Group Of Diseases Research Articles

Abstract 4135480: Effect of Time Since Heart Failure Diagnosis or Hospitalization on the Cost-effectiveness of Dapagliflozin in Patients with Heart Failure with Mildly Reduced or Preserved Ejection Fraction

Background: Previous studies have shown dapagliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), to be a cost-effective treatment option for patients with heart failure (HF) with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF) in multiple European settings. Research question: Is the cost-effectiveness of dapagliflozin treatment in HFpEF/HFmrEF modified by either the time since HFpEF/HFmrEF diagnosis or the time since the last hospitalization for heart failure (HHF) event? Methods: A Markov cohort transition model was built for the UK setting, informed by patient-level data from the randomized, placebo-controlled DELIVER trial. The patient population was subset according to categories of time since last HHF event (including no prior HHF) and time since HF diagnosis (further subset to those with no prior HHF). For each subgroup, disease evolution was characterized by transitions among health states defined by quartiles of the Kansas City Cardiomyopathy Questionnaire Total Symptom Scale. The risk of fatal (cardiovascular and non-cardiovascular) and non-fatal events of worsening HF were modelled, adjusting for baseline characteristics and time-updating health state. Incremental costs and quality-adjusted life-years (QALYs) were calculated for each subgroup to yield incremental cost-effectiveness ratios (ICERs). Results: The lowest ICERs were observed for subgroups with the shortest time from HF diagnosis (with and without prior HHF) or last HHF event (Figure 1). Across all subgroups, the calculated ICERs were below the UK willingness-to-pay (WTP) threshold of £20,000/QALY gained. Conclusions: In patients with HFpEF/HFmrEF, the cost-effectiveness of dapagliflozin improved (via lower ICERs) in the subgroups corresponding to earliest disease (least time since an HHF event or HF diagnosis) compared with groups of later disease and potentially delayed treatment initiation. These findings suggest early optimization of HF therapy with implementation of guideline-directed medical therapy, including SGLT2is, may improve economic value.

Identification of a 5-Plex Cytokine Signature that Differentiates Patients with Multiple Systemic Inflammatory Diseases.

Patients with non-infectious systemic inflammation may suffer from one of many diseases, including hyperinflammation (HI), autoinflammatory disorders (AID), and systemic autoimmune disease (AI). Despite their clinical overlap, the pathophysiology and patient management differ between these disorders. We aimed to investigate blood biomarkers able to discriminate between patient groups. We included 44 patients with active clinical and/or genetic systemic inflammatory disease (9 HI, 27 AID, 8 systemic AI) and 16 healthy controls. We quantified 55 serum proteins and combined multiple machine learning algorithms to identify five proteins (CCL26, CXCL10, ICAM-1, IL-27, and SAA) that maximally separated patient groups. High ICAM-1 was associated with HI. AID was characterized by an increase in SAA and decrease in CXCL10 levels. A trend for higher CXCL10 and statistically lower SAA was observed in patients with systemic AI. Principal component analysis and unsupervised hierarchical clustering confirmed separation of disease groups. Logistic regression modelling revealed a high statistical significance for HI (P = 0.001), AID, and systemic AI (P < 0.0001). Predictive accuracy was excellent for systemic AI (AUC 0.94) and AID (0.91) and good for HI (0.81). Further research is needed to validate findings in a larger prospective cohort. Results will contribute to a better understanding of the pathophysiology of systemic inflammatory disorders and can improve diagnosis and patient management.

Comprehensive Proteomics Profiling Identifies Circulating Biomarkers to Distinguish Hypertrophic Cardiomyopathy from Other Cardiomyopathies with Left Ventricular Hypertrophy.

