Common Pathophysiological Pathway Research Articles

Severity of kidney involvement as predictor of death, severe heart failure and renal events in patients with type 2 diabetes: Data from a prospective cohort

Type 2 diabetes is associated with an increased risk for end-stage renal disease and heart failure, contributing to premature death. All these 3 events are inter-related, suggesting common risk factors and/or pathophysiological pathways. The SURDIAGENE (SUrvie Rénale DIAbète et GENEtique) cohort is a single center hospital-based cohort of persons living with type 2 diabetes, recruiting participants at Poitiers university hospital, France, from 2002 to 2011 with further follow-up till 2015. Here, we describe the cumulative prevalence of hard renal events (sustained doubling of serum creatinine and/or renal replacement therapy), heart failure leading to hospitalization (HFH) and all-cause death, according to the KDIGO classification, which considers CKD stages according to CKD EPI equation [1–5] and albuminuria (A1, A2, A3) according to albumin/creatinine ratio with thresholds at 30 and 300 mg/g. We considered 1450 participants with KDIGO stage available at baseline. Considering a cumulated follow-up duration of 10,667 patient.years with 100 renal events, 247 HFH and 527 deaths, our study showed that the more severe the KDIGO stage, the higher the incidence rate not only for renal event, but also for HFH and for all-cause death. For instance, in CKD1A1 and CKD4A3 the incidence rates for hard renal events, HFH and death were 0.98 and 140.70, 4.46 and 107.09, 13.64 and 156.56 per 1000 patient.years, respectively. Interestingly, the incidence of renal event was lower than the incidence of all-cause death in all KDIGO stages, at variance with the data from recent renal outcome trials on SGLT2 inhibitors and finerenone. We conclude that KDIGO stages should be considered for renal but also for HFH risk classification. The analysis of the respective incidence of renal events and deaths in observational studies and RCTs deserves further evaluation in type 2 diabetes.

Biological Mechanism-based Neurology and Psychiatry: A BACE1/2 and Downstream Pathway Model.

In oncology, comprehensive omics and functional enrichment studies have led to an extensive profiling of (epi)genetic and neurobiological alterations that can be mapped onto a single tumor's clinical phenotype and divergent clinical phenotypes expressing common pathophysiological pathways. Consequently, molecular pathway-based therapeutic interventions for different cancer typologies, namely tumor type- and site-agnostic treatments, have been developed, encouraging the real-world implementation of a paradigm shift in medicine. Given the breakthrough nature of the new-generation translational research and drug development in oncology, there is an increasing rationale to transfertilize this blueprint to other medical fields, including psychiatry and neurology. In order to illustrate the emerging paradigm shift in neuroscience, we provide a state-of-the-art review of translational studies on the β-site amyloid precursor protein cleaving enzyme (BACE) and its most studied downstream effector, neuregulin, which are molecular orchestrators of distinct biological pathways involved in several neurological and psychiatric diseases. This body of data aligns with the evidence of a shared genetic/biological architecture among Alzheimer's disease, schizoaffective disorder, and autism spectrum disorders. To facilitate a forward-looking discussion about a potential first step towards the adoption of biological pathway-based, clinical symptom-agnostic, categorization models in clinical neurology and psychiatry for precision medicine solutions, we engage in a speculative intellectual exercise gravitating around BACE-related science, which is used as a paradigmatic case here. We draw a perspective whereby pathway-based therapeutic strategies could be catalyzed by highthroughput techniques embedded in systems-scaled biology, neuroscience, and pharmacology approaches that will help overcome the constraints of traditional descriptive clinical symptom and syndrome-focused constructs in neurology and psychiatry.

The possible association between neurodegenerative/demyelinating neurological disorders in achalasia patients.

The precise pathogenesis of achalasia is still unclear. Neurodegenerative and/or demyelinating disorders (NDD) appear to share some common pathophysiological pathways described in achalasia such as inflammation, autoimmune, mitochondrial dysfunction, and neurodegeneration. Jerie et al. have published on the October issue a prospective study assessing the prevalence of several NDD in achalasia patients. In this commentary, we shed some light on the possible link between achalasia and NDD as well as comment on the study by Jerie et al.

