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1.
Pediatr Nephrol ; 39(6): 1927-1935, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38196017

RESUMEN

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.


Asunto(s)
Lesión Renal Aguda , Mordeduras y Picaduras de Insectos , Avispas , Adulto , Niño , Animales , Humanos , Mordeduras y Picaduras de Insectos/complicaciones , Estudios Retrospectivos , Lesión Renal Aguda/etiología , Factores de Riesgo
2.
Immunology ; 168(4): 597-609, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36279244

RESUMEN

Immunoparalysis is associated with poorer outcomes in the paediatric intensive care unit (PICU) setting. We aimed to determine the group of patients with higher chances of immunoparalysis and correlate this status with increased risks of nosocomial infection and adverse clinical parameters. We conducted an exploratory study with prospective data collection in a university-affiliated tertiary medical, surgical, and cardiac PICU. Fifteen patients with multiple organ dysfunction syndrome were included over a period of 6 months. Monocyte's human leucocyte antigen (HLA)-DR expression and tumour necrosis factor (TNF)-α and interleukin (IL)-6 production were measured by flow-cytometry at three time points (T1 = 1-2 days; T2 = 3-5 days; T3 = 6-8 days). Using the paediatric logistic organ dysfunction-2 score to assess initial disease severity, we established the optimal cut-off values of the evaluated parameters to identify the subset of patients with a higher probability of immunoparalysis. A comparative analysis was performed between them. Sixty per cent were males; the median age was 4.1 years. Considering the presence of two criteria in T1 (classical monocytes mean fluorescence intensity [MFI] for HLA-DR ≤ 1758.5, area under the curve (AUC) = 0.775; and frequency of monocytes producing IL-6 ≤ 68.5%, AUC = 0.905) or in T3 (classical monocytes MFI of HLA-DR ≤ 2587.5, AUC = 0.675; and frequency of monocytes producing TNF-α ≤ 93.5%, AUC = 0.833), a variable to define immunoparalysis was obtained (100% sensitivity, 81.5% specificity). Forty per cent of patients were assigned to the immunoparalysis group. In this: a higher frequency of nosocomial infection (p = 0.011), vasoactive inotropic score (p = 0.014) and length of hospital stay (p = 0.036) was observed. In the subgroup with the diagnosis of sepsis/septic shock (n = 5), patients showed higher percentages of non-classical monocytes (p = 0.004). No mortality was recorded. A reduction in classical monocytes HLA-DR expression with lower frequencies of monocytes producing TNF-α and IL-6 during the first week of critical illness, appears to be a good marker of immunoparalysis; these findings relate to an increased risk of nosocomial infection and deleterious outcomes. The increased frequency of non-classical monocytes in patients with sepsis/septic shock is suggestive of a better prognosis.


Asunto(s)
Infección Hospitalaria , Sepsis , Choque Séptico , Masculino , Humanos , Niño , Preescolar , Femenino , Factor de Necrosis Tumoral alfa , Interleucina-6 , Enfermedad Crítica , Antígenos HLA-DR , Monocitos
3.
Pharmacol Res ; 195: 106885, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37634554

RESUMEN

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.


Asunto(s)
Fumar Cigarrillos , Sistemas Electrónicos de Liberación de Nicotina , Cese del Hábito de Fumar , Humanos
4.
Cell Mol Life Sci ; 79(8): 456, 2022 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-35904600

RESUMEN

During sepsis, the importance of alterations in cell metabolism is underappreciated. The cellular metabolism, which has a variable metabolic profile in different cells and disease stages, is largely responsible for the immune imbalance and organ failure associated with sepsis. Metabolic reprogramming, in which glycolysis replaces OXPHOS as the main energy-producing pathway, is both a requirement for immune cell activation and a cause of immunosuppression. Meanwhile, the metabolites produced by OXPHOS and glycolysis can act as signaling molecules to control the immune response during sepsis. Sepsis-induced "energy shortage" leads to stagnated cell function and even organ dysfunction. Metabolic reprogramming can alleviate the energy crisis to some extent, enhance host tolerance to maintain cell survival functions, and ultimately increase the adaptation of cells during sepsis. However, a switch from glycolysis to OXPHOS is essential for restoring cell function. This review summarized the crosstalk between metabolic reprogramming and immune cell activity as well as organ function during sepsis, discussed the benefits and drawbacks of metabolic reprogramming to show the contradictions of metabolic reprogramming during sepsis, and assessed the feasibility of treating sepsis through targeted metabolism. Using metabolic reprogramming to achieve metabolic homeostasis could be a viable therapy option for sepsis.


