The Hybrid Filler Technique: A 5-Year Retrospective Analysis.

BACKGROUND: The combination of calcium hydroxylapatite (CaHA) and hyaluronic acid fillers (CPM-HA, cohesive polydensified matrix-based hyaluronic acid fillers, Belotero® range, Merz Pharmaceuticals GmbH, Frankfurt, Germany), known as hybrid fillers, has emerged as a popular approach in aesthetic medicine. Premixed CaHA with CPM-HA offers several advantages, including enhanced tissue elevation and reduced early volume loss after injection. OBJECTIVE: The objective of the present study is to assess the safety of premixing CaHA and CPM-HA fillers for rejuvenation purposes or as an aesthetic harmonization treatment. METHODS: This retrospective study presents the clinical experience of two expert injectors who consistently used premixed CaHA and CPM-HA fillers for aesthetic treatments between March 2018 and December 2023. The premixed hybrid formulation was standardized and administered following a published protocol. A total of 2112 patients were treated, with meticulous follow-up over a minimum of one year. RESULTS: In the 2112 patients treated, only 5 minor adverse events (0.24%) were reported. The adverse events consisted of 4 non-inflammatory nodules of which 2 completely resolved with hyaluronidase, and 1 case of transient edema. Secondary findings consist of the treated areas, type of CPM-HA used and mixing ratios that were applied. CONCLUSION: The results from the current retrospective study, with the largest published cohort so far, are consistent with prior publications and strongly support a good safety profile of the CaHA:CPM-HA hybrid blend. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Premaxillary Graft with Costal Cartilage in Rhinoplasty: A Technique to Support the Nasal Tip.

BACKGROUND: Rhinoplasty is an ever-evolving field, with innovative techniques continually being developed to enhance both aesthetic and functional outcomes for patients. Increasingly, research has focused on the integral role of the facial skeleton in providing nasal support and projection. Central to the structural integrity of the nose is the maxillary bone, which occupies a pivotal position in the midface. METHODS: The objective of this study is to assess the outcomes of patients who underwent rhinoplasty involving the placement of a premaxillary graft fashioned from costal cartilage. The study aims to evaluate the graft's tolerance, stability, and potential complications. The patient cohort comprised individuals who underwent open approach rhinoplasty with premaxillary insufficiency, necessitating the placement of a costal cartilage graft anterior to the nasal spine, performed by the same surgeon between 2021 and 2022. A total of 38 patients, consisting of 5 men and 33 women aged between 18 and 58 years, were operated on during this period. RESULTS: Consistent maintenance of tip support was observed across all cases. Among the 33 patients, 20 were randomly chosen for a comparative assessment of the nasolabial angle in preoperative and postoperative profile photographs, demonstrating a statistically significant improvement. No complications such as graft displacement, scarring, extrusion, or infections were reported. CONCLUSION: The use of a premaxillary graft with costal cartilage appears to be a viable, well-tolerated option with favorable long-term outcomes. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Requested a Different Doctor: Developing and Evaluating an OSCE Assessing Core Skills in Supporting Trainees Facing Patient Discrimination.

BACKGROUND: Suboptimal support for colleagues experiencing discrimination can adversely impact clinician well-being and patient care. AIM: To describe resident performance and experience during an Objective Structured Clinical Examination (OSCE) case centered on supporting a trainee facing discrimination to inform enhanced, supportive learning environments. SETTING: Formative, internal medicine OSCE at a simulation center. PARTICIPANTS: 148 second-year residents across 2018, 2019, 2021, 2022. PROGRAM DESCRIPTION: Residents had 10 min to support a Muslim standardized intern (SI) experiencing discrimination from a patient. The SI rated resident performance across Supervision, Relationship Development, and Support domains and provided written feedback. Post-OSCE evaluations elicited resident reflections on case challenges. PROGRAM EVALUATION: Proficient residents (≥ 80% average score across domains, n = 85) performed better in all items, except in not acting defensive and collaborating with SI to develop follow-up plan, compared to non-proficient residents (n = 65). The SI described effective approaches to feeling supported, including using empathetic statements, stating personal stance on discrimination, exhibiting supportive body language, and verbalizing support. Stating knowledge of situation upfront was an area of improvement. Residents found engaging the distressed SI difficult. DISCUSSION: Use of an explicit discrimination OSCE case can help identify effective approaches to supporting targets of discriminatory patients to inform future training.

Design Optimization of a Novel Catalytic Approach for Transglucosylated Isomaltooligosaccharides into Dietary Polyols Structures by Leuconostoc mesenteroides Dextransucrase.

