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1.
Ann Med Surg (Lond) ; 86(5): 3154-3158, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38694359

RESUMO

Introduction and importance: Dengue fever is a mosquito-borne viral infection presenting with high-grade fever and other constitutional symptoms. Case presentation: This case report details a rare occurrence of lateral rectus palsy in an 18-year-old male subsequent to dengue infection. The patient initially presented with fever, a generalized tonic-clonic seizure (GTCS), and symptomatic hypoglycemia, leading to multiple organ dysfunction syndrome (MODS) necessitating intensive care. Remarkably, no haemorrhagic manifestations were observed. The MODS gradually resolved by the 12th day of admission, coinciding with the emergence of complaints about uniocular diplopia and right esotropia. Systemic examination, including a normal computed tomography (CT) head scan, did not reveal any abnormalities. Additionally, potential causes contributing to esotropia and diplopia were ruled out. The patient was subsequently managed expectantly for lateral rectus palsy following severe dengue. Follow-up assessments indicated a gradual improvement in esotropia and diplopia, and the patient was advised to continue the prescribed medications. Conclusion: This is the first documented case report of paralytic squint post-severe dengue in Nepal, emphasizing the importance of considering it as a differential diagnosis in tropical regions with endemic dengue infections. The case report advocates early identification and treatment of ophthalmic issues, notably with prednisolone, to achieve favourable outcomes, as evidenced by improvements in visual acuity, esotropia, and diplopia during follow-ups. Further research is essential to determine optimal treatment strategies for such neurological complications associated with dengue fever.

2.
Cureus ; 16(4): e59108, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38803787

RESUMO

Acute pancreatitis is a rare manifestation of acute myeloid leukemia which can be a presentation at the initial diagnosis or during or after the onset of the disease. Acute myeloid leukemia occurs due to the abnormal proliferation of undifferentiated hematopoietic stem cells in the bone marrow which alter the normal hematopoiesis. We report the case of a 32-year-old male admitted with a one-month history of fever and backache, followed by 15 days of blackish stool discoloration and two days of abdominal pain and reduced urine output. On clinical examination, he was hypoxic with respiratory distress with epigastric tenderness. Blood investigations and imaging were consistent with acute pancreatitis. A complete blood count with peripheral smear showed severe normocytic normochromic anemia and an increased myeloid series containing 50% myeloblasts and 30% monoblasts. Additionally, some cells displayed cytoplasmic vacuolations, with a reticulocyte count of 2%. These findings were suggestive of acute myeloid leukemia M5. Due to the poor Glasgow Coma Scale (GCS), he was intubated and placed on mechanical ventilation. Unfortunately, he did not improve despite treatment and succumbed to the illness.

3.
Front Immunol ; 15: 1394925, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690282

RESUMO

Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Abnormal activation of the immune system and disturbance of energy metabolism play a key role in the development of sepsis. In recent years, the Sirtuins (SIRTs) family has been found to play an important role in the pathogenesis of sepsis. SIRTs, as a class of histone deacetylases (HDACs), are widely involved in cellular inflammation regulation, energy metabolism and oxidative stress. The effects of SIRTs on immune cells are mainly reflected in the regulation of inflammatory pathways. This regulation helps balance the inflammatory response and may lessen cell damage and organ dysfunction in sepsis. In terms of energy metabolism, SIRTs can play a role in immunophenotypic transformation by regulating cell metabolism, improve mitochondrial function, increase energy production, and maintain cell energy balance. SIRTs also regulate the production of reactive oxygen species (ROS), protecting cells from oxidative stress damage by activating antioxidant defense pathways and maintaining a balance between oxidants and reducing agents. Current studies have shown that several potential drugs, such as Resveratrol and melatonin, can enhance the activity of SIRT. It can help to reduce inflammatory response, improve energy metabolism and reduce oxidative stress, showing potential clinical application prospects for the treatment of sepsis. This review focuses on the regulation of SIRT on inflammatory response, energy metabolism and oxidative stress of immune cells, as well as its important influence on multiple organ dysfunction in sepsis, and discusses and summarizes the effects of related drugs and compounds on reducing multiple organ damage in sepsis through the pathway involving SIRTs. SIRTs may become a new target for the treatment of sepsis and its resulting organ dysfunction, providing new ideas and possibilities for the treatment of this life-threatening disease.


