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The Egyptian Heart Journal : (EHJ) :... Jun 2024Amyloidosis, particularly wild-type transthyretin amyloidosis (ATTRwt), is an increasingly recognized cause of heart failure with preserved ejection fraction in the...
BACKGROUND
Amyloidosis, particularly wild-type transthyretin amyloidosis (ATTRwt), is an increasingly recognized cause of heart failure with preserved ejection fraction in the aging population. The complexity of managing ATTRwt in older patients underscores the necessity for individualized treatment approaches, yet clinical guidelines are lacking. This case report contributes to the understanding of ATTRwt management in the elderly, emphasizing the intricacies of medication tolerance and therapeutic decision-making.
CASE PRESENTATION
An 83-year-old Korean man with a history of hypertension presented with dyspnea and peripheral edema. Investigations including electrocardiography, transthoracic echocardiography, cardiac magnetic resonance, and Technetium pyrophosphate scintigraphy led to a diagnosis of ATTRwt cardiac amyloidosis. Initial management with heart failure medications, including an angiotensin-converting enzyme inhibitor, diuretic, and mineralocorticoid receptor antagonist, was modified due to evolving clinical presentations, such as hypotension and onset of atrial fibrillation. Challenges included intolerance to beta-blockers and bleeding complications from direct oral anticoagulant therapy. The patient's treatment journey highlighted the need for personalized management strategies in older ATTRwt patients.
CONCLUSIONS
This case illustrates the challenges in diagnosing and managing ATTRwt amyloidosis in the elderly, particularly the complexities in medication management due to the patient's age, comorbid conditions, and side effects. It underscores the importance of a tailored approach in managing ATTRwt in older populations and highlights the need for ongoing research and development of treatment strategies tailored to this demographic.
PubMed: 38888709
DOI: 10.1186/s43044-024-00507-0 -
Gene Regulation of Neutrophils Mediated Liver and Lung Injury through NETosis in Acute Pancreatitis.Inflammation Jun 2024Acute pancreatitis (AP) is one of the most common gastrointestinal emergencies, often resulting in self-digestion, edema, hemorrhage, and even necrosis of pancreatic...
Acute pancreatitis (AP) is one of the most common gastrointestinal emergencies, often resulting in self-digestion, edema, hemorrhage, and even necrosis of pancreatic tissue. When AP progresses to severe acute pancreatitis (SAP), it often causes multi-organ damage, leading to a high mortality rate. However, the molecular mechanisms underlying SAP-mediated organ damage remain unclear. This study aims to systematically mine SAP data from public databases and combine experimental validation to identify key molecules involved in multi-organ damage caused by SAP. Retrieve transcriptomic data of mice pancreatic tissue for AP, lung and liver tissue for SAP, and corresponding normal tissue from the Gene Expression Omnibus (GEO) database. Conduct gene differential analysis using Limma and DEseq2 methods. Perform enrichment analysis using the clusterProfiler package in R software. Score immune cells and immune status in various organs using single-sample gene set enrichment analysis (ssGSEA). Evaluate mRNA expression levels of core genes using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Validate serum amylase, TNF-α, IL-1β, and IL-6 levels in peripheral blood using enzyme-linked immunosorbent assay (ELISA), and detect the formation of neutrophil extracellular traps (NETs) in mice pancreatic, liver, and lung tissues using immunofluorescence. Differential analysis reveals that 46 genes exhibit expression dysregulation in mice pancreatic tissue for AP, liver and lung tissue for SAP, as well as peripheral blood in humans. Functional enrichment analysis indicates that these genes are primarily associated with neutrophil-related biological processes. ROC curve analysis indicates that 12 neutrophil-related genes have diagnostic potential for SAP. Immune infiltration analysis reveals high neutrophil infiltration in various organs affected by SAP. Single-cell sequencing analysis shows that these genes are predominantly expressed in neutrophils and macrophages. FPR1, ITGAM, and C5AR1 are identified as key genes involved in the formation of NETs and activation of neutrophils. qPCR and IHC results demonstrate upregulation of FPR1, ITGAM, and C5AR1 expression in pancreatic, liver, and lung tissues of mice with SAP. Immunofluorescence staining shows increased levels of neutrophils and NETs in SAP mice. Inhibition of NETs formation can alleviate the severity of SAP as well as the levels of inflammation in the liver and lung tissues. This study identified key genes involved in the formation of NETs, namely FPR1, ITGAM, and C5AR1, which are upregulated during multi-organ damage in SAP. Inhibition of NETs release effectively reduces the systemic inflammatory response and liver-lung damage in SAP. This research provides new therapeutic targets for the multi-organ damage associated with SAP.
