Phenotypes In People Research Articles

A biopsychosocial approach to phenotyping people with knee osteoarthritis awaiting total knee arthroplasty: A secondary cohort analysis

BackgroundPrevious research showed chronic post-total knee arthroplasty (TKA) pain in 20% of people with knee osteoarthritis (KOA). Various preoperative biopsychosocial-related factors have been described, but phenotyping people with KOA awaiting TKA based on these factors is still lacking. This could be relevant to understanding differences in TKA surgery responses. ObjectiveTo identify phenotypes in people with KOA awaiting TKA and differences in post-TKA pain based on preoperative biopsychosocial factors. MethodsPeople with KOA awaiting TKA in 4 hospitals in Belgium and the Netherlands were included. A cross-sectional latent profile analysis was conducted on structural, metabolic, functional, pain-related, psychological and social variables. Concurrent validity was tested using 3-step multinomial logistic regression. The difference in one-year post-TKA pain was examined with linear mixed model analysis. ResultsTwo hundred and seventeen participants were included in the latent profile analysis with a mean (SD) age of 65.5 (7.7) years, including 109 women. A model with 2 phenotypes differed in 14 out of 21 variables. Participants with phenotype 2 (28%) had a higher body mass index (BMI), higher chance of having less structural damage (KOA grade), lower mean quadriceps strength and physical function (Knee Society Scoring System functional and 30-second chair stand test), higher pain intensity, number of pain locations, and indices of central sensitisation (temporal summation, central sensitisation inventory score, and lower pressure pain thresholds), higher pain catastrophising, anxiety and depression, and higher post-TKA pain intensity compared to phenotype 1 (72%). Concurrent validity was confirmed in 3 out of 4 variables. ConclusionsPhenotype 2 (28%) with nociplastic pain characteristics in combination with worse psychological factors, BMI, functional and structural factors, and phenotype 1 (72%) not representing these characteristics were identified. Phenotype 2 had worse pain intensity scores after TKA compared to phenotype 1. Attention to the characteristics of phenotype 2 is warranted concerning post-TKA pain. Database registrationThe protocol is registered at ClinicalTrials.gov (NCT05380648).

Hereditary Transthyretin Amyloidosis Polyneuropathy.

In the last decade, we have witnessed dramatic improvements in the diagnosis, workup, management, and monitoring of patients with hereditary transthyretin amyloidosis (ATTRv). Updated imaging techniques (e.g., 99mTc-PYP scan) are increasingly being used in place of tissue biopsies for confirmation of disease. Novel treatments now include antisense oligonucleotide and RNA interference drugs, whereas new applications such as CRISPR and amyloid antibodies are being studied for potential use in the future. These treatments have dramatically improved quality of life and increased survival in patients with ATTRv. Despite these breakthroughs, many challenges remain. Some of these challenges include early recognition and diagnosis of ATTRv, monitoring and initiation of treatment in asymptomatic or paucisymptomatic carriers, adequate treatment in people with mixed phenotype (i.e., cardiac and neurological), and the emergence of new phenotypes in people living longer with the disease (i.e., central nervous system and ocular complications). Research in those areas of deficit is ongoing, and in the future, we may have preventive therapies, better biomarkers, more efficient therapies for organs that we cannot currently target, and enhanced diagnostic techniques with the help of novel imaging techniques and artificial intelligence. In this review, we will summarize the current knowledge about polyneuropathy related to ATTRv and its management, discuss methods to improve early diagnosis and monitoring, and discuss emerging trends.

Elexacaftor/Tezacaftor/Ivacaftor (ETI) Treatment Corrects the Salt-Losing Phenotype in People with Cystic Fibrosis

Elexacaftor/Tezacaftor/Ivacaftor (ETI) Treatment Corrects the Salt-Losing Phenotype in People with Cystic Fibrosis

SLC39A8.p.(Ala391Thr) is associated with poorer cognitive ability: a cross-sectional study of schizophrenia and the general UK population.

