Multiple-Digit Pigmented Bowen's Disease Induced by Human Papillomavirus in an Immunocompetent Child.

Introduction: Bowen's disease is a squamous cell carcinoma in situ, the most common malignancy of the nail unit. Presenting more frequently in the fingernails, common risk factors include ionizing radiation, oral exposure to arsenic or pesticides, dyskeratosis congenita, and quite commonly diverse subtypes of HPV. We report the first case of multiple periungual pigmented Bowen's disease in a pediatric patient. Case Presentation: A healthy 13-year-old boy presented with a 9-month history of a pigmented erythematous patch on the proximal nail fold of his 3rd right finger without associated symptoms. A punch biopsy was taken, and the diagnosis of Bowen's disease was made. The patient received photodynamic therapy and three cycles of imiquimod without response, and two new lesions appeared on the first and second right fingers. Surgical removal was performed on all lesions. A polymerase chain reaction detected an HPV type 16. Discussion/Conclusion: Multiple periungual Bowen's disease is rare, with the most frequent risk factors being HPV infection and chronic immunosuppression. Less than 10% of the cases present as longitudinal melanonychia. To date, there are no previous reports of multiple pigmented periungual Bowen's disease. HPV-induced Bowen's disease is usually present in adults aged between 22 and 89 years as persistent verrucae. In this case, koilocytosis and the fact that all lesions appeared on the right hand are suggestive of HPV infection.

[The FECYT seal of quality, a recognition and a stimulus for Archivos]. / El sello de calidad FECYT, un reconocimiento y un estímulo para Archivos.

Un año más, mediante esta nota editorial, damos cuenta de las estadísticas y los principales avances de nuestra revista. En cuanto a las estadísticas editoriales, que se detallan en los apartados posteriores, podemos afirmar que son las de una revista consolidada: flujo nutrido y constante de trabajos recibidos/publicados, tasas de aceptación y rechazo proporcionadas, tiempos de gestión razonables y diversidad en las autorías. El logro más destacable del 2023 fue superar con éxito el proceso de evaluación de la Octava edición de Evaluación de la calidad editorial y científica de las revistas científicas españolas, comúnmente conocido como 'Sello FECYT'….

Association of the rs1966265 and rs351855 FGFR4 Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico.

The aim of this study was to associate FGFR4 rs1966265 and rs351855 variants with colorectal cancer (CRC) in a Mexican population and to perform in silico analysis. Genomic DNA from 412 healthy individuals and 475 CRC patients was analyzed. In silico analysis was performed using the PolyPhen-V2, GEPIA, GTEx, and Cytoscape platforms. The GA genotype dominant model (GAAA) of rs1966265 and the AA genotype dominant and recessive models of rs351855 were identified as CRC risk factors (p < 0.05). CRC patients aged ≥ 50 years at diagnosis who consumed alcohol had a higher incidence of the rs351855 GA genotype than the control group (p < 0.05). Associations were observed between the rs1966265 GA genotype and patients with rectal cancer and stage III-IV disease. The rs351855 AA genotype was a risk factor for partial chemotherapy response, and the GA + AA genotype for age ≥ 50 years at diagnosis and rectal cancer was associated with a partial response to chemotherapy (p < 0.05). The AA haplotype was associated with increased susceptibility to CRC. In silico analysis indicated that the rs351855 variant is likely pathogenic (score = 0.998). Genotypic expression analysis in blood samples showed statistically significant differences (p < 0.05). EFNA4, SLC3A2, and HNF1A share signaling pathways with FGFR4. Therefore, rs1966265 and rs351855 may be potential CRC risk factors.

Amelioration of Cytogenotoxic Damage in Drug Abusers Supplemented with Folic Acid.

