Progression Of Several Diseases Research Articles

Progression of Peripheral Artery Disease Severity After Interventions for Intermittent Claudication

Progression of Peripheral Artery Disease Severity After Interventions for Intermittent Claudication

#1276 Clinical practice of complement inhibitor use in hemolytic uremic syndrome: findings from the European rare kidney disease registry

Abstract Background and Aims Over the last decade, significant advancements have emerged in the field of rare kidney diseases, notably the introduction of C5 inhibitor therapy. The C5 inhibition has transformed the prognosis for atypical Hemolytic Uremic Syndrome (aHUS), offering improved clinical outcomes. However, despite these advancements, the utilization of C5 inhibitor therapy varies significantly, with disparities in treatment duration, reasons for discontinuation, and consideration of extending treatment to patients with infectious HUS (iHUS). This variability is further compounded by the considerable cost associated with C5 inhibitor treatment. Method This retrospective cohort study utilized data from the ERKNet Registry. The study cohort comprised 608 HUS patients enrolled in the ERKNet Registry between November 2018 and September 2023. The dataset encompassed patient demographics, disease and diagnostic records, medication profiles, dialysis or transplantation requirements, kidney function monitoring at the last visit, and clinical outcomes. Results Among 230 aHUS patients, 23 underwent kidney transplantation. 11 received C5 inhibitor therapy before kidney failure. The majority of these patients had genetic aHUS with various mutations (3 CFH, 2 CFI, and 1 CD46). The only death in the study was from this group of patients, unresponsive to C5 Inhibition. Out of 175 aHUS patients treated with Eculizumab, 23 (13%) transitioned to Ravulizumab. Among 104 patients who discontinued C5 inhibitors, 14 (14%) had to resume treatment, half of them with genetic aHUS, with 3 cases of CD46 mutations, 2 cases CFHR5 mutations, and one each involving mutations in CFI and C3. Only two patients required dialysis.. Among 371 iHUS patients, 82 (22%) received C5 Inhibitor treatment. Conclusion In the context of aHUS, we found that discontinuing C5 inhibitors is generally safe, with a slightly higher relapse rate in patients with complement gene variants, though most relapses were mild, requiring dialysis in only a few cases. Long-term follow-up revealed a return to normal kidney function following TMA relapses. Transitioning from Eculizumab to Ravulizumab exhibited promising outcomes, with no relapses or kidney failures in 23 patients. Our analysis of C5 inhibitor use in iHUS emphasized its association with more severe disease progression. While some studies question C5 inhibitors' acute-phase efficacy, others report remarkable improvements in patients unresponsive to other treatments. Overall, our findings underscore the safety of discontinuation practices, the potential benefits of Ravulizumab, and the ongoing need for further research on C5 inhibitor treatment in iHUS.

#1949 Comparison of two commercial available primary human mesangial cell clones reveal differences