Assuntos
Metabolismo Energético , Estresse Oxidativo , Sepse , Sirtuínas , Humanos , Sepse/tratamento farmacológico , Sepse/imunologia , Sepse/metabolismo , Animais , Sirtuínas/metabolismo , Metabolismo Energético/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Inflamação/tratamento farmacológico , Inflamação/imunologia
4.
J Clin Med ; 13(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38673611

RESUMO

In patients with septic shock, compensatory tachycardia initially serves to maintain adequate cardiac output and tissue oxygenation but may persist despite appropriate fluid and vasopressor resuscitation. This sustained elevation in heart rate and altered heart rate variability, indicative of autonomic dysfunction, is a well-established independent predictor of adverse outcomes in critical illness. Elevated heart rate exacerbates myocardial oxygen demand, reduces ventricular filling time, compromises coronary perfusion during diastole, and impairs the isovolumetric relaxation phase of the cardiac cycle, contributing to ventricular-arterial decoupling. This also leads to increased ventricular and atrial filling pressures, with a heightened risk of arrhythmias. Ivabradine, a highly selective inhibitor of the sinoatrial node's pacemaker current (If or "funny" current), mitigates heart rate by modulating diastolic depolarization slope without affecting contractility. By exerting a selective chronotropic effect devoid of negative inotropic properties, ivabradine shows potential for improving hemodynamics in septic shock patients with cardiac dysfunction. This review evaluates the plausible mechanisms and existing evidence regarding the utility of ivabradine in managing patients with septic shock.

5.
Plants (Basel) ; 13(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38475409

RESUMO

Irrigating aquaculture wastewater in appropriate irrigation and drainage modes in paddy fields could reduce water and fertilizer loss. However, the precise mechanisms involved in the degradation and movement of nitrogen in various water and fertilizer modes are still not fully understood. This study involves conducting a controlled experiment using barrels to examine the effects of various water quality, irrigation and drainage methods, and fertilization levels. The aim is to analyze the patterns of nitrogen degradation, loss, migration, and absorption in surface water, underground drainage, and soil leakage at different depths. The results showed the following: (1) The paddy field has a significant purification effect on aquaculture wastewater after one day of irrigation, reached at 78.55-96.06%. (2) Aquaculture wastewater irrigation increased nitrogen concentration in the plough layer, which helps rice roots absorb nitrogen and boosts plant TN. (3) In special dry years, underground seepage is the predominant method of nitrogen loss, and underground drainage nitrogen concentration peaks 2-6 days after fertilization. (4) Under aquaculture wastewater irrigation, the TN loss load of II decreased by 27.65-42.45% than FSI. Compared with IA-80, the TN degradation rate of IA in surface water increased by 18.51%, TN loss load decreased by 5.48%, TN absorption rate significantly increased by 14.61%, and yield increased by 31.14% significantly. IA is recommended in special dry years, which can improve the TN absorption rate and ensure high yield while significantly reducing the loss load of nitrogen. The findings can provide a basis for the purification of aquaculture wastewater through paddy field ecosystems in response to fertilizer supply levels.

6.
World J Clin Cases ; 12(3): 637-642, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38322476

RESUMO

BACKGROUND: Early initiation of enteral feeding is recognized to play a crucial role in improving the outcomes of treatment of acute pancreatitis. However, the method of administration of enteral nutrition remains debatable. We present the experience of treating a patient with moderate-severe acute pancreatitis, at high risk of progressing to a severe or fatal condition, using a novel method of selective feeding with duodenal isolation. CASE SUMMARY: A 27-year-old female patient presented to the emergency unit of the hospital with a typical manifestation of acute pancreatitis. Despite a conventional treatment, the patient's condition deteriorated by day 2 of hospitalization. Using an endoscopic approach, a novel catheter PandiCath® was placed to the duodenum of the patient, isolating its segment between the duodenal bulb and the ligament of Treitz. In the isolated area created, a negative pressure was applied, followed by introduction of early selective enteral feeding. The patient's condition subsequently improved in a rapid manner, and no complications often associated with moderate-to-severe acute pancreatitis developed. CONCLUSION: Within 48 h of starting treatment with the novel method, it can prevent the development of multiple organ failure and, when combined with minimally invasive drainage methods, help prevent infection.