The missense SNP NC_000004.12:g.102267552C>T (SLC39A8.p.(Ala391Thr), rs13107325) in SLC39A8, which encodes a zinc transporter, has been linked to schizophrenia and is the likely causal variant for one of the genome-wide association loci associated with the disorder. We tested whether the schizophrenia-risk allele at p.(Ala391Thr) was associated with schizophrenia-related phenotypes, including positive, negative, and disorganised symptoms, cognitive ability, educational attainment, and age of psychosis onset, within three schizophrenia cohorts (combined N=1,232) and, with equivalent phenotypes, in a sample of population controls (UK Biobank, N=355,069). We used regression analyses controlling for age, sex, and population stratification. Within the schizophrenia cohorts, after correction for multiple testing, p.(Ala391Thr) was not significantly associated with any schizophrenia-related phenotypes. In the unaffected participants from the UK Biobank, the schizophrenia-risk allele at p.(Ala391Thr) was associated with significantly poorer cognitive ability and fluid intelligence, a lower probability of obtaining GCSEs or a degree-level qualification, and fewer years in education. There was no association between p.(Ala391Thr) and self-reported psychotic experiences in this cohort. The schizophrenia-risk allele was associated with poorer cognitive ability, but not psychotic experiences, in a volunteer sample drawn from of the general population. To determine whether p.(Ala391Thr) is associated with cognitive phenotypes in people with schizophrenia, and to understand the role of p.(Ala391Thr) in the aetiology of cognitive impairment in schizophrenia, larger independent samples are required.

Biopsychosocial phenotypes in people with HIV in the CHARTER cohort.

Neuropsychiatric complications such as neurocognitive impairment and depression are common in people with HIV despite viral suppression on antiretroviral therapy, but these conditions are heterogeneous in their clinical presentations and associated disability. Identifying novel biopsychosocial phenotypes that account for neurocognitive performance and depressive and functional symptoms will better reflect the complexities encountered in clinical practice and may have pathological and therapeutic implications. We classified 1580 people with HIV based on 17 features, including 7 cognitive domains, 4 subscales of the Beck depression inventory-II, 5 components of the patient's assessment of own functioning inventory, and dependence in instrumental and basic activities of daily living. A two-stage clustering procedure consisting of dimension reduction with self-organizing maps and Mahalanobis distance-based k-means clustering algorithms was applied to cross-sectional data. Baseline demographic and clinical characteristics were compared between the phenotypes, and their prediction on the biopsychosocial phenotypes was evaluated using multinomial logistic regression. Four distinct phenotypes were identified. Participants in Phenotype 1 overall did well in all domains. Phenotype 2 had mild-to-moderate depressive symptoms and the most substance use disorders. Phenotype 3 had mild-to-moderate cognitive impairment, moderate depressive symptoms, and the worst daily functioning; they also had the highest proportion of females and non-HIV conditions that could affect cognition. Phenotype 4 had mild-to-moderate cognitive impairment but with relatively good mood, and daily functioning. Multivariable analysis showed that demographic characteristics, medical conditions, lifetime cocaine use disorder, triglycerides, and non-antiretroviral therapy medications were important variables associated with biopsychosocial phenotype. We found complex, multidimensional biopsychosocial profiles in people with HIV that were associated with different risk patterns. Future longitudinal work should determine the stability of these phenotypes, assess factors that influence transitions from one phenotype to another, and characterize their biological associations.

Cross-cultural application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE): Cognitive phenotypes in people with temporal lobe epilepsy in India.

Efforts to understand the global variability in cognitive profiles in patients with epilepsy have been stymied by the lack of a standardized diagnostic system. This study examined the cross-cultural applicability of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) in a cohort of patients with temporal lobe epilepsy (TLE) in India that was diverse in language, education, and cultural background. A cohort of 548 adults with TLE from Mumbai completed a presurgical comprehensive neuropsychological evaluation. The IC-CoDE taxonomy was applied to derive cognitive phenotypes in the sample. Analyses of variance were conducted to examine differences in demographic and clinical characteristics across the phenotypes, and chi-squared tests were used to determine whether the phenotype distribution differed between the Mumbai sample and published data from a multicenter US sample. Using the IC-CoDE criteria, 47% of our cohort showed an intact cognitive profile, 31% a single-domain impairment, 16% a bidomain impairment, and 6% a generalized impairment profile. The distribution of cognitive phenotypes was similar between the Indian and US cohorts for the intact and bidomain phenotypes, but differed for the single and generalized domains. There was a larger proportion of patients with single-domain impairment in the Indian cohort and a larger proportion with generalized impairment in the US cohort. Among patients with single-domain impairment, a greater proportion exhibited memory impairment in the Indian cohort, whereas a greater proportion showed language impairment in the US sample, likely reflecting differences in language administration procedures and sample characteristics including a higher rate of mesial temporal sclerosis in the Indian sample. Our results demonstrate the applicability of IC-CoDE in a group of culturally and linguistically diverse patients from India. This approach enhances our understanding of cognitive variability across cultures and enables harmonized and inclusive research into the neuropsychological aspects of epilepsy.