BACKGROUND: Cytogenotoxic damage caused by the consumption of legal and illegal drugs in drug abusers has been demonstrated, primarily due to alterations in their antioxidant capacity, cellular repair mechanisms, and increased production of free radicals. Folic acid shows antioxidant activity by acting as a reducing agent, neutralizing present free radicals, and reducing genomic damage. METHODS: The intervention involved administering 15 mg of folic acid, divided into three doses per day, to a group of 44 drug abusers. The frequency of nuclear abnormalities (NAs) was determined; micronuclei (MNs), nuclear buds (NBUDs), binucleated cells (BNs), abnormally condensed chromatin (CC), karyorrhexis (KX), pyknotic nuclei (PNs), and karyolysis (KL) were determined at different pre-treatment (baseline) and post-treatment time points at 15 and 30 days. Additionally, a group of 44 healthy individuals was used as the control group. RESULTS: We observed a statistically significant decrease in the frequency of NAs in the drug abuser group (28.45 ± 17.74 before supplementation vs. 11.18 ± 7.42 at 15 days and 9.11 ± 10.9 at 30 days of supplementation). Specifically, it decreased the frequency of NBUDs, BNs, CC, KX, and PNs (p < 0.05). CONCLUSION: Our study demonstrates a clear improvement in cytogenotoxic damage in drug abusers supplemented with folic acid.

Cytogenotoxicity effects in addicts with multidrug consumption.

Drug abuse is considered a global health problem with serious social impact. In recent decades, changes in drug consumption patterns have shown a clear rising trend in the use of multiple drugs. Although the buccal micronucleus cytome (BMCyt) assay has evaluated cytotoxicity in drug abuse, there has not been an approach that takes into account this pattern of multiple drug use. Therefore, in this study, we evaluate for the first time the cytogenotoxic effects in multidrug users, and its correlation with the amount consumed and years of abuse. This study was conducted on 166 individuals by the BMCyt assay. A total of 83 individuals with a history of multiple licit (alcohol and tobacco) and at least one illicit drug abuse (marijuana, methamphetamines, cocaine, and/or inhalants), and 83 healthy individuals, non-drug abusers were analyzed. The results showed that drug abusers had higher frequencies of nuclear abnormalities nuclear buds, binucleated cells, pyknotic nuclei (PNs), karyorrhexis (KX), and abnormally condensed chromatin when compared with healthy controls. Moreover, results suggests that the use of licit and illicit drugs is related to cytogenotoxic damage, as was shown by an upward trend in the frequency of nuclear abnormalities identified in groups 1 (alcohol + tobacco + at least one illicit drug) and 2 (tobacco + at least one illicit drug). Furthermore, a positive correlation was found in the different groups, between the years and the amount of consumption of some drugs (alcohol, methamphetamine, and tobacco) with cytotoxicity markers such as KL, KX, and PNs.

El sello de calidad FECYT, un reconocimiento y un estímulo para Archivos / The FECYT seal of quality, a recognition and a stimulus for Archivos

Un año más, mediante esta nota editorial, damos cuenta de los principales avan-ces de nuestra revista y las estadísticas editoriales.En cuanto a las estadísticas editoriales, que se detallan en los apartados poste-riores, podemos afirmar que son las de una revista consolidada: flujo nutrido y constante de trabajos recibidos/publicados, tasas de aceptación y rechazo pro-porcionadas, tiempos de gestión razonables y diversidad en las autorías.El logro más destacable del 2023 fue superar con éxito el proceso de evaluación de la Octava edición de Evaluación de la calidad editorial y científica de las revistas científicas españolas, comúnmente conocido como ‘Sello FECYT’.El Sello de Calidad FECYT (Figura 1) identifica a aquellas publicaciones científicas que cumplen unos requisitos de profesionalización internacionalmente reconoci-dos. Gracias a este distintivo, muchas revistas científicas se han posicionado de manera importante en el ámbito nacional e internacional Este reconocimiento lo otorga la FECYT por un periodo de un año desde la resolu-ción definitiva, y la evaluación para su renovación se realizará de oficio por parte de la Fundación una vez finalizado dicho periodo (AU)

BRAF Inhibitors in Metastatic Colorectal Cancer and Mechanisms of Resistance: A Review of the Literature.