The Pathophysiological Relationship Between Migraine and SARS-CoV-2 Infection: A Comprehensive Literature Review

People with migraine, and individuals with other neurological conditions, have suffered in multiple aspects during the COVID-19 pandemic. This paper will discuss the factors that impacted the neurology department. The emergence of severe acute respiratory syndrome coronavirus 2 in late 2019 has generated new challenges in healthcare systems across the globe. Similar to the fields of pulmonology and cardiology that saw an increase in research, the neurology department was in search of possible relationships between COVID-19 and other medical conditions. Research on the possible common pathophysiological mechanism between COVID-19 and migraine is currently being studied. The most recent hypothesis suggests the following: migraine is caused by an increased release of calcitonin gene-related peptide from the trigeminal ganglion, which will cause an increase in nitric oxide and IL-1β, resulting in vasodilation and inducing hyperalgesia. COVID-19 causes an increase in nod-like receptor protein 3, which causes the production of IL-1β and again induces an inflammatory response. This review article looks at the mechanisms of migraine and COVID-19, and tries to link a common pathophysiological pathway between the two. This report also serves as a gateway for further research regarding possible management that could potentially target both of these mechanisms.

Blood pressure regulation change with ageing: in-depth analysis of 1439 subjects with arterial hypertension and autonomic neuropathy.

Introduction: Blood pressure (BP) regulation is affected by ageing through different mechanisms, including alteration of neural control. Blood pressure variability (BPV) and heart rate variability (HRV) reflect the interaction of BP control mechanisms, and both increased BPV and reduced HRV have been associated to increased cardiovascular morbidity and mortality. The objective of this study was to assess BPV and HRV in hypertensive subjects in different age ranges and to compare them with subjects with established primary cardiovascular dysautonomia, i.e., Parkinson and related diseases. Methods: The study will include 1,439 subjects, divided in three groups: 777 hypertensive subjects aged 40-55 years, 601 hypertensive subjects aged 75-95 years, and 61 patients with primary cardiovascular autonomic neuropathy. Short-term BPV will be assessed through standard deviation (SD), weighted standard deviation (wSD), average real variability (ARV), coefficient of variation (CV), and variability independent of mean (VIM) of 24h ambulatory BP monitoring (ABPM). HRV will be evaluated by SD and CV of heart rate measured during ABPM. Expected outcomes: The expected outcomes of this study include the comparison of overall BPV and mid-term HRV among the three study subgroups, in order to identify similarities and differences in these indexes and to highlight possible common pathophysiological pathways. Furthermore, the characteristics associated with higher BPV and HRV will be analyzed in the three subgroups and compared among them. Similarly, differences in dipping and orthostatic hypotension prevalence will be assessed and characteristics associated with non-dipping status and presence of orthostatic hypotension will be reported. Finally, the association of increased BPV and reduced HRV with organ damage and cardiovascular morbidity will be evaluated.

An Overview of Mindfulness-Oriented Addiction and Pain Recovery.

There is evidence that mindfulness-based interventions are effective as stress-reduction techniques in people with various stressor-related disorders. Research also shows overall improvement in mental health well-being in practitioners of mindfulness. However, there is limited literature probing the potential negative impacts of mindfulness practice. Relapse is a major challenge in substance use disorders (SUDs), particularly for people with chronic pain. There is an overlap between SUDs and chronic pain, which share common pathophysiological pathways that could contribute to poor pain control and mental instability. In this report, we discuss the possible effects of mindfulness on specified aspects of substance craving and chronic pain perception. We propose future directions for research in mindfulness practices to maximize the potential for relapse prevention and pain control.

PC027 / #1035 EFFICIENCY OF HOME-BASED TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) ON DYSFUNCTIONAL EATING BEHAVIOR IN WOMEN WITH FIBROMYALGIA: TRACK 2: BRAIN STIMULATION

Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain, non-restorative sleep, fatigue, cognitive changes, and depressive and anxiety symptoms. There is a high prevalence of overweight in these patients, around 80%. Studies demonstrate common pathophysiological pathways between FM and obesity, such as dysfunctional eating behavior and altered dopaminergic neurotransmission. In this context, the contribution of non-pharmacological interventions, in order to rebalance the dopaminergic system, such as transcranial direct current stimulation (tDCS), are important.