Abstract Background and Aims Mesangial cells and their matrix form the central stalk of the glomerulus but is often overlooked when studying glomerular function. The cells are however highly involved in glomerular function and crosstalk between the different cell types of the glomerulus. They are important in onset and progression of several glomerular diseases, such as IgA nephropathy and diabetic kidney disease. As mesangial cells have several functions and are involved in glomerular disease they are often used for in vitro work studying response to various stimuli and downstream signaling. This includes changes in the production and regulation or their matrix, proliferation, contractility, protein expression and release of different inflammatory mediators such as cytokines and growth factors [1]. Using primary cells when doing in vitro work is usually considered the best option, but there might be differences between origin of cells in their response and physiology. For this study, our aim was to compare two types of commercially available primary human mesangial cells from Cell systems (CS) and Novabiosis (NBS). Method For characterization of the CS and NBS mesangial cells, gene expression of commonly used mesangial cell markers, including KRT19, ACTA2, PDGFRA and PDGFRB, was analyzed with real time qPCR. Staining of smooth muscle actin was done in order to compare the phenotype of CS and NBS. To compare the cells, differences in protein expression were determined using proteomics. CS and NBS Cells were cultured in the same way and were also treated with PDGF-BB for 24 h to compare with untreated control. For further comparison, proliferation assay was used to compare proliferation after treating cells with PDGF-BB for 24 h. Results Both sources of cells expressed all markers, but there was a difference in level of gene expression. CS cells showed higher expression than NBS cells for all markers, apart from ACTA2. NBS cells had a more stellate phenotype whereas the CS cells were more elongated. There was a difference in proteins expressed by CS and NBS mesangial cells from our proteomics. The level of upregulation of proteins seen with proteomics was stronger for CS than NBS cells when treated with PDGF-BB. The number of proteins upregulated was also higher for CS than NBS cells. Both mesangial cell types had increased proliferation when treated with PDGF-BB, however CS cells were seen to grow faster in cell culture and seemed to be more responsive to the treatment with PDGF-BB. Conclusion In conclusion, this study compares two commercially available primary human mesangial cells and show that there is a difference between the two. The cell types react differently when treated with PDGF-BB and has some difference in what proteins they express. This needs to be considered when conducting cell culture experiments with mesangial cells, depending on what the aim and focus for the study is.

Prevalence, clinical and virological characteristics and short-term prognosis of hepatitis delta infection among patients with HIV/HBV in Nouakchott, Mauritania.

Patients living with HIV infection (PLWH) are at risk of acquiring HBV and HDV. The present study aimed to determine the prevalence and characteristics of HIV-HDV-HBV tri-infection in comparison with HIV-HBV coinfection and to estimate severities and outcomes of associated liver diseases in Mauritanian PLWH. Two-hundred-ninety-two consecutive HBsAg-positive PLWH were included (mean age: 37 years). Clinical data were recorded. Anti-HDV antibodies, HBV and HDV viral loads (VLs) and genotype were determined. APRI, FIB-4 and FibroScan were performed to evaluate the severity of liver disease. The anti-HDV antibodies prevalence was 37% and HDV RNA was positive in 40.7% of patients. Genetic diversities were found with HDV genotype 1 (93%) and HBV genotypes D (42.5%) and E (38%). The HBV VL was detectable in 108 patients at inclusion, and mutations associated with HBV resistance were found in 20. For almost all variables studied, including FIB-4 and APRI scores, no significant differences were found between anti-HDV-Ab positive or negative patients. FibroScan examination, which was performed in 110 patients at end-of-follow-up showed higher, but NS values, in HDV positive patients. After a mean follow-up of 24.55 ± 8.01 months (n = 217 patients), a highly significant worsening of APRI and FIB-4 scores was found. Moreover, patients with HDV showed more severe liver disease progression despite an efficient therapy. In a substantial Mauritanian cohort of relatively young PLWH, we found high HDV prevalence and worsening liver disease. In high-risk countries, screening for HDV and providing appropriate follow-up and treatments are warranted in PLWH.

Utility of artificial intelligence in the diagnosis and management of keratoconus: a systematic review

IntroductionThe application of artificial intelligence (AI) systems in ophthalmology is rapidly expanding. Early detection and management of keratoconus is important for preventing disease progression and the need for corneal transplant. We review studies regarding the utility of AI in the diagnosis and management of keratoconus and other corneal ectasias.MethodsWe conducted a systematic search for relevant original, English-language research studies in the PubMed, Web of Science, Embase, and Cochrane databases from inception to October 31, 2023, using a combination of the following keywords: artificial intelligence, deep learning, machine learning, keratoconus, and corneal ectasia. Case reports, literature reviews, conference proceedings, and editorials were excluded. We extracted the following data from each eligible study: type of AI, input used for training, output, ground truth or reference, dataset size, availability of algorithm/model, availability of dataset, and major study findings.ResultsNinety-three original research studies were included in this review, with the date of publication ranging from 1994 to 2023. The majority of studies were regarding the use of AI in detecting keratoconus or subclinical keratoconus (n=61). Among studies regarding keratoconus diagnosis, the most common inputs were corneal topography, Scheimpflug-based corneal tomography, and anterior segment-optical coherence tomography. This review also summarized 16 original research studies regarding AI-based assessment of severity and clinical features, 7 studies regarding the prediction of disease progression, and 6 studies regarding the characterization of treatment response. There were only three studies regarding the use of AI in identifying susceptibility genes involved in the etiology and pathogenesis of keratoconus.DiscussionAlgorithms trained on Scheimpflug-based tomography seem promising tools for the early diagnosis of keratoconus that can be particularly applied in low-resource communities. Future studies could investigate the application of AI models trained on multimodal patient information for staging keratoconus severity and tracking disease progression.