Association between Sarcopenia and Reduced Bone Mass: Is Osteosarcopenic Obesity a New Phenotype to Consider in Weight Management Settings?

Sarcopenic obesity (SO) is a frequent phenotype in people with obesity; however, it is unclear whether this links with an impaired bone status. In this study, we aimed to investigate the association between SO and low bone mass, and to assess the prevalence of a new entity that combines excessive fat deposition, reduced muscle mass and strength, and low bone mass defined as osteosarcopenic obesity (OSO). Body composition was completed by a DXA scan in 2604 participants with obesity that were categorized as with or without SO, and with low or normal bone mineral content (BMC). Participants with both SO and low BMC were defined as OSO. Among the entire sample, 901 (34.6%) participants met the criteria for SO. This group showed a reduced mean BMC (2.56 ± 0.46 vs. 2.85 ± 0.57, p < 0.01) and displayed a higher prevalence of individuals with low BMC with respect to those without SO (47.3% vs. 25.9%, p < 0.01). Logistic regression analysis showed that the presence of SO increases the odds of having low BMC by 92% [OR = 1.92; 95% CI: (1.60-2.31), p < 0.05] after adjusting for age, body weight, and body fat percentage. Finally, 426 (16.4%) out of the total sample were affected by OSO. Our findings revealed a strong association between SO and reduced bone mass in adults with obesity, and this introduces a new phenotype that combines body fat, muscle, and bone (i.e., OSO) and appears to affect 16% of this population.

2 Cross Cultural Application of the International Classification of Cognitive Disorders in Epilepsy (IC CoDE) Cognitive Phenotypes in People with Temporal Lobe Epilepsy in India

Objective:To apply the new IC-CoDE cognitive diagnostic taxonomy (Norman et al., 2020) to a large cohort of people with temporal lobe epilepsy (TLE) in India. The IC-CoDE taxonomy of cognitive diagnoses for 1,409 Englishspeaking adults with TLE from seven epilepsy centres in the U.S. has been published (McDonald et al., 2022). Initial results suggest that the IC-CoDE produces stable cognitive phenotypes across centres; however, its international applicability, including the suggested impairment cut-off needs to be considered across cultures and languages to avoid misclassification. The aim of this study was to apply the IC-CoDE to a population, outside of the U.S., diverse in language representation (i.e., bi/multi-lingual), assessment tools, normative data, and educational and cultural backgrounds to determine whether the same cognitive phenotypes and their relative frequencies would emerge.Participants and Methods:Data from 549 adults with TLE (mean age=27.14 (8.04), 60.47% males) from a tertiary referral hospital in Mumbai, India who had undergone a comprehensive neuropsychological evaluation (minimum two tests in at least 4 of the 5 cognitive domains: memory, language, executive function, attention/processing speed and visuospatial) were analysed using the ICCoDE criteria. The base rate of impairment for individual tests was calculated using a cutoff of 1.5 standard deviations (S.D.) below the normative mean. The cognitive diagnostic criteria were applied, and the distribution and base rate of cognitive phenotypes was compared to the published taxonomy data from the U.S. (McDonald et al., 2022).Results:In comparison to the U.S. cohort, the India group was relatively younger, lower in the education level, had a younger age at seizure onset and a shorter duration of the epilepsy. Application of the IC-CoDE taxonomy using a 1.5 S.D. cutoff revealed an Intact cognitive profile in 48% of patients, Single Domain impairment in 32%, Bi Domain impairment in 15% and Generalised impairment in 5%. These findings were mostly comparable to percentages reported in the U.S. cohorts with Intact profile (47%; c2= 0.158, p=0.690), Single Domain (29%; c2= 46.26, p&lt;0.01), Bi Domain (16%; c2= 0.298, p=0.585) and Generalised (8%; c2= 5.347, p=0.021) impairment. However, the most common impairment in the Single Domain group for the bi/multilingual India population was Memory (38%) followed by Attention (20%) and then Language (13%), diverging from the distribution in the U.S. data with maximum impairment in Language (49%) followed by Memory (32%) in the Single Domain Group.Conclusions:These findings demonstrate that the IC-CoDE can be applied internationally, and the broad taxonomy of cognitive diagnosis holds even in a culturally, linguistically diverse population. Differences in rates of impairments across specific domains emerged with language relatively preserved in the India bi/multilingual population, and memory more frequently impaired than observed in the multi-centre U.S. sample. These findings may reflect differences in demographics, rates of bi/multilingualism, normative data, language tools, or underlying neuropathology, which should be further explored to determine their impact on cognitive profiles.