Polyols, or sugar alcohols, are widely used in the industry as sweeteners and food formulation ingredients, aiming to combat the incidence of diet-related Non-Communicable Diseases. Given the attractive use of Generally Regarded As Safe (GRAS) enzymes in both academia and industry, this study reports on an optimized process to achieve polyols transglucosylation using a dextransucrase enzyme derived from Leuconostoc mesenteroides. These enzyme modifications could lead to the creation of a new generation of glucosylated polyols with isomalto-oligosaccharides (IMOS) structures, potentially offering added functionalities such as prebiotic effects. These reactions were guided by a design of experiment framework, aimed at maximizing the yields of potential new sweeteners. Under the optimized conditions, dextransucrase first cleared the glycosidic bond of sucrose, releasing fructose with the formation of an enzyme-glucosyl covalent intermediate complex. Then, the acceptor substrate (i.e., polyols) is bound to the enzyme-glucosyl intermediate, resulting in the transfer of glucosyl unit to the tested polyols. Structural insights into the reaction products were obtained through nuclear maneic resonance (NMR) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analyses, which revealed the presence of linear α(1 → 6) glycosidic linkages attached to the polyols, yielding oligosaccharide structures containing from 4 to 10 glucose residues. These new polyols-based oligosaccharides hold promise as innovative prebiotic sweeteners, potentially offering valuable health benefits.

Relationship between Problematic Internet Use and Depression in Young Latin American College Students.

(1) Problematic Internet use (PIU) in young people is a topic of great interest both in the field of addictions and mental health, but scientific evidence is limited in Latin America. The aim was to analyze the relationship between PIU and depression in Latin American college students. (2) Methods: The sample consisted of 1828 college students (63.7% women), aged between 18-30 years (M = 21.64 years). (3) Results: PIU was detected in 40.2% of cases, and severe or moderately severe depression in 31.7%. Rates of severe depression in students with PIU were 3.02 times higher than in those without PIU (χ2(3) = 168.443; p < 0.000). The presence of PIU was also statistically significantly higher among youth with depressive symptoms. Linear and logistic regression models for predicting PIU, show how the depression level constitutes a risk factor for PIU: seven times higher for severe depression; more than five times higher for moderate depression; and more than two times for mild depression. (4) Conclusions: There is a clear association between depression and PIU, suggesting that a higher level of depression would act as a predictor of PIU. However, this finding is exploratory. Future studies should clarify the directionality of the relationship between both variables.

Absence of Pathogenic Mutations and Strong Association With HLA-DRB1*11:01 in Statin-Naïve Early-Onset Anti-HMGCR Necrotizing Myopathy.

BACKGROUND AND OBJECTIVES: Immune-mediated necrotizing myopathy (IMNM) caused by antibodies against 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is an inflammatory myopathy that has been epidemiologically correlated with previous statin exposure. We characterized in detail a series of 11 young statin-naïve patients experiencing a chronic disease course mimicking a limb-girdle muscular dystrophy. With the hypothesis that HMGCR upregulation may increase immunogenicity and trigger the production of autoantibodies, our aim was to expand pathophysiologic knowledge of this distinct phenotype. METHODS: Clinical and epidemiologic data, autoantibody titers, creatine kinase (CK) levels, response to treatment, muscle imaging, and muscle biopsies were assessed. HMGCR expression in patients' muscle was assessed by incubating sections of affected patients with purified anti-HMGCR+ serum. Whole-exome sequencing (WES) with a special focus on cholesterol biosynthesis-related genes and high-resolution human leukocyte antigen (HLA) typing were performed. RESULTS: Patients, aged 3-25 years and mostly female (90.9%), presented with subacute proximal weakness progressing over many years and high CK levels (>1,000 U/L). Diagnostic delay ranged from 3 to 27 years. WES did not reveal any pathogenic variants. HLA-DRB1*11:01 carrier frequency was 60%, a significantly higher proportion than in the control population. No upregulation or mislocalization of the enzyme in statin-exposed or statin-naïve anti-HMGCR+ patients was observed, compared with controls. DISCUSSION: WES of a cohort of patients with dystrophy-like anti-HMGCR IMNM did not reveal any common rare variants of any gene, including cholesterol biosynthesis-related genes. HLA analysis showed a strong association with HLA-DRB1*11:01, previously mostly described in statin-exposed adult patients; consequently, a common immunogenic predisposition should be suspected, irrespective of statin exposure. Moreover, we were unable to conclusively demonstrate muscle upregulation/mislocalization of HMGCR in IMNM, whether or not driven by statins.

