Natural Outcome Research Articles

Instant cosmology

Instant Folded Strings (IFSs) are unconventional light strings that emerge when the string coupling increases with time. A particularly intriguing property of IFSs, especially relevant to cosmology, is that they violate the Null Energy Condition (NEC). In this paper, we begin to explore their cosmological effects. We find that NEC violation by IFSs is significantly suppressed in an expanding universe, leading to a universe that resembles our own, comprising matter, radiation, and dark energy. Upon closer examination, these components exhibit subtle, nonstandard traits that could be experimentally tested in the future. Notably, the origin of dark energy stems not only from the potential, as is usually the case, but also from the derivative of the potential with respect to the dilaton. This paves the way for a new approach to realizing inflation within string theory, addressing the Dine-Seiberg problem associated with dilaton stabilization, and perhaps even hinting at a novel mechanism to tackle the cosmological constant problem. Conversely, in a contracting universe, the effects of IFSs are amplified, making bouncing cosmologies a natural and prevalent outcome.

Collagen type VI regulates TGF-β bioavailability in skeletal muscle in mice.

Collagen VI-related disorders (COL6-RDs) are a group of rare muscular dystrophies caused by pathogenic variants in collagen VI genes (COL6A1, COL6A2, and COL6A3). Collagen type VI is a heterotrimeric, microfibrillar component of the muscle extracellular matrix (ECM), predominantly secreted by resident fibroadipogenic precursor cells in skeletal muscle. The absence or mislocalization of collagen VI in the ECM underlies the noncell-autonomous dysfunction and dystrophic changes in skeletal muscle with a yet elusive direct mechanistic link between the ECM and myofiber dysfunction. Here, we conducted a comprehensive natural history and outcome study in a mouse model of COL6-RDs (Col6a2-/- mice) using standardized (TREAT-NMD) functional, histological, and physiological parameters. Notably, we identify a conspicuous dysregulation of the TGF-β pathway early in the disease process and propose that the collagen VI-deficient matrix is not capable of regulating the dynamic TGF-β bioavailability both at baseline and in response to muscle injury. Thus, we propose a new mechanism for pathogenesis of the disease that links the ECM regulation of TGF-β with downstream skeletal muscle abnormalities, paving the way for the development and validation of therapeutics that target this pathway.

SAT-295 Functional cure of chronic HBV: natural history, determinants, and outcomes: a real-world experience from a tertiary liver center

SAT-295 Functional cure of chronic HBV: natural history, determinants, and outcomes: a real-world experience from a tertiary liver center

Conservatively managed non-functioning pituitary macroadenomas - cohort study from the UK Non-functioning Pituitary Adenoma Consortium.

Surveillance is often adopted for asymptomatic non-functioning pituitary macroadenomas (macroNFPAs). Due to low quality evidence, uncertainty remains on optimal frequency of imaging/biochemical monitoring and indications for surgery. We assessed the natural history and outcomes of patients with macroNFPA who had monitoring as initial management choice from the UK NFPA Consortium. Multicentre, retrospective, cohort study involving 21 UK endocrine departments. Clinical, imaging, hormonal data of 949 patients followed-up between January, 1, 2005 and March, 1, 2022 were analysed. Incidence rate for tumour enlargement was 9.8 per 100 patient-years (95%CI, 8.8-10.8), with cumulative probabilities 1.6%, 8.1%, 18.4%, 29.2%, 43.6% at 6-months, 1-year, 2-year, 3-year, 5-year follow-up, respectively; rates were higher in tumours abutting/displacing optic chiasm (OC) than those not in contact with it. Amongst macroNFPAs not in contact with OC showing enlargement within six months, none impacted visual fields. In tumours with enlargement and continued monitoring (median 2.6 years), further growth occurred in 60.5% (33.8% probability at 2-years), stability in 35.5%, shrinkage in 4.0%. Rates of new pituitary hormone deficits were 4.0%-4.9%, mainly driven by tumour enlargement. After transsphenoidal surgery, rates of hypopituitarism reversal were 12%-17% and of additional anterior pituitary hormone deficits 12%-15% (permanent vasopressin deficiency 3.5%). Our data provide evidence for monitoring protocols. MacroNFPAs not in contact with OC require less frequent imaging and first follow-up scan can be delayed to one year. After first enlargement, variable tumour behaviour can occur. New hypopituitarism in stable tumours is rare, challenging necessity of regular pituitary function assessment.