7.
J Clin Med ; 13(4)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38398351

RESUMO

BACKGROUND: Multiple organ dysfunction syndrome (MODS) is common in intensive care units (ICUs) and is associated with high mortality. Although there have been multiple investigations into a multitude of organ dysfunctions, little is known about the role of liver dysfunction. In addition, clinical and laboratory findings of liver dysfunction may occur with a significant delay. Therefore, the aim of this study was to investigate whether a liver function test, based on indocyanine green (ICG)-clearance, contains prognostic information for patients in the early phase of MODS. METHODS: The data of this analysis were based on the MODIFY study, which included 70 critically ill patients of a tertiary medical ICU in the early phase of MODS (≤24 h after diagnosis by an APACHE II score ≥ 20 and a sinus rhythm ≥ 90 beats per minute, with the following subgroups: cardiogenic (cMODS) and septic MODS (sMODS)) over a period of 18 months. ICG clearance was characterized by plasma disappearance rate = PDR (%/min); it was measured non-invasively by using the LiMON system (PULSION Medical Systems, Feldkirchen, Germany). The PDR was determined on the day of study inclusion (baseline) and after 96 h. The primary endpoint of this analysis was 28-day mortality. RESULTS: ICG clearance was measured in 44 patients of the MODIFY trial cohort, of which 9 patients had cMODS (20%) and 35 patients had sMODS (80%). Mean age: 59.7 ± 16.5 years; 31 patients were men; mean APACHE II score: 33.6 ± 6.3; 28-day mortality was 47.7%. Liver function was reduced in the total cohort as measured by a PDR of 13.4 ± 6.3%/min At baseline, there were no relevant differences between survivors and non-survivors regarding ICG clearance (PDR: 14.6 ± 6.1%/min vs. 12.1 ± 6.5%/min; p = 0.21). However, survivors showed better liver function than non-survivors after 96 h (PDR: 21.9 ± 6.3%/min vs. 9.2 ± 6.3%/min, p < 0.05). Consistent with these findings, survivors but not non-survivors show a significant improvement in the PDR (7.3 ± 6.3%/min vs. -2.9 ± 2.6%/min; p < 0.01) within 96 h. In accordance, receiver-operating characteristic curves (ROCs) at 96 h but not at baseline show a link between the PDR and 28-day mortality (PDR at 96 h: AUC: 0.87, 95% CI: 0.76-0.98; p < 0.01. CONCLUSIONS: In our study, we found that ICG clearance at baseline did not provide prognostic information in patients in the early stages of MODS despite being reduced in the total cohort. However, improvement of ICG clearance 96 h after ICU admission is associated with reduced 28-day mortality.

8.
Pediatr Nephrol ; 39(6): 1927-1935, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38196017

RESUMO

BACKGROUND: Acute kidney injury (AKI) is common in children with sepsis, chronic kidney disease, poisoning or other conditions. Wasp stings are recognized as an important etiology. Several retrospective studies have investigated AKI after wasp stings in adults, but research on children remains limited. METHODS: The study included 48 children with multiple organ dysfunction syndrome after wasp stings. Demographic data, clinical manifestations, laboratory findings, management and clinical outcomes were collected, and analyzed to identify early indicators or risk factors for AKI. RESULTS: 20 children (41.7%) developed AKI, and 28 (58.3%) did not. Serum creatine levels elevated mostly within 24 h from stings in children with AKI (16/20, 80%). Compared with non-AKI group, AKI group exhibited more cases with cola-colored urine, jaundice, and had higher sting numbers/body surface area (BSA) and higher revised sequential organ failure assessment scores (rSOFA) as well as higher levels of C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), lactate dehydrogenase (LDH), troponin (cTnI), creatine kinase (CK), and longer prothrombin time (PT). Both univariable and multivariable logistic regression analysis identified cola-colored urine as a potential early risk factor for AKI. CONCLUSIONS: The AKI group exhibited higher sting numbers/BSA, higher levels of CRP, ALT, AST, TBIL, LDH, cTnI, and CK, as well as longer PT (p < 0.05). Our findings also suggest that cola-colored urine may serve as an early indicator or potential risk factor for AKI after wasp stings in children, which is very easy to identify for first aiders or pediatricians.