Metastatic colorectal cancer (mCRC) with mutated BRAF exhibits distinct biological and molecular features that set it apart from other subtypes of CRC. Current standard treatment for these tumors involves a combination of chemotherapy (CT) and VEGF inhibitors. Recently, targeted therapy against BRAF and immunotherapy (IT) for cases with microsatellite instability (MSI) have been integrated into clinical practice. While targeted therapy has shown promising results, resistance to treatment eventually develops in a significant portion of responsive patients. This article aims to review the available literature on mechanisms of resistance to BRAF inhibitors (BRAFis) and potential therapeutic strategies to overcome them.

Localized Donor Area Acute Telogen Effluvium following Follicular Unit Extraction: Key Trichoscopic Findings.

Introduction: Telogen effluvium is a form of non-scarring alopecia characterized by an increased hair shedding rate induced by mechanical or inflammatory factors. Case Report: A 27-year-old healthy male patient presented with several itchy alopecic patches in the occipital region. The patient had undergone a follicular unit extraction 6 weeks before with complete recovery after 1 week. Upon trichoscopy, we found empty follicular openings, short regrowing hairs, and coudability hairs. A diagnosis of acute telogen effluvium was made, and the patient was started on betamethasone lotion for daily use as a means to treat pruritus. After 1 month, the patient presented an almost complete response. Conclusion: While acute telogen effluvium is commonly seen in the receptor area after a hair transplant, the incidence of the donor region as a presentation is unknown. Common trichoscopic findings in telogen effluvium include empty follicular openings, short regrowing hairs, and lack of other signs usually seen in other types of alopecia. This description was consistent with what we found in our patient. Trichoscopic findings can help in the diagnosis, and understanding its natural course, physicians can reassure the patient about the self-resolutive outcome of this condition.

Negation recognition in clinical natural language processing using a combination of the NegEx algorithm and a convolutional neural network.

BACKGROUND: Important clinical information of patients is present in unstructured free-text fields of Electronic Health Records (EHRs). While this information can be extracted using clinical Natural Language Processing (cNLP), the recognition of negation modifiers represents an important challenge. A wide range of cNLP applications have been developed to detect the negation of medical entities in clinical free-text, however, effective solutions for languages other than English are scarce. This study aimed at developing a solution for negation recognition in Spanish EHRs based on a combination of a customized rule-based NegEx layer and a convolutional neural network (CNN). METHODS: Based on our previous experience in real world evidence (RWE) studies using information embedded in EHRs, negation recognition was simplified into a binary problem ('affirmative' vs. 'non-affirmative' class). For the NegEx layer, negation rules were obtained from a publicly available Spanish corpus and enriched with custom ones, whereby the CNN binary classifier was trained on EHRs annotated for clinical named entities (cNEs) and negation markers by medical doctors. RESULTS: The proposed negation recognition pipeline obtained precision, recall, and F1-score of 0.93, 0.94, and 0.94 for the 'affirmative' class, and 0.86, 0.84, and 0.85 for the 'non-affirmative' class, respectively. To validate the generalization capabilities of our methodology, we applied the negation recognition pipeline on EHRs (6,710 cNEs) from a different data source distribution than the training corpus and obtained consistent performance metrics for the 'affirmative' and 'non-affirmative' class (0.95, 0.97, and 0.96; and 0.90, 0.83, and 0.86 for precision, recall, and F1-score, respectively). Lastly, we evaluated the pipeline against two publicly available Spanish negation corpora, the IULA and NUBes, obtaining state-of-the-art metrics (1.00, 0.99, and 0.99; and 1.00, 0.93, and 0.96 for precision, recall, and F1-score, respectively). CONCLUSION: Negation recognition is a source of low precision in the retrieval of cNEs from EHRs' free-text. Combining a customized rule-based NegEx layer with a CNN binary classifier outperformed many other current approaches. RWE studies highly benefit from the correct recognition of negation as it reduces false positive detections of cNE which otherwise would undoubtedly reduce the credibility of cNLP systems.

