Modified alar batten grafts for treatment in nasal valve dysfunction: Our experience.

OBJECTIVE: Alar batten grafts are used to treat in nasal valve dysfunction (NVD). They can be placed by open or closed rhinoplasty using rib, septal, or auricular concha cartilage. Our surgical team used a modified placement of the classic alar batten.We aim to describe these changes and to the technique and demonstrate that modified alar batten grafts can improve the effects of spreader grafts and classic alar batten grafts. METHODS: A retrospective study of 91 functional rhinoplasties was performed from March 2011 to November 2019 at a public university hospital in Murcia. The patients were divided into three groups. Group A included patients operated on using spreader grafts, group B included patients operated on using spreader grafts associated with alar batten grafts fixed to the caudal edge of the lateral crura of the lower lateral cartilage (LLC), and group C included patients operated on using modified alar batten grafts. RESULTS: A total of 91 functional rhinoplasties were performed, 31 patients were operated on in group A, 27 patients were operated on in group B, and 33 patients were operated on in group C. The success rate was 67.7% in group A, 70.4% in group B and 93.9% in group C. CONCLUSION: Modified alar batten grafts achieved better results than spreader grafts and spreader grafts associated with classic alar batten grafts. The size, position and placement of the sutures of modified alar batten grafts were the key factors in improving our results.

Generation of RRMS and PPMS specific iPSCs as a platform for modeling Multiple Sclerosis.

The advent of cellular reprogramming technology converting somatic cells into induced pluripotent stem cells (iPSCs) has revolutionized our understandings of neurodegenerative diseases that are otherwise hard to access and model. Multiple Sclerosis (MS) is a chronic demyelinating, inflammatory disease of central nervous system eventually causing neuronal death and accompanied disabilities. Here, we report the generation of several relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) iPSC lines from MS patients along with their age matched healthy controls from peripheral blood mononuclear cells (PBMC). These patient specific iPSC lines displayed characteristic embryonic stem cell (ESC) morphology and exhibited pluripotency marker expression. Moreover, these MS iPSC lines were successfully differentiated into neural progenitor cells (NPC) after subjecting to neural induction. Furthermore, we identified the elevated expression of cellular senescence hallmarks in RRMS and PPMS neural progenitors unveiling a novel drug target avenue of MS pathophysiology. Thus, our study altogether offers both RRMS and PPMS iPSC cellular models as a good tool for better understanding of MS pathologies and drug testing.

THREE-YEAR OUTCOMES IN A RANDOMIZED SINGLE-BLIND CONTROLLED TRIAL OF INTRAVITREAL RANIBIZUMAB AND ORAL SUPPLEMENTATION WITH DOCOSAHEXAENOIC ACID AND ANTIOXIDANTS FOR DIABETIC MACULAR EDEMA.

PURPOSE: To report 3-year results of a randomized single-blind controlled trial of intravitreal ranibizumab combined with oral docosahexaenoic acid (DHA) supplementation versus ranibizumab alone in patients with diabetic macular edema. METHODS: There were 26 patients (31 eyes) in the DHA group and 29 (38 eyes) in the control group. Ranibizumab (0.5 mg) was administered monthly for the first 4 months followed by a pro re nata (PRN) regimen. In the experimental group, patients received oral DHA supplementation (1,050 mg/day) (Brudyretina 1.5 g). RESULTS: At 36 months, mean decrease of central subfield macular thickness was higher in the DHA-supplementation group than in controls (275 ± 50 µm vs. 310 ± 97 µm) with significant differences at Months 25, 30, 33, and 34. Between-group differences in best-corrected visual acuity were not found, but the percentages of ETRDS gains >5 and >10 letters were higher in the DHA-supplementation group. Differences serum HbA1c, plasma total antioxidant capacity values, erythrocyte DHA content, and serum IL-6 levels were all significant in favor of the DHA-supplementation group. CONCLUSION: The addition of a high-rich DHA dietary supplement to intravitreal ranibizumab was effective to achieve better sustained improvement of central subfield macular thickness outcomes after 3 years of follow-up as compared with intravitreal ranibizumab alone.

Pseudoepitheliomatous Hyperplasia of the Larynx Requiring Total Laryngectomy.

BACKGROUND Pseudoepitheliomatous hyperplasia (PEH) is a reactive epithelial proliferation occurring secondary to infection, neoplasm, injury, and inflammation. The histopathological characteristics of PEH may lead to it being confused with well-differentiated squamous cell carcinoma (SCC). CASE REPORT We present here the case of a 57-year-old male patient, who was diabetic and a smoker, who presented with dysphonia. Although nasal endoscopy suggested SCC, morphological and immunophenotypical study of biopsy tissue ruled out malignancy. CONCLUSIONS As the prognosis worsened, the patient required several urgent surgical interventions due to bleeding abscesses and dyspnea. A total laryngectomy was performed.

Roadblocks in the Path of iPSC to the Clinic.