Asunto(s)
Fosforilación Oxidativa , Sepsis , Glucólisis , Humanos , Tolerancia Inmunológica , Transducción de Señal
5.
J Therm Biol ; 118: 103696, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37871397

RESUMEN

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.


Asunto(s)
Golpe de Calor , Células Madre Mesenquimatosas , Ratas , Masculino , Animales , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/prevención & control , Golpe de Calor/terapia , Citocinas , Inmunoglobulinas
6.
Artículo en Zh | MEDLINE | ID: mdl-37805430

RESUMEN

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.


Asunto(s)
Brucelosis , Síndrome de Fuga Capilar , Humanos , Síndrome de Fuga Capilar/diagnóstico , Síndrome de Fuga Capilar/etiología , Síndrome de Fuga Capilar/terapia , Insuficiencia Multiorgánica/etiología , Brucelosis/complicaciones
7.
Mol Biol Rep ; 49(4): 2985-2998, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35122598

RESUMEN

BACKGROUND: The most common cause of death in sepsis is MODS. We hope that miR-126 can regulate the differentiation of Th17/Treg, reduce the infiltration of inflammatory factors in peripheral blood and various organs and tissues, and improve organ function and prognosis in sepsis. METHODS AND RESULTS: Septic rat model was established by cecal perforation and ligation. miR-126 mimic and inhibitor were used to intervene sepsis. The experimental results showed that miR-126 mimic reduced the differentiation of Th17 and increased the differentiation of Treg in septic rats, resulting in the TNF-α, IL-6 and IL-17 were decreased in peripheral blood, the infiltration levels of TNF-α, IL-6 and IL-17 were decreased in lung, liver and kidney, the tissue damage degree of lung, liver and kidney were weakened, and the corresponding histopathological score decreased. Finally, the survival rate of septic rats was increased. However, after using miR-126 inhibitor, the levels of inflammatory factors and the degree of multiple organ injury in septic rats increased in varying degrees, and the prognosis of septic rats was worse. CONCLUSION: This study confirmed that miR-126 can regulate the differentiation of Th17/Treg, change the infiltration of inflammatory factors in peripheral blood, lung, liver and kidney of septic rats, alleviate MODS, and improve the organ function and prognosis of septic rats.


Asunto(s)
MicroARNs , Sepsis , Animales , Modelos Animales de Enfermedad , MicroARNs/genética , Insuficiencia Multiorgánica/genética , Ratas , Sepsis/genética , Linfocitos T Reguladores
8.
J Vector Borne Dis ; 59(4): 380-385, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36751770

RESUMEN

BACKGROUND & OBJECTIVES: Scrub typhus is a neglected tropical disease common in Asia and Africa. It usually presents with non-specific symptoms like fever, rashes, and lymphadenopathy. It has a varying range of clinical picture that often leads to misdiagnosis and initiation of non-specific treatment. This disease is thus associated with high morbidity and mortality. We aim to highlight the uncommon presentations of this common disease to create awareness regarding the unusual presentations of scrub typhus. METHODS: This prospective study was performed over a period of two months enrolling eleven adult patients with serological evidence of anti-scrub typhus IgM antibodies. RESULTS: All enrolled 11 cases [5 males (45.5%) and 6 females (54.5%)] were positive for anti-ST IgM antibodies and negative for other tested microbial agents. 7/11 (63.6%) patients were admitted with a clinical diagnosis of acute encephalitis syndrome (AES as per standard WHO definition), 3/11 (27.3%) patients presented with jaundice and 1/11 (9.1%) patients presented with rashes. Two out of 7 (28.6%) AES cases had developed peripheral gangrene of extremities. INTERPRETATION & CONCLUSION: Scrub typhus is a common tropical disease that can have various unusual clinical presentations like meningoencephalitis, vasculitis, acute kidney injury, jaundice, MODS. It closely mimics other infective etiologies making its diagnosis difficult. A high index of suspicion and clinical awareness is required in clinical practice to identify the different presentations of this disease so that early treatment can be initiated to reduce morbidity and mortality associated with this disease.


Asunto(s)
Exantema , Orientia tsutsugamushi , Tifus por Ácaros , Tifus Epidémico Transmitido por Piojos , Adulto , Masculino , Femenino , Humanos , Estudios Prospectivos , Tifus Epidémico Transmitido por Piojos/complicaciones , Tifus por Ácaros/diagnóstico , India , Inmunoglobulina M
9.
Liver Int ; 41(4): 810-818, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33314531

