Differences In Pathophysiology Research Articles

Comparative features of superior versus inferior hemisphere microvasculature dropout in open-angle glaucoma

PurposeThis study aimed to investigate differences in microvasculature dropout (MvD) between the superior and inferior hemispheres in glaucoma patients.Study designRetrospective and cross-sectional.MethodsFifty-eight eyes of 58 open-angle glaucoma patients (age 61.12 ± 10.19 years, mean deviation − 7.32 ± 6.36 dB) were included. MvD was detected with en face images from swept-source optical coherence tomography angiography. Blood flow at the optic nerve head was measured with laser speckle flowgraphy, represented as the mean blur rate in tissue (MBRT). Logistic and linear regression models adjusted for age, intraocular pressure, axial length, and circumpapillary retinal nerve fiber layer thickness were used to investigate the relationship between various factors and MvD angle in each hemisphere.ResultsThe presence of inferior MvD was related to peripapillary atrophy-β area (odds ratio = 14.10 [2.49–234.00], P = 0.019). Superior MvD angle was significantly related to MBRT in the superior quadrant (β = −0.31 [− 0.60 – −0.02], P = 0.037). Inferior MvD angle was significantly related to peripapillary atrophy-β area (β = 0.49 [0.21–0.77], P = 0.001).ConclusionsOnly superior MvD demonstrated a significant relationship with reduced ocular blood flow. In contrast, inferior MvD was associated with mechanical stress. These findings may suggest a potential difference in pathophysiology between superior and inferior MvD.

Sex-Based Mechanisms of Cardiac Development and Function: Applications for Induced-Pluripotent Stem Cell Derived-Cardiomyocytes.

Males and females exhibit intrinsic differences in the structure and function of the heart, while the prevalence and severity of cardiovascular disease vary in the two sexes. However, the mechanisms of this sex-based dimorphism are yet to be elucidated. Sex chromosomes and sex hormones are the main contributors to sex-based differences in cardiac physiology and pathophysiology. In recent years, the advances in induced pluripotent stem cell-derived cardiac models and multi-omic approaches have enabled a more comprehensive understanding of the sex-specific differences in the human heart. Here, we provide an overview of the roles of these two factors throughout cardiac development and explore the sex hormone signaling pathways involved. We will also discuss how the employment of stem cell-based cardiac models and single-cell RNA sequencing help us further investigate sex differences in healthy and diseased hearts.

Acromegaly in humans and cats: Pathophysiological, clinical and management resemblances and differences

ObjectiveAcromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to morphologic craniofacial and acral changes as well as cardiometabolic complications, but the phenotypic changes and clinical presentation of acromegaly differ across species. Here, we review the pathophysiology, clinical presentation and management of acromegaly in humans and cats, and we provide a systematic comparison between this disease across these different species. DesignA comprehensive literature review of pathophysiology, clinical features, diagnosis and management of acromegaly in humans and in cats was performed. ResultsAcromegaly is associated with prominent craniofacial changes in both species: frontal bossing, enlarged nose, ears and lips, and protuberant cheekbones are typically encountered in humans, whereas increased width of the head and skull enlargement are commonly found in cats. Malocclusion, prognathism, dental diastema and upper airway obstruction by soft tissue enlargement are reported in both species, as well as continuous growth and widening of extremities resulting in osteoarticular compromise. Increase of articular joint cartilage thickness, vertebral fractures and spine malalignment is more evident in humans, while arthropathy and spondylosis deformans may also occur in cats. Generalized organomegaly is equally observed in both species. Other similarities between humans and cats with acromegaly include heart failure, ventricular hypertrophy, diabetes mellitus, and an overall increased cardiometabolic risk. In GH-secreting pituitary tumours, local compressive effects and behavioral changes are mostly observed in humans, but also present in cats. Cutis verticis gyrata and skin tags are exclusively found in humans, while palmigrade/plantigrade stance may occur in some acromegalic cats.Serum IGF-1 is used for acromegaly diagnosis in both species, but an oral glucose tolerance test with GH measurement is only useful in humans, as glucose load does not inhibit GH secretion in cats. Imaging studies are regularly performed in both species after biochemical diagnosis of acromegaly. Hypophysectomy is the first line treatment for humans and cats, although not always available in veterinary medicine. ConclusionAcromegaly in humans and cats has substantial similarities, as a result of common pathophysiological mechanisms, however species-specific features may be found.

