-
Brain and Behavior Jun 2024To assess changes in neurovascular coupling (NVC) by evaluating the relationship between cerebral perfusion and brain connectivity in patients with end-stage renal...
PURPOSE
To assess changes in neurovascular coupling (NVC) by evaluating the relationship between cerebral perfusion and brain connectivity in patients with end-stage renal disease (ESRD) undergoing hemodialysis versus in healthy control participants. And by exploring brain regions with abnormal NVC associated with cognitive deficits in patients, we aim to provide new insights into potential preventive and therapeutic interventions.
MATERIALS AND METHODS
A total of 45 patients and 40 matched healthy controls were prospectively enrolled in our study. Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Arterial spin labeling (ASL) was used to calculate cerebral blood flow (CBF), and graph theory-based analysis of results from resting-state functional magnetic resonance imaging (rs-fMRI) was used to calculate brain network topological parameters (node betweenness centrality [BC], node efficiency [Ne], and node degree centrality [DC]). Three NVC biomarkers (CBF-BC, CBF-Ne, and CBF-DC coefficients) at the whole brain level and 3 NVC biomarkers (CBF/BC, CBF/Ne, and CBF/DC ratios) at the local brain region level were used to assess NVC. Mann-Whitney U tests were used to compare the intergroup differences in NVC parameters. Spearman's correlation analysis was used to evaluate the relationship among NVC dysfunctional pattern, cognitive impairment, and clinical characteristics multiple comparisons were corrected using a voxel-wise false-discovery rate (FDR) method (p < .05).
RESULTS
Patients showed significantly reduced global coupling coefficients for CBF-Ne (p = .023) and CBF-BC (p = .035) compared to healthy controls. Coupling ratios at the local brain region level were significantly higher in patients in 33 brain regions (all p values < .05). Coupling ratio changes alone or accompanied by changes in CBF, node properties, or both CBF and node properties were identified. In patients, negative correlations were seen between coupling ratios and MoCA scores in many brain regions, including the left dorsolateral superior frontal gyrus, the bilateral median cingulate and paracingulate gyri, and the right superior parietal gyrus. The correlations remained even after adjusting for hemoglobin and hematocrit levels.
CONCLUSION
Disrupted NVC may be one mechanism underlying cognitive impairment in dialysis patients.
Topics: Humans; Male; Female; Middle Aged; Magnetic Resonance Imaging; Neurovascular Coupling; Kidney Failure, Chronic; Cognitive Dysfunction; Brain; Adult; Cerebrovascular Circulation; Renal Dialysis; Neuroimaging; Aged; Prospective Studies; Mental Status and Dementia Tests; Nerve Net
PubMed: 38923330
DOI: 10.1002/brb3.3598 -
Arquivos Brasileiros de Cardiologia 2024Heart failure (HF) contributes to a high burden of hospitalization, and its form of presentation is associated with disease prognosis.
BACKGROUND
Heart failure (HF) contributes to a high burden of hospitalization, and its form of presentation is associated with disease prognosis.
OBJECTIVES
To describe the association of hemodynamic profile of acute HF patients at hospital admission, based on congestion (wet/dry) and perfusion (cold/warm), with mortality, hospital length of stay and risk of readmission.
METHODS
Cohort study, with patients participating in the "Best Practice in Cardiology" program, admitted for acute HF in Brazilian public hospitals between March 2016 and December 2019, with a six-month follow-up. Characteristics of the population and hemodynamic profile at admission were analyzed, in addition to survival analysis using Cox proportional hazard model for associations between hemodynamic profile at admission and mortality, and logistic regression for the risk of rehospitalization, using a statistical significance level of 5%.
RESULTS
A total of 1,978 patients were assessed, with mean age of 60.2 (±14.8) years and mean left ventricular ejection fraction of 39.8% (±17.3%). A high six-month mortality rate (22%) was observed, with an association of cold hemodynamic profiles with in-hospital mortality (HR=1.72, 95%CI 1.27-2.31; p < 0.001) and six-month mortality (HR= 1.61, 95%CI 1.29-2.02). Six-month rehospitalization rate was 22%, and higher among patients with wet profiles (OR 2.30; 95%CI 1.45-3.65; p < 0.001).
CONCLUSIONS
Acute HF is associated with high mortality and rehospitalization rates. Patient hemodynamic profile at admission is a good prognostic marker of this condition.
Topics: Humans; Heart Failure; Male; Female; Middle Aged; Brazil; Hemodynamics; Aged; Hospital Mortality; Acute Disease; Patient Readmission; Length of Stay; Prognosis; Hospitalization; Risk Factors; Cohort Studies; Patient Admission
PubMed: 38922272
DOI: 10.36660/abc.20230699 -
Toxins Jun 2024Snakebite envenoming is a neglected tropical disease that causes >100,000 deaths and >400,000 cases of morbidity annually. Despite the use of mouse models, severe local...