How buildings change the fundamental allometry

We demonstrate that the original fundamental allometry alone cannot accurately describe the relationship between urban area and population size. Instead, building height is a third factor that interplays with area and population. To illustrate this, we propose a straightforward model based on the idea that city area is the result of people’s desire to live close to one another while also having sufficient living space . This leads to a more general form of fundamental allometry (relating area, population, and building height). We support our theoretical analysis with an empirical examination of data from 32 countries. Our findings indicate that building height influences the residuals of the fundamental allometric relationship: cities with taller buildings generally fall below the regression curve of area versus population, while those with shorter buildings tend to be above it. This suggests that building height is not merely a natural outcome of our derivation but also extends beyond the fundamental allometry, playing an additional role in shaping urban structure.

Natural history, management, and outcomes of cerebellar cavernous malformations: A retrospective study of 130 patients.

Data on the natural history and management of cerebellar cavernous malformations (CMs) is limited. This study aims to identify factors associated with hemorrhage risk, assess management strategies, and compare outcomes between conservative and surgical management in patients with cerebellar CMs. We retrospectively reviewed 130 patients with cerebellar CMs treated at our center (1990-2023). Data on clinical presentation, lesion characteristics, management strategies, and outcomes were analyzed. Annual hemorrhage risk was calculated. Surgical outcomes were assessed based on the persistence of CM-related symptoms and the presence of postoperative complications. Statistical analyses identified factors associated with hemorrhage, symptomatic presentation, and surgical outcomes. Of 130 patients (53.8% female; median age of 48.5 years (IQR: 26.75)), 41 (31.5%) presented with hemorrhage, and 20 (15.4%) had focal neurological deficits. Median lesion size measured 12mm (IQR 8mm) in size and were primarily located in the hemispheres (n = 89, 68.5%), with fewer in the vermis (n = 21, 16.2%), peduncle (n = 20, 15.4%), and dentate nucleus (n = 9, 6.9%). The annual hemorrhage risk for incidental lesions was 1.19%, while rehemorrhage risk for initially hemorrhagic lesions was 8.35%. Surgery was performed in 31 patients (23.8%), mostly for hemorrhage (n = 15, 48.4%) or cerebellar symptoms (n = 7, 22.6%). Postoperative complications were reported in three patients. At a median follow-up of 1.11 years (IQR 5.15 years), 22 patients (18.2%) had persistent symptoms, two developed new symptoms, and two experienced worsening symptoms from hypertrophic olivary degeneration. There was no CM- related mortality, and only one patient experienced moderate CM-related disability (mRS = 3). Cerebellar CMs generally have a benign course with hemorrhage risks compared to supratentorial and brainstem lesions. Conservative management is recommended for incidental lesions, while surgery should be reserved for symptomatic, accessible cases.

Gene signatures and genotype-phenotype correlations of sensorineural hearing loss in Noonan syndrome and related RASopathies

Hearing loss frequently occurs in Noonan syndrome and related RASopathies (NS-RAS), with conductive hearing loss being common. However, the genotypic and phenotypic features of sensorineural hearing loss (SNHL) in NS-RAS, as well as genotype-phenotype correlations, remain unknown. Leveraging in-house database for syndromic deafness (N = 1666), we analyzed the genomic landscape and clinical phenotypes of 94 NS-RAS families with genetically confirmed via targeted panel sequencing. In particular, we explored the genetic signature of SNHL in NS-RAS and provided a detailed description of the auditory characteristics of SNHL, including its natural progression and outcomes of audiological rehabilitation. Additionally, molecular modeling and functional assays were conducted to explore how PTPN11 variants with distinct auditory phenotypes affect downstream signaling pathways. Resultantly, eighteen (19.1%) exhibited SNHL, predominantly with PTPN11 (88.9%) and RAF1 (11.1%) variants. Of these patients, the majority exhibited severe-to-profound SNHL with congenital onset, and cochlear implantation yielded favorable auditory outcomes. The remaining patients maintained normal hearing throughout the follow-up periods. The PTPN11 variants linked to SNHL compromise autoinhibition between the N-SH2 and PTP domains or disrupts the interaction between the C-SH2 domain and phosphorylated tyrosine (pTyr), showing a gain-of-function effect on the RAS/ERK cascade. Specifically, those variants associated with high penetrance and severe expressivity significantly enhanced ERK phosphorylation more than the variants associated with low penetrance and milder expressivity. This is the first cohort study on NS-RAS in South Korea, elucidating the gene signatures and phenotypic characteristics of SNHL and suggesting genotype-auditory phenotype correlations that inform clinical practice.

