Optical coherence tomography biomarkers indicating visual enhancement in diabetic macular edema resolved through anti-VEGF therapy: OCT biomarkers in resolved DME.

PURPOSE: to investigate the structural features and extended visual results in eyes affected by diabetic retinopathy (DR) and diabetic macular edema (DME) that have been successfully treated with anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Individuals (39 eyes of 39 patients) who had undergone long-term follow-up and demonstrated evidence of resolved DME after at least 2 years of follow-up following the initiation of anti-VEGF therapy were included. During the ""study visit"", structural OCT scans were examined to assess qualitative features indicative of neuroretina or retinal pigment epithelium distress. Additionally, a quantitative assessment of the inner and outer retinal thicknesses was conducted for topographical analysis. RESULTS: The most robust qualitative association observed with BCVA at the "study visit" was linked to the presence of DRIL (p = 0.043) and the appearance of the ELM. (p = 0.045). Regarding quantitative parameters, a strong correlation was noted between the visual acuity during the "study visit" and the foveal and parafoveal thicknesses of both the inner and outer retina (p < 0.001). CONCLUSIONS: Changes in the status of ELM, the presence of DRIL, and the thicknesses of the foveal and parafoveal regions can act as OCT biomarkers, signifying prolonged visual improvements in eyes that have experienced resolved DME after undergoing anti-VEGF therapy.

Association of Copresence of Pathogenic Variants Related to Amyotrophic Lateral Sclerosis and Prognosis.

BACKGROUND AND OBJECTIVES: Despite recent advances, it is not clear whether the various genes/genetic variants related to amyotrophic lateral sclerosis (ALS) interact in modifying patients' phenotype. The aim of this study was to determine whether the copresence of genetic variants related to ALS has interactive effects on the course of the disease. METHODS: The study population includes 1,245 patients with ALS identified through the Piemonte Register for ALS between 2007 and 2016 and not carrying superoxide dismutase type 1, TAR DNA binding protein, and fused in sarcoma pathogenic variants. Controls were 766 Italian participants age-matched, sex-matched, and geographically matched to cases. We considered Unc-13 homolog A (UNC13A) (rs12608932), calmodulin binding transcription activator 1 (CAMTA1) (rs2412208), solute carrier family 11 member 2 (SLC11A2) (rs407135), and zinc finger protein 512B (ZNF512B) (rs2275294) variants, as well as ataxin-2 (ATXN2) polyQ intermediate repeats (≥31) and chromosome 9 open reading frame 72 (C9orf72) GGGGCC intronic expansions (≥30). RESULTS: The median survival time of the whole cohort was 2.67 years (interquartile range [IQR] 1.67-5.25). In univariate analysis, only C9orf72 (2.51 years, IQR 1.74-3.82; p = 0.016), ATXN2 (1.82 years, IQR 1.08-2.33; p < 0.001), and UNC13A C/C (2.3 years, IQR 1.3-3.9; p < 0.001) significantly reduced survival. In Cox multivariable analysis, CAMTA1 also emerged to be independently related to survival (hazard ratio 1.13, 95% CI 1.001-1.30, p = 0.048). The copresence of 2 detrimental alleles/expansions was correlated with shorter survival. In particular, the median survival of patients with CAMTA1 G/G+G/T and UNC13A C/C alleles was 1.67 years (1.16-3.08) compared with 2.75 years (1.67-5.26) of the patients not carrying these variants (p < 0.001); the survival of patients with CAMTA1 G/G+G/T alleles and ATXN2 ≥31 intermediate polyQ repeats was 1.75 years (0.84-2.18) (p < 0.001); the survival of patients with ATXN2 ≥31 polyQ repeats and UNC13A C/C allele was 1.33 years (0.84-1.75) (p < 0.001); the survival of patients with C9ORF72 ≥30 and UNC13A C/C allele was 1.66 years (1.41-2.16). Each pair of detrimental alleles/expansions was associated to specific clinical phenotypes. DISCUSSION: We showed that gene variants acting as modifiers of ALS survival or phenotype can act on their own or in unison. Overall, 54% of patients carried at least 1 detrimental common variant or repeat expansion, emphasizing the clinical impact of our findings. In addition, the identification of the interactive effects of modifier genes represents a crucial clue for explaining ALS clinical heterogeneity and should be considered when designing and interpreting clinical trials results.

Arterial blood gas analysis: base excess and carbonate are predictive of noninvasive ventilation adaptation and survival in amyotrophic lateral sclerosis.

Objective: To investigate the role of arterial blood gas (ABG) analysis parameters (blood carbon dioxide, pCO2; oxygen, pO2; carbonate, HCO3-; standard base excess, SBE) in monitoring respiratory function and ventilation compliance after noninvasive mechanical ventilation (NIV) adaptation, predicting survival in ALS patients. Methods: We selected the first ABG performed after NIV start in ALS patients followed from 2000 to 2015 in Turin ALS Center. Correlations between ABG parameters and survival were calculated. Risk for death/tracheostomy was computed at modifying ABG parameters by using Cox regression models, adjusted for the main prognostic factors. Kaplan-Meier curves were then performed and compared. Results: A total of 186 post-NIV ABGs were included. HCO3- and SBE showed a significant correlation with survival after NIV (respectively, R = -0.183, p = 0.018 and R = -0.200, p = 0.010). Risk for death/tracheostomy after NIV was significantly higher at increasing HCO3- and SBE blood levels, especially when HCO3- was >29 mmol/L and SBE >4 mmol/L (respectively, HR 1.466, 95% CI 1.068-2.011, p = 0.018 and HR = 1.411, 95% CI 1.030-1.32, p = 0.032). Survival in NIV was higher in patients with HCO3- < 29.0 mmol/L and SBE < 4.0 mmol/L. Conclusions: HCO3- and SBE blood levels are markers of ventilation compliance, tolerance and efficacy, being able to predict survival after NIV start in ALS.