Adult Pompe disease: Analysis of 13 patients. / Enfermedad de Pompe del adulto: análisis de 13 pacientes.

INTRODUCTION: Pompe Disease (PD) is a lysosomal disorder caused by a deficiency of the enzyme acid alpha-glucosidase (GAA), primarily manifesting as a progressive myopathy with early respiratory involvement. Enzyme replacement therapy (ERT) is available since 2006. MATERIALS AND METHODS: We describe 13 patients with partial GAA deficiency, followed at Hospital 12 de Octubre, 8 of whom were receiving treatment. RESULTS: 8 patients exhibit symptoms, all with late onset. They display axial and proximal weakness predominantly in the lower limbs but maintain autonomous gait. Five patients require non-invasive mechanical ventilation due to respiratory insufficiency. All symptomatic patients receive ERT, and in 7/8 (87.5%), there is a decline in motor and pulmonary function after an average of 8.25 years of treatment (baseline and post-treatment FVC and 6MWT mean 86.6% vs 70.8% and 498 vs 430 meters, respectively). CONCLUSION: Not all patients with partial GAA deficiency experience symptoms of PD, and symptomatic patients, despite ERT with recombinant alpha-glucosidase, mostly experience a gradual decline in motor and respiratory function.

Attitudes Toward Implicit Bias Among Athletic Trainers.

Implicit biases are attitudes, emotions, or stereotypes that occur in an unconscious manner and have the potential to negatively affect behaviors, actions, and decisions. Recent studies have suggested that even when certain factors are controlled for, health care workers do not provide equitable care to patients from different demographics. When patients are not receiving equitable health care, there is a potential for disparities in patient-related outcomes. The purpose of this study was to determine attitudes toward implicit bias among athletic trainers. A secondary purpose of this study was to assess differences and correlations between attitudes toward implicit bias and demographic factors including age, years of experience, gender identity, sexual orientation, and race. Participants were recruited for this study by emailing athletic trainers from publicly available staff directories at institutions of higher education and high schools, and athletic training education program directors. The survey consisted of questions gathering demographic information and questions taken from the Attitudes Toward Implicit Bias Instrument. A total of 218 athletic trainers (age = 38 [11] y, years of certified experience = 14 [11] y) opened and completed the survey. On average, participants scored 71.0 [11.2] on the Attitudes Toward Implicit Bias Instrument. This mean score indicated that the average participant felt that implicit bias had the potential to negatively impact patient care and needed to be addressed through education. There was a significant, negligible negative correlation between age and attitudes toward implicit bias (r[216] = -.157, P = .02). Examining implicit bias among athletic trainers warrants further research to understand how implicit bias can negatively affect access to equitable health care opportunities. The development of high-quality interventions for identifying and addressing implicit bias is crucial to ensuring optimal patient outcomes in athletic training and all medical settings.

Decoding the muscle transcriptome of patients with late onset Pompe disease reveals markers of disease progression.

Late-onset Pompe Disease (LOPD) is a rare genetic disorder caused by the deficiency of acid alpha-glucosidase leading to progressive cellular dysfunction due to the accumulation of glycogen in the lysosome. The mechanism of relentless muscle damage - a classic manifestation of the disease - has been extensively studied by analysing the whole muscle tissue; however, little, if any, is known about transcriptional heterogeneity among nuclei within the multinucleated skeletal muscle cells. This is the first report of application of single nuclei RNA sequencing to uncover changes in the gene expression profile in muscle biopsies from eight patients with LOPD and four muscle samples from age and gender matched healthy controls. We matched these changes with histology findings using GeoMx Spatial Transcriptomics to compare the transcriptome of control myofibers from healthy individuals with non-vacuolated (histologically unaffected) and vacuolated (histologically affected) myofibers of LODP patients. We observed an increase in the proportion of slow and regenerative muscle fibers and macrophages in LOPD muscles. The expression of the genes involved in glycolysis was reduced, whereas the expression of the genes involved in the metabolism of lipids and amino acids was increased in non-vacuolated fibers, indicating early metabolic abnormalities. Additionally, we detected upregulation of autophagy genes, and downregulation of the genes involved in ribosomal and mitochondrial function leading to defective oxidative phosphorylation. The upregulation of the genes associated with inflammation, apoptosis and muscle regeneration was observed only in vacuolated fibers. Notably, enzyme replacement therapy - the only available therapy for the disease - showed a tendency to restore metabolism dysregulation, particularly within slow fibers. A combination of single nuclei RNA sequencing and spatial transcriptomics revealed the landscape of normal and the diseased muscle, and highlighted the early abnormalities associated with the disease progression. Thus, the application of these two new cutting-edge technologies provided insight into the molecular pathophysiology of muscle damage in LOPD and identified potential avenues for therapeutic intervention.