Financing repurposed drugs for rare diseases: a case study of Unravel Biosciences.

BACKGROUND: We consider two key challenges that early-stage biotechnology firms face in developing a sustainable financing strategy and a sustainable business model: developing a valuation model for drug compounds, and choosing an appropriate operating model and corporate structure. We use the specific example of Unravel Biosciences-a therapeutics platform company that identifies novel drug targets through off-target mechanisms of existing drugs and then develops optimized new molecules-throughout the paper and explore a specific scenario of drug repurposing for rare genetic diseases. RESULTS: The first challenge consists of producing a realistic financial valuation of a potential rare disease repurposed drug compound, in this case targeting Rett syndrome. More generally, we develop a framework to value a portfolio of pairwise correlated rare disease compounds in early-stage development and quantify its risk profile. We estimate the probability of a negative return to be [Formula: see text] for a single compound and [Formula: see text] for a portfolio of 8 drugs. The probability of selling the project at a loss decreases from [Formula: see text] (phase 3) for a single compound to [Formula: see text] (phase 3) for the 8-drug portfolio. For the second challenge, we find that the choice of operating model and corporate structure is crucial for early-stage biotech startups and illustrate this point with three concrete examples. CONCLUSIONS: Repurposing existing compounds offers important advantages that could help early-stage biotech startups better align their business and financing issues with their scientific and medical objectives, enter a space that is not occupied by large pharmaceutical companies, and accelerate the validation of their drug development platform.

Holarctic Species in the Pluteus podospileus Clade: Description of Six New Species and Reassessment of Old Names.

We studied the taxonomy of Pluteus podospileus and similar species using morphological and molecular (nrITS, TEF1-α) data, including a detailed study of the type collections of P. inflatus var. alneus, Pluteus minutissimus f. major, and P. granulatus var. tenellus. Within the P. podospileus complex, we phylogenetically confirmed six species in Europe, five in Asia, and eight in North America. Based on our results, we recognize P. seticeps as a separate species occurring in North America, while P. podospileus is limited to Eurasia. We describe six new species and a new variety: P. absconditus, P. fuscodiscus, P. gausapatus, P. inexpectatus, P. millsii, and P. notabilis and its variety, P. notabilis var. insignis. We elevate Pluteus seticeps var. cystidiosus to species rank as Pluteus cystidiosus. Based on the holotype of P. inflatus var. alneus, collections of P. inflatus identified by Velenovský, and several modern collections, we resurrect the name P. inflatus. Based on molecular analyses of syntypes of Pluteus minutissimus f. major and a holotype of Pluteus granulatus var. tenellus, we synonymize them under P. inflatus. We also increase our knowledge about the morphology and distribution of P. cutefractus.

Single-cell lineage capture across genomic modalities with CellTag-multi reveals fate-specific gene regulatory changes.

Complex gene regulatory mechanisms underlie differentiation and reprogramming. Contemporary single-cell lineage-tracing (scLT) methods use expressed, heritable DNA barcodes to combine cell lineage readout with single-cell transcriptomics. However, reliance on transcriptional profiling limits adaptation to other single-cell assays. With CellTag-multi, we present an approach that enables direct capture of heritable random barcodes expressed as polyadenylated transcripts, in both single-cell RNA sequencing and single-cell Assay for Transposase Accessible Chromatin using sequencing assays, allowing for independent clonal tracking of transcriptional and epigenomic cell states. We validate CellTag-multi to characterize progenitor cell lineage priming during mouse hematopoiesis. Additionally, in direct reprogramming of fibroblasts to endoderm progenitors, we identify core regulatory programs underlying on-target and off-target fates. Furthermore, we reveal the transcription factor Zfp281 as a regulator of reprogramming outcome, biasing cells toward an off-target mesenchymal fate. Our results establish CellTag-multi as a lineage-tracing method compatible with multiple single-cell modalities and demonstrate its utility in revealing fate-specifying gene regulatory changes across diverse paradigms of differentiation and reprogramming.