Snakebite envenoming is a neglected tropical disease that causes >100,000 deaths and >400,000 cases of morbidity annually. Despite the use of mouse models, severe local envenoming, defined by morbidity-causing local tissue necrosis, remains poorly understood, and human-tissue responses are ill-defined. Here, for the first time, an ex vivo, non-perfused human skin model was used to investigate temporal histopathological and immunological changes following subcutaneous injections of venoms from medically important African vipers ( and ) and cobras ( and ). Histological analysis of venom-injected ex vivo human skin biopsies revealed morphological changes in the epidermis (ballooning degeneration, erosion, and ulceration) comparable to clinical signs of local envenoming. Immunostaining of these biopsies confirmed cell apoptosis consistent with the onset of necrosis. RNA sequencing, multiplex bead arrays, and ELISAs demonstrated that venom-injected human skin biopsies exhibited higher rates of transcription and expression of chemokines (CXCL5, MIP1-ALPHA, RANTES, MCP-1, and MIG), cytokines (IL-1β, IL-1RA, G-CSF/CSF-3, and GM-CSF), and growth factors (VEGF-A, FGF, and HGF) in comparison to non-injected biopsies. To investigate the efficacy of antivenom, SAIMR Echis monovalent or SAIMR polyvalent antivenom was injected one hour following or venom treatment, respectively, and although antivenom did not prevent venom-induced dermal tissue damage, it did reduce all pro-inflammatory chemokines, cytokines, and growth factors to normal levels after 48 h. This ex vivo skin model could be useful for studies evaluating the progression of local envenoming and the efficacy of snakebite treatments.
Topics: Humans; Skin; Necrosis; Animals; Cytokines; Snake Bites; Elapid Venoms; Viper Venoms; Inflammation; Viperidae; Chemokines
PubMed: 38922170
DOI: 10.3390/toxins16060276 -
Neurology International Jun 2024The collateral system is a compensatory mechanism activated in the acute phase of an ischemic stroke. It increases brain perfusion to the hypoperfused area. Arteries of...
The collateral system is a compensatory mechanism activated in the acute phase of an ischemic stroke. It increases brain perfusion to the hypoperfused area. Arteries of the Willis' circle supply antegrade blood flow, while pial (leptomeningeal) arteries direct blood via retrograde flow. The aim of our retrospective study was to investigate the relationship between both collateral systems, computed tomography perfusion (CTP) values, and functional outcomes in acute stroke patients. Overall, 158 patients with anterior circulation stroke who underwent mechanical thrombectomy were included in the study. We analyzed the presence of communicating arteries and leptomeningeal arteries on computed tomography angiography. Patients were divided into three groups according to their collateral status. The main outcomes were the rate of functional independence 3 months after stroke (modified Rankin scale score, mRS) and mortality rate. Our study suggests that the collateral status, as indicated by the three groups (unfavorable, intermediate, and favorable), is linked to CT perfusion parameters, potential recuperation ratio, and stroke outcomes. Patients with favorable collateral status exhibited smaller core infarct and penumbra volumes, higher mismatch ratios, better potential for recuperation, and improved functional outcomes compared to patients with unfavorable or intermediate collateral status.
PubMed: 38921950
DOI: 10.3390/neurolint16030046 -
Journal of Fungi (Basel, Switzerland) May 2024Pulmonary mucormycosis (PM) is an invasive and potentially fatal fungal infection, with () being the most common pathogen. The routine therapy for this infection...
Oral Isavuconazole Combined with Nebulized Inhalation and Bronchoscopic Administration of Amphotericin B for the Treatment of Pulmonary Mucormycosis: A Case Report and Literature Review.
Pulmonary mucormycosis (PM) is an invasive and potentially fatal fungal infection, with () being the most common pathogen. The routine therapy for this infection includes surgery and antifungal agents. However, the therapeutic effects of single agents are unsatisfactory due to the rapid progression of mucormycosis, while not all patients can tolerate surgery. Innovative treatment methods like combination therapy await validations of their clinical efficacy. We report a case of PM that was diagnosed via metagenomics next-generation sequencing (mNGS) of black drainage fluid from the patient's lung. The patient eventually recovered and was discharged after a combination therapy of oral isavuconazole, inhaled amphotericin B, and local perfusion of amphotericin B through bronchoscopy, which may be a promising strategy for the treatment of PM, especially for cases where surgery is not possible. A retrospective study of 297 cases in a literature review highlights the different treatment methods used in clinical practice.
