Thyroglobulin Value Predict Iodine-123 Imaging Result in Differentiated Thyroid Cancer Patients.

Background: In differentiated thyroid cancer (DTC) patients, the response to initial treatments is evaluated 6-12 months after radioiodine therapy (RIT) according to the 2015 American Thyroid Association (2015 ATA) criteria. In selected patients, diagnostic 131-radioiodine whole-body scintigraphy (Dx-WBS) is recommended. We evaluated the diagnostic performance of 123I-Dx-WBS-SPECT/CT imaging in detecting incomplete structural responses in the early follow-up of DTC patients and, additionally, derived optimized basal-Tg value as a yardstick for scintigraphic imaging. Methods: We reviewed the records of 124 low or intermediate-risk DTC patients with negative anti-thyroglobulin antibody. All patients had undergone (near)-total-thyroidectomy followed by RIT. The response to initial treatments was evaluated 6-12 months after RIT. Results: According to the 2015 ATA criteria, 87, 19 and 18 DTC patients were classified to have excellent response (ER), indeterminate/incomplete biochemical response (BIndR/BIR) or structural incomplete response (SIR), respectively. Among patients with less than ER, 18 had a positive 123I-Dx-WBS-SPECT/CT. Metastatic disease at 123I-Dx-WBS-SPECT/CT mainly involved lymph nodes within the central compartment, and corresponding neck ultrasound examinations were negative. The ROC curve analysis was performed to define the best basal-Tg cut-off (i.e., 0.39 ng/mL; AUC = 0.852) able to discriminate patients with and without positive 123I-Dx-WBS-SPECT/CT, respectively. The overall sensitivity, specificity, accuracy, PPV and NPV were 77.8%, 89.6%, 87.9%, 56.0% and 95.9%, respectively. Basal-Tg cut-off was an independent risk factor for having a positive 123I-Dx-WBS-SPECT/CT. Conclusion:123I-Dx-WBS-SPECT/CT identified lymph node metastases in 14/37 patients with less than ER and a negative neck ultrasound, thus modifying the management of such patients. The diagnostic performance of 123I-Dx-WBS-SPECT/CT significantly increased in patients with basal-Tg values ≥ 0.39 ng/mL.

Preliminary Findings of the Role of FAPi in Prostate Cancer Theranostics.

Prostate cancer (PCa) is the most frequently diagnosed cancer worldwide and the second most common cause of cancer-related deaths among men. Progress in molecular imaging has magnified its clinical management; however, an unmet clinical need involves the identification of new imaging biomarkers that complement the gold standard of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in cases of clinically significant PCa that do not express PSMA. Fibroblast activation protein (FAP) is a type II transmembrane serine overexpressed in many solid cancers that can be imaged through quinoline-based PET tracers derived from an FAP inhibitor (FAPi). Preliminary results of FAPi application in PCa (in PSMA-negative lesions, and in comparison with fluorodeoxyglucose-FDG) are now available in the literature. FAP-targeting ligands for PCa are not limited to detection, but could also include therapeutic applications. In this preliminary review, we provide an overview of the clinical applications of FAPi ligands in PCa, summarising the main results and highlighting contemporary strengths and limitations.

Descemet membrane endothelial keratoplasty graft detachments in superior versus temporal approach.

PURPOSE: To evaluate the difference in Descemet Membrane Endothelial Keratoplasty (DMEK) graft detachment rate comparing superior versus temporal main incision approach. METHODS: Retrospective comparative study on patients who underwent DMEK surgery for Fuchs endothelial dystrophy or bullous keratopathy with main wound incision performed at either 90° in the superior approach, or at 180°/0° in the temporal approach. All main incisions were secured with a single 10-0 nylon suture at the end of surgery. Data collected were donor age and gender, endothelial cell counts, graft diameter, recipient age and gender, indication for transplant, surgeon grade, re-bubbling rate, air fill in the anterior chamber (AC) at day one and intra- and early postoperative complications. RESULTS: 187 eyes were included in the study. 99 eyes had DMEK surgery with superior approach, while 88 eyes had temporal approach. The two groups had no differences in donor age and sex, endothelial cell counts, graft diameter, recipient age and sex, indication for transplant, surgeon grade, and air fill in the anterior chamber at day one. Re-bubbling rate was 38.4% for surgeries performed with superior access and 29.5% for those with temporal access(p = 0.186). After exclusion of patients with intraoperative and/or postoperative complication, the difference in re-bubbling rate was higher, although non-significant (37.5% and 25% for superior and temporal approach respectively, p = 0.098). CONCLUSION: The temporal approach in DMEK showed a trend towards a clinically significant lower rate of post-operative re-bubbling compared to the superior approach, however, no statistically significant difference was noted comparing the two approaches, which both remain feasible options in DMEK surgery.