Mining the chemical diversity of the hemp seed (Cannabis sativa L.) metabolome: discovery of a new molecular family widely distributed across hemp.

Hemp (Cannabis sativa L.) is a widely researched industrial crop with a variety of applications in the pharmaceutical, nutraceutical, food, cosmetic, textile, and materials industries. Although many of these applications are related to its chemical composition, the chemical diversity of the hemp metabolome has not been explored in detail and new metabolites with unknown properties are likely to be discovered. In the current study, we explored the chemical diversity of the hemp seed metabolome through an untargeted metabolomic study of 52 germplasm accessions to 1) identify new metabolites and 2) link the presence of biologically important molecules to specific accessions on which to focus on in future studies. Multivariate analysis of mass spectral data demonstrated large variability of the polar chemistry profile between accessions. Five main groups were annotated based on their similar metabolic fingerprints. The investigation also led to the discovery of a new compound and four structural analogues, belonging to a previously unknown chemical class in hemp seeds: cinnamic acid glycosyl sulphates. Although variability in the fatty acid profiles was not as marked as the polar components, some accessions had a higher yield of fatty acids, and variation in the ratio of linoleic acid to α-linolenic acid was also observed, with some varieties closer to 3:1 (reported as optimal for human nutrition). We found that that cinnamic acid amides and lignanamides, the main chemical classes of bioactive metabolites in hemp seed, were more concentrated in the Spanish accession Kongo Hanf (CAN58) and the French accession CAN37, while the Italian cultivar Eletta Campana (CAN48) demonstrated the greatest yield of fatty acids. Our results indicate that the high variability of bioactive and novel metabolites across the studied hemp seed accessions may influence claims associated with their commercialization and inform breeding programs in cultivar development.

AURKA Gene Variants rs1047972, and rs8173 Are Associated With Breast Cancer.

PURPOSE: Association between variants rs1047972 and rs8173 of the AURKA gene in healthy women and breast cancer (BC) in a Mexican population. METHODS: Genomic DNA samples from 409 healthy women and 572 patients with BC were analyzed for variants rs1047972 and rs8173 of the AURKA gene by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: TT genotype (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.22-5.11; p = 0.0015) and the T allele (OR, 1.16; 95% CI, 1.23-2.12; p = 0.0007) of the rs1047972 variant were associated as risk susceptibility for BC relative to the control group. Contrarily, the GG genotype (OR, 0.64; 95% CI, 0.43-0.94; p = 0.029) was associated as a protective factor of susceptibility of BC of the variant rs8173 of the AURKA gene. Differences were observed in the patients with BC who were carriers of the CT genotype of the rs1047972 variant with overweight, obesity, estrogen receptor-positive plus obesity, Ki-67 (≥ 20%) plus history familial positive of cancer; and for variant rs8173 the BC patients who were CG carriers and presented chemotherapy gastric toxicity, hormonal receptor positive plus chemotherapy gastric toxicity, and menopause status plus chemotherapy gastric toxicity (p < 0.05). Two common haplotypes were identified in the study groups: CG and TC genotypes, were associated as a protective and risk factor, respectively (p < 0.05). CONCLUSION: Variants rs1047972 and rs8173 of the AURKA gene and the TC haplotype were associated as risk susceptibility factors for BC in this population.

Association of the rs8720 and rs12587 KRAS Gene Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico.