Assuntos
Injúria Renal Aguda , Mordeduras e Picadas de Insetos , Vespas , Adulto , Criança , Animais , Humanos , Mordeduras e Picadas de Insetos/complicações , Estudos Retrospectivos , Injúria Renal Aguda/etiologia , Fatores de Risco
9.
JHEP Rep ; 6(2): 100984, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38293685

RESUMO

Background & Aims: Lipid droplet (LD) accumulation in cells and tissues is understood to be an evolutionarily conserved tissue tolerance mechanism to prevent lipotoxicity caused by excess lipids; however, the presence of excess LDs has been associated with numerous diseases. Sepsis triggers the reprogramming of lipid metabolism and LD accumulation in cells and tissues, including the liver. The functions and consequences of sepsis-triggered liver LD accumulation are not well known. Methods: Experimental sepsis was induced by CLP (caecal ligation and puncture) in mice. Markers of hepatic steatosis, liver injury, hepatic oxidative stress, and inflammation were analysed using a combination of functional, imaging, lipidomic, protein expression and immune-enzymatic assays. To prevent LD formation, mice were treated orally with A922500, a pharmacological inhibitor of DGAT1. Results: We identified that liver LD overload correlates with liver injury and sepsis severity. Moreover, the progression of steatosis from 24 h to 48 h post-CLP occurs in parallel with increased cytokine expression, inflammatory cell recruitment and oxidative stress. Lipidomic analysis of purified LDs demonstrated that sepsis leads LDs to harbour increased amounts of unsaturated fatty acids, mostly 18:1 and 18:2. An increased content of lipoperoxides within LDs was also observed. Conversely, the impairment of LD formation by inhibition of the DGAT1 enzyme reduces levels of hepatic inflammation and lipid peroxidation markers and ameliorates sepsis-induced liver injury. Conclusions: Our results indicate that sepsis triggers lipid metabolism alterations that culminate in increased liver LD accumulation. Increased LDs are associated with disease severity and liver injury. Moreover, inhibition of LD accumulation decreased the production of inflammatory mediators and lipid peroxidation while improving tissue function, suggesting that LDs contribute to the pathogenesis of liver injury triggered by sepsis. Impact and Implications: Sepsis is a complex life-threatening syndrome caused by dysregulated inflammatory and metabolic host responses to infection. The observation that lipid droplets may contribute to sepsis-associated organ injury by amplifying lipid peroxidation and inflammation provides a rationale for therapeutically targeting lipid droplets and lipid metabolism in sepsis.