Relationship between cognitive function in individuals with diabetic foot ulcer and mortality

BackgroundDiabetic foot ulcer (DFU) is a common diabetes mellitus (DM) complication. Individuals with DM and a DFU achieved significantly lower scores in cognitive tests than those without a DFU. We investigated whether baseline cognitive function in individuals with a DFU is a determinant of mortality.MethodsA prospective study using data collected during a case–control study conducted in 2010–2012 whereby 90 participants with a DFU (mean age at baseline 58.28 ± 6.95 years, 75.6% male) took the paper and pencil and the NeuroTrax battery of cognitive tests. Depression was assessed, and the DFU status was evaluated. In 2020, information pertaining to participants’ vital status (dead/alive) was collected and the relationship between baseline cognitive status and vital status was assessed.ResultsDuring a median follow-up of 6.8 years (range 0.2–9.5), 39 participants died (43.3%). Individuals alive vs. those who had died during follow-up had a higher global cognitive score at baseline (92.16 ± 10.95 vs. 87.18 ± 12.24, p = 0.045), but increased risk was not found. Individuals who were alive vs. those who had died during follow-up had statistically significantly higher baseline executive function, reaction time and digit symbol substitution test results. However, after adjustment for glycosylated hemoglobin (HbA1c), microvascular and macrovascular complications, no relationship between cognitive tests and mortality remained significant.ConclusionsThe higher mortality rate among people with type 2 DM and a DFU was not significant after adjustment for HbA1c, micro- and macrovascular complications. There may be common pathophysiological pathways to both DM complications and cognitive impairment, which may contribute to increased mortality. Further studies are warranted.

Assessment of Kidney Dysfunction in Patients with Chronic Heart Failure

BACKGROUND: Heart failure and kidney disease share common pathophysiological pathways which can lead to mutual dysfunction, known as cardiorenal syndrome. The formation of cardiorenal syndrome in patients with chronic heart failure (CHF) is a natural manifestation of a functionally interconnected process at the organ level. Renal dysfunction is a common and independent factor in the progression of the disease, a high incidence of cardiovascular events, and death in the population. AIM: The aim of the study of the relationship between kidney dysfunction and the clinical course of the disease, quality of life, and indicators of the left ventricular systolic function in patients with CHF. MATERIALS AND METHODS: The study involved 150 patients with CHF I–III functional class according to the New York Heart Association. Exercise tolerance (6 min walk test) was assessed, the clinical condition was assessed using the clinical assessment scale, and the quality of life of patients with CHF (QoL) was assessed according to the Minnesota QOL questionnaire. An assessment of the functional state of the kidneys was carried out: The level of serum creatinine was determined; glomerular filtration rate (GFR) was calculated using the calculation formulas CKD-EPI. The assessment of renal blood flow was carried out using the ultrasound apparatus “SONOACEX6” (Korea). The structural and functional state of the myocardium and the process of left ventricle (LV) remodeling were assessed using the “MEDISON ACCUVIX V20” echocardiograph (Korea), using a 3.25 MHz transducer in standard echocardiographic positions, by the transthoracic method in accordance with the recommendations of the American Association of Echocardiography. RESULTS: The results of the study of physical performance according to 6 min walk test in patients of Group I with CHF GFR >60 ml/min/1.73 m2 were 363.59 ± 7.6 m, respectively. The decrease in the distance traveled according to the 6 min walk test data in Group II of patients with eGFR ≤60 ml/min/1.73 m2, exercise tolerance was more pronounced than in patients of Group I and this figure was 248.7 ± 11.0 m, which was 46.2% lower than the results of Group I of the study (p < 0.001). Analysis of the parameters of clinical manifestations according to the data of the clinical assessment scale showed that in patients of Group I, the total score was 5.5 ± 0.13 points. In CHF patients with renal dysfunction, changes were also noted at the level of the lobar and segmental renal arteries, characterized by a significant increase in pulsatility index and resistance index, there was a decrease in speed indicators during diastole, systole, and the average blood flow velocity. Further analysis of the parameters of LV systolic function ejection fraction (EF), as well as fractional shortening of the LV in systole (Fs%), showed that in Group II, these indicators had significant differences with Group I. There was a significant difference in EF by 10.5% and 25.4% and Fs% by 11.2% (p < 0.001). CONCLUSION: In CHF patients with impaired renal function, changes in renal blood flow were characterized by a significant increase in pulsatile and resistive indices, a decrease in the rate of renal blood flow at the level of the lobar and segmental renal arteries.

Non-alcoholic fatty liver disease-related fibrosis and sarcopenia: An altered liver-muscle crosstalk leading to increased mortality risk.