Colorectal cancer (CRC) is a major global health challenge and one of the top 10 cancers in Mexico. Lifestyle and genetic factors influence CRC development, prognosis, and therapeutic response; identifying risk factors, such as the genes involved, is critical to understanding its behavior, mechanisms, and prognosis. The association between KRAS gene variants (rs8720 and rs12587) and CRC in the Mexican population was analyzed. We performed in silico analysis and analyzed 310 healthy individuals and 385 CRC patients using TaqMan assays and real-time PCR. The CC and GG genotypes of rs8720 and rs12587 were identified as CRC risk factors (p < 0.05). The CC and TC genotypes of the rs8720 were associated with rectal cancer, age over 50 years, moderately differentiated histology, and advanced cancer stage. TG and GG genotypes of the rs12587 variant were a risk factor in the CRC group, in patients with stage I-II, males, and stage III-IV non-chemotherapy response. The TG haplotype is protected against CRC. The combined CCGG genotype was linked to CRC risk. In silico analysis revealed that the rs12587 and rs8720 variants could influence KRAS gene regulation via miRNAs. In conclusion, rs8720 and rs12587 variants of the KRAS gene were associated with CRC risk and could influence KRAS regulation via miRNAs.

Micronuclei and nuclear buds in amniotic tissue of rats treated with cyclophosphamide.

Fetal development can be altered by DNA damage caused by maternal exposure to chemical, physical, or biological agents during gestation. One method of assessing genotoxicity is to detect micronuclei (MNs) and/or nuclear abnormalities. This can be performed in vivo and requires only frequently dividing tissues, such as amniotic tissue (AT), which is in contact with the fetal environment and is composed of very thin layers of cells. This study evaluated the presence of MNs, nucleoplasmic bridges, and nuclear buds (NBs) in the fetal AT following maternal exposure to cyclophosphamide (CP) during pregnancy. Pregnant Wistar rats were divided into a negative control group and an experimental group that was orally administered CP (10 mg/kg). Daily blood smears were obtained from pregnant rats on days 14-19 of gestation. The rats were dissected, and fetal ATs were obtained on the 19th day of gestation. The MN and NB frequencies in AT cells were analyzed using a fluorescence microscope (100 ×). Micronucleated erythrocytes in the peripheral blood of the control rats were also assessed. Micronucleated polychromatic erythrocyte frequencies were significantly higher than those in the controls. Polychromatic erythrocyte frequencies were lower in CP-treated rats than in controls at 48-120 h. Fetuses in the CP-treated group also showed a significant increase in MNs and NBs in AT cells. In conclusion, AT could be used for analyzing MNs and NBs in rats following maternal exposure to a genotoxic agent and as a viable alternative for analyzing the integrity of fetal DNA during gestation.

Single-cell lineage tracing reveals hierarchy and mechanism of adipocyte precursor maturation.

White adipose tissue is crucial in various physiological processes. In response to high caloric intake, adipose tissue may expand by generating new adipocytes. Adipocyte precursor cells (progenitors and preadipocytes) are essential for generating mature adipocytes, and single-cell RNA sequencing provides new means to identify these populations. Here, we characterized adipocyte precursor populations in the skin, an adipose depot with rapid and robust generation of mature adipocytes. We identified a new population of immature preadipocytes, revealed a biased differentiation potential of progenitor cells, and identified Sox9 as a critical factor in driving progenitors toward adipose commitment, the first known mechanism of progenitor differentiation. These findings shed light on the specific dynamics and molecular mechanisms underlying rapid adipogenesis in the skin.

Chronic Administration of Diethylnitrosamine and 2-Acetylaminofluorene Induces Hepatocellular Carcinoma in Wistar Rats.