Background: Distinguishing hypertrophic cardiomyopathy (HCM) from other cardiomyopathies with left ventricular hypertrophy (LVH), such as hypertensive LVH, transthyretin amyloid cardiomyopathy (ATTR-CM), and aortic stenosis (AS), is sometimes challenging. Using plasma proteomics profiling, we aimed to identify circulating biomarkers and dysregulated signaling pathways specific to HCM. Methods: In this multicenter case-control study, plasma proteomics profiling was performed in cases with HCM and controls with hypertensive LVH, ATTR-CM, and AS. Two-thirds of patients enrolled earlier in each disease group were defined as the training set, and the remaining one-third as the test set. Protein concentrations in HCM were compared with those in hypertensive LVH (comparison 1), ATTR-CM (comparison 2), and AS (comparison 3). Candidate proteins that meet the following 2 criteria were selected: (1) Higher abundance in HCM throughout all 3 comparisons or lower abundance in HCM throughout all 3 comparisons with univariable P<0.05 and |log2(fold change)| >0.5 in both the training and test sets and (2) Independently associated with HCM with multivariable P<0.05 after adjusting for clinical parameters significantly different between HCM and controls. Using the selected candidate proteins, a logistic regression model to distinguish HCM from controls was developed in the training set and applied to the test set. Finally, pathway analysis was performed in each comparison using proteins with different abundance. Results: Overall, 4,979 proteins in 1,415 patients (HCM, n=879; hypertensive LVH, n=331; ATTR-CM, n=169; AS, n=36) were analyzed. Of those, 5 proteins were selected as candidate proteins. The logistic regression model with these 5 proteins had an area under the receiver-operating-characteristic curve of 0.86 (95% CI 0.82-0.89) in the test set. The MAPK and HIF-1 pathways were dysregulated in HCM throughout the 3 comparisons. Conclusions: This study identified circulating biomarkers that distinguish HCM from other cardiomyopathies with LVH independently from confounders and revealed signaling pathways associated with HCM.

The association between oral diseases and neurodegenerative disorders.

The association between cognitive neurodegenerative disease and oral diseases has been under great interest recently. Several studies have suggested a connection between periodontitis and Alzheimer's disease (AD) or other neurodegenerative disorders. This study aimed to review the potential mechanisms between oral diseases and neurodegenerative diseases. The study was executed as a literature review of English-language publications from 2018-2022. The databases used for the search were PubMed, Cochrane, Scopus, and Web of Science. The search phrases used were "neurodegenerative diseases" AND "oral health" and "neurodegenerative diseases" AND "oral diseases." The linkage between the two disease groups was observed in several distinct publications and several potential mechanisms were found. The link between periodontitis and AD proved to be the most significant. The effect was accentuated in elderly people where individuals possessed also other risk factors for neurodegenerative diseases and had generally worse oral health conditions. Oral diseases may be risks for neurodegenerative changes along many different pathways. Good oral health should be acknowledged as a potential preventative or risk-reducing act against neurodegenerative diseases.

CTNI-23. DIFFERENT GUT MICROBIOTA COMPOSITION IS ASSOCIATED WITH CHEMOTHERAPY EFFICACY IN PATIENTS WITH DIFFERENT TYPES OF CENTRAL NERVOUS SYSTEM CANCER

Abstract BACKGROUND The relationship between central nervous system cancers and the gut microbiota (GM) is not well understood. The purpose of this study is to retrospective analyze the differences between the composition of the gut microbiota in patients with different neurologic tumors and their correlation with chemotherapy efficacy. METHODS A total of 44 patients participated in the study and were divided into four groups: gliocytoma (GA), medulloblastoma (MB), germ cell tumors (GT), and diffuse large B-cell lymphoma (DB) based on their pathological diagnosis. Fecal samples were collected from patients for 16S amplicon sequencing to analyze GM composition. Moreover, all the patients were classified into completed response (CR), stable disease (SD), and progressive disease (PD) groups based on the clinical outcomes of chemotherapy. PLS-DA analysis and heatmap analysis were used to reveal the correlation between GM composition and outcomes of chemotherapy. RESULTS Phyla taxa comparison showed the detailed GM composition among these four groups. The phylum of Bacteroidetes was higher in GA group when compared to the other groups. And the phylum of Fusobacteria could only be found in GA and MB groups while the phylum of Verrucomicrobia showed a significant accumulation in DB group. the genera of Ruminococcus, Gemmiger, and Parasutterella were accumulated in the patients with the completed response of chemotherapy. Besides, patients in SD group had higher abundance of the genera of Prevotella, Tyzzerella, and Odoribacter. While patients in PD group showed the higher abundance of Streptcoccus, Fusobacterium, Lachnospira, and Holemanella. CONCLUSION We firstly drew the GM composition profile of the patients with GA, MB, GT, and DB to show the different GM composition of the diseases. Moreover, the gut microbiota composition correlates with chemotherapy outcomes in central nervous system cancer patients so may serve as a potential biomarker for predicting chemotherapy efficacy.