#2709 Genome wide association study regarding disturbed AVF patency

Abstract Background and Aims Veins are frequently exposed to arterial circulation, as coronary artery bypass grafts (CABG) and as a peripheral venous bypass to treat atherosclerotic disease, or in the case of arterio-venous fistulas (AVF) to provide a vascular access for hemodialysis. Therapeutic success is dependent on proficient venous remodeling after introduction in the arterial circulation to sustain the increased hemodynamic pressure. Frequently observed adverse outcomes after the aforementioned procedures include the stenosis or total occlusion of the vein, requiring surgical or interventional treatment or leading to bypass/ AVF failure. Hereditary factors associated with disturbed venous patency have been previously investigated in all three conditions. For example, distinct VEGF-A as well as TGF-beta polymorphisms have been identified to correlate with AVF failure. In the present analysis we aimed at investigating whether genetic polymorphisms associated with disturbed venous patency after AVF creation are similar to findings in CABG and peripheral bypass patients in a genome wide association study. Method The analyses were conducted in White Europeans (N= 425,406) in the UK Biobank using regenie software. This software employs a linear mixed model that accounts for the impact of population structure and individual relatedness. Out of approximately 805,000 variants, we selected 606,201 high-quality variants to construct a relatedness model for regenie. These selected variants were identified by a genotyping rate exceeding 80%, minor allele frequencies greater than 1%, and Hardy-Weinberg equilibrium p-values below 10^-8. We adjusted for age, sex, BMI, smoking, and history venous thromboembolism. We assessed the association of 9,757,417 imputed SNPs, each having a minimum allele count of 12 and a minimum info score of 0.3. Results In total, 768 patients underwent at least 1 surgery for AVF creation. Out of those, 341 (44.4%) had a recorded procedure or diagnosis associated with disturbed fistula patency. The controls included 6067 CABGs and 384 peripheral bypasses with 76 (1.3%) and 67 (17.4%) recorded events, respectively. We found no genome wide significant associations for the tested SNPs and patency-related AVF complications (Fig. 1). Additionally, we also found no genome wide significant associations after combining the phenotypes (Fig. 2). Conclusion Multiple studies have evaluated genetic associations and adverse clinical outcomes after AVF creation. Nevertheless, the generalizability of these findings might be limited at least partially due to small sample sizes. While the sample size of the present analysis is similar to previous research efforts and therefore also comparably low, the lack of consistency in results might be suggestive of the difficulties research in this field faces. Additionally, we found no indication that impaired venous patency after AVF creation is related to complications after coronary or peripheral bypass surgery regarding genetic patient profiles. However, whether this is due to differences in pathophysiology and related genetic predispositions or due to the limited sample size and incidence rates of the present study remains to be determined in follow-up investigations.

Sex in cardiovascular disease: Why this biological variable should be considered in in vitro models.

Cardiovascular disease (CVD), the world's leading cause of death, exhibits notable epidemiological, clinical, and pathophysiological differences between sexes. Many such differences can be linked back to cardiovascular sexual dimorphism, yet sex-specific in vitro models are still not the norm. A lack of sex reporting and apparent male bias raises the question of whether in vitro CVD models faithfully recapitulate the biology of intended treatment recipients. To ensure equitable treatment for the overlooked female patient population, sex as a biological variable (SABV) inclusion must become commonplace in CVD preclinical research. Here, we discuss the role of sex in CVD and underlying cardiovascular (patho)physiology. We review shortcomings in current SABV practices, describe the relevance of sex, and highlight emerging strategies for SABV inclusion in three major in vitro model types: primary cell, stem cell, and three-dimensional models. Last, we identify key barriers to inclusive design and suggest techniques for overcoming them.

Acromegaly in humans, cats and dogs: epidemiological, pathophysiological, clinical and management resemblances and differences

Acromegaly in humans, cats and dogs: epidemiological, pathophysiological, clinical and management resemblances and differences

Impact of Sex and Diabetes in Patients with Heart Failure.