Phosphodiesterase-10A Inverse Changes in Striatopallidal and Striatoentopeduncular Pathways of a Transgenic Mouse Model of DYT1 Dystonia.

We report that changes of phosphodiesterase-10A (PDE10A) can map widespread functional imbalance of basal ganglia circuits in a mouse model of DYT1 dystonia overexpressing mutant torsinA. PDE10A is a key enzyme in the catabolism of second messenger cAMP and cGMP, whose synthesis is stimulated by D1 receptors and inhibited by D2 receptors preferentially expressed in striatoentopeducuncular/substantia nigra or striatopallidal pathways, respectively. PDE10A was studied in control mice (NT) and in mice carrying human wild-type torsinA (hWT) or mutant torsinA (hMT). Quantitative analysis of PDE10A expression was assessed in different brain areas by rabbit anti-PDE10A antibody immunohistochemistry and Western blotting. PDE10A-dependent cAMP hydrolyzing activity and PDE10A mRNA were also assessed. Striatopallidal neurons were identified by rabbit anti-enkephalin antibody.In NT mice, PDE10A is equally expressed in medium spiny striatal neurons and in their projections to entopeduncular nucleus/substantia nigra and to external globus pallidus. In hMT mice, PDE10A content selectively increases in enkephalin-positive striatal neuronal bodies; moreover, PDE10A expression and activity in hMT mice, compared with NT mice, significantly increase in globus pallidus but decrease in entopeduncular nucleus/substantia nigra. Similar changes of PDE10A occur in hWT mice, but such changes are not always significant. However, PDE10A mRNA expression appears comparable among NT, hWT, and hMT mice.In DYT1 transgenic mice, the inverse changes of PDE10A in striatoentopeduncular and striatopallidal projections might result over time in an imbalance between direct and indirect pathways for properly focusing movement. The decrease of PDE10A in the striatoentopeduncular/nigral projections might lead to increased intensity and duration of D1-stimulated cAMP/cGMP signaling; conversely, the increase of PDE10A in the striatopallidal projections might lead to increased intensity and duration of D2-inhibited cAMP/cGMP signaling.SIGNIFICANCE STATEMENT In DYT1 transgenic mouse model of dystonia, PDE10A, a key enzyme in cAMP and cGMP catabolism, is downregulated in striatal projections to entopeduncular nucleus/substantia nigra, preferentially expressing D1 receptors that stimulate cAMP/cGMP synthesis. Conversely, in DYT1 mice, PDE10A is upregulated in striatal projections to globus pallidus, preferentially expressing D2 receptors that inhibit cAMP/cGMP synthesis. The inverse changes to PDE10A in striatoentopeduncular/substantia nigra and striatopallidal pathways might tightly interact downstream to dopamine receptors, likely resulting over time to increased intensity and duration respectively of D1-stimulated and D2-inhibited cAMP/cGMP signals. Therefore, PDE10A changes in the DYT1 model of dystonia can upset the functional balance of basal ganglia circuits, affecting direct and indirect pathways simultaneously.

A rare case of postauricular spontaneous keloid in an elderly patient.

Keloid represents an exuberant wound healing response, usually secondary to trauma, inflammation, surgery, or burns. Spontaneous keloid formation is rare and it is controversial whether it is really spontaneous. It usually occurs in young people, and it is rare in elderly. Its main features are the infiltration of surrounding normal tissue, the rare regression and the evolution over time. We report the case of an 81 -year -old man with unexpected spontaneous keloid lesion in the right postauricular region. The diagnosis was hard to be performed because of the patient's age, the anatomical site of the lesion and the absence of skin trauma or injury history. Only the histological examination allowed us to perform the right diagnosis.

Repair of postauricular defects using a new technique: the swallowtail flap.

We describe a case of an 81-year-old patient, where we used a new technique for the reconstruction of postauricular defects (of 3 x 4 cm diameter). The swallowtail flap is an advancement flap that allows getting beyond the repair of the defect, providing an excellent aesthetic result because the scar is masked in the neck and retroauricular folds and does not alter the shape and projection of the ear.

Short-scar surgical approach for the treatment of glomus tumor of the digit.

BACKGROUND: A glomus tumor is a biologically benign neoplasm. The traditional surgical approach to treat this tumor boasts the lowest recurrence rates but may cause nail deformities. OBJECTIVE: A short-scar surgical approach was applied, with the aim of preserving the aesthetics of the nail. METHODS: Between January 1999 and January 2009, 25 patients who underwent surgery for a glomus tumor were included in the study. All patients underwent radical resection with three different surgical approaches based on the location of the tumor. RESULTS: All patients who were operated on had complete regression of pain immediately after surgery and at postsurgery follow-ups. CONCLUSION: The treatment of glomus tumors consists of surgical excision, which is successful if properly executed. Excision of sensitive afferent nervous fibers is a prerequisite to achieve regression of pain. A short-scar surgical approach ensures complete eradication of the tumor and preservation of nail aesthetics.