Wide possibilities of topical therapy in the treatment of patients with infectious and inflammatory diseases of the pharynx

Despite medical advances, infectious and inflammatory upper respiratory diseases are the most common groups of diseases among outpatients. Viruses induce acute respiratory diseases in most patients; however, bacterial and “atypical” pathogens can cause exacerbations of chronic diseases such as adenoiditis, tonsillitis, pharyngitis and others. Prescribing etiotropic drugs to patients with infectious and inflammatory diseases of the pharynx can reduce the effectiveness of the therapy due to the growth of antimicrobial resistance. Increasing etiotropic drug resistance of some pathogens requires the selection of alternative agents for patients with infectious and inflammatory diseases of the pharynx. The non-specific prophylaxis of the latter is aimed to activate inner defense mechanisms using bacterial lysates (BL). Based on a review of the literature, the article discusses the features of the use and clinical effectiveness of topical BL in infectious and inflammatory diseases of the pharynx. BL are an important supplementation to the standard therapy regimen for inflammatory upper respiratory diseases, which contributes to the restoration of the immune response autoregulation, a reliable decrease in the frequency and duration of acute forms and exacerbations of chronic upper respiratory diseases, and reduced use of antibiotics and antipyretics. Evidence of possible mechanisms to correct immunity in infectious and inflammatory diseases of the pharynx, as well as a review of the clinical effectiveness of the medicine was demonstrated by example of Imudon. Its beneficial use to treat disease in the acute period is associated with its focal action on the infectious and inflammatory lesions. The drug is effective at any stage of the disease and can be used for prophylactic purposes due to activation of mucosal immunity in the respiratory tract. The high efficiency of Imudon is determined by its ability to activate phagocytosis and production of specific immunoglobulins by plasma cells, which reduces the risk of relapses and chronicity of the disease.

QLTI-13. A REVIEW OF THE BEST TREATMENT STRATEGY FOR NEUROFIBROMATOSIS TYPE 2 PATIENTS THROUGH A SINGLE-CENTER RETROSPECTIVE STUDY: HOW TO ORCHESTRATE MULTIMODAL TREATMENT OPTIONS

Abstract PURPOSE Neurofibromatosis type 2(NF2) is an autosomal-dominant tumor predisposition syndrome that affects the whole neuro-axis and causes various neurological symptoms decreasing the quality of life throughout the patient’s lifespan. However, due to the diversity of related diseases and the complexity of treatment, there are many cases in which only partial treatments are performed, the timing of the treatment is missed, and inappropriate treatment modality selection is made despite the intervention of many clinicians. Therefore, to increase the overall understanding of the disease, the single-institution experience was analyzed. MATERIALS AND METHODS Between 1998 and 2022, a total of 80 patients who clinically suspected NF2 visited our Brain Tumor Center. After excluding the patients with follow-up loss, the remaining 48 patients were finally analyzed. The patient’s symptoms, diagnosis process, treatment process, and outcomes were analyzed. RESULTS The average age at the time of symptom onset was 31.0(2-63) year-old. Hearing impairment was the major primary symptom(46.8%) among the patients. Five patients(10.9%) had family history of NF2. Thirty-five patients(76.1%) was clinically diagnosed as a NF2 for the bilateral vestibular schwannomas, and 34 patients(73.9%) had intracranial meningiomas, and 37 patients(80.4%) had spinal lesions at the time of diagnosis. Eleven patients were genetically confirmed as NF2. For vestibular schwannomas, 16 patients had surgical resection and 20 patients took gamma-knife surgery as a primary or secondary treatment. For intracranial meningiomas, 16 patients had surgical resection, 13 patients took gamma-knife surgery, and 15 patients took conventional radiation therapy as a primary or secondary treatment. Ventriculo-peritoneal shunt due to increased intracranial pressure was performed in 4 patients(8.7%). For spinal lesions, 16 patients had surgical resection. CONCLUSION NF2 is a disease group requiring a multidisciplinary team approach. The key to treatment is to set and implement a treatment sequence and method tailored to each patient. For this, an overall understanding of the disease and the treatment options is essential.