Comparing the Effect of Exercise and Metformin on Pancreatic Beta Cell Function in Nigerians with Prediabetes: A Randomized Controlled Trial

Prediabetes is an important risk factor for the development of type 2 diabetes and is common in Nigeria. Effective intervention can reverse the underlying pathogenesis of pancreatic beta-cell dysfunction in prediabetes. Several studies have reported the prevalence of prediabetes across Nigeria, but lack information on the effect of intervention or natural outcome on pancreatic beta-cell function among Nigerians with prediabetes. The objective of this study was to determine and compare the effect of moderate exercise and metformin on pancreatic beta-cell function among participants with prediabetes. Using a randomized placebo-controlled design, fifty-four Nigerians with prediabetes were selected using simple random sampling. They were offered treatment with metformin, moderate exercise, or placebo and followed up for 12 weeks. Pancreatic beta-cell function was assessed before and after the interventions, and the outcome was compared. Forty-nine participants with prediabetes completed the study. After 12 weeks of intervention, participants in both the exercise and metformin groups had an increase in pancreatic beta-cell function compared to placebo. However, the exercise group had a greater increase in beta-cell function from the baseline with HOMA-B=61.9 (CI=-4.3±141.5) compared to 57.1(CI=-4.3±141.5) in the metformin group (p-value<0.05). Among Nigerians with prediabetes, moderate exercise and metformin interventions compared to placebo improve pancreatic beta-cell function. However, moderate exercise resulted in a greater increase in pancreatic beta-cell function compared to metformin intervention. The participants from this trial need to be followed up for a longer period to assess the long-term effects of these interventions.

Prevalence, Progression and Clinical Outcomes of Mitral Valve Prolapse: A Systematic Review and Meta-Analysis.

The prevalence of mitral valve prolapse (MVP) varies across populations and age groups; its natural history and clinical outcomes remain unclear. This meta-analysis established the prevalence of MVP in the general population, in associated syndromes and at different ages. It also determined the rate of progression and the incidence of adverse outcomes. A systematic search identified original reports on the prevalence of MVP and related outcomes. 83 studies met inclusion: 47 (n=992 944) non-syndrome associated; 31 (n=3067) syndrome associated. 5 (n=1287) described mitral regurgitation progression or adverse outcomes. In the general population the prevalence was 1.35% but higher in hospital cohorts (8.7%). Age-stratified prevalence was 0.5%, 1.8%, 2.7% and 2.0% in neonates, children, adolescents and adults, respectively. Meta-regression and subgroup analysis found no significant difference (p=0.81) across ages but revealed a significantly higher prevalence in older compared to young adults (2.87%vs. 0.67%, p=0.01). Prevalence rates were markedly higher in patients with genetic syndromes. Mitral regurgitation (MR) progressed at 5.5 per 100 person-years, overall. Event rates for all-cause mortality, development of heart failure and need for mitral valve intervention were 1.7, 1.0 and 1.2 per 100 person-years, respectively. MVP is common, with greater prevalence in syndromes. Although more common with age, MVP is observed in infants. MVP related MR is progressive, especially in moderate MR, and there is a signal of excess mortality for unclear reasons. Valve services must manage the whole life journey and the potential risks associated with MVP.

Literature Review on Stock Price Predictions with reference to Machine Learning Approaches and Statistical Methods

An Indian stock market is an open market where businesses and individuals can increase revenues. Organizations use the stock market to buy and sell shares. The interest rate and the supply of shares determine the cost of shares. Trading/exchanging refers to purchasing and selling shares. Only Listed Companies are permitted to do so. Vast sums of money have recently been traded on stock exchanges worldwide. National economies are intricately linked, and the performance of their stock exchanges has a significant impact. As a final outcome, they are connected with macroeconomic variables and have a more direct impact on everyday life. They form a mechanism with critical and urgent social consequences as a natural outcome. Investors who trade stocks must have access to timely information in order to make wise decisions. Additionally, stock price behavior is unpredictable and challenging to forecast. These factors make stock price forecasting a critical and hard process to find the value of a particular share. This paper highlights the various research aspects applied to stock price predictions of shocks using machine learning approaches and statistical methods.