PubMed: 38921374
DOI: 10.3390/jof10060388 -
Current Oncology (Toronto, Ont.) May 2024Ischemia-reperfusion injury (IRI) during liver transplantation has been implicated in the recurrence of hepatocellular carcinoma (HCC). This systematic review aimed to... (Review)
Review
Oncologic Outcomes of Interventions to Decrease Allograft Ischemia-Reperfusion Injury within Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma: A Systematic Review.
Ischemia-reperfusion injury (IRI) during liver transplantation has been implicated in the recurrence of hepatocellular carcinoma (HCC). This systematic review aimed to evaluate interventions to reduce IRI during liver transplantation for HCC and their impact on oncologic outcomes. A comprehensive literature search retrieved four retrospective studies involving 938 HCC patients, utilising interventions such as post-operative prostaglandin administration, hypothermic machine perfusion, and normothermic machine perfusion. Overall, treated patients exhibited reduced post-operative hepatocellular injury and inflammation and significantly enhanced recurrence-free survival. Despite these promising results, the impact of these interventions on overall survival remains unclear. This underscores the imperative for further prospective research to comprehensively understand the efficacy of these interventions in HCC patients undergoing transplantation. The findings highlight the potential benefits of these strategies while emphasising the need for continued investigation into their overall impact.
Topics: Humans; Reperfusion Injury; Liver Transplantation; Carcinoma, Hepatocellular; Liver Neoplasms; Treatment Outcome; Allografts
PubMed: 38920705
DOI: 10.3390/curroncol31060221 -
Diseases (Basel, Switzerland) Jun 2024The placenta exerts a crucial role in fetus growth and development during gestation, protecting the fetus from maternal drugs and chemical exposure. However, diverse... (Review)
Review
BACKGROUND
The placenta exerts a crucial role in fetus growth and development during gestation, protecting the fetus from maternal drugs and chemical exposure. However, diverse drugs and chemicals (xenobiotics) can penetrate the maternal placental barrier, leading to deleterious, adverse effects concerning fetus health. Moreover, placental enzymes can metabolize drugs and chemicals into more toxic compounds for the fetus. Thus, evaluating the molecular mechanisms through which drugs and chemicals transfer and undergo metabolism across the placental barrier is of vital importance. In this aspect, this comprehensive literature review aims to provide a holistic approach by critically summarizing and scrutinizing the potential molecular processes and mechanisms governing drugs and chemical transfer and metabolism across the placental barrier, which may lead to fetotoxicity effects, as well as analyzing the currently available experimental methodologies used to assess xenobiotics placental transfer and metabolism.
METHODS
A comprehensive and in-depth literature review was conducted in the most accurate scientific databases such as PubMed, Scopus, and Web of Science by using relevant and effective keywords related to xenobiotic placental transfer and metabolism, retrieving 8830 published articles until 5 February 2024. After applying several strict exclusion and inclusion criteria, a final number of 148 relevant published articles were included.
RESULTS
During pregnancy, several drugs and chemicals can be transferred from the mother to the fetus across the placental barrier by either passive diffusion or through placental transporters, resulting in fetus exposure and potential fetotoxicity effects. Some drugs and chemicals also appear to be metabolized across the placental barrier, leading to more toxic products for both the mother and the fetus. At present, there is increasing research development of diverse experimental methodologies to determine the potential molecular processes and mechanisms of drug and chemical placental transfer and metabolism. All the currently available methodologies have specific strengths and limitations, highlighting the strong demand to utilize an efficient combination of them to obtain reliable evidence concerning drug and chemical transfer and metabolism across the placental barrier. To derive the most consistent and safe evidence, in vitro studies, ex vivo perfusion methods, and in vivo animal and human studies can be applied together with the final aim to minimize potential fetotoxicity effects.
CONCLUSIONS
Research is being increasingly carried out to obtain an accurate and safe evaluation of drug and chemical transport and metabolism across the placental barrier, applying a combination of advanced techniques to avoid potential fetotoxic effects. The improvement of the currently available techniques and the development of novel experimental protocols and methodologies are of major importance to protect both the mother and the fetus from xenobiotic exposure, as well as to minimize potential fetotoxicity effects.
PubMed: 38920546
DOI: 10.3390/diseases12060114 -
Frontiers in Cardiovascular Medicine 2024Left ventricular (LV) wall motion assessment is an important adjunct in addition to perfusion defects in assessing ischemic changes. This study aims to investigate the...
BACKGROUND
Left ventricular (LV) wall motion assessment is an important adjunct in addition to perfusion defects in assessing ischemic changes. This study aims to investigate the feasibility and utility of performing feature tracking (FT) in pediatric patients with coronary anomalies undergoing dobutamine stress CMR to assess wall motion abnormalities (WMA) and perfusion defects.