Temporary Delayed Hypersensitivity Reaction to Botulinum Toxin-A After COVID-19 Vaccination: A Case Series.

PURPOSE: The occurrence of a hypersensitivity reaction with the injection of botulinum toxin type A (BTX-A) in cosmetic use is a rare complication. We report the largest case series of temporary delayed hypersensitivity reaction (DHR) with BTX-A following COVID-19 vaccination and the first cases to incobotulinum toxin A (incoBTX-A). METHODS: A retrospective multicentric case series of patients who developed a DHR to BTX-A after COVID-19 vaccination. RESULTS: Twelve patients were treated with BTX-A injections for the management of facial rhytids. The age range was between 29 and 45 years. Ten (83.3%) were female. Ten (83.3%) patients received incoBTX-A, and two received onabotulinum toxin A (onaBTX-A). All patients had COVID-19 vaccination (mRNA vaccine) between 1 and 7 months before. Within an average time of 24 h after BTX-A injection, all patients developed progressive facial swelling and erythema that were more prominent at the injection points. Intradermal allergic tests to BTX-A were performed in six (50%) patients, and the results were all negative. Adequate clinical control was achieved with systemic corticosteroids and antihistamines. After 1 year with no further vaccination, a new BTX-A treatment (provocation test) was performed in all patients with no secondary effects. CONCLUSION: Previous COVID-19 vaccination and the absence of new adverse events with further BTX-A injections suggest a temporary DHR. Clinicians should be aware of the importance of immunization history and its potential post-vaccine immunogenic effects with BTX-A. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Jawline Sharp Contouring With Hybrid Filler.

BACKGROUND: Having a well-defined jawline is a sign of youth and attractiveness among both men and women. Soft tissue fillers, such as calcium hydroxylapatite (CaHA) and hyaluronic acid (HA) fillers, offer nonsurgical alternatives for rejuvenating the lower face and enhancing the jawline. The aim of this study was to investigate the use of a premixed combination of HA with cohesive polydensified matrix technology (CPM, Belotero Intense, CPM-I) and CaHA to create a sharply defined jawline. METHODS: A total of 126 patients were enrolled in the study and treated with a premixed combination of CPM-I and CaHA using a retrograde fanning injection technique with cannulas. The injection volumes and product ratios were customized according to the patients' needs. RESULTS: The cohort consisted of 75 females and 51 males. The average injected volume of premixed CaHA:CPM-I was 5.83 mL. In the majority of patients, a 1:1 syringe ratio of CaHA:CPM-I was applied (n = 81, 64.2%). No adverse events were reported during the 6-month follow-up period. CONCLUSION: The hybrid filler approach investigated in this study shows promise for achieving well-defined, long-lasting jawline contours. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Ego4D: Around the World in 3,000 Hours of Egocentric Video.

We introduce Ego4D, a massive-scale egocentric video dataset and benchmark suite. It offers 3,670 hours of daily-life activity video spanning hundreds of scenarios (household, outdoor, workplace, leisure, etc.) captured by 931 unique camera wearers from 74 worldwide locations and 9 different countries. The approach to collection is designed to uphold rigorous privacy and ethics standards, with consenting participants and robust de-identification procedures where relevant. Ego4D dramatically expands the volume of diverse egocentric video footage publicly available to the research community. Portions of the video are accompanied by audio, 3D meshes of the environment, eye gaze, stereo, and/or synchronized videos from multiple egocentric cameras at the same event. Furthermore, we present a host of new benchmark challenges centered around understanding the first-person visual experience in the past (querying an episodic memory), present (analyzing hand-object manipulation, audio-visual conversation, and social interactions), and future (forecasting activities). By publicly sharing this massive annotated dataset and benchmark suite, we aim to push the frontier of first-person perception. Project page: https://ego4d-data.org/.

Guidelines for NGS procedures applied to prenatal diagnosis by the Spanish Society of Gynecology and Obstetrics and the Spanish Association of Prenatal Diagnosis.