PubMed: 38884700
DOI: 10.1007/s10753-024-02071-w -
Drug Discoveries & Therapeutics Jun 2024Malnutrition is a common problem among hospitalized older patients. Peripheral parenteral nutrition (PN) can improve patient outcomes but can also lead to complications...
Malnutrition is a common problem among hospitalized older patients. Peripheral parenteral nutrition (PN) can improve patient outcomes but can also lead to complications that affect future treatment. Older inpatients, in particular, are expected to be prone to these catheter-related complications. However, the impact of peripheral PN on older inpatients has been rarely investigated. In the current study, the impact of PN on short peripheral catheters (SPCs) was evaluated by comparing signs and symptoms at the time of catheter removal between 22 patients with PN and 27 without. In addition to external clinical assessment, sonographic investigations of the SPC site were performed. The prevalence of external signs and symptoms of complications was similar between the patients (all P > 0.05). However, subcutaneous edema was found by ultrasound in > 80% of patients with PN, compared with 55.6% of those without PN (P = 0.051). Unlike cases without PN, all patients with PN who presented with external signs and symptoms developed subcutaneous edema (P = 0.022). Multivariate analysis demonstrated that administration of PN was independently associated with subcutaneous edema (adjusted odds ratio = 6.88, 95% confidence interval = 1.083-75.486, P = 0.040). For several decades, phlebitis has been the primary focus of complications related to peripheral PN in clinical settings. However, our results imply that peripheral PN causes subcutaneous edema, which can lead to catheter failure in older inpatients. This study contributes to understanding the etiology of catheter failure during peripheral PN in this population.
PubMed: 38880602
DOI: 10.5582/ddt.2024.01029 -
Microvascular Research Jun 2024Ischemic stroke occurs due a blockage in the blood flow to the brain, leading to damage to the nervous system. The prevalent morbidities resulting from stroke include...
Ischemic stroke occurs due a blockage in the blood flow to the brain, leading to damage to the nervous system. The prevalent morbidities resulting from stroke include post-stroke infection, as sepsis. Additionally, oxidative stress is recognized for inducing functional deficits in peripheral organs during sepsis. Therefore, sex differences in stroke exist and we aimed to investigate the peripheral oxidative stress caused by sepsis after stroke in male and female rats. Wistar rats (male and female) were divided into sham+sham, middle cerebral artery occlusion (MCAO) + sham, sham+ cecal ligation and perforation (CLP) and MCAO+CLP groups to males and female rats. Animals were subjected to MCAO or sham and after 7 days, were subjected to sepsis by CLP or sham. After 24 h, serum, total brain, lung, liver, heart, and spleen were collected. Brain edema, myeloperoxidase (MPO) activity, nitrite/nitrate (N/N) concentration, oxidative damage to lipids and proteins, and catalase activity were evaluated. Brain edema was observed only in male rats in MCAO+CLP group compared to MCAO+sham. Regarding MPO activity, an increase was verified in male in different organs and serum in MCAO+CLP group. For N/N levels, the increase was more pronounced in females submitted to MCAO+CLP. In general, to oxidative stress, an increase was only observed in animals exposed to MCAO+CLP, or with a greater increase in this group compared to the others. The findings provided the first indication that animals exposed to MCAO exhibit a heightened vulnerability to the harmful impacts of sepsis, as evidenced by brain edema and peripheral oxidative stress, and this susceptibility is dependent of sex.
PubMed: 38880383
DOI: 10.1016/j.mvr.2024.104711 -
Journal of Orthopaedic Surgery and... Jun 2024Postoperative pulmonary complications (PPCs) are among the most severe complications following total hip arthroplasty revision (THAR), imposing significant burdens on...
BACKGROUND
Postoperative pulmonary complications (PPCs) are among the most severe complications following total hip arthroplasty revision (THAR), imposing significant burdens on individuals and society. This study examined the prevalence and risk factors of PPCs following THAR using the NIS database, identifying specific pulmonary complications (SPCs) and their associated risks, including pneumonia, acute respiratory failure (ARF), and pulmonary embolism (PE).