Heart failure (HF) is a complex clinical syndrome with a growing global health burden. This review explores the intersection of HF, diabetes mellitus, and sex, highlighting epidemiological patterns, pathophysiological mechanisms, and treatment implications. Despite similar HF prevalence in men and women, diabetes mellitus (DM) appears to exert a more pronounced impact on HF outcomes in women. Pathophysiological differences involve cardiovascular risk factors, severe left ventricular dysfunction, and coronary artery disease, as well as hormonal influences and inflammatory markers. Diabetic cardiomyopathy introduces a sex-specific challenge, with women experiencing common adverse outcomes related to increased fibrosis and myocardial remodeling. Treatment strategies, particularly sodium-glucose cotransporter 2 inhibitors, exhibit cardiovascular benefits, but their response may differ in women. The link between HF and DM is bidirectional, with diabetes significantly increasing the risk of HF, and vice versa. Additionally, the impact of diabetes on mortality appears more pronounced in women than in men, leading to a modification of the traditional gender gap observed in HF outcomes. A personalized approach is crucial, and further research to improve outcomes in the complex interplay of HF, diabetes, and sex is needed.

Risk Stratification of Patients with Psoriatic Arthritis and Ankylosing Spondylitis for Treatment with Tofacitinib: A Review of Current Clinical Data.

In this commentary, we review clinical data which helps inform individualized benefit-risk assessment for tofacitinib in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). ORAL Surveillance, a safety trial of patients ≥ 50years of age with rheumatoid arthritis (RA) and cardiovascular risk factors, found increased rates of safety outcomes (including major adverse cardiovascular events [MACE], malignancies excluding non-melanoma skin cancer, and venous thromboembolism) with tofacitinib versus tumor necrosis factor inhibitors (TNFi). Post hoc analyses of ORAL Surveillance have identified subpopulations with different relative risk versus TNFi; higher risk with tofacitinib was confined to patients ≥ 65years of age and/or long-time current/past smokers, and specifically for MACE, patients with a history of atherosclerotic cardiovascular disease (ASCVD). In patients without these risk factors, risk differences between tofacitinib and TNFi could not be detected. Given differences in demographics, pathophysiology, and comorbidities, we sought to examine whether the risk stratification observed in RA is also appropriate for PsA and AS. Data from the PsA tofacitinib development program show low absolute risk of safety outcomes in patients < 65years of age and never smokers, and low MACE risk in patients with no history of ASCVD, consistent with results from ORAL Surveillance. No MACE, malignancies, or venous thromboembolism were reported in the tofacitinib AS development program. The mechanism of the ORAL Surveillance safety findings is unknown, and there are no similar prospective studies of sufficient size and duration. Accordingly, it is appropriate to use a precautionary approach and extrapolate differentiating risk factors identified from ORAL Surveillance (age ≥ 65years, long-time current/past smoking, and history of ASCVD) to PsA and AS. We recommend an individualized approach to treatment decisions based on these readily identifiable risk factors, in line with updated labeling for Janus kinase inhibitors and international guidelines for the treatment of PsA and AS.Trial Registration: NCT02092467, NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02281552, NCT02187055, NCT02831855, NCT00413699, NCT00661661, NCT01877668, NCT01882439, NCT01976364, NCT00678210, NCT01710046, NCT01241591, NCT01186744, NCT01276639, NCT01309737, NCT01163253, NCT01786668, NCT03502616.

Age and Sex Differences in Pediatric Neuropathic Pain and Complex Regional Pain Syndrome: A Scoping Review.