10.
Clin Res Cardiol ; 113(2): 260-275, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37717230

RESUMO

BACKGROUND: To potentially improve impaired vasomotion of patients with multiple organ dysfunction syndrome (MODS), we tested whether an electromagnetic field of low flux density coupled with a biorhythmically defined impulse configuration (Physical Vascular Therapy BEMER®, PVT), in addition to standard care, is safe and feasible and might improve disturbed microcirculatory blood flow and thereby improve global haemodynamics. METHODS: In a prospective, monocentric, one-arm pilot study, 10 MODS patients (APACHE II score 20-35) were included. Patients were treated, in addition to standard care, for 4 days with PVT (3 treatment periods of 8 min each day; day 1: field intensity 10.5 µT; day 2:14 µT, day 3:17.5 µT; day 4:21.0 µT). Primary endpoint was the effect of PVT on sublingual microcirculatory perfusion, documented by microvascular flow index (MFI). Patient safety, adverse events, and outcomes were documented. RESULTS: An increase in MFI by approximately 25% paralleled 4-day PVT, with the increase starting immediately after the first PVT and lasting over the total 4-day treatment period. Concerning global haemodynamics (secondary endpoints), halving vasopressor use within 24 h, and haemodynamic stabilisation paralleled 4-day PVT with an increase in cardiac index, stroke volume index, and cardiac power index by 30%-50%. No adverse events (AEs) or serious adverse events (SAEs) were classified as causally related to the medical product (PVT) or study. Three patients died within 28 days and one patient between 28 and 180 days. CONCLUSION: PVT treatment was feasible and safe and could be performed without obstruction of standard patient care. An increase in microcirculatory blood flow, a rapid reduction in vasopressor use, and an improvement in global haemodynamics paralleled PVT treatment. Findings of this pilot study allowed forming a concept for a randomized trial for further proof.


Assuntos
Campos Eletromagnéticos , Insuficiência de Múltiplos Órgãos , Humanos , Insuficiência de Múltiplos Órgãos/terapia , Microcirculação/fisiologia , Estudos Prospectivos , Projetos Piloto
12.
Front Aging ; 4: 1260053, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37780864

RESUMO

Background: The immune-inflammatory response is the basis of the pathophysiology of SARS-Cov-2 infection. In severe cases of COVID-19 uncontrolled systemic inflammatory response causes multiorgan dysfunction (MODS), as the most common immediate cause of death. Unfavorable outcome of the COVID-19 most often occurs in elderly patients. The aim of the study was to establish parameters with prognostic significance in severe cases of COVID-19 according to life years, laboratory markers of sepsis and MODS, as well as the number of peripheral CD4+ and CD8+T lymphocytes in 20 consecutively selected critically ill patients. Results: Eleven subjects were male, 9 female, mean age 73.45 ± 11.59, among which the oldest patient was 94 and the youngest 43 years. All the patients met the sepsis and MODS criteria. Increased age and low CD4+ and CD8+T cell counts were identified as independent predictors of death. Only the two youngest patients (43 and 50 years old) survived 28 days, and they are the only ones with a CD4 lymphocyte count above 500 cells/mm3. Conclusion: Senescence of the immune system is mostly characterized by reduced regenerative capacity of adaptive immunity with diminished ability to respond to new antigens and a manifested proinflammatory phenotype. Additional reduction of protective capacity by further deterioration of T cell quantity and quality due to sepsis itself and mutual interaction of senescent T cells and vascular endothelial cells in the induction of cytokine storm represent two complementary vicious cycles in the development of sepsis-related multiorgan dysfunction.

13.
J Therm Biol ; 118: 103696, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37871397

RESUMO

Heatstroke (HS) causes multiple organ dysfunction syndrome (MODS) with a mortality rate of 60% after hospitalization. Currently, there is no effective and targeted approach for the treatment of HS. Despite growing evidence that mesenchymal stem cells (MSCs) may reduce multiorgan damage and improve survival through immunomodulatory effects in several diseases, no one has tested whether MSCs have immunomodulatory effects in heatstroke. The present study focused on pathological changes and levels of the cytokines and immunoglobulins to investigate the mechanisms underlying the protective effect and the anti-inflammatory effects of MSCs. We found that MSCs treatment significantly reduced the 28-day mortality rate (P < 0.05), the levels of hepatic and renal function markers on day 1 (P < 0.01) and the pathological lesion scores of multiple organs in HS rats. The levels of IgG1, IgM, and IgA of the HS + MSC group was significantly higher than that in HS group on days 3 and 28(P < 0.05). In conclusion, MSCs contribute to protecting against multiorgan injury, reducing pro-inflammatory cytokines, stabilizing immunoglobulins, and reducing the mortality rate of HS rats.