Farnesoid X receptor modulator 12β-(m-methyl-benzoyl)-11,12-dihydro oleanolic acid represses liver fibrosis by inhibiting ERK/p38 signaling pathways

Liver fibrosis is a common pathological process in the progression of several chronic liver diseases to cirrhosis and hepatocellular carcinoma. Therefore, the development of medications that can repress the progress of liver fibrosis is essential. We discovered that initially, 12β-(m-methyl-benzoyl)-11,12-dihydro oleanolic acid (12d-OA), a farnesoid X receptor (FXR) modulator, possessed potential anti-fibrotic properties. Through an in-depth study, we revealed that 12d-OA not only inhibited the expression of fibrogenic markers in the LX-2 cells and HSC-T6 cells but also exhibited significant protective effects against liver injury and liver fibrosis in bile duct ligation (BDL) rats. Further exploration of its molecular mechanism indicated that 12d-OA exerted antifibrotic activity by inhibiting the extracellular signal-regulated kinase (ERK)/stress-activated protein kinase (p38) signaling pathways. Consequently, the great effects of 12d-OA in vitro and in vivo suggest that it may be a good candidate for liver fibrosis.

Clinical and Demographic Characteristics of Pyruvate Kinase Deficiency Patients: A Comprehensive Case Series Analysis.

Introduction Pyruvate kinase deficiency (PKD) is a rare autosomal recessive disorder characterized by mutations in the PKLR gene, causing impaired glycolysis in red blood cells and leading to diverse clinical manifestations. The prevalence of PKD in Saudi Arabia remains understudied, particularly in the context of consanguinity and non-specialized medical facilities. Methods We conducted a retrospective analysis of seven PKD patients of Arab ethnicity, focusing on demographics, medical history, clinical features, laboratory results, treatments, and outcomes. Results Our patient cohort comprised five males and two females, aged 10 to 38 years, of Arab ethnicity. Consanguinity was prevalent, and hereditary connections were identified in five patients. PKD exhibited varying clinical presentations, with early-onset symptoms including neonatal jaundice and symptomatic anemia. One patient experienced severe hepatic disease progression leading to multiorgan failure. Blood transfusions were universally required, indicating the severity of the disorder. Anemia severity varied among patients, with diverse hematological irregularities. Splenectomy was performed for most patients, improving hemoglobin levels and transfusion needs in some cases. Iron chelation was administered, although iron overload persisted. Thrombocytosis and venous thromboembolism were observed post splenectomy. Jaundice and gallstones were common, leading to cholecystectomy. Laboratory findings remained consistent, with heightened reticulocyte counts and altered enzyme levels. Discussion PKD is a rare disorder characterized by diverse clinical manifestations. Prevalence estimation is complex due to various factors, and its diagnosis is challenged by clinical similarities with other disorders. Our cohort exhibited a spectrum of complications, highlighting the necessity for tailored interventions. Iron overload remained a concern, necessitating continuous monitoring. Although endocrine disorders and osteoporosis were absent in our cohort, vigilance is essential due to the disease's progressive nature. Genetic factors were prominent, supporting the genetic basis of PKD. Splenectomy improved anemia but had a limited impact on gallstones. Iron overload management and bone health remain crucial considerations. Conclusion This study offers comprehensive insights into the clinical and demographic characteristics of PKD patients, illustrating the complex nature of the disorder. The findings underscore the need for personalized management strategies and vigilant monitoring to address the diverse clinical manifestations and challenges associated with PKD.