Age and sex differences may exist in the frequency (incidence, prevalence) or symptoms of neuropathic pain (NP) and complex regional pain syndrome (CRPS) due to biopsychosocial factors (eg, neurodevelopment, physiological and hormonal changes, psychosocial differences) that evolve through childhood and adolescence. Age and sex differences may have implications for evaluating screening and diagnostic tools and treatment interventions. To map the existing literature on pediatric NP and CRPS with respect to age and sex distributions, and age and sex differences in symptomology and frequency. A scoping literature review was conducted. Databases were searched from inception to January 2023. Data were collected on study design, setting, demographics, and age and sex differences in frequency and symptoms. Eighty-seven studies were included. Distribution of participants with CRPS (n=37 studies) was predominantly early adolescence (10 to 14y) and female sex, while NP (n=42 studies) was most commonly reported throughout adolescence (10 to 19y) in both sexes. Forty-one studies examined age and sex differences in frequency; 6 studies reported higher frequency in adolescence. Very few studies (n=11) examined differences in symptomology. Large epidemiological studies are required to further understand age and sex differences in frequency of pediatric NP and CRPS. Age and sex differences must be considered when evaluating screening and diagnostic tools and treatment interventions to ensure relevance and validity to both sexes and across ages. Validated tools will improve understanding of age-dependent and sex-dependent differences in symptoms, pathophysiology, and psychosocial impact of pediatric NP and CRPS.

The dilemma of neuroprotection trials in times of successful endovascular recanalization.

The "translational roadblock" between successful animal stroke studies and neutral clinical trials is usually attributed to conceptual weaknesses. However, we hypothesized that rodent studies cannot inform the human disease due to intrinsic pathophysiological differences between rodents and humans., i.e., differences in infarct evolution. To verify our hypothesis, we employed a mixed study design and compared findings from meta-analyses of animal studies and a retrospective clinical cohort study. For animal data, we systematically searched pubmed to identify all rodent studies, in which stroke was induced by MCAO and at least two sequential MRI scans were performed for infarct volume assessment within the first two days. For clinical data, we included 107 consecutive stroke patients with large artery occlusion, who received MRI scans upon admission and one or two days later. Our preclinical meta-analyses included 50 studies with 676 animals. Untreated animals had a median post-reperfusion infarct volume growth of 74%. Neuroprotective treatments reduced this infarct volume growth to 23%. A retrospective clinical cohort study showed that stroke patients had a median infarct volume growth of only 2% after successful recanalization. Stroke patients with unsuccessful recanalization, by contrast, experienced a meaningful median infarct growth of 148%. Our study shows that rodents have a significant post-reperfusion infarct growth, and that this post-reperfusion infarct growth is the target of neuroprotective treatments. Stroke patients with successful recanalization do not have such infarct growth and thus have no target for neuroprotection.

The GUTFIT Cohort: Identifying dietary intake of Chinese New Zealanders with functional constipation

Distinct pathophysiology has been identified with disorders of gut-brain interactions (DGBI), including functional constipation (FC)(1,2), yet the causes remain unclear. Identifying how modifiable factors (i.e., diet) differ depending on gastrointestinal health status is important to understand relationships between dietary intake, pathophysiology, and disease burden of FC. Given that dietary choices are culturally influenced, understanding ethnicity-specific diets of individuals with FC is key to informing appropriate symptom management and prevention strategies. Despite distinct genetic and cultural features of Chinese populations with increasing FC incidence(3), DGBI characteristics are primarily described in Caucasian populations(2). We therefore aimed to identify how dietary intake of Chinese individuals with FC differs to non-Chinese individuals with FC, relative to healthy controls. The Gastrointestinal Understanding of Functional Constipation In an Urban Chinese and Urban non-Chinese New Zealander Cohort (GUTFIT) study was a longitudinal case-control study using systems biology to investigate the multi-factorial aetiology of FC. Here we conducted a cross-sectional dietary intake assessment, comparing Chinese individuals with FC (Ch-FC) against three control groups: a) non-Chinese with FC (NCh-FC) b) Chinese without FC (Ch-CON) and c) non-Chinese without FC (NCh-CON). Recruitment from Auckland, New Zealand (NZ) identified Chinese individuals based on self-identification alongside both parents self-identifying as Chinese, and FC using the ROME IV criteria. Dietary intake was captured using 3-day food diaries recorded on consecutive days, including one weekend day. Nutrient analysis was performed by Foodworks 10 and statistical analysis with SPSS using a generalised linear model (ethnicity and FC status as fixed factors). Of 78 enrolled participants, 66 completed the study and 64 (39.4 ± 9.2 years) completed a 3-day food diary at the baseline assessment. More participants were female (84%) than male (16%). FC and ethnicity status allocated participants into 1 of 4 groups: Ch-FC (n = 11), Ch-CON (n = 18), NCh-FC (n = 16), NCh-CON (n = 19). Within NCh, ethnicities included NZ European (30%), non-Chinese Asian (11%), Other European (11%), and Latin American (2%). Fibre intake did not differ between Ch-FC and NCh-FC (ethnicity × FC status interaction p&gt;0.05) but was independently lower overall for FC than CON individuals (21.8 ± 8.7 versus 27.0 ± 9.7 g, p&lt;0.05) and overall for Ch than NCh (22.1 ± 8.0 versus 27.0 ± 10.4 g, p&lt;0.05). Carbohydrate, protein, and fat intakes were not different across groups (p&gt;0.05 each, respectively). In the context of fibre and macronutrient intake, there is no difference between Ch-FC and NCh-FC. Therefore, fibre and macronutrients are unlikely to contribute to potential pathophysiological differences in FC between ethnic groups. A more detailed assessment of dietary intake concerning micronutrients, types of fibre, or food choices may be indicated to ascertain whether other dietary differences exist.