This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a hepatocarcinogenesis model induced by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Thirteen rats weighing 180 to 200 g were divided into two groups: control and treated. Rats in the treated group were administered an intraperitoneal (i.p.) injection of DEN (50 mg/kg/week) and an intragastric (i.g.) dose of 2-AAF (25 mg/kg/week) for 18 weeks. The treated group had significant increases in their total cholesterol, HDL-C, AST, ALT, ALKP, and GGT levels. Furthermore, a histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa that were distributed between the portal triads and collagen fibers through the hepatic sinusoids. The gene expressions of 24 genes related to fibrosis, inflammation, apoptosis, cell growth, angiogenesis, lipid metabolism, and alpha-fetoprotein (AFP) were analyzed; only TGFß, COL1α1, CYP2E1, CAT, SOD, IL6, TNF-α, and ALB showed significant differences when both groups were compared. Additionally, lung histopathological alterations were found in the treated group, suggesting metastasis. In this model, the chronic administration of DEN+2-AAF induces characteristic alterations of hepatocellular carcinoma in Wistar rats without AFP gene expression changes, highlighting different signatures in hepatocellular carcinoma heterogeneity.

Indocyanine green angiography-guided thyroidectomy versus conventional thyroidectomy for preserving parathyroid function: study protocol for a randomized single-blind controlled trial.

Introduction: Angiography with indocyanine green (ICG) fluorescence performed before thyroidectomy would allow identification of the vascularization of parathyroid glands, maximizing efforts for preserving functioning glands intraoperatively. The rationale of the study was based on the hypothesis that showing the vascular pattern of the parathyroid glands by means of ICG angiography before performing the thyroidectomy could prevent permanent hypoparathyroidism. Methods and analysis: We propose a randomized single-blind controlled and multicenter clinical trial to assess the efficacy and safety of ICG angiography-guided thyroidectomy to identify the vascular pattern of the parathyroid glands versus conventional thyroidectomy in patients scheduled for elective total thyroidectomy. Patients will be randomized 1:1 to ICG angiography-guided thyroidectomy (experimental group) or conventional thyroidectomy (control group). Patients in the experimental group will undergo ICG angiography before thyroidectomy to identify the feeding vessels of the parathyroid glands and then, post-thyroidectomy ICG angiography to predict immediate parathyroid gland function by scoring the degree of fluorescence of the glands. Patients in the control group will undergo post-thyroidectomy ICG angiography only. The primary outcome measure will be the rate of patients with permanent hypoparathyroidism. Secondary outcome measures will be rate of postoperative hypoparathyroidism, the percentage of well vascularized parathyroid glands remaining in situ, the levels of iPTH and serum calcium after surgery and the influence of the type of vascular pattern of the parathyroid glands over these outcomes, as well as the safety profile of ICG angiography. Discussion: The results will contribute to adopt a new surgical strategy based on intraoperative ICG angiography before performing total thyroidectomy, according to which the rate of permanent hypoparathyroidism could be substantially reduced. Clinical trial registration: ClinicalTrials.gov. identifier NCT05573828.

Effects of GLP-1 receptor agonists on neurological complications of diabetes.

Emerging evidence suggests that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) could be an interesting treatment strategy to reduce neurological complications such as stroke, cognitive impairment, and peripheral neuropathy. We performed a systematic review to examine the evidence concerning the effects of GLP-1 RAs on neurological complications of diabetes. The databases used were Pubmed, Scopus and Cochrane. We selected clinical trials which analysed the effect of GLP-1 RAs on stroke, cognitive impairment, and peripheral neuropathy. We found a total of 19 studies: 8 studies include stroke or major cardiovascular events, 7 involve cognitive impairment and 4 include peripheral neuropathy. Semaglutide subcutaneous and dulaglutide reduced stroke cases. Liraglutide, albiglutide, oral semaglutide and efpeglenatide, were not shown to reduce the number of strokes but did reduce major cardiovascular events. Exenatide, dulaglutide and liraglutide improved general cognition but no significant effect on diabetic peripheral neuropathy has been reported with GLP-1 RAs. GLP-1 RAs are promising drugs that seem to be useful in the reduction of some neurological complications of diabetes. However, more studies are needed.