METHODS
The National Inpatient Sample (NIS) database was used for this cross-sectional study. The analysis included patients undergoing THAR based on NIS from 2010 to 2019. Available data include demographic data, diagnostic and procedure codes, total charges, length of stay (LOS), hospital information, insurance information, and discharges.
RESULTS
From the NIS database, a total of 112,735 THAR patients in total were extracted. After THAR surgery, there was a 2.62% overall incidence of PPCs. Patients with PPCs after THAR demonstrated increased LOS, total charges, usage of Medicare, and in-hospital mortality. The following variables have been determined as potential risk factors for PPCs: advanced age, pulmonary circulation disorders, fluid and electrolyte disorders, weight loss, congestive heart failure, metastatic cancer, other neurological disorders (encephalopathy, cerebral edema, multiple sclerosis etc.), coagulopathy, paralysis, chronic pulmonary disease, renal failure, acute heart failure, deep vein thrombosis, acute myocardial infarction, peripheral vascular disease, stroke, continuous trauma ventilation, cardiac arrest, blood transfusion, dislocation of joint, and hemorrhage.
CONCLUSIONS
Our study revealed a 2.62% incidence of PPCs, with pneumonia, ARF, and PE accounting for 1.24%, 1.31%, and 0.41%, respectively. A multitude of risk factors for PPCs were identified, underscoring the importance of preoperative optimization to mitigate PPCs and enhance postoperative outcomes.
Topics: Humans; Arthroplasty, Replacement, Hip; Risk Factors; Postoperative Complications; Male; Female; Retrospective Studies; Incidence; Aged; Middle Aged; Cross-Sectional Studies; Databases, Factual; Pulmonary Embolism; Reoperation; Length of Stay; Lung Diseases; United States; Pneumonia; Adult; Aged, 80 and over; Respiratory Insufficiency; Inpatients
PubMed: 38877587
DOI: 10.1186/s13018-024-04836-3 -
Journal of Bodywork and Movement... Jul 2024In this case report a new approach called neurofascialvascular training (NFVT) is described. NFVT consists of two mechanisms which improve mechanosensitivity in carpal...
INTRODUCTION
In this case report a new approach called neurofascialvascular training (NFVT) is described. NFVT consists of two mechanisms which improve mechanosensitivity in carpal tunnel syndrome (CTS). The first involves increased blood flow in the nerve microcirculation, while the second stimulates the reciprocal sliding between the thin sheets of connective tissue inside the nerve. The goal of these two actions is to squeeze, mobilize and reduce intraneural edema. The novelty of this approach is the simultaneous involvement of multiple physiological systems to reduce nerve mechanosensitivity. This case report describes the rehabilitation progress achieved by NFVT in a patient with CTS.
MAIN SYMPTOMS AND/OR IMPORTANT CLINICAL FINDINGS
A 64-year-old woman complaining of nocturnal pain and tingling with severe impairment of sleep quality for two years was diagnosed at CTS.
THERAPEUTIC INTERVENTIONS
The patient underwent nine 30-min exercise sessions of NFVT.
OUTCOMES
At each session and at the last follow-up 3 months after the end of treatment the following tests were performed: the upper limb neurodynamic test1 (ULNT1), the Hand Grip Meter and the Phdurkan test. Furthermore ultrasound, numerical rating scale and the Boston Carpal Tunnel Questionnaire (BCTQ) were also adopted.
CONCLUSION
NFVT can improve symptoms and motor dysfunction in a patient with CTS.
TAKE-AWAY LESSON
In the presence of mild carpal tunnel syndrome, active neurofascialvascular training that increases peripheral blood flow and targets fascial tissue within the peripheral nervous system can resolve symptoms and produce significant improvement within a few months of starting treatment.
Topics: Humans; Carpal Tunnel Syndrome; Female; Middle Aged; Exercise Therapy; Hand Strength
PubMed: 38876659
DOI: 10.1016/j.jbmt.2023.10.003 -
European Journal of Pharmacology Jun 2024Pain is a common public health problem and remains as an unmet medical need. Currently available analgesics usually have limited efficacy or are accompanied by many...
