p < 0.01), with no heterogeneity. At 6 months, a non-significant but borderline difference in visual gain was shown between in the two groups (MD = 5.1; 95%CI = -0.3-10.5; p = 0.06), with no heterogeneity. Three-month analysis of CMT revealed a greater reduction in the DEX group (MD = -80.2; 95%CI =-149.1-11.2; p = 0.02), but with significant heterogeneity. A sensitivity analysis excluding the only retrospective non-randomized study allowed to reduce heterogeneity, but no difference in 3-months CMT change was found between the two groups (MD = -50.0; 95%CI = -106.2-6.2; p = 0.08). At 6 months, no difference in CMT change was shown between the two groups (MD = -48.5; 95%CI = -120.5-23.5; p = 0.19), with significant heterogeneity. Conclusions: Intraoperative dexamethasone implant in eyes undergoing vitrectomy for ERM provided a better visual outcome at 3 months compared to ERM vitrectomy without the implant, with limited evidence of better anatomic outcome as well. Further studies are needed to ascertain whether dexamethasone implant would ensure a significant long-term visual benefit as a result of a faster reduction of macular thickening.

Standardized Flanged Intrascleral Intraocular Lens Fixation with the Double-Needle Technique for Cataract Luxation in the Vitreous Chamber during Phacoemulsification.

PURPOSE: To assess the visual and refractive outcome of immediate intraoperative vitrectomy and intrascleral intraocular lens implantation using a "standardized" sutureless Yamane technique during cataract luxation in the vitreous chamber as a complication of phacoemulsification. DESIGN: A prospective, interventional, consecutive case series. MATERIALS AND METHODS: Twelve patients underwent vitrectomy and intrascleral intraocular lens fixation using a standardized Yamane technique as the primary procedure during complicated phacoemulsification. Patients were evaluated preoperatively and 6 months postoperatively for best-corrected distance visual acuity, correspondence to the preoperative refractive target in the spherical equivalent, endothelial cell count, and complications. RESULTS: Mean preoperative best-corrected visual acuity was 1.16 ± 0.3 logarithm of the minimum angle of resolution (logMAR), the endothelial cell count was 1910.5 ± 297.64, and target refraction at baseline was -0.197 ± 0.087. Postoperatively, best-corrected visual acuity was significantly improved; the mean value was 0.05 logMAR ± 0.06. Mean baseline target refraction in the spherical equivalent was -0.20 ± -0.09 (range: -0.08 to -0.37), and mean final refraction was -0.44 ± -0.14 (range: -0.25 to -0.75) with no significant difference (p=0.87). No complication was registered intra- and postoperatively. CONCLUSION: Standardization of the Yamane technique seemed a valuable option for patients who had complicated phacoemulsification to achieve a predictable refractive outcome. Synopsis. The predictable refractive outcome could be achieved with the immediate standardized Yamane technique in patients with intraoperative cataract luxation in the vitreous chamber during phacoemulsification.

Topical Liposomal Ozonated Oil in Complicated Corneal Disease: A Report on Three Clinical Cases.

Infectious and traumatic corneal diseases require adequate therapy against infection and promote re-epithelialization. The appearance of multidrug-resistant bacterial strains, induced by excessive use of antibiotics in the treatment of infectious diseases, has urged researchers to study new antimicrobial formulations. Ozonated oils have demonstrated antiseptic (antibacterial, antifungal and antiviral) and reparative properties and can be proposed for the prevention and treatment of acute and chronic local infections, as an alternative to conventional topical antimicrobials. In ocular treatment, ozonated oil can exert tissue repair and anti-inflammatory and bactericidal activity. Moreover, its specific formulation makes it well tolerated and biocompatible with the ocular surface. Herein, we report on three cases of corneal inflammation (dendritic epithelial keratitis, corneal injuries caused by olive leaves, and neurotrophic corneal ulcer), treated with liposomal ozonated oil (Ozodrop®, FB VISION S.p.a. San Benedetto del Tronto, Italy), successfully resolved using topical liposomal ozonated oil.

TGF-ß Serum Levels in Diabetic Retinopathy Patients and the Role of Anti-VEGF Therapy.