Assuntos
Golpe de Calor , Células-Tronco Mesenquimais , Ratos , Masculino , Animais , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/prevenção & controle , Golpe de Calor/terapia , Citocinas , Imunoglobulinas
14.
Artigo em Chinês | MEDLINE | ID: mdl-37805430

RESUMO

Brucellosis can lead to pathological changes of multiple systems. Capillary leak syndrome (CLS) is a clinical syndrome caused by different reasons, mainly characterized by hypotension, hypoproteinemia and systemic edema. The condition is critical and the clinical manifestations are complex, and multiple organ dysfunction syndrome (MODS) may occur in severe cases. CLS caused by brucellosis is extremely rare. The diagnosis and treatment of a patient with brucellosis complicated with CLS and MODS was analyzed in this paper, in order to improve the knowledge of clinicians about brucellosis and its complications.


Assuntos
Brucelose , Síndrome de Vazamento Capilar , Humanos , Síndrome de Vazamento Capilar/diagnóstico , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/terapia , Insuficiência de Múltiplos Órgãos/etiologia , Brucelose/complicações
15.
Front Immunol ; 14: 1217366, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711629

RESUMO

Sepsis represents a global health concern, and patients with severe sepsis are at risk of experiencing MODS (multiple organ dysfunction syndrome), which is associated with elevated mortality rates and a poorer prognosis. The development of sepsis involves hyperactive inflammation, immune disorder, and disrupted microcirculation. It is crucial to identify targets within these processes to develop therapeutic interventions. One such potential target is Panx1 (pannexin-1), a widely expressed transmembrane protein that facilitates the passage of molecules smaller than 1 KDa, such as ATP. Accumulating evidence has implicated the involvement of Panx1 in sepsis-associated MODS. It attracts immune cells via the purinergic signaling pathway, mediates immune responses via the Panx1-IL-33 axis, promotes immune cell apoptosis, regulates blood flow by modulating VSMCs' and vascular endothelial cells' tension, and disrupts microcirculation by elevating endothelial permeability and promoting microthrombosis. At the level of organs, Panx1 contributes to inflammatory injury in multiple organs. Panx1 primarily exacerbates injury and hinders recovery, making it a potential target for sepsis-induced MODS. While no drugs have been developed explicitly against Panx1, some compounds that inhibit Panx1 hemichannels have been used extensively in experiments. However, given that Panx1's role may vary during different phases of sepsis, more investigations are required before interventions against Panx1 can be applied in clinical. Overall, Panx1 may be a promising target for sepsis-induced MODS. Nevertheless, further research is needed to understand its complex role in different stages of sepsis fully and to develop suitable pharmaceutical interventions for clinical use.


Assuntos
Células Endoteliais , Insuficiência de Múltiplos Órgãos , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Apoptose , Inflamação , Proteínas de Membrana
16.
Pharmacol Res ; 195: 106885, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37634554

RESUMO

Electronic nicotine delivery systems (ENDS), which are becoming increasingly popular in many parts of the world, have recently become more sophisticated in terms of their more active content and better controlled vaporisation. This review begins by describing how cigarette smoking led to the development of ENDS as a means of combatting nicotine addiction. ENDS are usually categorised as belonging to one of only three main generations, but a fourth has been added in order to differentiate the latest, most powerful, most advanced and innovative that have improved heating efficiency. Descriptions of the principal substances contained in ENDS are followed by considerations concerning the risk of toxicity due to the presence of albeit low concentrations of such a variety of compounds inhaled over a long time, and the increasingly widespread use of ENDS as a means of smoking illicit drugs. We also review the most widely used pharmacotherapeutic approaches to smoking cessation, and recent epidemiological data showing that ENDS can help some people to stop smoking. However, in order to ensure their appropriate regulation, there is a need for higher-quality evidence concerning the health effects and safety of ENDS, and their effectiveness in discouraging tobacco smoking.


Assuntos
Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Abandono do Hábito de Fumar , Humanos
17.
Front Immunol ; 14: 1220028, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37533854

RESUMO

Background: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection. Methods: We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05). Results: Comparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation (RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared to those who recovered more rapidly from MODS (n=27). These neutrophil transcripts present in early samples predicted Prolonged MODS or death when compared to patients who recovered, however in paired longitudinal samples, they were not differentially expressed over time. Instead, five genes involved in protein metabolism and/or adaptive immunity signaling pathways (RPL3, MRPL3, HLA-DMB, EEF1G, CD8A) were associated with MODS recovery within a week. Conclusion: Thus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome.