The Role of Magnetic and Rotation Axis Alignment in Driving Fast Radio Burst Phenomenology

Abstract We propose a scenario that can describe a broad range of fast radio burst (FRB) phenomenology, from nonrepeating bursts to highly prolific repeaters. Coherent radio waves in these bursts are produced in the polar cap region of a magnetar, where magnetic field lines are open. The angle between the rotation and magnetic axes, relative to the angular size of the polar cap region, partially determines the repetition rate and polarization properties of FRBs. We discuss how many of the properties of repeating FRBs—such as their lack of periodicity, energetics, small polarization angle (PA) swing, spectro–temporal correlation, and inferred low source density— are explained by this scenario. The systematic PA swing and the periodic modulation of long-duration bursts from nonrepeaters are also natural outcomes. We derive a lower limit of about 400 on the Lorentz factor of FRB sources applying this scenario to bursts with a linear polarization degree greater than 95%.

Hybrid Fillers Personal Experience of Premixing Calcium Hydroxylapatite and Hyaluronic Acid for Natural Face Reshaping.

This retrospective study evaluates the efficacy and safety of premixed calcium hydroxylapatite (CaHA) and hyaluronic acid (HA) hybrid fillers for facial reshaping and rejuvenation, focusing on natural outcomes with long-term follow-up over 12 months. Forty-six patients (ages 45-65) underwent hybrid filler treatments using a 1:1 premixed formulation of CaHA and HA. Injection techniques targeted specific facial zones using cannulas for subdermal delivery. Standardized 3D imaging and the Merz Aesthetics Scale (CR-MASJ) were used to assess lifting effects and volume restoration. The Global Aesthetic Improvement Scale (GAIS) measured patient satisfaction. Improvements in skin laxity, volume restoration, and facial contouring were noted as early as 3 months post-treatment and sustained through 12 months. Premixed hybrid fillers demonstrated enhanced biostimulatory effects compared with standalone CaHA or HA, promoting neocollagenesis and providing immediate and lasting results. Adverse events were minimal, with no significant complications reported. Premixing CaHA and HA offers a safe, effective, and reproducible technique for natural facial reshaping and rejuvenation. The combination enhances skin quality while providing immediate volumization and long-term collagen stimulation, meeting the aesthetic expectations of patients seeking minimally invasive anti-aging solutions.

A combination of fat grafting with inferior dermal flap in breast reconstruction following prophylactic mastectomy: A cohort study.

Breast reconstruction following prophylactic mastectomy in women with ptotic or hypertrophic breasts often poses challenges. We describe a combined technique of large-volume fat grafting (>100mL) and an inferior dermal flap, aiming to improve aesthetic outcomes and patient satisfaction. We conducted a retrospective analysis of 21 patients undergoing immediate breast reconstruction with the described technique. All patients were asked to complete the BREAST-Q questionnaire preoperatively and at least 12 months postoperatively (median interval: 20 months). Statistical analysis (Wilcoxon signed-rank test) was used to assess changes in satisfaction and well-being; aesthetic outcomes were scored by an independent, multidisciplinary team. Among 13 patients with complete BREAST-Q data, satisfaction with the breasts increased significantly from a median score of 38-85 (p=0.002), psychosocial well-being from 57-70 (p=0.045), and physical well-being (chest) from 68 to 81 (p=0.045). Sexual well-being rose from 47-63 (p=0.023). Aesthetic evaluation by an independent panel showed notable improvements in breast symmetry, shape, and overall appearance. Minimal and asymptomatic fat necroses or oil liponecrotic pseudocysts were observed. Combining large-volume fat grafting with an inferior dermal flap appears promising for women with ptotic breasts, yielding high satisfaction and low complication rates. Despite requiring multiple operative stages, this autologous reconstruction technique may offer a less invasive alternative for high-risk patients seeking natural outcomes without implants.

Alagille Syndrome: Unraveling the Complexities of Genotype-Phenotype Relationships and Exploring Avenues for Improved Diagnosis and Treatment.