RESUMEN

BACKGROUND & AIMS: Pyogenic liver abscesses (PLA) are space-occupying lesions in the liver that produce high morbidity and mortality. The clinical characteristics and prognosis of abscesses is different depending on the bacterial culture results and require different strategies for management. The aim of this study was to investigate the clinical characteristics and prognostic factors of patients with PLA. METHODS: Clinical features, laboratory tests and etiology of PLA between 2006 to 2011 and 2012 to 2017 in a single hospital were retrospectively reviewed. The incidence and mortality of PLA caused by Escherichia coli and Klebsiella pneumoniae were compared and the risk factors for multiple organ dysfunction (MODS) and endophthalmitis were evaluated. RESULTS: Among the 1,572 PLA patients, the proportion with PLA increased from 333 (21.2%) in 2006-2011 to 1,239 (78.8%) in 2012-2017 without any investigation and treatment procedure differences. K pneumoniae was the main isolate in analysed pus cultures (85.6%). The mortality rate of patients with K pneumoniae infection was lower in the latter period (6.7% vs 0.7%, P = .035). Multivariate analyses revealed that age, fever, MODS and length of hospital stay were factors affecting poor prognosis (death + unhealed/uncured) in PLA patients after treatment and that cardiovascular disease, pleural effusion and pulmonary infection were risk factors for MODS, while diabetes mellitus was the only risk factor for endophthalmitis. Most patients (95.5%) with PLA recovered after abscess drainage/puncture and antibiotic therapy. CONCLUSIONS: Pleural effusion, fever, MODS and length of hospital stays were factors useful in predicting PLA outcomes.


Asunto(s)
Absceso Piógeno Hepático , Antibacterianos/uso terapéutico , Escherichia coli , Humanos , Klebsiella pneumoniae , Absceso Piógeno Hepático/diagnóstico , Absceso Piógeno Hepático/epidemiología , Absceso Piógeno Hepático/terapia , Estudios Retrospectivos , Factores de Riesgo
10.
Environ Res ; 197: 111188, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33894240

RESUMEN

"Sub-ohm" atomizers with reduced resistance can deliver more power than conventional electronic cigarettes. Typical battery outputs are 100 W or more. These devices are particularly popular among young users, and can be a significant source of volatile carbonyls in the indoor environment. Emissions from next-generation sub-ohm vaping products were characterized by determining e-liquid consumption and volatile aldehydes emissions for several combinations of popular high-power configurations. Tests explored the effect of dilution air flow (air vent opening), puffing volume, and coil assembly configuration. The mass of liquid consumed per puff increased as the puff volume increased from 50 to 100 mL, then remained relatively constant for larger puff volumes up to 500 mL. This is likely due to mass transfer limitations at the wick and coil assembly, which reduced the vaporization rate at higher puff volumes. Carbonyl emission rates were systematically evaluated using a 0.15 Ω dual coil atomizer as a function of the puffing volume and dilution air flow, adjusted by setting the air vents to either 100% (fully open), 50%, 25%, or 0% (closed). The highest formaldehyde emissions were observed for the lowest puff volume (50 mL) when the vents were closed (48 ng mg-1), opened at 25% (39 ng mg-1) and at 50% (32 ng mg-1). By contrast, 50-mL puffs with 100% open vents, and puff volumes >100 mL for any vent aperture, generated formaldehyde yields of 20 ng mg-1 or lower, suggesting that a significant cooling effect resulted in limited carbonyl formation. Considering the effect of the coil resistance when operated at a voltage of 3.8 V, the amount of liquid evaporated per puff decreased as the resistance increased, in the order of 0.15 Ω > 0.25 Ω > 0.6 Ω, consistent with decreasing aerosol temperatures measured at the mouthpiece. Three different configurations of 0.15 Ω coils (dual, quadruple and octuple) were evaluated, observing significant variability. No clear trend was found between carbonyl emission rates and coil resistance or configuration, with highest emissions corresponding to a 0.25 Ω dual coil atomizer. Carbonyl emission rates were compared with those determined using the same methodology for conventional e-cigarettes (lower power tank systems), observing overall lower yields for the sub-ohm devices.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Vapeo , Aerosoles , Aldehídos
11.
Qual Health Res ; 31(4): 703-712, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33213262

RESUMEN

In this article, we explore the context and determinants of pod-mod electronic cigarette (ECIG) use among college students aged 18 to 24 in the United States. We conducted semi-structured interviews with 55 students (M age = 20 years, 56% female, 65% White) on three campuses in the Northwest, Midwest, and Southeast. We performed a thematic analysis. Students described ECIG use by peers, increased ECIG exposure and prevalence in college, and school-related stress as reasons for vaping. Pod-mod features such as convenience, design, easy concealment, and flavors made vaping more appealing. Negative aspects of vaping included addiction, cost, and possible health consequences. Most viewed vaping as a college behavior and intended to quit after graduation. Our results show that the college environment plays a major role in young adult ECIG use. These findings can inform the development of targeted interventions to prevent and control uptake of ECIGs by young adults.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Vapeo , Adulto , Femenino , Humanos , Masculino , Instituciones Académicas , Estudiantes , Estados Unidos , Universidades , Adulto Joven
12.
Int J Mol Sci ; 22(14)2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-34299201