Selective laser capsulotomy complications: Management and prevention.

PURPOSE: To report how to manage and prevent the incomplete laser cut and following uncut tags of anterior capsular lens, performed using the selective laser capsulotomy. METHODS: We describe three possible approaches: peeling the anterior capsulotomy disc with forceps, breaking the tags using the cystotomy needle tip, or cutting them using a 23-G vitrectomy scissors. RESULTS: Using the 23-G vitrectomy scissors resulted in no complication. Peeling the anterior capsulotomy using the forceps instead caused zonular stress with subsequent risks of zonular dialysis, whereas using the cystotomy needle tip resulted in irregular capsulotomy rim and weakness all along the capsulotomy edge where micro tears caused a tear during the rest of cataract surgery. CONCLUSION: Incomplete laser cut and subsequent discontinuous capsulotomy results in the presence of multiple tags which create strong adherence between the central capsulotomy disc and the peripheral capsule. Key steps of the procedure to prevent an incomplete laser cut, which are the anterior lens capsule staining and laser beam focusing, and how to correctly manage them, which may shorten the learning curve and enhance the outcomes.

Artificial iris implantation in congenital aniridia: A systematic review.

Congenital aniridia is a rare, panocular disorder with a main phenotypic characteristic of a partial or complete absence of the iris existing alongside other ocular morbidities such as cataract, keratopathy, optic nerve and foveal hypoplasia, and nystagmus. The iris abnormality, however, often leads to symptoms such as photophobia, glare, and decreased visual acuity, as well as cosmetic dissatisfaction. Current management options for the iris deficit include colored iris contact lenses, corneal tattooing, and tinted contact lenses. Symptoms arising from small iris defects can be resolved with surgical management using micro-tying suture techniques such as McCannel or Siepser. Currently, larger iris defects can be treated with artificial iris implants. New prosthetic options range from colored intraocular lenses to flexible custom-made silicone iris implants. With a range of therapeutic options available and given the challenges of multiple comorbidities in aniridia, we evaluate the literature relating to the use of artificial iris implants in congenital aniridia, with a focus on the different surgical implantation techniques, the clinical outcomes achieved, complications occurred, and risk of bias of the studies included.

Posterior stromal ripples increase risk of Descemet's membrane endothelial keratoplasty graft detachment worsening over time.

PURPOSE: To evaluate anterior segment optical coherence tomography (AS-OCT) features of Descemet's membrane endothelial keratoplasty (DMEK) grafts associated with graft attachment worsening over time. METHODS: Retrospective case series on patients who received uncomplicated DMEK surgery and for whom subsequent AS-OCT data were available for analysis. Patients' demographics and surgical details were collected. AS-OCT was analysed for graft detachment axial extension, presence of posterior stromal ripples, quadrant involvement (location and number), degree of detachment extension, peripheral roll, presence and amount of air in the anterior chamber (AC). Features associated with re-bubbling and graft detachment worsening over time were identified. RESULTS: A total of 147 patients with a mean age of 70.8 ± 9.8 years (63% females) were included. AS-OCT was performed at 2.9 ± 2.4 days after surgery. AS-OCT factors associated with re-bubbling were posterior stromal ripples (p = 0.004) and detachment axial extension (p < 0.001). At first follow-up, of the 147 DMEK, 67 showed complete attachment and 80 partial detachment. In those cases of initially completely attached grafts, posterior stromal ripples were associated with the risk of subsequent graft detachment (p = 0.014) together with recipient age (p = 0.043), phaco-combined surgery (p = 0.018) and AS-OCT timing (p = 0.033); while, in the initially partially detached grafts, detachment worsening was associated with posterior stromal ripples (p = 0.025), detachment axial extension (p = 0.003), degrees of detachment involvement (p = 0.029), peripheral roll-in shape (p = 0.033) and presence of air in the AC (p = 0.032). Relative risk (RR) of graft detachment worsening in patients with moderate/severe posterior stromal ripples was 1.75 (95% CI = 1.09-2.81). CONCLUSION: Posterior stromal ripples and detachment axial extension >1/3 of graft surface area were the main risk factors for detachment worsening over time, and patients showing these features should be monitored closely to identify the need for re-bubbling at an early stage, thus improving surgical outcomes.