Exploring the Intersection of Narcolepsy and Attention Deficit Hyperactivity Disorder: Similarities, Differences, and Clinical Implications

Narcolepsy and attention deficit hyperactivity disorder (ADHD) are distinct neurobiological conditions characterized by overlapping symptoms, including excessive daytime sleepiness and cognitive dysfunction. Despite their differences in etiology and pathophysiology, recent studies have highlighted a potential association between the two disorders, with a significant prevalence of ADHD symptoms observed in narcolepsy patients. This narrative review explores the similarities and differences between narcolepsy and ADHD, focusing on their shared symptomatology, neurobiological mechanisms, challenges in diagnosis, and treatment implications. While both disorders exhibit disruptions in dopaminergic and noradrenergic neurotransmitter systems, differential diagnosis remains challenging due to overlapping clinical presentations. Polysomnography findings, such as appearance of sleep onset rapid eye movements in narcolepsy patients, provide important distinctions that enable accurate diagnosis. Treatment strategies often involve stimulant medications for symptom management; however, nonpharmacological interventions, such as cognitive behavioral therapy, have been shown to have the potential to improve patient outcomes. Clinicians must consider the possibility of coexisting narcolepsy in ADHD patients and vice versa to ensure appropriate treatment selection and optimal patient care. Further research is needed to refine diagnostic criteria, elucidate the complex interplay between the two disorders, and develop personalized therapeutic approaches. A multidisciplinary approach involving sleep specialists, neurologists, psychiatrists, and psychologists is essential to address the diverse biopsychosocial needs of patients with concurrent narcolepsy and ADHD.

Cardiogenic shock-sex-specific risk factors and outcome differences.

Cardiogenic shock (CS) remains a high-mortality condition despite technological and therapeutic advances. One key to potentially improving CS prognosis is understanding patient heterogeneity and which patients may benefit most from different treatment options, a key element of which is sex differences. While cardiovascular diseases (CVDs) have historically been considered a male-dominant condition, the field is increasingly aware that females are also a substantial portion of the patient population. While estrogen has been implicated in protective roles against CVD and tissue hypoxia, its role in CS remains unclear. Clinically, female CS patients tend to be older, have more severe comorbidities and are more likely to have non-acute myocardial infarction etiologies with preserved ejection fractions. Female CS patients are more likely to receive pharmacotherapy while less likely to receive mechanical circulatory support. There is increased short-term mortality in females, although long-term mortality is similar between the sexes. More sex-specific and age-stratified research needs to be done to fully understand the relevant pathophysiological differences in CS, to better recognize and manage CS patients and reduce its mortality.

Differences in Pathophysiology and Treatment Efficacy Based on Heterogeneous Out-of-Hospital Cardiac Arrest.

Out-of-hospital cardiac arrest (OHCA) is heterogeneous in terms of etiology and severity. Owing to this heterogeneity, differences in outcome and treatment efficacy have been reported from case to case; however, few reviews have focused on the heterogeneity of OHCA. We conducted a literature review to identify differences in the prognosis and treatment efficacy in terms of CA-related waveforms (shockable or non-shockable), age (adult or pediatric), and post-CA syndrome severity and to determine the preferred treatment for patients with OHCA to improve outcomes.