In the last few decades, the loss of skeletal muscle mass and function, known as sarcopenia, has significantly increased in prevalence, becoming a major global public health concern. On the other hand, the prevalence of non-alcoholic fatty liver disease (NAFLD) has also reached pandemic proportions, constituting the leading cause of hepatic fibrosis worldwide. Remarkably, while sarcopenia and NAFLD-related fibrosis are independently associated with all-cause mortality, the combination of both conditions entails a greater risk for all-cause and cardiac-specific mortality.Interestingly, both sarcopenia and NAFLD-related fibrosis share common pathophysiological pathways, including insulin resistance, chronic inflammation, hyperammonemia, alterations in the regulation of myokines, sex hormones and growth hormone/insulin-like growth factor-1 signaling, which may explain reciprocal connections between these two disorders. Additional contributing factors, such as the gut microbiome, may also play a role in this relationship. In skeletal muscle,phosphatidylinositol 3-kinase/Akt and myostatin signaling are the central anabolic and catabolic pathways, respectively, and the imbalance between them can lead to muscle wasting in patients with NAFLD-related fibrosis. In this review, we summarize the bidirectional influence between NAFLD-related fibrosis and sarcopenia, highlighting the main potential mechanisms involved in this complex crosstalk, and we discuss the synergistic effects of both conditions in overall and cardiovascular mortality.

Targeting Gut Microbiota as a Novel Strategy for Prevention and Treatment of Hypertension, Atrial Fibrillation and Heart Failure: Current Knowledge and Future Perspectives.

Cardiovascular diseases (CVDs) remain the major public health concern worldwide. Over the last two decades, a considerable amount of literature has been published on gut microbiota (GMB) composition and its metabolites, involved in the pathophysiology of CVDs, including arterial hypertension, atrial fibrillation, and congestive heart failure. Although many types of medicines are available to treat CVD, new therapeutic tools are needed to improve clinical outcomes. A challenge that often arises in the researchers’ community is how to manipulate the GMB to manage cardiovascular risk factors. Therapeutic strategies designed to manipulate GMB composition and/or its metabolites include dietary approaches, prebiotics/probiotics supplementation, and fecal microbiota transplantation (FMT). In this review, we have focused on three main cardiovascular pathologies (arterial hypertension, atrial fibrillation and heart failure) due to their shared common pathophysiological pathways and structural changes in myocardium, such as inflammation, hypertrophy, fibrosis, and myocardial remodeling. The main aims of the review are: (1) to summarize current knowledge on the key pathophysiologic links between GMB and CVDs, and (2) discuss the results of the studies on GMB modulation for the prevention and treatment of selected CVDs.

Nonmalignant Central Airway Obstruction: Options for Challenging Cases.

Benign central airway obstruction is commonly referred as nonmalignant central airway obstruction (NMCAO). This is in part related to its lack of benign nature and significant life-quality impairment in patients. It is a pathologic entity with various etiologies and therefore a wide range of therapeutic options are available. Evidence regarding the optimal management that could provide a sustained restoration of airway patency is lacking. The lack of a common pathophysiologic pathway translating into a nonspecific symptom presenting as NMCAO has complicated treatment standardization and subsequently limited solid research to favor of one approach over another one. Our intent is to describe the limited evidence of the most utilized nonsurgical treatment for NMCAO as well as some upcoming promising therapeutic options such as mitomycin C injection, microdebrider, biodegradable stents, radiotherapy, Hybrid Knife, and endoluminal spray cryotherapy. Our goal with this manuscript is to motivate other authors to venture into prospective, multicenter, open-label trials aimed to describe long-term outcomes in patients with NMCAO.

Single Nucleotide Polymorphisms (SNP) and SNP-SNP Interactions of the Surfactant Protein Genes Are Associated With Idiopathic Pulmonary Fibrosis in a Mexican Study Group; Comparison With Hypersensitivity Pneumonitis.