Carlevale intraocular lens opacification after Descemet stripping automated endothelial keratoplasty.

PURPOSE: To report a case of sutureless scleral-fixated (SSF) Carlevale intraocular lens (IOL) opacification following Descemet stripping automated endothelial keratoplasty (DSAEK) surgery. METHODS: An 82-year-old man underwent combined SSF Carlevale IOL implant and DSAEK surgery for aphakic endothelial decompensation. Surgery was uneventful, while the postoperative period was complicated by multiple graft detachments requiring re-bubbling. After four re-bubbling procedures, the corneal graft attached and cleared over time. RESULTS: 29 months after combined SSF IOL implant and DSAEK surgery, the patient presented with decreased vision due to IOL opacification affecting the visual axis. CONCLUSION: Although combined SSF IOL and DSAEK surgery is an overall safe and effective procedure for aphakic endothelial decompensation, risk of IOL opacification due to anterior chamber air injection is higher when using hydrophilic IOLs and in cases requiring multiple re-bubbling, therefore, intraocular lens material should be chosen after considering the risks and benefits.

COVID-19 AdenoviralVector Vaccine and Central Retinal Vein Occlusion.

PURPOSE: The purpose of this article is to report a case of sudden onset ischemic retinal central vein occlusion after a second dose of COVID-19 adenoviral vector vaccine. CASE REPORT/OBSERVATIONS: A 54-year-old woman with systemic arterial hypertension developed ischemic central retinal vein occlusion in her right eye on day 2 after the second dose of COVID-19 adenoviral vector vaccine ChAdOx1 nCoV-19/ AZD1222, Oxford-AstraZeneca. CONCLUSION: Adenoviral vector vaccine promotes both cellular and humoral immune responses, increasing the level of inflammatory cytokines. These cytokines are the same implied in the possible pathogenesis of central retinal vein occlusion. Subsequently, we recommend informing patients at risk of possible ocular adverse events, which require urgent evaluation.

Myopia: Mechanisms and Strategies to Slow Down Its Progression.

This topical review aimed to update and clarify the behavioral, pharmacological, surgical, and optical strategies that are currently available to prevent and reduce myopia progression. Myopia is the commonest ocular abnormality; reinstated interest is associated with high and increasing prevalence, especially but not, in the Asian population and progressive nature in children. The growing global prevalence seems to be associated with both genetic and environmental factors such as spending more time indoor and using digital devices, particularly during the coronavirus disease 2019 pandemic. Various options have been assessed to prevent or reduce myopia progression in children. In this review, we assess the effects of several types of measures, including spending more time outdoor, optical interventions such as the bifocal/progressive spectacle lenses, soft bifocal/multifocal/extended depth of focus/orthokeratology contact lenses, refractive surgery, and pharmacological treatments. All these options for controlling myopia progression in children have various degrees of efficacy. Atropine, orthokeratology/peripheral defocus contact and spectacle lenses, bifocal or progressive addition spectacles, and increased outdoor activities have been associated with the highest, moderate, and lower efficacies, respectively.

Blast Wound Dehiscence During Descemet Membrane Endothelial Keratoplasty Rebubbling in a Previous Penetrating Keratoplasty: A Case Report.