SARS-CoV-2 Infection and Alpha-Synucleinopathies: Potential Links and Underlying Mechanisms

Alpha-synuclein (α-syn) is a 140-amino-acid, intrinsically disordered, soluble protein that is abundantly present in the brain. It plays a crucial role in maintaining cellular structures and organelle functions, particularly in supporting synaptic plasticity and regulating neurotransmitter turnover. However, for reasons not yet fully understood, α-syn can lose its physiological role and begin to aggregate. This altered α-syn disrupts dopaminergic transmission and causes both presynaptic and postsynaptic dysfunction, ultimately leading to cell death. A group of neurodegenerative diseases known as α-synucleinopathies is characterized by the intracellular accumulation of α-syn deposits in specific neuronal and glial cells within certain brain regions. In addition to Parkinson’s disease (PD), these conditions include dementia with Lewy bodies (DLBs), multiple system atrophy (MSA), pure autonomic failure (PAF), and REM sleep behavior disorder (RBD). Given that these disorders are associated with α-syn-related neuroinflammation—and considering that SARS-CoV-2 infection has been shown to affect the nervous system, with COVID-19 patients experiencing neurological symptoms—it has been proposed that COVID-19 may contribute to neurodegeneration in PD and other α-synucleinopathies by promoting α-syn misfolding and aggregation. In this review, we focus on whether SARS-CoV-2 could act as an environmental trigger that facilitates the onset or progression of α-synucleinopathies. Specifically, we present new evidence on the potential role of SARS-CoV-2 in modulating α-syn function and discuss the causal relationship between SARS-CoV-2 infection and the development of parkinsonism-like symptoms.

Cervicovaginal lavages uncover growth factors as key biomarkers for early diagnosis and prognosis of endometrial cancer

Endometrial cancer (EC) rates are continuing to rise and it remains the most common gynecologic cancer in the US. Existing diagnostic methods are invasive and can cause pain and anxiety. Hence, there is a need for less invasive diagnostics for early EC detection. The study objective was to evaluate the utility of growth factors collected through minimally invasive cervicovaginal lavage (CVL) sampling as diagnostic and prognostic biomarkers for EC. CVL samples from 192 individuals undergoing hysterectomy for benign or malignant conditions were collected and used to quantify the concentrations of 19 growth and angiogenic factors using multiplex immunoassays. Patients were categorized based on disease groups: benign conditions (n = 108), endometrial hyperplasia (n = 18), and EC (n = 66). EC group was stratified into grade 1/2 endometrial endometrioid cancer (n = 53) and other EC subtypes (n = 13). Statistical associations were assessed using receiver operating characteristics, Spearman correlations and hierarchical clustering. Growth and angiogenic factors: angiopoietin-2, endoglin, fibroblast activation protein (FAP), melanoma inhibitory activity, and vascular endothelial growth factor-A (VEGF-A) were significantly (p < 0.0001) elevated in EC patients. A multivariate model combining 11 proteins with patient age and body mass index exhibited excellent discriminatory potential (area under curve = 0.918) for EC, with a specificity of 90.7% and a sensitivity of 87.8%. Moreover, angiopoietin-2, FAP and VEGF-A significantly (p < 0.05–0.001) associated with tumor grade, size, myometrial invasion, and mismatch repair status. Our results highlight the innovative use of growth and angiogenic factors collected through CVL sampling for the detecting endometrial cancer, showcasing not only their diagnostic potential but also their prognostic value.

Investigation of Novel Isatinylhydantoin Derivatives as Potential Anti-Kinetoplastid Agents.