PB1243 Comparison of Quality of Life and Bleeding Phenotypes in People with Congenital Hemophilia A: Longitudinal Study from the PicnicHealth Database of PROMIS®-29 v2.0 Scores

PB1243 Comparison of Quality of Life and Bleeding Phenotypes in People with Congenital Hemophilia A: Longitudinal Study from the PicnicHealth Database of PROMIS®-29 v2.0 Scores

Sarcopenic Obesity Phenotypes in Patients With HIV: Implications for Cardiovascular Prevention and Rehabilitation

BackgroundWe aimed to describe prevalence, incidence, and risk factors for sarcopenic obesity (SO) phenotypes in people living with HIV (PWH) and their association with subclinical cardiovascular disease (CVD). MethodsObservational, longitudinal study of PWH. A minimum of 1 criterion was necessary to diagnose sarcopenia: weak hand grip (HG), low appendicular skeletal muscle index (ASMI), short physical performance battery (SPPB < 11). Obesity was defined as body mass index (BMI) ≥ 30 kg/m2 or visceral adipose tissue (VAT) ≥ 160 cm2. These variables combined generated 5 SO phenotypes: severe SO: low HG + low ASMI + low SPPB + high BMI; SO1: weak HG + high VAT; SO2: weak HG + high BMI; SO3: low ASMI + high VAT; SO4: low ASMI + high BMI. Subclinical CVD was defined as carotid intima-media thickness (IMT) ≥ 1 mm, presence of carotid plaque, or coronary artery calcification (CAC) score > 10. ResultsAmong 2379 male PWH 72%, median age was 52 years, median HIV vintage 21 years, and median BMI 24 kg/m2. Two PWH had severe SO. The prevalence of SO1-SO4 was 19.7%, 3.6%, 20.8% and 0.8%, respectively. Incidence of SO1-SO4 was 6.90, 1.2, 5.6, and 0.29 × 100 person-years, respectively. SO1 was associated with risk of IMT ≥ 1, and SO3 with risk of CAC score > 10. ConclusionsThere was a large variability in incidence and prevalence of SO phenotypes. The presence of SO may have important implications for cardiovascular prevention and cardiac rehabilitation of PWH who suffered events.

Carpal Tunnel Syndrome: Neuropathic Pain Associated or Not with a Nociplastic Condition.

Carpal tunnel syndrome (CTS) has been traditionally classified as primarily a neuropathic condition with or without pain. Precision medicine refers to an evidence-based method of grouping patients based on their susceptibility to biology, prognosis of a particular disease, or in their response to a specific treatment, and tailoring specific treatments accordingly. In 2021, the International Association for the Study of Pain (IASP) proposed a grading system for classifying patients into nociceptive, neuropathic, or nociplastic phenotypes. This position paper presents data supporting the possibility of subgrouping individuals with specific CTS related-pain into nociceptive, neuropathic, nociplastic or mixed-type phenotypes. Carpal tunnel syndrome is a neuropathic condition but can also be comorbid with a nociplastic pain condition. The presence of extra-median symptoms and the development of facilitated pain processing seem to be signs suggesting that specific CTS cases can be classified as the nociplastic pain phenotype. The clinical responses of therapeutic approaches for the management of CTS are inconclusive. Accordingly, the ability to identify the predominant pain phenotype in patients with CTS could likely be problematic for producing efficient treatment outcomes. In fact, the presence of a nociplastic or mixed-type pain phenotype would explain the lack of clinical effect of treatment interventions targeting the carpal tunnel area selectively. We propose a clinical decision tree by using the 2021 IASP classification criteria for identifying the predominant pain phenotype in people with CTS-related pain, albeit CTS being a priori a neuropathic pain condition. The identification of a nociplastic-associated condition requires a more nuanced multimodal treatment approach to achieve better treatment outcomes.