PURPOSE: The purpose of this study was to describe a rare complication of Descemet membrane endothelial keratoplasty (DMEK) rebubbling. METHODS: An 86-year-old woman with bilateral penetrating keratoplasty (PK) performed 20 years previously for Fuchs endothelial dystrophy underwent DMEK surgery for endothelial corneal decompensation in the left eye. Surgery was complicated in the postoperative period by repeated DMEK graft detachments requiring rebubbling. RESULTS: The third rebubbling procedure caused a traumatic PK wound dehiscence at the graft-host junction with full-thickness opening of approximately 180 degrees. PK wound dehiscence was resutured in the theater, DMEK lenticule was removed from the eye, and the full-thickness graft was repeated. CONCLUSIONS: DMEK graft rebubbling in patients with previous PK may lead to traumatic wound dehiscence. Avoidance of excessive increases in intraocular pressure during the rebubbling procedure should be encouraged to decrease the risk of this rare complication.

Comparison of immediate versus delayed implant placement in a failed implant site: A retrospective analysis of early implant survival.

PURPOSE: To compare immediate and delayed implant replacement at failed implant sites to evaluate the factors associated with early failure of second implants after replacement. MATERIALS AND METHODS: Data regarding early implant failure followed by replacement with another fixture in a private practice setting between 2003 and 2019 were analysed retrospectively. Early failure was defined as loss of the dental implant within 6 months of placement. The impact of patient-level (age, sex, diabetes, smoking history) and implant-level (timing of implant replacement, timing of prosthetic loading, bone grafting) variables on the early failure rate of second implants after replacement was evaluated. Due to the hierarchical structure of the data, a multivariate multilevel mixed-effects Poisson regression analysis was performed. RESULTS: A total of 109 patients (63 men and 46 women) diagnosed with early implant failure at 124 implant sites were included in the present study. Fifty-eight implants were immediately replaced at the time of removal of the failed implant (test group), whereas 66 were replaced after a healing period of 2 to 4 months (delayed approach; control group). A total of 15 implants failed after replacement in 11 patients during the first 6 months of follow-up. Of these, nine failures (15.25%) occurred in seven patients (13.21%) after immediate replacement, and six (9.09%) occurred in four patients (7.02%) who underwent delayed replacement. No statistically significant differences were detected between the two groups (P = 0.431). CONCLUSIONS: No significant differences in implant survival at sites of previous failure were found according to the timing of implant replacement.

Early preablation rhTSH-stimulated thyroglobulin predicts outcome of differentiated thyroid cancer (DTC) patients.

AIM: Total thyroidectomy and risk-adapted 131-radioiodine therapy (RaIT) are the treatments of choice in differentiated thyroid cancer (DTC) patients. The response to treatments is assessed 6-12 months after RaIT. However, thyroglobulin (Tg) values obtained just before RaIT also provide reliable informations on patients'outcome. As available data were mostly obtained in hypothyroid status, we evaluated the predictive role of preablation-Tg in patients underwent RaIT after rhTSH stimulation. MATERIAL AND METHODS: We enrolled 299 low-to-intermediate risk DTC patients underwent rhTSH-stimulated RaIT (standard protocol). Serum Tg levels were measured before rhTSH administration (basal Tg), before RaIT (early-stimulated Tg), and 2 days after RaIT (late-stimulated Tg). The early response assessment was done 12 months after RaIT according to 2015 American Thyroid Association (2015 ATA) criteria. RESULTS: Most patients (277/299, 92.6%) had an excellent response (ER) to RaIT, while 15/299 (5.1%) and 7/299 (2.3%) patients showed biochemical incomplete/indeterminate response or persistent structural disease, respectively. At receiver operating characteristic analysis, the optimal cutoff to predict ER was set at 1.55 (AUC = 0.792), 2.6 (AUC = 0.931), and 4.9 (AUC = 0.874) ng/mL, for basal, early-, and late-stimulated Tg, respectively. The overall sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for basal, early-, and late-stimulated Tg were 50%, 96.7%, 93.3%, 55%, and 96.1%; 90.9%, 84.5%, 84.9%, 31.7%, and 99.1%; and 90.9%, 71.8%, 73.2%, 20.4%, and 99%, respectively. In univariate and multivariate logistic regression analysis, early-stimulated Tg cutoff resulted as an independent prognostic marker for predicting ER regardless of gender, age, histotype, histological variant, tumor size, risk classification, and stage of disease. CONCLUSION: Early-stimulated Tg is a reliable diagnostic tool for predicting the response to primary treatment of DTC.