Neglected tropical diseases are a group of infectious diseases with a high endemicity in developing countries of Africa, Asia, and the Americas. Treatment for these diseases depends solely on chemotherapy, which is associated with severe side effects, toxicity, and the development of parasitic resistance. This highlights a critical need to develop new and effective drugs to curb these diseases. As a result, a series of novel isatinylhydantoin derivatives were synthesized and evaluated for in vitro anti-kinetoplastid activity against seven human- or animal-infective Trypanosoma and two human-infective Leishmania species. The synthesized derivatives were tested for potential cytotoxicity against human, animal, and parasite host-related cell lines. The isatinylhydantoin hybrid 4 b bearing 5-chloroisatin and p-bromobenzyl moieties, showed strong trypanocidal activity against blood-stage T. congolense parasites; however, the promising in vitro trypanocidal potency of 4 b could not be translated to in vivo treatment efficacy in a preliminary animal study. Compounds 5, 2 b, and 5 b, were the most active against amastigotes of L. donovani, showing higher leishmanicidal activity than the reference drug, amphotericin B. These compounds were identified as early antileishmanicidal leads, and future investigations will focus on confirming their antileishmanial potential through in vivo efficacy evaluation as well as their exact mechanism of action.

Deficiency of muscle-generated brain-derived neurotrophic factor causes inflammatory myopathy through reactive oxygen species-mediated necroptosis and pyroptosis

Idiopathic inflammatory myopathy (commonly known as myositis) is a group of immune-related diseases characterized by muscle damage, weakness, and fatigue with unknown causes. Although overactivated innate immunity is a widely believed cause of myositis onset, the mechanism that provokes and maintains a high immune response in myositis patients is still unclear. This study aims to test if brain-derived neurotrophic factor (BDNF) deficiency per se is sufficient to cause myositis and determine its underlying mechanism. We found that ablating BDNF production in skeletal muscle is sufficient to trigger myositis development in mice. Muscle-specific Bdnf knockout (MBKO) mice displayed extensive myocyte necrosis, mononuclear cell infiltration, and myophagocytosis. In association with these damages, elevated production of pro-inflammatory cytokines such as interleukin (IL) 23, IL-1β, IL-18, and tumor necrosis factor α (TNFα) was found in the muscle of MBKO mice. Disruption of sarcolemma integrity was also detected in MBKO mice, which is a result of necroptosis executioner Mixed lineage kinase domain-like protein (MLKL) and pyroptosis executioner Gasdermin D (GSDMD) activation. Mechanistically, diminishing BDNF synthesis in myotubes enhances the accumulation of mitochondrial reactive oxygen species (mtROS), which sensitizes the cells towards TNFα-induced receptor-interacting protein kinase (RIPs) activation and promotes the formation of NLR family pyrin domain containing 3 (NLRP3)-containing inflammasome. BDNF deficiency-induced cell death could be alleviated by scavenging mtROS, suppressing the activity of GSDMD, or inhibiting receptor-interacting kinase 3 (RIP3). Similarly, supplementation of BDNF mimetics, suppression of RIP3 activity, increasing the intramyocellular antioxidant, or enhancing mitophagy ameliorated the myopathies of MBKO mice and improved their muscle strength. Together, our study demonstrates that insufficient BDNF production in mouse muscle causes the development of pathological features of myositis via enhancing oxidative stress, necroptosis, and pyroptosis in myofibers.

Utilising Hyperspectral Autofluorescence Imaging in the Objective Assessment of Disease State and Pain in Patients with Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is a chronic inflammatory disease resulting in joint swelling and pain. Treatment options can be reliant on disease activity scores (DAS) incorporating patient global assessments, which are quantified via visual analogue scales (VAS). VAS can be subjective and not necessarily align with clinical symptoms, such as inflammation, resulting in a disconnect between the patient’s and practitioners’ experience. The development of more objective assessments of pain would enable a more targeted and personalised management of pain within individuals with RA and have the potential to improve the reliability of assessments in research. Using emerging light-based hyperspectral autofluorescence imaging (HAI) technology, we aimed to objectively differentiate disease and pain states based on the analysis of synovial tissue (ST) samples from RA patients. In total, 22 individuals with RA were dichotomised using the DAS in 28-joint counts (DAS-28) into an inactive (IA) or active disease (active-RA) group and then three sub-levels of pain (low, mid, high) based on VAS. HAI was performed on ST sections to identify and quantify the most prominent fluorophores. HAI fluorophore analysis revealed a distinct separation between the IA-RA and active-RA mid-VAS cohort, successfully determining disease state. Additionally, the separation between active-RA Mid-VAS and active RA High-VAS cohort suggests that HAI could be used to objectively separate individuals based on pain severity.