Comparison of β-Cell Function and Insulin Sensitivity Between Normal-Weight and Obese Chinese With Young-Onset Type 2 Diabetes.

Normal-weight individuals with usual-onset type 2 diabetes had reduced beta-cell function and greater insulin sensitivity compared to their obese counterparts. The relative contribution of beta-cell dysfunction and insulin resistance to young-onset type 2 diabetes (YOD) among normal-weight individuals is not well established. In 44 individuals with YOD (24 normal-weight and 20 obese) and 24 healthy controls with normoglycemia (12 normal-weight and 12 obese), we conducted 2-h 12mmol/L hyperglycemic clamps to measure acute (0-10 minute) and steady-state (100-120 minute) insulin and C-peptide responses, and insulin sensitivity index. Normal-weight individuals with YOD had lower acute insulin response, steady-state insulin and C-peptide responses, and higher insulin sensitivity index compared to their obese counterparts with YOD. When compared to BMI-matched healthy controls, normal-weight individuals with YOD had lower acute and steady-state insulin and C-peptide responses but similar insulin sensitivity index. The impairment of steady-state beta-cell response relative to healthy controls was more pronounced in normal-weight versus obese individuals with YOD. In conclusion, normal-weight Chinese with YOD exhibited worse beta-cell function but preserved insulin sensitivity relative to obese individuals with YOD and BMI-matched healthy individuals with normoglycemia. The selection of glucose-lowering therapy should account for pathophysiological differences underlying YOD between normal-weight and obese individuals.

A Comparative Review of Typical and Atypical Optic Neuritis: Advancements in Treatments, Diagnostics, and Prognosis.

Optic neuritis (ON) is a debilitating condition thatthrough various mechanisms, including inflammation or demyelination of the optic nerve, can result in partial or total permanent vision loss if left untreated. Accurate diagnosis and promptly initiated treatment are imperative related to the potential of permanent loss of vision if left untreated, which can lead to a significant reduction in the quality of life in affected patients. ONis subtyped as "typical" or "atypical" based on underlying causative etiology. The etiology of ON can be differentiated when appropriate diagnostic testing is performed. Using history taking, neuroimaging, and visual testing to localize the underlying pathology of ON in a time-sensitive manner is critical in mitigating these unsatisfactory outcomes. Herein, we examine the differences in presentation, pathophysiology, and treatments of typical ON causes, like multiple sclerosis (MS), and atypical causes such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) ON. The present investigation places focus on both neuroimaging and visual imaging in the differentiation of ON. Additionally, this review presents physicians with a better understanding of different presentations, treatments, and prognoses of ON.

Impact of biological sex on valvular heart disease, interventions, and outcomes.

Valvular heart disease (VHD) is common, affecting>14% of individuals aged >75, and is associated with morbidity, including heart failure and arrhythmia, and risk of early mortality. Increasingly, important sex differences are being found between males and females with VHD. These sex differences can involve the epidemiology, pathophysiology, presentation, diagnosis, and outcomes of the disease. Females are often disadvantaged, and female sex has been shown to be associated with delayed diagnosis and inferior outcomes in various forms of VHD. In addition, the unique pathophysiologic state of pregnancy is associated with increased risk for maternal and fetal morbidity and mortality in many forms of VHD. Therefore, understanding and recognizing these sex differences, and familiarity with the attendant risks of pregnancy and management of pregnant females with VHD, is of great importance for any primary care or cardiovascular medicine practitioner caring for the female patient. This review will outline sex differences in aortic, mitral, pulmonic, and tricuspid VHD, with particular focus on differences in pathophysiology, clinical presentation, and outcomes. In addition, the pathophysiology and management implications of pregnancy will be discussed.