WS04.03 Elexacaftor/tezacaftor/ivacaftor (ETI) treatment corrects the salt-losing phenotype in people with cystic fibrosis (pwCF)

Objectives: PwCF have an increased risk for fluid and electrolyte imbalances caused by continuous fluid and salt loss. Congruently, guidelines advocate increased salt intake. Understanding how CFTR modulators affect fluid and electrolyte homeostasis is important to provide guidance for pwCF treated with ETI. In this study, we investigate the effect of ETI treatment on blood pressure and fluid- and electrolyte homeostasis in pwCF.

Using the method of molecular genetic typing to determine variants of the weak antigen D in the diagnosis of Rh-affiliation

Background. Determination of Rh-affiliation is mandatory for donors and recipients, surgical patients, pregnant women, etc. There are variants of the D antigen that are difficult to identify by serological methods, for example, a weak D antigen.&#x0D; Aim. Determination of Rh-affiliation using genotyping in difficult cases, when the use of serological methods does not allow obtaining a reliable result.&#x0D; Material and methods. We studied blood samples from donors (n=18), pregnant women (n=17) and patients with hematological diseases (n=15): 22 men and 28 women, median age 36 years (25 to 54 years). Serologically, antigen D was determined by gel technology in ID-cards and in an indirect antiglobulin test with anti-D-IgG reagent. Weak D antigen variants were diagnosed and phenotype determined using polymerase chain reaction with allele-specific primers. For significance of differences in the frequency of types of weak antigen D, a nonparametric statistical method using a two-tailed Fisher's exact test was used. Differences were considered statistically significant at p 0.05.&#x0D; Results. The use of genotyping made it possible to detect the presence of a weak antigen D in 41 samples. Its specificity was represented by the following types: 1; 1.1; 2; 3. Other types of weak antigen D [4; 4.0; 4.1; 4.2 (DAR); 5; 11; 14; 15; 17] were absent. The study of the phenotype of erythrocyte antigens of the Rhesus system using genotyping revealed the predominance of the Ccee phenotype in people with a weak D antigen. Significant differences in the frequency of types of this antigen were revealed.&#x0D; Conclusion. The use of molecular genetic typing made it possible to determine the types of the weak antigen D and to accurately determine the Rh-affiliation of the subjects.

Exploring pain phenotypes in people with early knee osteoarthritis:the multicenter osteoarthritis study (most)

Exploring pain phenotypes in people with early knee osteoarthritis:the multicenter osteoarthritis study (most)

Machine Learning Approaches to Understand Cognitive Phenotypes in People With HIV.

Cognitive disorders are prevalent in people with HIV (PWH) despite antiretroviral therapy. Given the heterogeneity of cognitive disorders in PWH in the current era and evidence that these disorders have different etiologies and risk factors, scientific rationale is growing for using data-driven models to identify biologically defined subtypes (biotypes) of these disorders. Here, we discuss the state of science using machine learning to understand cognitive phenotypes in PWH and their associated comorbidities, biological mechanisms, and risk factors. We also discuss methods, example applications, challenges, and what will be required from the field to successfully incorporate machine learning in research on cognitive disorders in PWH. These topics were discussed at the National Institute of Mental Health meeting on "Biotypes of CNS Complications in People Living with HIV" held in October 2021. These ongoing research initiatives seek to explain the heterogeneity of cognitive phenotypes in PWH and their associated biological mechanisms to facilitate clinical management and tailored interventions.

Can we characterize A-P/IAP behavioural phenotypes in people with chronic pain?

Two behavioural phenotypes in healthy people have been delineated based on their intrinsic attention to pain (IAP) and whether their reaction times (RT) during a cognitively-demanding task are slower (P-type) or faster (A-type) during experimental pain. These behavioural phenotypes were not previously studied in chronic pain populations to avoid using experimental pain in a chronic pain context. Since pain rumination (PR) may serve as a supplement to IAP without needing noxious stimuli, we attempted to delineate A-P/IAP behavioural phenotypes in people with chronic pain and determined if PR can supplement IAP. Behavioural data acquired in 43 healthy controls (HCs) and 43 age-/sex-matched people with chronic pain associated with ankylosing spondylitis (AS) was retrospectively analyzed. A-P behavioural phenotypes were based on RT differences between pain and no-pain trials of a numeric interference task. IAP was quantified based on scores representing reported attention towards or mind-wandering away from experimental pain. PR was quantified using the pain catastrophizing scale, rumination subscale. The variability in RT was higher during no-pain trials in the AS group than HCs but was not significantly different in pain trials. There were no group differences in task RTs in no-pain and pain trials, IAP or PR scores. IAP and PR scores were marginally significantly positively correlated in the AS group. RT differences and variability were not significantly correlated with IAP or PR scores. Thus, we propose that experimental pain in the A-P/IAP protocols can confound testing in chronic pain populations, but that PR could be a supplement to IAP to quantify attention to pain.