The impact of preoperative renal insufficiency on the outcomes of patients with pancreatic cancer undergoing pancreaticoduodenectomy.

This study evaluated the impact of renal function impairment on long-term survival outcomes and adjuvant therapy in patients with pancreatic cancer undergoing pancreaticoduodenectomy (PD). In this study, 264 patients who underwent PD for pancreatic head cancer between 2011 and 2021 were retrospectively analyzed. The patients were subsequently categorized into three groups according to the estimated glomerular filtration rate: normal group (> 90 mL/min/1.73 m2, n = 73), moderate group (45-90 mL/min/1.73 m2, n = 176), and severe group (< 45 mL/min/1.73 m2, n = 15). The primary outcomes evaluated were postoperative complications, overall survival (OS), and relapse-free survival (RFS). Additionally, the completion of adjuvant therapy and risk factors for adjuvant therapy discontinuation were analyzed. The total proportion of patients with complications was significantly higher in the severe group (p = 0.008). The proportion of patients with severe complications (Clavien-Dindo classification ≥ IIIa) did not significantly differ between the chronic kidney disease (CKD) groups (p = 0.730). The proportion of patients in whom adjuvant therapy was completed was notably lower in the severe group (p = 0.011). Multiple logistic regression analysis revealed that CKD groups and hemoglobin levels ≤ 11.5g/dL were independent predictors of adjuvant therapy completion failure (p = 0.016 and p = 0.016). There was no significant difference in the OS and RFS rates between the CKD groups (p = 0.499, p = 0.688). In patients with pancreatic cancer and CKD, performing PD safely may be feasible; however, adjuvant therapy completion is challenging.

Peculiarities of the course of gestation in women with a history of reproductive loss

Aim. Тo assess the frequency of extragenital pathology, features of obstetric and gynecological history and the course of pregnancy in women with a history of reproductive loss. Materials and methods. The study was conducted on the basis of the Municipal non-profit enterprise “Maternity house No. 9” of the Zaporizhzhia City Council with the involvement of 75 pregnant women with one reproductive loss in history. The control group consisted of 30 women without a history of reproductive loss. Women who had reproductive losses were divided into 2 groups. Group I (main group) includes 38 pregnant women who registered for pregnancy and began their participation in this study after the start of a full-scale war on the territory of Ukraine. II (comparison) group included 37 women who were registered for pregnancy before the start of the full-scale war. It should be noted that 17 pregnant women (44.7 %) had the status of an internally displaced person. The average age of women in group I was 30.10 ± 5.86 years, in group II – 28.80 ± 6.07 years, and 26.50 ± 4.95 years in the control group. The anamnesis data and features of the course of gestation were studied in all patients. Management of pregnancy and childbirth of women was carried out in accordance with the current Orders of the Ministry of Health of Ukraine. Variational and statistical processing of the results was carried out using the Statistica 13 program. Results. According to the results of the study, it was established that the frequency of extragenital pathology in women with one reproductive loss was higher, compared to women who had no such experience. Diseases of the cardiovascular and urinary systems occupy a leading place in this category of women. According to obstetric and gynecological anamnesis, a significant predominance among women of I and II groups of diseases of the reproductive system, compared to women of the control group, was established. Also, in the corresponding groups, a high frequency of miscarriage was established both in the period up to 12 weeks (28.95 % in the I group, 43.2 % in the II group against 6.67 % in the control group), and in the period of 12–22 weeks (34.20 % in the I group, 29.73 % in the II group vs. 13.33 % in the control group). Conclusions. Based on the conducted analysis, a high frequency of pregnancy complications was established for pregnant women who had a history of one reproductive loss. This contingent of women also has a high frequency of extragenital and gynecological concomitant pathology. Such results make it possible to assume a connection between the presence of one reproductive loss in women in the anamnesis and gestational complications of the next pregnancy.