Gene expression analysis identifies two distinct molecular clusters of idiopatic epiretinal membranes.

Idiopathic epiretinal membranes (ERMs) are fibrocellular membranes containing extracellular matrix proteins and epiretinal cells of retinal and extraretinal origin. iERMs lead to decreased visual acuity and their pathogenesis has not been completely defined. Aim of this study was to provide a molecular characterization of iERMs by gene expression analysis. To this purpose, 56 iERMs obtained by pars plana vitrectomy were analyzed for the expression levels of genes encoding biomarkers of the cellular and molecular events occurring in iERMs. RT-qPCR analysis showed significant differences in the levels of cell population, extracellular matrix and cytokine/growth factor biomarkers among the iERMs investigated. Hierarchical clustering of RT-qPCR data identified two distinct iERM clusters, Cluster B samples representing transcriptionally "activated" iERMs when compared to transcriptionally "quiescent" Cluster A specimens. Further, Cluster B could be subdivided in two subgroups, Cluster B1 iERMs, characterized by a marked glial cell activation, and Cluster B2 samples characterized by a more pro-fibrotic phenotype. Preoperative decimal best-corrected visual acuity and post-surgery inner segment/outer grading values were higher in Cluster A patients, that showed a prevalence of fovea-attached type iERMs with near-normal inner retina, than in Cluster B patients, that presented more severe clinical and spectral domain optical coherence tomography (SD-OCT) features. In conclusion, this molecular characterization has identified two major clusters of iERM specimens with distinct transcriptional activities that reflect different clinical and SD-OCT features of iERM patients. This retrospective work paves the way to prospective whole-genome transcriptomic studies to allow a molecular classification of iERMs and for the identification of molecular signature(s) of prognostic and therapeutic significance.

Systemic thromboembolic adverse events in patients treated with intravitreal anti-VEGF drugs for neovascular age-related macular degeneration: an update.

Introduction: Intravitreal anti-VEGF is the most effective therapy for wet AMD, although systemic effects on the endothelium cannot be excluded. Areas covered: The purpose of this review was to evaluate risk of thromboembolic events associated with intravitreal anti-VEGF. Expert opinion: Current data are insufficient to confirm the safety of these compounds, due to the paucity of specific studies. Thus, pharmacovigilance for all anti-VEGF should be improved to verify the true role of anti-VEGF in the occurrence of systemic adverse events.

Effects of metformin extended release compared to immediate release formula on glycemic control and glycemic variability in patients with type 2 diabetes.

PURPOSE: The purpose of this study is to evaluate, in a randomized clinical trial, the effects of metformin immediate release (IR) compared with metformin extended release (XR) on the gastrointestinal tolerability and glycemic control. MATERIALS AND METHODS: We enrolled 253 Caucasian patients with type 2 diabetes not well controlled by diet (glycated hemoglobin [HbA1c] >7.0% and <8.5%). Patients were randomized to metformin IR or metformin XR for a period of 6 months at the maximum tolerated dose. The average dose of metformin IR used was 2,000±1,000 mg/day, while that of metformin XR was 1,000±500 mg/day. We evaluated body weight, HbA1c, fasting and postprandial glucose, fasting plasma insulin (FPI) and homeostasis model assessment insulin resistance (HOMA-IR), lipid profile, and levels of some adipocytokines, including tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), visfatin, and vaspin. Moreover, at the baseline and after 6 months, we administered patients some validated questionnaires to assess patients' satisfaction toward treatments. RESULTS: After 6 months, both formulations gave a similar reduction in body weight and body mass index (BMI); however, metformin XR gave a greater improvement in glycemic control, FPI, and HOMA-IR, compared with both baseline and metformin IR. A reduction in total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol was observed with metformin XR compared with IR. Levels of TNF-α, hs-CRP, and vaspin were reduced by metformin XR but not by the IR formulation. Metformin XR also raised the levels of visfatin. CONCLUSION: Metformin XR formulation seems to be more effective than metformin IR in improving glyco-metabolic control, lipid profile, and levels of some adipocytokines in patients with type 2 diabetes mellitus.

Evaluation of the Effects of Mesoglycan on Some Markers of Endothelial Damage and Walking Distance in Diabetic Patients with Peripheral Arterial Disease.