GDF15 ameliorates sepsis-induced lung injury via AMPK-mediated inhibition of glycolysis in alveolar macrophage

Growth differentiation factor 15 (GDF15) as a stress response cytokine is involved in the development and progression of several diseases associated with metabolic disorders. However, the regulatory role and the underlying mechanisms of GDF15 in sepsis remain poorly defined. Our study analyzed the levels of GDF15 and its correlations with the clinical prognosis of patients with sepsis. In vivo and in vitro models of sepsis were applied to elucidate the role and mechanisms of GDF15 in sepsis-associated lung injury. We observed strong correlations of plasma GDF15 levels with the levels of C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and lactate as well as Sequential Organ Failure Assessment (SOFA) scores in patients with sepsis. In the mouse model of lipopolysaccharide-induced sepsis, recombinant GDF15 inhibited the proinflammatory responses and alleviated lung tissue injury. In addition, GDF15 decreased the levels of cytokines produced by alveolar macrophages (AMs). The anti-inflammatory effect of glycolysis inhibitor 2-DG on AMs during sepsis was mediated by GDF15 via inducing the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α) and the expression of activating transcription factor 4 (ATF4). Furthermore, we explored the mechanism underlying the beneficial effects of GDF15 and found that GDF15 inhibited glycolysis and mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) signaling via promoting AMPK phosphorylation. This study demonstrated that GDF15 inhibited glycolysis and NF-κB/MAPKs signaling via activating AMP-activated protein kinase (AMPK), thereby alleviating the inflammatory responses of AMs and sepsis-associated lung injury. Our findings provided new insights into novel therapeutic strategies for treating sepsis.

Covid-19 A Comprehensive Review of Signs, Symptoms, Diagnosis, and Treatment Strategies

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted global health. This review aims to provide a comprehensive overview of the signs, symptoms, diagnosis, and treatment modalities of COVID-19. The clinical presentation of COVID-19 varies widely, ranging from asymptomatic or mild symptoms to severe respiratory distress and multiorgan failure. Common symptoms include fever, cough, fatigue, and dyspnea, with less frequent symptoms such as anosmia, ageusia, and gastrointestinal symptoms. Diagnosis primarily relies on reverse transcription-polymerase chain reaction (RT-PCR) testing of respiratory specimens. However, imaging modalities such as chest X-ray and Antibody Test Antigen test in diagnosis, especially in cases with atypical presentations. Treatment strategies include supportive care, antiviral therapy, and, in severe cases, and other intensive care measures. The development and distribution of vaccines have been pivotal in controlling the spread of the virus. Despite significant progress in understanding and managing COVID-19, ongoing research is crucial to refine diagnostic strategies, develop effective therapies, and improve patient outcomes. Antiviral drugs, such as remdesivir, poxolovid, molonupiravir, have been widely used to inhibit viral replication and reduce the severity and duration of symptoms. Immunomodulators, including tocilizumab have been used to target specific pathways involved in the hyperinflammatory response seen in severe COVID-19. Monoclonal antibodies, such as casirivimab/imdevimab and sotrovimab, have been employed for passive immunization to neutralize the virus and reduce the risk of severe disease progression

Observing the Clinical Course of Duchenne Muscular Dystrophy in Medicaid Real-World Healthcare Data.