Alagille syndrome (ALGS) is a rare genetic disorder caused by mutations in the JAG1 and NOTCH2 genes, leading to a wide range of clinical manifestations. This review explores the complex genetic and clinical landscape of ALGS, emphasizing the challenges in understanding genotype-phenotype relationships due to its rarity and the lack of suitable research models. The review projects a clinical overview of the disease, emphasizing the influence of potential gene modifiers on its clinical presentation and the lack of mechanistic studies for over 100 mutations identified in the last 24 years from various populations, representing a significant gap in our current knowledge and advocating for further exploration. The review addresses the diagnostic challenges posed by the variable expressivity and overlapping symptoms of ALGS. It summarizes current treatment options and discusses emerging approaches such as antisense oligonucleotides (ASOs) and gene therapies. Further, the need for improved diagnostic tools, a deeper understanding of the underlying mechanisms, and the development of targeted therapies are emphasized using zebrafish and mice models, as well as genome editing for variant analysis and stem cell organoid models for disease modeling and drug discovery. The importance of cohort-based studies in understanding the natural history and outcomes of ALGS in diverse populations is highlighted. The review concludes by emphasizing the need for multi-disciplinary collaborative research to address the challenges in ALGS diagnosis, prognosis, and treatment, particularly for underrepresented populations.

Chirurgie prophylactique mammaire, place du DIEP

Chirurgie prophylactique mammaire, place du DIEP

Expanding Indications to Dorsal Preservation Rhinoplasty.

Expanding Indications to Dorsal Preservation Rhinoplasty.

Research of tricuspid regurgitation associated with cardiac implantable electronic devices

Tricuspid regurgitation associated with cardiac implantable electronic devices (CIED) constitutes a significant subset of secondary tricuspid regurgitation, characterized by a multifactorial etiology involving pacing lead-mediated mechanical interference and CIED-related systemic factors. The pathogenesis of CIED-related tricuspid regurgitation encompasses direct mechanical trauma or functional disruption of the tricuspid valve apparatus by pacing leads, pacing mode-induced hemodynamic alterations, and clinical risk factors such as permanent atrial fibrillation, apical pacing, and high right ventricular pacing burden. The natural progression and clinical outcomes of CIED-related tricuspid regurgitation parallel those of tricuspid regurgitation stemming from other etiologies. Advanced imaging modalities, including echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, enable precise diagnosis and longitudinal assessment of CIED-related tricuspid regurgitation. Management strategies emphasize multidisciplinary collaboration as well as integration of preventive approaches-such as refined lead implantation techniques and tailored pacing modalities-with therapeutic interventions ranging from pharmacotherapy to surgical valve repair or replacement. This article reviews the current understanding of CIED-related tricuspid regurgitation to provide a reference for clinical practice and research.

THE IMPACT OF TECHNOLOGY ON THE ENVIRONMENT OF BALOCHISTAN: AN INTERPLAY BETWEEN TECHNOLOGICAL INNOVATION AND SUSTAINABILITY DEVELOPMENT GOALS (SDGS) IN BALOCHISTAN AND THE INTEGRATION OF ENVIRONMENTAL IMPACT ASSESSMENT (EIA) IN PROPOSING A STRATEGIC MITIGATION FRAMEWORK FOR BALOCHISTAN

Technology based innovation and advancement would subsequently be the use of progressing information to practical applications accompanied by the design of smart devices/equipment. In the current era in Balochistan, it is a time of phenomenal transformation that mankind right now lives in-one in which technology upgradation reshapes our way of living but at the same times causes irreversible environmental changes and also results in resource depletion.The advent of new innovations was introduced with the industrial revolution resulting in a paradigm shift from conventional to new assembling approaches in Europe and the US during the period around 1760 to 1840. This has been proceeded with augmented industrialization and further technology design alterations across the globe including Balochistan, Pakistan. However the ramifications of these innovation to the climate, biotic/abiotic component of the environment, natural/non-renewable resources, regional communities etc have incorporated in the exploitation and harming of our mother nature and our planet Earth. These advancements have infact unfavourably impacted Balochistan in two primary ways; pollution and thedepletion of natural resources.Therefore, it is crucial to critically explore the impact of technology on the environment of Balochistan in order to comprehend and achieve the targets and goals of SDGs. In addition, it is crucial to implement Environmental Impact Assessment (EIA) which serves as an essential strategic tool to assess the likely natural outcomes of technology advancement, ensuring that both short-term and long-term impacts are understood and mitigated to attain sustainability for future generations.