PURPOSE OF REVIEW: The goal of this paper is to highlight the major challenges in the translation of human pluripotent stem cells into a clinical setting. RECENT FINDINGS: Innate features from human induced pluripotent stem cells (hiPSCs) positioned these patient-specific cells as an unprecedented cell source for regenerative medicine applications. Immunogenicity of differentiated iPSCs requires more research towards the definition of common criteria for the evaluation of innate and host immune responses as well as in the generation of standardized protocols for iPSC generation and differentiation. The coming years will resolve ongoing clinical trials using both human embryonic stem cells (hESCs) and hiPSCs providing exciting information for the optimization of potential clinical applications of stem cell therapies. SUMMARY: Rapid advances in the field of iPSCs generated high expectations in the field of regenerative medicine. Understanding therapeutic applications of iPSCs certainly needs further investigation on autologous/allogenic iPSC transplantation.

Anatomical variants and bilateral lacrimal pathways surgery: avoiding unnecessary surgery.

Success rates (SR) of transcanalicular diode laser-assisted dacryocystorhinostomy (TCL DCR) may be affected by the presence of nasal anatomical variations and additionally by whether or not the pathology is bilateral. The aim is to determine whether it is necessary to perform preliminary nasal anatomical variations surgery and to determine whether bilateral cases may be operated simultaneously. We extracted the patients undergoing simultaneous bilateral TCL DCR and we compared SR across the different groups using ANOVA, Chi-square testing and logistical regression. 159 Lacrimal pathways were operated: 89 unilateral and 35 bilateral. Non-nasal anatomical variations (non-NAV) unilateral surgery returned a success of 72.72%. The mean SR for nasal anatomical variations (NAV) unilateral surgery was 70.1%. The SR for non-NAV bilateral surgery was 60.86%. The mean SR for nasal anatomical variations bilateral surgery was 58.33%. As we identified no significant differences in the SR for NAV and non-NAV patients, we can avoid simultaneous corrective surgery.

Interspecies Chimerism with Mammalian Pluripotent Stem Cells.

Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos.

COMBINED INTRAVITREAL RANIBIZUMAB AND ORAL SUPPLEMENTATION WITH DOCOSAHEXAENOIC ACID AND ANTIOXIDANTS FOR DIABETIC MACULAR EDEMA: Two-Year Randomized Single-Blind Controlled Trial Results.

PURPOSE: To assess the 2-year effectiveness of intravitreal ranibizumab combined with a dietary supplement rich in docosahexaenoic acid (DHA) plus antioxidants in 62 patients with diabetic macular edema. METHODS: In a randomized single-blind controlled study, 33 subjects (42 eyes) received intravitreal ranibizumab alone and 29 (34 eyes) combined with DHA (1,050 mg/day). Monthly ranibizumab (0.5 mg) was given for the first 4 months followed by on as-needed treatment. RESULTS: At 24 months, the difference between groups in the decrease of central subfield macular thickness was significant in favor of the DHA supplementation group (95% confidence interval of the difference 7.20-97.656; P = 0.024), although improvement in best-corrected visual acuity measured in the Early Treatment Diabetic Retinopathy Study letters did not reach statistical significance (95% confidence interval 5.4-11.2, P < 0.66). At 24 months, gains of >5 and >10 letters were significantly higher in the DHA supplementation group as compared with controls when the worse and better seeing eyes were considered but other differences at 12 months and 24 months were not found. CONCLUSION: Intravitreal ranibizumab combined with DHA supplementation reduced central subfield macular thickness after 2 years of follow-up as compared with ranibizumab alone in patients with diabetic macular edema. This anatomical improvement was accompanied by a trend for an amelioration of vision.

In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration.

Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.

Influence of Septal Deviation on the Prognosis of Transcanalicular Diode Laser-Assisted Dacryocystorhinostomy.

Purpose. The objective of the present study is to determine whether the success rate in transcanalicular diode laser-assisted dacryocystorhinostomy (TCL DCR) is influenced by the variant septal deviation (SD). Methods. Patients were divided into two groups: one including operated lacrimal pathways (LP) with no anatomical nasosinusal variants and the other group of LP with SD. This study began on January 1, 2008, and ended on December 31, 2010, at Morales Meseguer Hospital. Variables were compared by means of ANOVA and a logistic regression model (LOGIT). Results. Out of the 159 LP operated on, 102 had no nasosinusal anatomic variant, but 39 LP were associated with SD. The first group evidenced a success rate of 67.64%, while the second group evidenced a success rate of 66.7%. Conclusion. We found no significant statistical differences between the success rates in the two groups (with SD and no anatomical variants). So we could avoid previous or concomitant septoplasty in some cases (mild and moderate SD).

An alternative pluripotent state confers interspecies chimaeric competency.

Pluripotency, the ability to generate any cell type of the body, is an evanescent attribute of embryonic cells. Transitory pluripotent cells can be captured at different time points during embryogenesis and maintained as embryonic stem cells or epiblast stem cells in culture. Since ontogenesis is a dynamic process in both space and time, it seems counterintuitive that these two temporal states represent the full spectrum of organismal pluripotency. Here we show that by modulating culture parameters, a stem-cell type with unique spatial characteristics and distinct molecular and functional features, designated as region-selective pluripotent stem cells (rsPSCs), can be efficiently obtained from mouse embryos and primate pluripotent stem cells, including humans. The ease of culturing and editing the genome of human rsPSCs offers advantages for regenerative medicine applications. The unique ability of human rsPSCs to generate post-implantation interspecies chimaeric embryos may facilitate our understanding of early human development and evolution.