Duchenne muscular dystrophy (DMD) is a rare, severe progressive neuromuscular disease. Health insurance claims allow characterization of population-level real-world outcomes, based on observed healthcare resource use. An analysis of data specific to those with Medicaid insurance is presently unavailable. The objective was to describe the real-world clinical course of DMD based on claims data from Medicaid-insured individuals in the USA. Individuals with DMD were identified from the MarketScan Multi-State Medicaid datasets (2013-2018). Diagnosis and procedure codes from healthcare claims were used to characterize the occurrence of DMD-relevant clinical observations; categories were scoliosis, cardiovascular-related, respiratory and severe respiratory-related, and neurologic/neuropsychiatric. Age-restricted analyses were conducted to focus on the ages at which DMD-relevant clinical observations were more likely to be captured, and to better understand the impact of both age and follow-up time. Of 2007 patients with DMD identified, median (interquartile range) age at index was 14 (9-20) years, and median follow-up was 3.1 (1.6-4.7) years. Neurologic and neuropsychiatric observations were most frequently identified, among 49.3% of the cohort; followed by cardiovascular (48.5%), respiratory (38.1%), scoliosis (36.3%), and severe respiratory (25.0%). Prevalence estimates for each category were higher when analyzed within age-restricted subgroups; and increased as follow-up time increased. This study is the first to use diagnosis and procedure codes from real-world Medicaid claims to document the clinical course in DMD. Findings were consistent with previously published estimates from commercially insured populations and clinical registries; and contribute to the expanding body of real-world evidence around clinical progression of patients with DMD.

The role of anoctamin 1 in liver disease.

Liver diseases include all types of viral hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), cirrhosis, liver failure (LF) and hepatocellular carcinoma (HCC). Liver disease is now one of the leading causes of disease and death worldwide, which compels us to better understand the mechanisms involved in the development of liver diseases. Anoctamin 1 (ANO1), a calcium-activated chloride channel (CaCC), plays an important role in epithelial cell secretion, proliferation and migration. ANO1 plays a key role in transcriptional regulation as well as in many signalling pathways. It is involved in the genesis, development, progression and/or metastasis of several tumours and other diseases including liver diseases. This paper reviews the role and molecular mechanisms of ANO1 in the development of various liver diseases, aiming to provide a reference for further research on the role of ANO1 in liver diseases and to contribute to the improvement of therapeutic strategies for liver diseases by regulating ANO1.

A pseudo-targeted metabolomics for discovery of potential biomarkers of cardiac hypertrophy in rats

Cardiac hypertrophy (CH) is one of the stages in the occurrence and development of severe cardiovascular diseases, and exploring its biomarkers is beneficial for delaying the progression of severe cardiovascular diseases. In this research, we established a comprehensive and highly efficient pseudotargeted metabolomics method, which demonstrated a superior capacity to identify differential metabolites when compared to traditionaluntargeted metabolomics. The intra/inter-day precision and reproducibility results proved the method is reliable and precise. The established method was then applied to seek the potential differentiated metabolic biomarkers of cardiac hypertrophy (CH) rats, and oxylipins, phosphorylcholine (PC), lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE), Krebs cycle intermediates, carnitines, amino acids, and bile acids were disclosed to be the possible differentiate components. Their metabolic pathway analysis revealed that the potential metabolic alterations in CH rats were mainly associated with phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, citrate cycle, glyoxylate and dicarboxylate metabolism, and tyrosine metabolism. In sum, this research provided a comprehensiveand reliable LC-MS/MS MRM platform for pseudo-targeted metabolomics investigation of disease condition, and some interesting potential biomarkers were disclosed for CH, which merit further exploration in the future.