Assuntos
Infecções Bacterianas , Influenza Humana , Humanos , Insuficiência de Múltiplos Órgãos/genética , Influenza Humana/genética , Influenza Humana/complicações , Transcriptoma , Fenótipo , Hospitalização , Infecções Bacterianas/complicações
18.
Front Vet Sci ; 10: 1141978, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37456965

RESUMO

Objective: This case report describes a successful outcome in the treatment of a patient with joint supplement toxicity, which resulted in seizures, severe acidemia, hyperglycemia, hypernatremia, and multiple organ dysfunction. Previous case reports have been published, but this patient presented with different clinical signs and had additional biochemical abnormalities. Treatment modalities varied in this case report, and the patient was discharged sooner than those mentioned in previous reports. Case summary: A 9-year-old spayed female Maltese mix was presented to a specialty hospital for joint supplement toxicity. Presenting clinical signs were vomiting and seizures. Primary biochemical abnormalities consisted of hypernatremia, hyperglycemia, acidemia, azotemia, and elevated liver enzymes. Treatment involved lowering the sodium quickly given the neurologic signs on presentation. Other treatment modalities consisted of sodium bicarbonate, insulin, and liver protectants. The patient responded quickly and was discharged after 3 days in the hospital. New or unique information provided: This case report is different in that the patient was having seizures and was also hyperglycemic, in addition to the expected abnormalities of hypernatremia, acidemia, and multiple organ dysfunction. It also differs from prior reports in that the treatment of hypernatremia was managed as an acute process. This case report describes differing clinical signs, biochemical abnormalities, and treatment modalities that may have led to the discharge from the hospital in a shorter time.

19.
Mol Biotechnol ; 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37515659

RESUMO

This study aims to reveal the metabolic differences between SDC-1 knockout mice and wild-type mice and the metabolic differences caused by shock in SDC-1 knockout mice by integrating transcriptomics and metabolomics. A total of 1009 differential metabolites were differentially expressed based on untargeted metabolomics and high-resolution mass spectrometry detection techniques. According to Kyoto Encyclopedia of Genes and Genomes enrichment, SDC-1 knockout significantly altered fat digestion and absorption, GnRH signaling pathway, fructose and mannose metabolism, and some other amino-related metabolic pathways and significantly modulated positively regulated longevity regulatory pathways, longevity regulatory pathways-worm, nicotinamide and niacinamide metabolism, and vitamin digestion and absorption pathways after its shock. Our findings indicate that SDC-1 knockout may have potential therapeutic effects in hemorrhagic shock by increasing nicotinamide metabolism.

20.
Genes (Basel) ; 14(6)2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37372314

RESUMO

We are interested in detecting a departure from the baseline in a longitudinal analysis in the context of multiple organ dysfunction syndrome (MODS). In particular, we are given gene expression reads at two time points for a fixed number of genes and individuals. The individuals can be subdivided into two groups, denoted as groups A and B. Using the two time points, we compute a contrast of gene expression reads per individual and gene. The age of each individual is known and it is used to compute, for each gene separately, a linear regression of the gene expression contrasts on the individual's age. Looking at the intercept of the linear regression to detect a departure from the baseline, we aim to reliably single out those genes for which there is a difference in the intercept among those individuals in group A and not in group B. In this work, we develop testing methodology for this setting based on two hypothesis tests-one under the null and one under an appropriately formulated alternative. We demonstrate the validity of our approach using a dataset created by bootstrapping from a real data application in the context of multiple organ dysfunction syndrome (MODS).


Assuntos
Insuficiência de Múltiplos Órgãos , Humanos , Insuficiência de Múltiplos Órgãos/genética , Insuficiência de Múltiplos Órgãos/diagnóstico , Modelos Lineares , Expressão Gênica
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