OBJECTIVE: This document addresses the clinical application of next-generation sequencing (NGS) technologies for prenatal genetic diagnosis and aims to establish clinical practice recommendations in Spain to ensure uniformity in implementing these technologies into prenatal care. METHODS: A joint committee of expert obstetricians and geneticists was created to review the existing literature on fetal NGS for genetic diagnosis and to make recommendations for Spanish healthcare professionals. RESULTS: This guideline summarises technical aspects of NGS technologies, clinical indications in prenatal setting, considerations regarding findings to be reported, genetic counselling considerations as well as data storage and protection policies. CONCLUSIONS: This document provides updated recommendations for the use of NGS diagnostic tests in prenatal diagnosis. These recommendations should be periodically reviewed as our knowledge of the clinical utility of NGS technologies, applied during pregnancy, may advance.

Serum Folate, Red Blood Cell Folate, and Zinc Serum Levels Are Related with Gestational Weight Gain and Offspring's Birth-Weight of Adolescent Mothers.

BACKGROUND: Gestational weight gain below or above the Institute of Medicine recommendations has been associated with adverse perinatal and neonatal outcomes. Very few studies have evaluated the association between serum and red blood cell folate concentrations and gestational weight gain in adolescents. Additionally, zinc deficiency during pregnancy has been associated with impaired immunity, prolonged labor, preterm and post-term birth, intrauterine growth restriction, low birth weight, and pregnancy-induced hypertension. OBJECTIVE: The purpose of our study is to evaluate the association between serum concentrations of zinc, serum folate, and red blood cell folate, with the increase in gestational weight and the weight and length of the newborn in a group of adolescent mothers from Mexico City. RESULTS: In our study, 406 adolescent-neonate dyads participated. The adolescents' median age was 15.8 years old. The predominant socioeconomic level was middle-low (57.8%), single (57%), 89.9% were engaged in home activities, and 41.3% completed secondary education. Excessive gestational weight gain was observed in 36.7% of cases, while insufficient gestational weight gain was noted in 38.4%. Small for gestational age infants were observed in 20.9% of the sample. Low serum folate (OR 2.1, 95% CI 1.3-3.3), decreased red blood cell folate (OR 1.6, 95% CI 1.0-2.6), and reduced serum zinc concentrations (OR 3.3, 95% CI 2.1-5.2) were associated with insufficient gestational weight gain. Decreased serum zinc levels (OR 1.2, 95% CI 1.2-3.4) were linked to an increased probability of delivering a baby who is small for their gestational age. CONCLUSIONS: Low serum folate, red blood cell folate, and serum zinc concentrations were associated with gestational weight gain and having a small gestational age baby. Both excessive and insufficient gestational weight gain, as well as having a small gestational age baby, are frequent among adolescent mothers.

Evaluation of the neuroprotective effect of antipsychotics by serum quantification of protein S100B.

OBJECTIVE: This research delves into the intricate interplay between antipsychotic medications and neuroprotection focusing on the S100B protein-a central player in the regulation of neuroapoptotic activity. METHOD: Blood samples were collected to assess serum S100B protein levels using an immunoassay of immunoelectrochemiluminescence. The first two samples were collected with a 3-month interval between each, and the third sample was obtained 6 months after the previous one. Changes in S100B protein levels throughout the study were assessed using Friedman's ANOVA test. This was followed by the Wilcoxon signed-rank test with Bonferroni correction to account for multiple comparisons. RESULTS: This study involved 40 patients diagnosed with severe mental disorders (34 schizophrenia, 4 schizoaffective disorder, 1 bipolar disorder, and 1 borderline personality disorder). These patients had been receiving antipsychotic treatment for an average duration of 17 years. The results revealed that the S100B protein remained within physiological levels (median values 39.0 ng/L for the first sample, median values 41.0 ng/L for the second sample, and median values 40.5 ng/L for the third sample) with no significant changes (p = 0.287), with all anti-psychotic medicaments values consistently below 50 ng/L, a lower value compared to maximum range of 105 ng/L. Importantly, there were no significant differences in S100B protein levels between patients on monotherapy and those on combination antipsychotic therapy (p = 0.873), suggesting that combination therapy did not increase neuroapoptotic activity. CONCLUSIONS: These findings provide compelling evidence for the potential neuroprotective effects of long-term antipsychotic treatment in individuals with severe mental disorders. By maintaining physiological levels of the S100B protein, antipsychotic medications may help protect against neuronal damage and dysfunction. This research contributes valuable insights into the neuroprotective mechanisms of antipsychotic drugs, enhancing our understanding of their potential benefits in the treatment of severe mental disorders.