Pregnant women with COVID-19 ARDS on the intensive care unit

Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk of severe disease progression. Comorbidities, such as chronic arterial hypertension, diabetes mellitus, advanced maternal age and high body mass index, may predispose to severe disease. The management of pregnant COVID-19patients on the intensive care unit (ICU) is challenging and requires careful consideration of maternal, fetal and ethical issues. Description and discussion of intensive care treatment strategies and perinatal anesthesiological management in patients with COVID-19 acute respiratory distress syndrome (CARDS). We analyzed the demographic data, maternal medical history, clinical intensive care management, complications, indications and management of extracorporeal membrane oxygenation (ECMO) and infant survival of all pregnant patients treated for severe CARDS in the anesthesiological ICU of aGerman university hospital between March and November 2021. The cohort included 9 patients with amean age of 30.3 years (range 26-40years). The gestational age ranged from 21 + 3 weeks to 37 + 2 weeks. None of the patients had been vaccinated against SARS-CoV‑2. Of the nine patients seven were immigrants and communication was hampered by inadequate Central European language skills. Of the patients five had aPaO2/FiO2 index < 150 mm Hg despite escalated invasive ventilation (FiO2 > 0.9 and a positive end-expiratory pressure [PEEP] of 14 mbar) and were therefore treated with repeated prolonged prone positioning maneuvers (5-14 prone positions for 16 h each, atotal of 47prone positioning treatments) and 2 required treatment with inhaled nitric oxide and venovenous ECMO. The most common complications were bacterial superinfection of the lungs, urinary tract infection and delirium. All the women and five neonates survived. All newborns were delivered by cesarean section, two patients were discharged home with an intact pregnancy and two intrauterine fetal deaths were observed. None of the newborns tested positive for SARS-CoV‑2 at birth. High survival rates are possible in pregnant patients with CARDS. The peripartum management of pregnant women with CARDS requires close interdisciplinary collaboration and should prioritize maternal survival in early pregnancy. In our experience, prolonged prone positioning, an essential evidence-based cornerstone in the treatment of ARDS, can also be safely used in advanced stages of pregnancy. Inhaled nitric oxide (iNO) and ECMO should be considered as life-saving treatment options for carefully selected patients. For cesarean section, neuraxial anesthesia can be safely performed in patients with mild CARDS if well planned but the therapeutic anticoagulation recommended for COVID-19 may increase the risk of bleeding complications, making general anesthesia amore viable alternative, especially in severe disease.

Impressive Response to TANDEM Peptide Receptor Radionuclide Therapy with 177Lu/225AcDOTA-LM3 Somatostatin Receptor Antagonist in a Patient with Therapy-Refractory, Rapidly Progressive Neuroendocrine Neoplasm of the Pancreas.

The present report describes the history of a 58-year-old woman with a rapidly progressing neuroendocrine pancreatic tumor (initially G2) presenting with extensive liver, bone, and lymph node metastases. Previous treatments included chemotherapy, hemithyroidectomy for right lobe metastasis, Peptide Receptor Radionuclide Therapy (PRRT) with [177Lu]Lu-DOTATATE, Lanreotide, Everolimus, and liver embolization. Due to severe disease progression, after a liver biopsy revealing tumor grade G3, PRRT with the somatostatin receptor antagonist LM3 was initiated. [68Ga]GaDOTA-LM3 PET/CT showed intense tracer uptake in the liver, pancreatic tumor, lymph nodes, and bone metastases. Three TANDEM-PRRT cycles using [177Lu]LuDOTA-LM3 and [225Ac]AcDOTA-LM3, administered concurrently, resulted in significant improvement, notably in liver metastases, hepatomegaly reduction, the complete regression of bone and lymph node metastases, and primary tumor improvement. Partial remission was confirmed by positron emission tomography/computed tomography, chest-abdomen-pelvis contrast-enhanced computed tomography, and magnetic resonance of the abdomen, with marked clinical improvement in pain, energy levels, and quality of life, enabling full resumption of physical activity.

Lysosomal genes contribute to Parkinson’s disease near agriculture with high intensity pesticide use