Surfactant proteins (SPs) are important for normal lung function and innate immunity of the lungs and their genes have been identified with significant genetic variability. Changes in quantity or quality of SPs due to genetic mutations or natural genetic variability may alter their functions and contribute to the host susceptibility for particular diseases. Alternatively, SP single nucleotide polymorphisms (SNPs) can serve as markers to identify disease risk or response to therapies, as shown for other genes in a number of other studies. In the current study, we evaluated associations of SFTP SNPs with idiopathic pulmonary fibrosis (IPF) by studying novel computational models where the epistatic effects (dominant, additive, recessive) of SNP-SNP interactions could be evaluated, and then compared the results with a previously published hypersensitivity pneumonitis (HP) study where the same novel models were used. Mexican Hispanic patients (IPF=84 & HP=75) and 194 healthy control individuals were evaluated. The goal was to identify SP SNPs and SNP-SNP interactions that associate with IPF as well as SNPs and interactions that may be unique to each of these interstitial diseases or common between them. We observed: 1) in terms of IPF, i) three single SFTPA1 SNPs to associate with decreased IPF risk, ii) three SFTPA1 haplotypes to associate with increased IPF risk, and iii) a number of three-SNP interactions to associate with IPF susceptibility. 2) Comparison of IPF and HP, i) three SFTPA1 and one SFTPB SNP associated with decreased risk in IPF but increased risk in HP, and one SFTPA1 SNP associated with decreased risk in both IPF and HP, ii) a number of three-SNP interactions with the same or different effect pattern associated with IPF and/or HP susceptibility, iii) one of the three-SNP interactions that involved SNPs of SFTPA1, SFTPA2, and SFTPD, with the same effect pattern, was associated with a disease-specific outcome, a decreased and increased risk in HP and IPF, respectively. This is the first study that compares the SP gene variants in these two phenotypically similar diseases. Our findings indicate that SNPs of all SFTPs may play an important role in the genetic susceptibility to IPF and HP. Importantly, IPF and HP share some SP genetic variants, suggesting common pathophysiological mechanisms and pathways regarding surfactant biogenesis, but also some differences, highlighting the diverse underlying pathogenic mechanisms between an inflammatory-driven fibrosis (HP) and an epithelial-driven fibrosis (IPF). Alternatively, the significant SNPs identified here, along with SNPs of other genes, could serve as markers to distinguish these two devastating diseases.

Structural and Hemodynamic Changes of the Right Ventricle in PH-HFpEF.

One of the most important diagnostic challenges in clinical practice is the distinction between pulmonary hypertension (PH) due to primitive pulmonary arterial hypertension (PAH) and PH due to left heart diseases. Both conditions share some common characteristics and pathophysiological pathways, making the two processes similar in several aspects. Their diagnostic differentiation is based on hemodynamic data on right heart catheterization, cardiac structural modifications, and therapeutic response. More specifically, PH secondary to heart failure with preserved ejection fraction (HFpEF) shares features with type 1 PH (PAH), especially when the combined pre- and post-capillary form (CpcPH) takes place in advanced stages of the disease. Right ventricular (RV) dysfunction is a common consequence related to worse prognosis and lower survival. This condition has recently been identified with a new classification based on clinical signs and progression markers. The role and prevalence of PH and RV dysfunction in HFpEF remain poorly identified, with wide variability in the literature reported from the largest clinical trials. Different parenchymal and vascular alterations affect the two diseases. Capillaries and arteriole vasoconstriction, vascular obliteration, and pulmonary blood fluid redistribution from the basal to the apical district are typical manifestations of type 1 PH. Conversely, PH related to HFpEF is primarily due to an increase of venules/capillaries parietal fibrosis, extracellular matrix deposition, and myocyte hypertrophy with a secondary “arteriolarization” of the vessels. Since the development of structural changes and the therapeutic target substantially differ, a better understanding of pathobiological processes underneath PH-HFpEF, and the identification of potential maladaptive RV mechanisms with an appropriate diagnostic tool, become mandatory in order to distinguish and manage these two similar forms of pulmonary hypertension.

Effect of Tricuspid Regurgitation on the Reported Quality of Life and Subsequent Outcomes in Patients With Atrial Fibrillation.