Transforming growth factor ß1 (TGFß1) is a proinflammatory cytokine that has been implicated in the pathogenesis of diabetic retinopathy (DR), particularly in the late phase of disease. The aim of the present study was to validate serum TGFß1 as a diagnostic and prognostic biomarker of DR stages. Thirty-eight subjects were enrolled and, after diagnosis and evaluation of inclusion and exclusion criteria, were assigned to six groups: (1) healthy age-matched control, (2) diabetic without DR, (3) non-proliferative diabetic retinopathy (NPDR) naïve to treatment, (4) NPDR treated with intravitreal (IVT) aflibercept, (5) proliferative diabetic retinopathy (PDR) naïve to treatment and (6) PDR treated with IVT aflibercept. Serum levels of vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF) and TGFß1 were measured by means of enzyme-linked immunosorbent assay (ELISA). Foveal macular thickness (FMT) in enrolled subjects was evaluated by means of structural-optical coherence tomography (S-OCT). VEGF-A serum levels decreased in NPDR and PDR patients treated with aflibercept, compared to naïve DR patients. PlGF serum levels were modulated only in aflibercept-treated NPDR patients. Particularly, TGFß1 serum levels were predictive of disease progression from NPDR to PDR. A Multivariate ANOVA analysis (M-ANOVA) was also carried out to assess the effects of fixed factors on glycated hemoglobin (HbA1c) levels, TGFß1, and diabetes duration. In conclusion, our data have strengthened the hypothesis that TGFß1 would be a biomarker and pharmacological target of diabetic retinopathy.

An adult case of idiopathic internal carotid-internal jugular vein arteriovenous fistula.

Carotid-jugular fistula is an abnormal connection between the carotid artery and/or its branches and jugular vein. It can develop either because of trauma or spontaneous causes. Traumatic fistula may occur after head injuries and can range from minor falls to severe penetrating wounds. Traumatic fistula may also result from endovascular therapy; however, these fistulas may be congenital arteriovenous connections that open spontaneously in the setting of collagen vascular disease, atherosclerotic disease, hypertension, or childbirth. Spontaneous fistulas between internal carotid artery and internal jugular vein are very exceptional diseases; therefore, this case is presented for its rare incidence in literature.

A proteomic approach for the characterization of C677T mutation of the human gene methylenetetrahydrofolate reductase.

Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of methylenetetrahydrofolate (CH2H4folate) to methyltetrahydrofolate (CH3H4folate). The C677T mutation is a common polymorphism of the human enzyme that leads to the replacement of Ala222Val, thermolability of MTHFR, and mild elevation of plasma homocysteine levels. A mild hyperhomocysteinemia is known to be risk factor for cardiovascular and thrombotic diseases, ischemic stroke, neural tube defects, late on-set dementia, and pregnancy complications. Human plasma of subjects carrying the C677T mutation in the MTHFR gene has been investigated for their protein pattern in order to identify novel molecular hallmarks. 2-D analysis of the plasma protein allowed the identification of a specific pattern associated with the TT mutant genotype. Noteworthy, we found one spot shifted to a more basic pI in mutant individuals, and MS identification corresponded to vitamin D-binding protein (DBP or group component (Gc) globulin). MS/MS peptide sequencing allowed to discriminate different allelic variants in the investigated clinical groups. These data confirmed by molecular genetic analysis highlight the novel association between the C677T MTHFR genotype with the Gc2 polymorphism of the DBP. Moreover, we found a quantitative reduction of Apolipoprotein A-I in mutant individuals, which was associated, in previous studies by others to an increased cardiovascular risk.

Plasma cytokine levels in migraineurs and controls.

BACKGROUND: The vasoactive peptide, calcitonin gene-related peptide (CGRP), is released from primary afferent neurons in the trigemino-vascular circulation during migraine headache. CGRP at physiological concentrations and possibly via stimulation of its selective receptors on T-cells, triggers the secretion of cytokines. Cytokines play an important role in several physiological and pathological settings such as immunology, inflammation, and pain. OBJECTIVE: To investigate plasma levels of pro- and anti-inflammatory cytokines in migraineurs and healthy controls. METHODS: We studied 25 migraine patients, during and outside attacks, and 18 healthy control subjects measuring plasma levels of IL-6, IL-10, tumor necrosis factor alpha (TNFalpha), IL-4, IL-1 beta, and IL-2 using ELISA. RESULTS: Circulating levels of IL-10, TNFalpha, and IL-1 beta during attacks were significantly higher in comparison to their levels outside attacks (P=.0003, P=.03, and P=.05, respectively). IL-10 and TNF serum levels were higher in patients studied soon after headache onset and lower over time (P=.004 and P=.05). CONCLUSION: Our results suggest that TNFalpha, IL-1 beta, and IL-10 may be involved in the pathogenesis of migraine attacks.