METHOD
This is a retrospective study where 10 patients with an inducible first-pass perfusion (FPP) defect and 10 without were selected. Global LV circumferential strain/strain rate (GCS/GCSR) was measured at rest and at peak stress (systole and diastole) using a commercially available feature tracking software. Peak GCS and GCSR were compared to indexed wall motion score (WMSI) between groups with and without FPP defect and in subjects with and without WMA.
RESULTS
The median age of patients was 13.5 years (Q1, 11 years; Q3, 15 years). Five subjects had qualitatively WMA at peak stress. A moderate correlation of GCS with WMSI at peak stress (0.48, = 0.026) and a significant difference between GCS at rest and stress in patients with no inducible WMA ( = 0.007) were seen. No significant difference was noted in GCS between rest and stress in patients with WMA ( = 0.13). There was a larger absolute GCS/GCSR at peak stress in subjects with no inducible FPP defect or WMA.
CONCLUSION
Smaller absolute GCS and a lack of significant change in GCS at peak stress in those with inducible WMA or perfusion defect are suggestive of compromised LV deformation in subjects with inducible WMA. Given these findings, GCS derived from CMR-FT may be used to objectively assess WMA in pediatric patients undergoing stress CMR.
PubMed: 38919544
DOI: 10.3389/fcvm.2024.1380630 -
Frontiers in Nutrition 2024Human milk, due to its unique composition, is the optimal standard for infant nutrition. Osteopontin (OPN) is abundant in human milk but not bovine milk. The addition of... (Review)
Review
Human milk, due to its unique composition, is the optimal standard for infant nutrition. Osteopontin (OPN) is abundant in human milk but not bovine milk. The addition of bovine milk osteopontin (bmOPN) to formula may replicate OPN's concentration and function in human milk. To address safety concerns, we convened an expert panel to assess the adequacy of safety data and physiological roles of dietary bmOPN in infancy. The exposure of breastfed infants to human milk OPN (hmOPN) has been well-characterized and decreases markedly over the first 6 months of lactation. Dietary bmOPN is resistant to gastric and intestinal digestion, absorbed and cleared from circulation within 8-24 h, and represents a small portion (<5%) of total plasma OPN. Label studies on hmOPN suggest that after 3 h, intact or digested OPN is absorbed into carcass (62%), small intestine (23%), stomach (5%), and small intestinal perfusate (4%), with <2% each found in the cecum, liver, brain, heart, and spleen. Although the results are heterogenous with respect to bmOPN's physiologic impact, no adverse impacts have been reported across growth, gastrointestinal, immune, or brain-related outcomes. Recombinant bovine and human forms demonstrate similar absorption in plasma as bmOPN, as well as effects on cognition and immunity. The panel recommended prioritization of trials measuring a comprehensive set of clinically relevant outcomes on immunity and cognition to confirm the safety of bmOPN over that of further research on its absorption, distribution, metabolism, and excretion. This review offers expert consensus on the adequacy of data available to assess the safety of bmOPN for use in infant formula, aiding evidence-based decisions on the formulation of infant formula.
PubMed: 38919388
DOI: 10.3389/fnut.2024.1404303 -
Annals of Vascular Diseases Jun 2024Distal bypass surgery's effect on tissue blood pressure beyond a focal angiosome remains debated. This study assessed tissue blood pressure in both direct...
Distal bypass surgery's effect on tissue blood pressure beyond a focal angiosome remains debated. This study assessed tissue blood pressure in both direct revascularized angiosome (DRA) and indirect revascularized angiosome (IRA) after bypass surgery, utilizing repeated skin perfusion pressure (SPP) measurements. Twenty-nine limbs in 27 chronic limb-threatening ischemia (CLTI) patients (22 males and five females, age: 70.2 ± 9.3 years) who received distal bypass surgery were enrolled. SPP measurements were conducted for the DRA and IRA at 10 time intervals, encompassing both preoperative and postoperative periods of every 3-5 days until 30 days. In total, 486 SPP measurements were collected from 58 measurement sites, and the transition of the SPP at the DRA was 35.4-62.5-59.5-70.2-58.2-62.2-63.1-63.6-63.8-73.4 mmHg and IRA was 29.4-53.4-53.7-58.8-51.3-63.1-47.9-62.1-57.6-61.0 mmHg. No significant differences were observed between SPP at the DRA and IRA. Fifteen wounds on the DRA (63%) and five on the IRA (100%) healed. Distal bypass improves SPP in both direct and IRAs of CLTI patients. These data indicated distal bypass improves tissue blood flow at entire foot regardless of angiosomes.
PubMed: 38919324
DOI: 10.3400/avd.oa.23-00105