BackgroundAtrial fibrillation and heart failure (HF) possess mutual risk factors and share a common pathophysiological pathway. Tricuspid regurgitation (TR) is a known predictor of adverse events in patients with HF. However, its implications on patients with atrial fibrillation in its early stage remain unknown.Methods and ResultsData of 2211 patients without previous HF diagnosis were extracted from a prospective, multicenter registry of newly diagnosed patients with atrial fibrillation. TR was categorized as absent, mild, moderate, and severe based on the American Society of Echocardiography recommendations. The primary outcome was time to first hospitalization for HF after enrollment. The Atrial Fibrillation Effects on Quality‐of‐Life scores were compared. Overall, 1107 patients (50.1%) had TR (42.3%, 7.2%, and 0.6% for mild, moderate, and severe, respectively). During follow‐up (median 730 [interquartile range, 366–731] days), 44 patients (2.0%) experienced HF hospitalization, and the incidence increased with severity of TR (P<0.001). TR was an associated predictor of the primary outcome (hazard ratio [HR]: 2.51, P=0.050; HR: 6.19, P=0.008; for moderate and severe TR versus no TR). Changes in AFEQT overall score were negatively related to TR severity (8.7±17.5 versus 8.5±17.0 versus 3.1±17.5 versus 1.4±11.8, absent versus mild versus moderate versus severe TR, respectively), although it was not an independent predictor after adjustments.ConclusionsTR severity at atrial fibrillation diagnosis was an associated predictor of subsequent hospitalization for HF, which may warrant the need for a more intensive follow‐up and HF‐related management.

Development of Open-Angle Glaucoma in Adults With Seropositive Rheumatoid Arthritis in Korea

Although evidence is emerging that autoimmunity may be associated with neurodegeneration in glaucoma (beyond intraocular pressure-mediated damage), there is limited evidence connecting rheumatoid arthritis (RA), the most common autoimmune disease, with the risk of developing primary open-angle glaucoma (POAG). To investigate whether RA is associated with increased risk of POAG among Korean older adults. A nationwide propensity-matched cohort study was conducted using data from the Korean National Health Insurance Service-Senior cohort from 2002 to 2013. Data analysis was performed from November 2020 to July 2021. New onset RA. The main outcome was development of POAG. The Kaplan-Meier method was used to calculate the cumulative incidence of POAG, and the incidence rate of POAG was estimated using a Poisson regression. A Cox proportional hazards regression model was used to investigate associations between RA and risk of POAG. Among 10 245 participants, 7490 (73.1%) were women, and the mean (SD) age was 67.70 (4.84) years. A total of 2049 patients with incident seropositive RA and 8196 time-dependent, propensity score-matched, risk-set controls were included. POAG developed in 86 of 2049 patients with RA and 254 of 8196 matched controls. The cumulative incidence of POAG was higher in the RA cohort than in the matched controls. In the RA cohort, the incidence rate of POAG was 981.8 cases per 100 000 person years (95% CI, 794.3-1213.7 cases per 100 000 person years), whereas in the matched controls, the incidence rate was 679.5 cases per 100 000 person years (95% CI, 600.8-768.3 cases per 100 000 person years). Patients with RA were more likely to develop POAG than the matched controls (hazard ratio [HR], 1.44; 95% CI, 1.13-1.84). Increased POAG risk in the RA cohort was predominantly observed 2 years into the follow-up period (HR, 1.83; 95% CI, 1.28-2.61) and in those aged 75 years or older (HR, 2.12; 95% CI, 1.34-3.35). These findings suggest that RA is associated with a higher risk of developing POAG, especially within 2 years after diagnosis or among patients aged 75 years or older. There may be a common pathophysiological pathway between RA and POAG that is possibly immune mediated, and the nature of this association warrants further investigation.

The association between striae gravidarum and perineal lacerations during labor.

ObjectiveStriae gravidarum (SG) and perineal lacerations are common occurrences during late pregnancy and labor. It has been hypothesized that both conditions may share a common pathophysiological pathway through changes in the connective tissue. We aimed to investigate a possible association between these two conditions and whether the presence of SG may predict perineal lacerations.MethodsWe conducted a prospective cohort study that included women who gave birth at the Soroka University Medical Center (SUMC), Beer-Sheva, Israel. Those who provided informed consent were examined for the presence of SG using the Davey scoring system to determine the severity of abdominal SG. Clinical and obstetrical characteristics and the presence and degree of perineal tears were retrieved from the computerized patients’ records. Univariate analysis was carried using appropriate statistical tests.ResultsA total of 187 women were recruited. Of those, 81 (43.3%) did not have SG, 24 (12.8%) 43 (23%) and 39 (20.9%) had mild, moderate and severe SG, respectively. Women with SG were significantly older and had a higher body mass index (p<0.01 for both). Delivery characteristics, mode of delivery, and gestational age were comparable between the groups; however, women with SG gave birth to significantly larger neonates (p<0.01). Seventy-one (31%) women had suffered from 1st or 2nd-degree perineal tears, and none had 3rd or 4th-degree perineal tears. No significant differences were found in rates of perineal tears between women with and without SG (p = 0.91), regardless of SG severity (p = 0.38).ConclusionsIn our study, SG was not associated with perineal tears. This information may be used as reassurance when giving antepartum consultation to women with SG, even in severe cases.