Ginger Extract Improves Cognitive Dysfunction via Modulation of Gut Microbiota-Derived Short-Chain Fatty Acids in D-Galactose/Ovariectomy-Induced Alzheimer-Like Disease.

Alzheimer's disease (AD) is the most common form of dementia with complex causes and limited treatment options. Recent research has suggested a connection between the progression of AD and the activity of gut microbiota. Ginger, a plant known for its anti-inflammatory, antioxidant, and neuroprotective properties, has gained attention as a potential treatment for alleviating AD symptoms. In this study, we induced an AD model in female rats through ovariectomy and D-galactose injection and then investigated the protective effects of oral administration of ginger ethanolic extract. We assessed changes in short-chain fatty acids (SCFAs), learning and memory abilities, neuroinflammatory markers in plasma, and the hippocampus, as well as histological changes in the intestine and hippocampus in sham-operated, diseased, and treatment groups. Oral administration of ginger ethanolic extract improved gut microbiota activity, increased SCFA levels, and enhanced the expression of tight junction proteins. Additionally, ginger extract reduced the concentrations of TNF-α and IL-1β in both plasma and the hippocampus. Furthermore, it significantly reduced cell death and amyloid plaque deposition in the hippocampal tissue. These physiological changes resulted in improved performance in learning and memory tasks in rats treated with ginger compared with the disease group. These findings provide compelling evidence for the beneficial effects of ginger on the gut-brain axis, leading to improvements in learning and memory through the reduction of neuroinflammation.

Conceptual Contextualization of Neutrophilic Dermatoses

Abstract: Neutrophilic dermatoses are defined as inflammatory skin diseases characterized by sterile infiltration of polymorphonuclear neutrophils into various cutaneous layers. Although, in many cases, neutrophilic dermatoses represent the cutaneous counterpart of autoinflammatory diseases, this is not always the case, and there are other causes associated with this group of diseases, such as the administration of certain drugs or an underlying tumor. However, understanding the autoinflammatory context in which most of these entities develop, as well as their close relationship with autoimmunity, is key to comprehending their pathogenesis. In addition, understanding the mechanisms by which neutrophils migrate to the dermis and become activated is fundamental for interpreting the morphological findings of these biopsies. Finally, the description of a new group of neutrophilic dermatoses in recent years, in relation to keratinization disorders, has been crucial for understanding the best therapeutic approach for these difficult-to-manage entities.

Influence of disease activity and gonadal status on bone mineral density and turnover in acromegaly.

The purpose of this study was to evaluate the impact of disease activity and gonadal status on bone mineral density (BMD) and turnover markers (BTMs) in individuals with acromegaly. Subjects underwent laboratory tests for PTH, 25-hydroxyvitamin D, calcium, phosphorus, osteocalcin (OC) and C-telopeptide (CTX-1) and bone densitometry at the lumbar spine (LS), femoral neck (FN) and total hip (TH). Sixty participants (48.6 ± 11.0years; 66,7% female) were included in this cross-sectional study. Phosphorus, OC, CTX-1, and LS BMD were greater in the active disease group than in the controlled/cured disease group (P = 0.025, P < 0.001, P = 0.007, and P = 0.016, respectively). When analyzing gonadal status, phosphorus, OC and CTX-1 were greater in the hypogonadal group than in the eugonadal group (P = 0.017, P = 0.015, and P = 0.033, respectively). Patients with hypogonadism had a higher prevalence of reduced bone mass compared to eugonadal patients (44 vs. 17%, P = 0.023). This study revealed increased levels of phosphorus and BTMs in patients with active acromegaly. In this group, the greater LS BMD values are likely due to the anabolic effects of GH and IGF-1 and/or to the influence of LS arthropathy. Moreover, hypogonadism negatively impacts bone metabolism in acromegaly, leading to elevated BTMs and a higher prevalence of reduced bone mass in individuals affected by both conditions.