The aim of this study was to evaluate the variation of some parameters involved in peripheral artery disease progression in diabetic patients with peripheral artery disease after six months of mesoglycan [...].

Effects of a Combination of Berberis aristata, Silybum marianum and Monacolin on Lipid Profile in Subjects at Low Cardiovascular Risk; A Double-Blind, Randomized, Placebo-Controlled Trial.

The aim of this study was to evaluate the efficacy and safety of an anti-hypercholesterolemic agent containing Berberis aristata, Silybum marianum and monacolin K and KA in a sample of Caucasian patients at low cardiovascular risk according to Framingham score. The primary outcome was to evaluate the effects of this nutraceutical combination on lipid profile; the secondary outcome was to evaluate the effect on some inflammatory markers, in particular high sensitivity C-reactive protein and tumor necrosis factor-α interleukin-6. One hundred and forty-three patients were randomized to placebo or Berberol® K, once a day, during the dinner, for 3 months, in a randomized, double-blind, placebo-controlled trial. We recorded a significant reduction of fasting plasma glucose with Berberol® K compared to placebo (-12.2%, p < 0.05). Moreover, we recorded an increase of fasting plasma insulin with Berberol® K both compared to baseline and to placebo (+9.9%, p < 0.05). Accordingly, the homeostasis model assessment (HOMA) index obtained after treatment with Berberol® K was lower than the one in the placebo group (-2.8%, p < 0.05). No variations of lipid profile were observed with placebo, while there was a significant decrease of total cholesterol (-20.5%, p < 0.05), triglycerides (-17.7%, p < 0.05), and low density lipoprotein (LDL) cholestero (-27.8%, p < 0.05) with Berberol® K, compared to placebo. There was a decrease of high sensitivity C-reactive protein (-30.8%, p < 0.05), and interleukin-6 (-25.0%, p < 0.05), with Berberol® K compared to placebo. In conclusion, combining different hypocholesterolemic nutraceutical agents such as Berberis aristata, Silybum marianum and monacolin K and KA could be effective and safe to obtain a reduction of lipid profile and an improvement of inflammatory parameters.

Enalapril/lercanidipine combination on markers of cardiovascular risk: a randomized study.

The aim of this study was to evaluate enalapril/lercanidipine combination effects on markers of cardiovascular risk stratification in hypertensive patients. A total of 359 patients were randomized to enalapril 20 mg, lercanidipine 10 mg, or enalapril/lercanidipine 20/10 mg fixed combination. We evaluated blood pressure (BP), fasting plasma glucose (FPG), lipid profile, lipoprotein(a) (Lp[a]), soluble receptor for advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40 L), serum myeloperoxidase (MPO), high sensitivity C-reactive protein (Hs-CRP), and tumor necrosis factor-α (TNF-α). We recorded a decrease of BP in all groups, with the enalapril/lercanidipine combination being more effective in reducing BP compared with single monotherapies. Lipid profile or FPG were not affected by various treatments. Lercanidipine, but not enalapril, improved Lp(a) levels compared with baseline, with enalapril/lercanidipine having a greater effect on Lp(a) reduction. All treatments increased sRAGE levels, and decreased sCD40 L and MPO, even if enalapril/lercanidipine combination was more effective than single monotherapies. TNF-α and Hs-CRP were greater reduced by enalapril/lercanidipine combination compared with enalapril (P < .05 for both). The enalapril/lercanidipine fixed combination was more effective than single monotherapies in decreasing BP, but also in improving markers of cardiovascular risk stratification in hypertensive patients.

Inflammation and macular oedema after pars plana vitrectomy.

Cystoid macular oedema (CMO) is a major cause of reduced vision following intraocular surgery. Although the aetiology of CMO is not completely clarified, intraocular inflammation is known to play a major role in its development. The macula may develop cytotoxic oedema when the primary lesion and fluid accumulation occur in the parenchymatous cells (intracellular oedema) or vasogenic oedema when the primary defect occurs in the blood-retinal barrier and leads to extracellular fluid accumulation (extracellular oedema). We report on the mechanisms of CMO formation after pars plana vitrectomy and associated surgical procedures and discuss possible therapeutic approaches.