Multisystem derangements in frailty and sarcopenia: a source for biomarker discovery.

Multisystem derangements, encompassing metabolic, musculoskeletal and stress-response systems, occur during aging and are associated with the development of physical frailty and sarcopenia. These modular changes are relevant sources for the identification of biomarkers for the two conditions. Here, we provide an up-to-date overview on existing biomarkers of physical frailty and sarcopenia and discuss emerging approaches for biomarker discovery. Inflammatory, metabolic and hematologic markers are shared between physical frailty and sarcopenia. Gut microbial derivatives and damage-associated molecular patterns transferred via extracellular vesicles have been indicated as possible gut-muscle axis regulators and candidate markers of physical frailty and sarcopenia. Mediators of metabolic, musculoskeletal and stress-response system dysregulation are shared by physical frailty and sarcopenia and indicate the existence of common pathophysiological pathways. Multiplatform biomarker analyses have been proposed as an innovating approach for tracking the multifaceted and dynamic nature of physical frailty and sarcopenia. Upon validation, the identified biomarkers may support diagnostic makeup and tracking of the two conditions in both research and clinical settings.

Sarcopenic Dysphagia, Malnutrition, and Oral Frailty in Elderly: A Comprehensive Review

Frailty is a highly prevalent condition in the elderly that has been increasingly considered as a crucial public health issue, due to the strict correlation with a higher risk of fragility fractures, hospitalization, and mortality. Among the age-related diseases, sarcopenia and dysphagia are two common pathological conditions in frail older people and could coexist leading to dehydration and malnutrition in these subjects. “Sarcopenic dysphagia” is a complex condition characterized by deglutition impairment due to the loss of mass and strength of swallowing muscles and might be also related to poor oral health status. Moreover, the aging process is strictly related to poor oral health status due to direct impairment of the immune system and wound healing and physical and cognitive impairment might indirectly influence older people’s ability to carry out adequate oral hygiene. Therefore, poor oral health might affect nutrient intake, leading to malnutrition and, consequently, to frailty. In this scenario, sarcopenia, dysphagia, and oral health are closely linked sharing common pathophysiological pathways, disabling sequelae, and frailty. Thus, the aim of the present comprehensive review is to describe the correlation among sarcopenic dysphagia, malnutrition, and oral frailty, characterizing their phenotypically overlapping features, to propose a comprehensive and effective management of elderly frail subjects.

Perinatal Hyperoxia and Developmental Consequences on the Lung-Brain Axis.

Approximately 11.1% of all newborns worldwide are born preterm. Improved neonatal intensive care significantly increased survival rates over the last decades but failed to reduce the risk for the development of chronic lung disease (i.e., bronchopulmonary dysplasia (BPD)) and impaired neurodevelopment (i.e., encephalopathy of prematurity (EoP)), two major long-term sequelae of prematurity. Premature infants are exposed to relative hyperoxia, when compared to physiological in-utero conditions and, if needed to additional therapeutic oxygen supplementation. Both are associated with an increased risk for impaired organ development. Since the detrimental effects of hyperoxia on the immature retina are known for many years, lung and brain have come into focus in the last decade. Hyperoxia-induced excessive production of reactive oxygen species leading to oxidative stress and inflammation contribute to pulmonary growth restriction and abnormal neurodevelopment, including myelination deficits. Despite a large body of studies, which unraveled important pathophysiological mechanisms for both organs at risk, the majority focused exclusively either on lung or on brain injury. However, considering that preterm infants suffering from BPD are at higher risk for poor neurodevelopmental outcome, an interaction between both organs seems plausible. This review summarizes recent findings regarding mechanisms of hyperoxia-induced neonatal lung and brain injury. We will discuss common pathophysiological pathways, which potentially link both injured organ systems. Furthermore, promises and needs of currently suggested therapies, including pharmacological and regenerative cell-based treatments for BPD and EoP, will be emphasized. Limited therapeutic approaches highlight the urgent need for a better understanding of the mechanisms underlying detrimental effects of hyperoxia on the lung-brain axis in order to pave the way for the development of novel multimodal therapies, ideally targeting both severe preterm birth-associated complications.