ASSOCIATION BETWEEN INFLAMMATORY BOWEL DISEASE AND HIDRADENITIS SUPPURATIVA: A SINGLE-CENTER RETROSPECTIVE STUDY

Abstract BACKGROUND Studies have shown an association between inflammatory bowel disease (IBD) and hidradenitis suppurativa (HS), but there is conflicting data on whether it is more associated with Crohn’s disease (CD) versus ulcerative colitis (UC). In addition, the natural course and outcomes of patients with comorbid IBD and HS are unknown. The purpose of this study was to compare the clinical characteristics and disease course of patients with both IBD and HS compared with those of patients with isolated IBD or isolated HS. METHODS A retrospective chart review was conducted for patients who were seen at a single tertiary health system in New York City between 1/1/2016 and 5/31/2023. Of 970 patients diagnosed with HS by dermatologists, 35 had both confirmed IBD and HS. These patients were matched 1:1:1 with control cases having isolated IBD and isolated HS, based on age, sex, race, duration of the disease, and IBD type. Clinical variables related to HS and IBD were collected, including demographics, comorbid conditions, markers of disease severity, and treatment. RESULTS Of the 35 patients with both HS and IBD, 24 were female and 11 were male, with a median age of 34 years (range 14-81). Of patients with documented race, 16 were White (46%), 8 were Black (14%), and 5 were South Asian (23%). Six patients had UC, while 29 had CD. The median age at diagnosis of IBD was 19 (range 12-24) and of HS was 24 (range 20-36). IBD diagnosis preceded HS diagnosis in 26 patients, whereas HS preceded IBD in only 3 patients. When compared with the isolated IBD group, patients with comorbid CD and HS more often had perianal CD (55% vs 21%, p < 0.01). When compared for IBD-related outcomes, there were more frequent IBD-related hospitalizations in the comorbid IBD and HS group (0.29 vs 1.38, p = 0.02). The median number of biologics tried was 2 (p = 0.7), and anti-TNF biologics were used in 32 patients (p = 0.5). Combination therapy of biologics and immunomodulators was required in 13 patients (p = 0.04). As for extraintestinal manifestation, peripheral arthritis had a significant difference between the comorbid group and the isolated IBD group (p = 0.05). When compared for HS-related outcomes, the severity of HS assessed by the Hurley stage and the number of past surgical treatments did not significantly differ between the comorbid IBD and HS group and the isolated HS group. CONCLUSION In this single-center study with a diverse population, there was a high proportion of South Asian patients. Patients with comorbid IBD and HS more often had CD than UC, and the proportion of patients with PFCD was higher than in the isolated IBD group. IBD exhibited more severe disease progression, necessitating more frequent combination therapy and hospitalizations, while HS severity was similar when compared with patients with isolated IBD or HS, respectively.

Tafamidis in octogenarians with wild-type transthyretin cardiac amyloidosis: an international cohort study.

In real-world, wild-type transthyretin cardiomyopathy is increasingly diagnosed in patients ≥ 80 years old (octogenarians), although being underrepresented in randomized clinical trials. Specific data on natural course and outcome under tafamidis treatment in octogenarians are therefore scarce. The impact of tafamidis treatment on mortality in real-world wild-type transthyretin cardiomyopathy octogenarians was studied. An international, multicentre cohort study of 710 consecutive wild-type transthyretin cardiomyopathy patients with mean follow-up of 2.2 ± 1.8 years for all-cause mortality endpoint was performed. The cohort consisted of 58.5% (415/710) octogenarians (85 ± 4 years, 74.2% male). Before tafamidis availability, natural course in octogenarians (148/257) vs. non-octogenarians (109/257) was poor, with 16% 1-year and 71% 5-year mortality vs. 8% and 47%, respectively (P < .001). Since tafamidis availability, 70.1% (253/361) octogenarians were initiated on tafamidis vs. 83.7% (231/276) non-octogenarians (P < .001). Tafamidis discontinuation was similar (octogenarians 10.3% and non-octogenarians 7.4%; P = .260). Overall tafamidis treated vs. untreated octogenarians had better unadjusted survival (P < .001), with 5% 1-year and 24% 3-year mortality. Tafamidis treatment associated with lower mortality after propensity score matching on baseline variables, including age, National Amyloidosis Centre stage, and New York Heart Association class in on average 394 subjects [hazard ratio (HR) = 0.53, 95% confidence interval (CI) 0.34-0.84, P = .007], also in octogenarians (HR = 0.57, 95% CI 0.33-1.01, P = .053). Neither age at diagnosis (P = .217) nor at treatment initiation (P = .154) interacted with tafamidis mortality benefit. Octogenarians had poorer survival despite tafamidis, when initiated at ≥90 years (HR = 3.3, 95% CI 1.10-9.53, P = .033) and National Amyloidosis Centre Stage ≥3 (HR = 2.4, 95% CI 0.87-6.46, P = .090). Real-world tafamidis treatment improves survival without age affecting treatment efficacy, although mortality remains considerable in octogenarians.