Parkinson’s disease (PD), the second most common neurodegenerative disorder, develops sporadically, likely through a combination of polygenic and environmental factors. Previous studies associate pesticide exposure and genes involved in lysosomal function with PD risk. We evaluated the frequency of variants in lysosomal function genes among patients from the Parkinson’s, Environment, and Genes (PEG) study with ambient pesticide exposure from agricultural sources. 757 PD patients, primarily of White European/non-Hispanic ancestry (75%), were screened for variants in 85 genes using a custom amplicon panel. Variant enrichment was calculated against the Genome Aggregation Database (gnomAD). Enriched exonic variants were prioritized by exposure to a cluster of pesticides used on cotton and severity of disease progression in a subset of 386 patients subdivided by race/ethnicity. Gene enrichment analysis identified 36 variants in 26 genes in PEG PD patients. Twelve of the identified genes (12/26, 46%) had multiple enriched variants and/or a single enriched variant present in multiple individuals, representing 61% (22/36) of the observed variation in the cohort. The majority of enriched variants (26/36, 72%) were found in genes contributing to lysosomal function, particularly autophagy, and were bioinformatically deemed functionally deleterious (31/36, 86%). We conclude that, in this study, variants in genes associated with lysosomal function, notably autophagy, were enriched in PD patients exposed to agricultural pesticides suggesting that altered lysosomal function may generate an underlying susceptibility for developing PD with pesticide exposure. Further study of gene-environment interactions targeting lysosomal function may improve understanding of PD risk in individuals exposed to pesticides.

Biomarkers and Therapeutic Interventions for Cardiorenal Syndrome: A Literature Review.

Acute or chronic cardiac and renal failure interact to worsen both organs' states in cardiorenal syndrome (CRS), a complicated medical disorder. This review covers biomarkers and therapeutic strategies in CRS management, highlighting current advancements and future prospects. A Scopus, Google Scholar, and PubMed search technique was used to examine relevant material from 2019-2024. Troponin and NT-proBNP are important cardiac biomarkers for CRS severity assessment, disease progression, and therapy options. Serum creatinine, cystatin C, and NGAL also reveal renal function and prognosis. In CRS, albuminuria, a measure of renal function and chronic kidney disease severity, is related to poor outcomes.Diuretics and ultrafiltration reduce fluid excess in CRS, while RAAS inhibitors increase survival and reverse cardiac remodeling in heart failure patients. SGLT2 inhibitors may protect the kidneys and heart. In certain cardiac diseases, non-pharmacological methods like ICDs and CRT may help. This review concludes with advancements in CRS biomarkers and treatment. Cardiac and renal biomarkers can predict CRS and SGLT2 inhibitors may improve CRS therapy. Research is required to improve these therapies and investigate other therapeutic ways to improve patient outcomes.

Correlation of lesion severity with bacterial changes in Treponeme-Associated Hoof Disease from free-roaming wild elk (Cervus canadensis)

BackgroundTreponeme-Associated Hoof Disease (TAHD) is a polybacterial, multifactorial disease affecting free-ranging wild elk (Cervus canadensis) in the Pacific Northwest. Previous studies have indicated a bacterial etiology similar to digital dermatitis in livestock, including isolation of Treponema species from lesions. The lesions appear to progress rapidly from ulcerative areas in the interdigital space or along the coronary band to severe, ulcerative, necrotic, proliferative lesions under-running the hoof wall, perforating the sole, and contributing to hoof elongation, deformity, and overgrowth. Eventually the lesions undermine the laminal structure leading to sloughing of the hoof horn capsule. The objective of this study was to characterize the bacterial communities associated with hoof lesions, which were categorized into 5 stages or disease grade severities, with 0 being unaffected tissue and 4 being sloughed hoof capsule. We also wanted to determine if the etiology of TAHD through morphological changes was dominated by Treponema, as observed in hoof diseases in livestock.ResultsThe bacterial 16S rRNA gene was sequenced from 66 hoof skin biopsy samples representing 5 lesion grades from samples collected by Washington Department of Fish and Wildlife as part of a voluntary hunter program. Analysis of the relative abundance of bacterial sequences showed that lesions were dominated by members of the bacterial phyla Proteobacteria, Firmicutes, Spirochaetes, Bacteroidetes and Actinobacteria. In lesion samples, members of the genus Treponema, Porphyromonas, and Mycoplasma increased with lesion severity. Association analysis indicated frequent identification of Treponema with Porphyromonas, Bacteroides and other anaerobic Gram-positive cocci.ConclusionsThe bacterial 16S rRNA gene sequencing confirmed the presence of Treponema species at all stages of TAHD lesions, treponeme specie-specific PCR and histopathology, indicating that the morphological changes are a continual progression of disease severity with similar bacterial communities. Association and abundance of these other pathogenic genera within lesions may mean synergistic role with Treponema in hoof disease pathogenesis. Characterizing bacteria involved in lesion development, and their persistence during disease progression, provides evidence for science-based management decisions in TAHD infected elk populations.