Pain is a common public health problem and remains as an unmet medical need. Currently available analgesics usually have limited efficacy or are accompanied by many adverse side effects. To achieve satisfactory pain relief by multimodal analgesia, new combinations of nefopam and gabapentinoids (pregabalin/gabapentin) were designed and assessed in inflammatory, osteoarthritis and neuropathic pain. Isobolographic analysis was performed to analyze the interactions between nefopam and gabapentinoids in carrageenan-induced inflammatory pain, mono-iodoacetate-induced osteoarthritis pain and paclitaxel-induced peripheral neuropathic pain in mice. The anti-inflammatory effect and motor performance of monotherapy or their combinations were evaluated in the carrageenan-induced inflammatory responses and rotarod test, respectively. Nefopam (1, 3, 5, 10, 30 mg/kg, p.o.), pregabalin (3, 6, 12, 24 mg/kg, p.o.) or gabapentin (25, 50, 75, 100 mg/kg, p.o.) dose-dependently reversed mechanical allodynia in three pain models. Isobolographic analysis indicated that the combinations of nefopam and gabapentinoids exerted synergistic anti-nociceptive effects in inflammatory, osteoarthritis, and neuropathic pain mouse models, as evidenced by the experimental ED (median effective dose) falling below the predicted additive line. Moreover, the combination of nefopam-pregabalin/gabapentin alleviated carrageenan-induced inflammation and edema, and also prevented gabapentinoids-related sedation or ataxia by lowering their effective doses. Collectively, the co-administration of nefopam and gabapentinoids showed synergistic analgesic effects and may result in improved therapeutic benefits for treating pain.
PubMed: 38876275
DOI: 10.1016/j.ejphar.2024.176738 -
Cardiovascular Research Jun 2024SCUBE2 (Signal peptide-CUB-epidermal growth factor-like domain-containing protein 2) is a secreted or membrane-bound protein originally identified from endothelial cells...
AIMS
SCUBE2 (Signal peptide-CUB-epidermal growth factor-like domain-containing protein 2) is a secreted or membrane-bound protein originally identified from endothelial cells (ECs). Our previous work showed that SCUBE2 forms a complex with E-cadherin and stabilizes epithelial adherens junctions (AJs) to promote epithelial phenotypes. However, it remains unclear whether SCUBE2 also interacts with vascular endothelial (VE)-cadherin and modulates EC barrier function. In this study, we investigated whether and how SCUBE2 in ECs regulates vascular barrier maintenance.
METHODS AND RESULTS
We showed that SCUBE2 colocalized and interacted with VE-cadherin and VE-protein tyrosine phosphatase (VE-PTP) within EC AJs. Furthermore, SCUBE2 knockdown disrupted EC AJs and increased EC permeability. Expression of EC SCUBE2 was suppressed at both mRNA and protein levels via the nuclear factor-κB (NF-κB) signaling pathway in response to pro-inflammatory cytokines or permeability-inducing agents. In line with these findings, EC-specific deletion of Scube2 (EC-KO) in mice impaired baseline barrier function and worsened vascular leakiness of peripheral capillaries after local injection of histamine or vascular endothelial growth factor. EC-KO mice were also sensitive to pulmonary vascular hyperpermeability and leukocyte infiltration in response to acute endotoxin- or influenza virus-induced systemic inflammation. Meanwhile, EC-specific SCUBE2-overexpressing mice were protected from these effects. Molecular studies suggested that SCUBE2 acts as a scaffold molecule enabling VE-PTP to dephosphorylate VE-cadherin, which prevents VE-cadherin internalization and stabilizes EC AJs. As such, loss of SCUBE2 resulted in hyperphosphorylation of VE-cadherin at tyrosine 685, which led to its endocytosis, thus destabilizing EC AJs and reducing barrier function. All of these effects were exacerbated by inflammatory insults.
CONCLUSIONS
We found that SCUBE2 contributes to vascular integrity by recruiting VE-PTP to dephosphorylate VE-cadherin and stabilize AJs, thereby promoting EC barrier function. Moreover, our data suggest that genetic overexpression or pharmacological upregulation of SCUBE2 may help to prevent vascular leakage and edema in inflammatory diseases.
PubMed: 38870316
DOI: 10.1093/cvr/cvae132 -
CNS Neuroscience & Therapeutics Jun 2024The extent of perihematomal edema following intracerebral hemorrhage (ICH) significantly impacts patient prognosis, and disruption of the blood-brain barrier (BBB)...