Mid-pregnancy allopregnanolone levels and trajectories of perinatal depressive symptoms

Perinatal depression is a major cause of disability for individuals giving birth worldwide, with detrimental effects on short- and long-term parental and child outcomes. There is emerging evidence that the neuroactive steroid hormone allopregnanolone is implicated in the pathophysiology and course of perinatal mood symptoms. However, no study thus far has examined allopregnanolone levels whilst making use of longitudinal data on depressive symptom trajectories throughout the perinatal period. The present study investigated levels of allopregnanolone at gestational week 17 of 252 participants in relation to perinatal depressive symptom trajectories, with a secondary aim of exploring the role of history of depression as an effect modifier. Four perinatal depressive symptom trajectories were investigated: controls (no depressive symptoms throughout perinatal period) (N=161), antepartum (depressive symptoms prenatally with postpartum remission) (N=31), postpartum-onset (no depressive symptoms during pregnancy, development of depressive symptoms postpartum) (N=23), and persistent (depressive symptoms throughout the perinatal period) (N=37). Results show that for every one nmol/l increase in allopregnanolone, there was 7% higher odds for persistent depressive symptoms (OR 1.07, 95% CI 1.01–1.14) compared to controls. No association was seen for antepartum and postpartum-onset depressive symptoms. History of depression did not modify the association between allopregnanolone and perinatal depressive symptom trajectories. These results show the role of allopregnanolone for persistent depressive symptoms and strengthen the hypothesis of differences in pathophysiology among the trajectories.

Right Heart Remodeling and Outcomes in Patients With Tricuspid Regurgitation: A Literature Review and Meta-Analysis

BackgroundFunctional tricuspid regurgitation (TR) can develop either because of right ventricular (RV) remodeling (ventricular functional TR) and/or right atrial dilation (atrial functional TR). ObjectivesThis meta-analysis aimed to investigate the association between right heart remodeling and long-term (>1 year) all-cause mortality in patients with significant TR (at least moderate, ≥2+). MethodsMEDLINE, ISI Web of Science, and SCOPUS databases were searched. Studies reporting data on at least 1 RV functional parameter and long-term all-cause mortality in patients with significant TR were included. This study was designed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) requirements. ResultsOut of 8,902 studies, a total of 14 were included, enrolling 4,394 subjects. The duration of follow-up across the studies varied, ranging from a minimum of 15.5 months to a maximum of 73.2 months. Overall, long-term all-cause mortality was 31% (95% CI: 20%-41%; P ≤ 0.001). By means of meta-regression analyses, an inverse relation was found between tricuspid annular plane systolic excursion (11 studies enrolling 3,551 subjects, −6.3% [95% CI: −11.1% to −1.4%]; P = 0.011), RV fractional area change (9 studies, 2,975 subjects, −4.4% [95% CI: −5.9% to −2.9%]; P < 0.001), tricuspid annular dimension (7 studies, 2,986 subjects, −4.1% [95% CI: −7.6% to −0.5%]; P = 0.026), right atrial area (6 studies, 1,920 subjects, −1.9% [95% CI: −2.5% to −1.3%]; P < 0.001) and mortality. ConclusionsRV dysfunction parameters are associated to worse clinical outcomes in patients with TR, whereas right atrial dilatation is linked to a better prognostic outcome. Further studies are needed to unravel the pathophysiological differences within the functional TR spectrum. (Right heart remodeling and outcomes in patients with tricuspid regurgitation; CRD42023418667)

Gender Differences in Adults With Chronic Rhinosinusitis: A Scoping Review.

Gender differences in chronic rhinosinusitis (CRS) have been demonstrated in many studies over the last 15 years. The purpose of this scoping review is to investigate the current knowledge on gender differences in CRS and to analyze the gaps in the literature. A systematic search of PubMed, Cochrane Library, and Embase databases was performed. This scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Studies that evaluated gender differences in CRS were included in the review. Of the 523 abstracts reviewed, a total of 23 studies met the criteria for inclusion. Articles consisted of retrospective and prospective cohort studies. They were divided into 3 categories based on whether they evaluated gender differences in (1) presentation and baseline quality of life, (2) pathophysiology, and/or (3) outcomes of treatment. Eleven studies addressed differences in presentation, 5 addressed differences in pathophysiology, and 10 dealt with differences in outcomes after surgical or medical management. Most of the studies showed worse baseline QoL secondary to CRS in women, with outcome of treatment being similar in both genders. The experience of CRS appears to vary between genders, with women experiencing a greater subjective burden of disease than men, though with similar outcomes after treatment. Further research is indicated, particularly involving the pathophysiology of CRS, to fully understand the underlying causes of these discrepancies.