A rare KMT2A::CBL transcript in an acute monoblastic leukemia patient with an unfavorable outcome

BackgroundLysine [K] methyltransferase 2A (KMT2A, previously known as MLL) gene rearrangements are common in acute leukemias of various lineages and are associated with features such as chemotherapy resistance and rapid relapse. KMT2A::CBL is a rare fusion of unknown pathogenesis generated by a unique interstitial deletion of chromosome 11 that has been reported across a wide age range in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. The leukemogenic effect of the KMT2A::CBL rearrangement and its association with clinical prognosis have not been well clarified.Methods and resultsWe report the case of a 64-year-old female who was diagnosed with acute monoblastic leukemia (M5a) and who acquired the rare KMT2A::CBL fusion. The patient received multiple cycles of therapy but did not achieve remission and eventually succumbed to severe infection and disease progression. Additionally, we characterized the predicted KMT2A-CBL protein structure in this case to reveal the underlying leukemogenic mechanisms and summarized reported cases of hematological malignancies with KMT2A::CBL fusion to investigate the correlation of gene rearrangements with clinical outcomes.ConclusionsThis report provides novel insights into the leukemogenic potential of the KMT2A::CBL rearrangement and the correlation between gene rearrangements and clinical outcomes.

The low expression of matrix metalloproteinases: a key to longevity?

Over the past few decades, it has become clear that an excessive activity of matrix metalloproteinases (MMPs) can accelerate the progression and fatal outcomes of several serious age-related diseases, including atherosclerotic coronary heart disorders and various types of malignancies. These proteolytic enzymes mediate the degradation and remodeling of the extracellular matrix through cleaving its various components, thereby affecting many critical functions of surrounding cells and intercellular communication. Consequently, the low expression levels of MMPs can be important in the prevention and treatment of such chronic life-threatening pathologies, contributing to the better quality of life and longer life expectancy. In this review article, the pathogenic proteolytic roles of MMPs are examined in more detail, especially in the cases of heart attack and stroke as well as cancer invasion and metastasis, showing that these enzymes can be considered not only as diagnostic and prognostic biomarkers but also as important therapeutic targets in the fight against many age- and lifestyle-related serious disorders. The identification and development of suppressing agents with a selective activity towards specific MMPs have, however, still remained a complex and complicated challenge, in which natural plant-derived compounds are increasingly recognized as promising leads for the new-generation inhibitors.

Liver transplantation in a patient with severe cystic fibrosis

Cystic fibrosis (CF) is a severe progressive hereditary disease associated with mutations in the CFTR gene, characterized by multiple organ pathology, including the upper and lower respiratory tract, gastrointestinal and reproductive tracts, and the endocrine system. Despite new therapy, which significantly increases survival among patients with cystic fibrosis, the development of complications of this disease is still a factor affecting the duration and quality of life. The aim of the study is to demonstrate a clinical case of severe course of cystic fibrosis in a patient with meconium ileus, cystic fibrosis-associated diabetes mellitus, pulmonary and arterial hypertension, cirrhosis, who was under the observation of specialists of the Department of Cystic fibrosis of the Research Clinical Institute of Childhood of the Ministry of Health of the Moscow Region and National Medical Research Center of Transplantology and Artificial Organs named after V. I. Shumakov and underwent death donor liver transplantation. New methods of diagnosis and therapy of complications allow timely detection and control of their course, while maintaining a satisfactory quality of life for the patient