AIMS
The extent of perihematomal edema following intracerebral hemorrhage (ICH) significantly impacts patient prognosis, and disruption of the blood-brain barrier (BBB) exacerbates perihematomal edema. However, the role of peripheral IL-10 in mitigating BBB disruption through pathways that link peripheral and central nervous system signals remains poorly understood.
METHODS
Recombinant IL-10 was administered to ICH model mice via caudal vein injection, an IL-10-inhibiting adeno-associated virus and an IL-10 receptor knockout plasmid were delivered intraventricularly, and neurobehavioral deficits, perihematomal edema, BBB disruption, and the expression of JAK1 and STAT3 were evaluated.
RESULTS
Our study demonstrated that the peripheral cytokine IL-10 mitigated BBB breakdown, perihematomal edema, and neurobehavioral deficits after ICH and that IL-10 deficiency reversed these effects, likely through the IL-10R/JAK1/STAT3 signaling pathway.
CONCLUSIONS
Peripheral IL-10 has the potential to reduce BBB damage and perihematomal edema following ICH and improve patient prognosis.
Topics: Animals; STAT3 Transcription Factor; Cerebral Hemorrhage; Brain Edema; Janus Kinase 1; Interleukin-10; Signal Transduction; Male; Mice; Receptors, Interleukin-10; Mice, Inbred C57BL; Mice, Knockout; Blood-Brain Barrier
PubMed: 38867395
DOI: 10.1111/cns.14796 -
Perfusion Jun 2024For veno-arterial extracorporeal membrane oxygenation (ECMO), the femoral artery is the preferred cannulation site (femoro-femoral: Vf-Af). This results in retrograde...
RATIONALE
For veno-arterial extracorporeal membrane oxygenation (ECMO), the femoral artery is the preferred cannulation site (femoro-femoral: Vf-Af). This results in retrograde aortic flow, which increases the left ventricular afterload and can lead to severe pulmonary edema and thrombosis of the cardiac chambers. Right axillary artery cannulation (femoral-axillary: Vf-Aa) provides partial anterograde aortic flow, which may prevent some complications. This study aimed to compare the 90-day mortality and complication rates between VF-AA and VF-AF.
METHODS
Consecutive adult patients with cardiogenic shock who received peripheral VA-ECMO between 2013 and 2019 at our institution were retrospectively included. The exclusion criteria were refractory cardiac arrest, multiple VA-ECMO implantations due to vascular access changes, weaning failure, or ICU readmission. A statistical approach using inverse probability of treatment weighting was used to estimate the effect of the cannulation site on the outcomes. The primary endpoint was the 90-day mortality. The secondary endpoints were vascular access complications, stroke, and other complications related to retrograde blood flow. Outcomes were estimated using logistic regression analysis.
RESULTS
VA-ECMO was performed on 534 patients. Patients with refractory cardiac arrest ( = 77 (14%)) and those supported by multiple VA-ECMO ( = 92, (17%)) were excluded. Out of the 333 patients studied ( = 209 Vf-Aa; = 124 VF-AF), the main indications for VA-ECMO implantation were post-cardiotomy (33%, = 109), dilated cardiomyopathy (20%, = 66), post-cardiac transplantation (15%, = 50), acute myocardial infarction (14%, = 46) and other etiologies (18%, = 62). The median SOFA score was 9 [7-11], and the crude 90-day mortality rate was 53% ( = 175). After IPTW, the 90-day mortality was similar in the Vf-Aa and VF-AF groups (54% vs 58%, IPTW-OR = 0.84 [0.54-1.29]). Axillary artery cannulation was associated with significantly fewer local infections (OR = 0.21, 95% CI:0.09-0.51), limb ischemia (OR = 0.37, 95% CI:0.17-0.84), bowel ischemia (OR = 0.16, 95% CI:0.05-0.51) and pulmonary edema (OR = 0.52, 95% CI:0.29-0.92) episodes, but with a higher rate of stroke (OR = 2.87, 95% CI:1.08-7.62) than femoral artery cannulation.
CONCLUSION
Compared to VF-AF, axillary cannulation was associated with similar 90-day mortality rates. The high rate of stroke associated with axillary artery cannulation requires further investigation.
PubMed: 38867368
DOI: 10.1177/02676591241261330