Quantitative and Computational Spinal Imaging in Neurodegenerative Conditions and Acquired Spinal Disorders: Academic Advances and Clinical Prospects

Introduction: Quantitative spinal cord imaging has facilitated the objective appraisal of spinal cord pathology in a range of neurological conditions both in the academic and clinical setting. Diverse methodological approaches have been implemented, encompassing a range of morphometric, diffusivity, susceptibility, magnetization transfer, and spectroscopy techniques. Advances have been fueled both by new MRI platforms and acquisition protocols as well as novel analysis pipelines. The quantitative evaluation of specific spinal tracts and grey matter indices has the potential to be used in diagnostic and monitoring applications. The comprehensive characterization of spinal disease burden in pre-symptomatic cohorts, in carriers of specific genetic mutations, and in conditions primarily associated with cerebral disease, has contributed important academic insights. Methods: A narrative review was conducted to examine the clinical and academic role of quantitative spinal cord imaging in a range of neurodegenerative and acquired spinal cord disorders, including hereditary spastic paraparesis, hereditary ataxias, motor neuron diseases, Huntington’s disease, and post-infectious or vascular disorders. Results: The clinical utility of specific methods, sample size considerations, academic role of spinal imaging, key radiological findings, and relevant clinical correlates are presented in each disease group. Conclusions: Quantitative spinal cord imaging studies have demonstrated the feasibility to reliably appraise structural, microstructural, diffusivity, and metabolic spinal cord alterations. Despite the notable academic advances, novel acquisition protocols and analysis pipelines are yet to be implemented in the clinical setting.

Genetic Insights into Congenital Cardiac Septal Defects—A Narrative Review

Congenital heart diseases (CHDs) are a group of complex diseases characterized by structural and functional malformations during development in the human heart; they represent an important problem for public health worldwide. Within these malformations, septal defects such as ventricular (VSD) and atrial septal defects (ASD) are the most common forms of CHDs. Studies have reported that CHDs are the result of genetic and environmental factors. Here, we review and summarize the role of genetics involved in cardiogenesis and congenital cardiac septal defects. Moreover, treatment regarding these congenital cardiac septal defects is also addressed.

Meniscal allograft transplantation in patients with substantial cartilage disease led to a sustained long-term improvement in patient-reported outcome measures.

Due to a lack of consensus regarding effective treatment options in young patients, the indications of meniscal allograft transplantation (MAT) have widened to include those with substantial cartilage disease. The aim of this study was to report the long-term patient-reported outcome measures (PROMs) and allograft survival rates for patients with substantial cartilage disease. A review of the prospectively maintained database was performed. Patients with International Cartilage Repair Society 3b or above cartilage grading in either their femur or tibia were classified as having substantial cartilage disease. Postoperative International Knee Documentation Committee, Tegner, Knee Injury and Osteoarthritis Outcome Score and Lysholm were compared between those with and without substantial cartilage disease. Kaplan-Meir analysis was used to assess the survival rates. Survival was defined as revision or removal of allograft or conversion to arthroplasty. Data from 422 patients were included in the analysis with 129 patients found to have full-thickness chondral lesions and 281 patients without full-thickness chondral lesions. The mean follow-up was 6.33 (SD 3.48) years for the cohort. The mean age for the entire cohort was 30 (SD 9.23). Patients in substantial cartilage disease group underwent meniscal transplantation at an older age (32 [standard deviation {SD} 8.47] years vs. 29 [SD 9.35] years [p < 0.001]). There was no significant difference in PROMs between the two groups up to 10 years postoperatively (p > 0.05). The substantial cartilage disease group had significantly lower survival rates compared to those without (80.62% vs. 94.32%). MAT in the context of substantial cartilage disease was associated with an improvement in PROMs up to 10 years with no difference to the group without substantial cartilage disease. The PROMs in combination with the long-term survival rates in this study can be used to counsel patients preoperatively. Level IV.