Metabolomics and Lipidomics Signatures of Insulin Resistance and Abdominal Fat Depots in People Living with Obesity.

The liver, skeletal muscle, and adipose tissue are major insulin target tissues and key players in glucose homeostasis. We and others have described diverse insulin resistance (IR) phenotypes in people at risk of developing type 2 diabetes. It is postulated that identifying the IR phenotype in a patient may guide the treatment or the prevention strategy for better health outcomes in populations at risk. Here, we performed plasma metabolomics and lipidomics in a cohort of men and women living with obesity not complicated by diabetes (mean [SD] BMI 36.0 [4.5] kg/m2, n = 62) to identify plasma signatures of metabolites and lipids that align with phenotypes of IR (muscle, liver, or adipose tissue) and abdominal fat depots. We used 2-step hyperinsulinemic-euglycemic clamp with deuterated glucose, oral glucose tolerance test, dual-energy X-ray absorptiometry and abdominal magnetic resonance imaging to assess muscle-, liver- and adipose tissue- IR, beta cell function, body composition, abdominal fat distribution and liver fat, respectively. Spearman's rank correlation analyses that passed the Benjamini-Hochberg statistical correction revealed that cytidine, gamma-aminobutyric acid, anandamide, and citrate corresponded uniquely with muscle IR, tryptophan, cAMP and phosphocholine corresponded uniquely with liver IR and phenylpyruvate and hydroxy-isocaproic acid corresponded uniquely with adipose tissue IR (p &lt; 7.2 × 10-4). Plasma cholesteryl sulfate (p = 0.00029) and guanidinoacetic acid (p = 0.0001) differentiated between visceral and subcutaneous adiposity, while homogentisate correlated uniquely with liver fat (p = 0.00035). Our findings may help identify diverse insulin resistance and adiposity phenotypes and enable targeted treatments in people living with obesity.

A Comparison of Self-reported Pain Measures Between Sensory Phenotypes in HIV-associated Sensory Neuropathy

Painful HIV-associated neuropathy (HIV-SN) is a prevalent co-morbidity of HIV infection. Sensory phenotyping, using quantitative sensory testing (QST) could allow for improved stratification to guide personalized treatment. However, previous methods of QST interpretation have demonstrated limited association with self-reported pain measures. This study sought to identify differences in self-reported pain measures between composite QST-derived sensory phenotypes, and to examine any differences in participants reporting multi-site, multi-etiology chronic pain. In this cross-sectional observational study of participants with HIV (n = 133), individuals were allocated to neuropathy and neuropathic pain groups through clinical assessment and nerve conduction testing. They completed symptom-based questionnaires and underwent standardized QST. Participants were assigned, by pre-determined algorithm, to a QST-derived sensory phenotype. Symptoms were compared between sensory phenotypes. Symptom characteristics and Neuropathic Pain Symptom Inventory scores differed between QST-derived sensory phenotypes: ‘sensory loss’ was associated with more paroxysmal and paraesthetic symptoms compared to ‘thermal hyperalgesia’ and ‘healthy’ phenotypes (P = .023–0.001). Those with painful HIV-SN and additional chronic pain diagnoses were more frequently allocated to the ‘mechanical hyperalgesia’ phenotype compared to those with painful HIV-SN alone (P = .006). This study describes heterogeneous sensory phenotypes in people living with HIV. Differences in self-reported pain outcomes between sensory phenotypes has the potential to guide future stratified trials and eventually more targeted therapy. PerspectiveThis article presents quantitative sensory testing derived phenotypes, thought to reflect differing pathophysiological pain mechanisms and relates them to self-reported pain measures in people with HIV infection. This could help clinicians stratify patients to individualize analgesic interventions more effectively.