Hand Rejuvenation with Customizable Hybrid Fillers: Premixed Calcium Hydroxyapatite and Hyaluronic Acid.

INTRODUCTION: Hand aging is a prevalent concern characterized by the atrophy of local soft tissues and increased visibility of vessels and tendons. Hyaluronic acid (HA) and calcium hydroxyapatite (CaHA) are well-established treatments for addressing this issue. While hybrid filler containing HA and CaHA has been proposed for facial rejuvenation, studies investigating its efficacy for hand rejuvenation are lacking. OBJECTIVE: This study aims to assess the safety and efficacy of a premixed hybrid filler containing calcium hydroxyapatite (CaHA) and hyaluronic acid (HA) for hand rejuvenation. METHODS: A prospective, double-blind, controlled trial was conducted. The control arm (CA) received conventional subdermal treatment with CaHA at a 1:1 dilution. The intervention arm (IA) underwent hybrid treatment, consisting of CaHA at a 1:1 dilution combined with 1 ml of low-density HA. Evaluation was performed subjectively using the Global Aesthetic Improvement Scale (GAIS) and the Manchester Hand Grading System (MHGS), and objectively using cutometry, corneometry, and ultrasound. RESULTS: Both the CA and the IA exhibited high rates of patient satisfaction and satisfaction as assessed by blinded evaluators. Although numerical superiority was observed in the IA, no statistical difference was found between the two groups. Significant improvements in hydration, elasticity, and skin thickness were observed in both arms, with no discernible difference between them. Greater ultrasound echogenicity was noted in the IA, which, as indicated by existing literature, may suggest enhanced biostimulation. No adverse effects were reported in either arm. CONCLUSION: Premixed filler containing HA and CaHA for hand rejuvenation appears to be a safe and effective approach. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Sex Differences in Transthyretin Cardiac Amyloidosis: Unraveling the Complexities in Epidemiology, Pathophysiology, Diagnosis, and Treatment.

Transthyretin cardiac amyloidosis (ATTR-CA) is characterised by the deposition of transthyretin amyloid fibrils in the heart. ATTR-CA affects both men and women although there is evidence of sex differences in prevalence and clinical presentation. PURPOSE OF REVIEW: This review paper aims to comprehensively examine and synthesise the existing literature on sex differences in ATTR-CA. RECENT FINDINGS: The prevalence of ATTR-CA is higher in males although the male predominance is more apparent in older patients in the wild type form and in TTR genetic variants that predominantly result in a cardiac phenotype in the hereditary variant. Women tend to have less left ventricular hypertrophy (LVH) and a higher ejection fraction at clinical presentation which may contribute to a later diagnosis although the prognosis appears to be similar in both sexes. Female sex is a predictor of a good response to tafamidis 20 mg in TTR polyneuropathy but otherwise there are no data on sex differences in the efficacy of other treatments for ATTR-CA. It is crucial to define specific sex differences in ATTR-CA. A lower cut-off value for LVH in women may be needed to improve diagnosis. It is necessary to increase female representation in clinical trials to better understand possible sex differences in therapeutic management.

Remarkable clinical improvement with oral nucleoside treatment in a patient with adult-onset TK2 deficiency: A case report.

OBJECTIVES: Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile mitochondrial DNA depletion syndromes to adult-onset mitochondrial myopathies characterized by ophthalmoplegia-plus phenotypes with early respiratory involvement. Treatment with pyrimidine nucleosides has recently shown striking effects on survival and motor outcomes in the more severe infantile-onset clinical forms. We present the response to treatment in a patient with adult-onset TK2d. METHODS: An adult with ptosis, ophthalmoplegia, facial, neck, and proximal muscle weakness, non-invasive nocturnal mechanical ventilation, and dysphagia due to biallelic pathogenic variants in TK2 received treatment with 260 mg/kg/day of deoxycytidine (dC) and deoxythymidine (dT) under a Compassionate Use Program. Prospective motor and respiratory assessments are presented. RESULTS: After 27 months of follow-up, the North Star Ambulatory Assessment improved by 11 points, he walked 195 m more in the 6 Minute-Walking-Test, ran 10 s faster in the 100-meter time velocity test, and the Forced Vital Capacity stabilized. Growth Differentiation Factor-15 (GDF15) levels, a biomarker of respiratory chain dysfunction, normalized. The only reported side effect was dose-dependent diarrhea. DISCUSSION: Treatment with dC and dT can significantly improve motor performance and stabilize respiratory function safely in patients with adult-onset TK2d.