The bleeding phenotype in people with nonsevere hemophilia

AbstractDetailed information on the onset, frequency, and severity of bleeding in nonsevere hemophilia is limited. We aimed to assess the bleeding phenotype of persons with nonsevere hemophilia and to analyze the association between baseline factor VIII/IX (FVIII/IX) levels and the joint bleeding rate. In the DYNAMO (Dynamic Interplay Between Bleeding Phenotype and Baseline Factor Level in Moderate and Mild Hemophilia A and B) study, an international multicenter cohort, we included males with nonsevere hemophilia (FVIII/IX, 0.02-0.35 IU/mL) aged 12 to 55 years. Information on age at first treated (joint) bleed, annual bleeding rates (ABRs), and annual joint bleeding rates (AJBRs) was collected from the medical files. The association between baseline FVIII/IX levels and the joint bleeding rate was assessed by using a frailty model for recurrent events. In total, 304 persons (70 with moderate hemophilia and 234 with mild hemophilia) were included. The median age was 38 years (interquartile range [IQR], 25-49 years), and the median baseline FVIII/IX level was 0.12 IU/mL (IQR, 0.05-0.21 IU/mL). In total, 245 (81%) persons had experienced at least 1 bleed, and 156 (51%) had experienced at least 1 joint bleed. The median age at first bleed and first joint bleed was 8 and 10 years, respectively. The median ABR and AJBR was 0.2 (IQR, 0.1-0.5) and 0.0 (IQR, 0.0-0.2). From baseline FVIII/IX levels 0.02 to 0.05 IU/mL to >0.25 IU/mL, the median ABR decreased from 0.6 (IQR, 0.2-1.4) to 0.1 (IQR, 0.0-0.2) and the AJBR from 0.2 (IQR, 0.0-0.4) to 0.0 (IQR, 0.0-0.0). Baseline FVIII/IX was inversely associated with the joint bleeding rate (P < .001). Low bleeding rates were observed in persons with nonsevere hemophilia. However, one-half of all adolescents and adults had experienced a joint bleed.

Serum metabolomic profiles associated with subclinical and clinical cardiovascular phenotypes in people with type 2 diabetes

BackgroundAtherosclerotic cardiovascular diseases (CVD) is the leading cause of death in diabetes, but the full range of biomarkers reflecting atherosclerotic burden and CVD risk in people with diabetes is unknown. Metabolomics may help identify novel biomarkers potentially involved in development of atherosclerosis. We investigated the serum metabolomic profile of subclinical atherosclerosis, measured using ankle brachial index (ABI), in people with type 2 diabetes, compared with the profile for symptomatic CVD in the same population.MethodsThe Edinburgh Type 2 Diabetes Study is a cohort of 1,066 individuals with type 2 diabetes. ABI was measured at baseline, years 4 and 10, with cardiovascular events assessed at baseline and during 10 years of follow-up. A panel of 228 metabolites was measured at baseline using nuclear magnetic resonance spectrometry, and their association with both ABI and prevalent CVD was explored using univariate regression models and least absolute shrinkage and selection operator (LASSO). Metabolites associated with baseline ABI were further explored for association with follow-up ABI and incident CVD.ResultsMean (standard deviation, SD) ABI at baseline was 0.97 (0.18, N = 1025), and prevalence of CVD was 35.0%. During 10-year follow-up, mean (SD) change in ABI was + 0.006 (0.178, n = 436), and 257 CVD events occurred. Lactate, glycerol, creatinine and glycoprotein acetyls levels were associated with baseline ABI in both univariate regression [βs (95% confidence interval, CI) ranged from − 0.025 (− 0.036, − 0.015) to − 0.023 (− 0.034, − 0.013), all p < 0.0002] and LASSO analysis. The associations remained nominally significant after adjustment for major vascular risk factors. In prospective analyses, lactate was nominally associated with ABI measured at years 4 and 10 after adjustment for baseline ABI. The four ABI-associated metabolites were all positively associated with prevalent CVD [odds ratios (ORs) ranged from 1.29 (1.13, 1.47) to 1.49 (1.29, 1.74), all p < 0.0002], and they were also positively associated with incident CVD [ORs (95% CI) ranged from 1.19 (1.02, 1.39) to 1.35 (1.17, 1.56), all p < 0.05].ConclusionsSerum metabolites relating to glycolysis, fluid balance and inflammation were independently associated with both a marker of subclinical atherosclerosis and with symptomatic CVD in people with type 2 diabetes. Additional investigation is warranted to determine their roles as possible etiological and/or predictive biomarkers for atherosclerotic CVD.