RESUMEN

The COVID-19 pandemic examines not only the state of actual health care but also the state of fundamental medicine in various countries. Pro-inflammatory processes extend far beyond the classical concepts of inflammation. They manifest themselves in a variety of ways, beginning with extreme physiology, then allostasis at low-grade inflammation, and finally the shockogenic phenomenon of "inflammatory systemic microcirculation". The pathogenetic core of critical situations, including COVID-19, is this phenomenon. Microcirculatory abnormalities, on the other hand, lie at the heart of a specific type of general pathological process known as systemic inflammation (SI). Systemic inflammatory response, cytokine release, cytokine storm, and thrombo-inflammatory syndrome are all terms that refer to different aspects of SI. As a result, the metabolic syndrome model does not adequately reflect the pathophysiology of persistent low-grade systemic inflammation (ChSLGI). Diseases associated with ChSLGI, on the other hand, are risk factors for a severe COVID-19 course. The review examines the role of hypoxia, metabolic dysfunction, scavenger receptors, and pattern-recognition receptors, as well as the processes of the hemophagocytic syndrome, in the systemic alteration and development of SI in COVID-19.


Asunto(s)
COVID-19/patología , Síndrome de Liberación de Citoquinas/complicaciones , Inflamación/complicaciones , Linfohistiocitosis Hemofagocítica/complicaciones , SARS-CoV-2/aislamiento & purificación , COVID-19/inmunología , COVID-19/terapia , COVID-19/virología , Humanos
13.
Anaesthesist ; 70(1): 42-70, 2021 01.
Artículo en Alemán | MEDLINE | ID: mdl-32997208

RESUMEN

BACKGROUND: The present guidelines ( http://leitlinien.net ) focus exclusively on cardiogenic shock due to myocardial infarction (infarction-related cardiogenic shock, ICS). The cardiological/cardiac surgical and the intensive care medicine strategies dealt with in these guidelines are essential to the successful treatment and survival of patients with ICS; however, both European and American guidelines on myocardial infarction and heart failure and also position papers on cardiogenic shock focused mainly on cardiological aspects. METHODS: Evidence on the diagnosis, monitoring and treatment of ICS was collected and recommendations compiled in a nominal group process by delegates of the German Cardiac Society (DGK), the German Society for Medical Intensive Care Medicine and Emergency Medicine (DGIIN), the German Society for Thoracic and Cardiovascular Surgery (DGTHG), the German Society for Anaesthesiology and Intensive Care Medicine (DGAI), the Austrian Society for Internal and General Intensive Care Medicine (ÖGIAIM), the Austrian Cardiology Society (ÖKG), the German Society for Prevention and Rehabilitation of Cardiovascular Diseases (DGPR) and the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), under the auspices of the Working Group of the Association of Medical Scientific Societies in Germany (AWMF). If only poor evidence on ICS was available, general study results on intensive care patients were inspected and presented in order to enable analogue conclusions. RESULTS: A total of 95 recommendations, including 2 statements were compiled and based on these 7 algorithms with defined instructions on the course of treatment.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Infarto del Miocardio , Austria , Cuidados Críticos , Humanos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/etiología , Choque Cardiogénico/terapia
14.
Epidemiol Mikrobiol Imunol ; 70(3): 161-167, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34641690

RESUMEN

Tuberculosis diagnosis and drug susceptibility testing (DST) are considered a priority for prompt initiation of effective therapy, increasing the chance of cure, decreasing the development of resistance, and reducing transmission. AIM: Our objective was to evaluate currently applied diagnostic tools for tuberculosis including microscopic examination, GeneXpert, culture, and microscopic observation drug susceptibility (MODS) assay, investigating MODS assay usage for second line DST against culture based methods. MATERIAL AND METHODS: In this study the 120 sputum samples collected from suspected cases were over one year duration from December 2018 to January 2020. The samples were subjected to ZN microscopic examination, GeneXpert, MODS assay, and culture for detection of mycobacteria. Moreover, resistance to 5 drugs: isoniazid, rifampicin, ofloxacin, levofloxacin, and amikacin were tested using MODS against the proportion method. RESULTS: The sensitivity and specificity of the MODS assay were similar culture method with the advantage of obtaining the results in a median time of 10.7 days. Whereas the specificity of ZN and GeneXpert was high among untreated cases and decreased in subjects with a history of treatment. Monoresistance was the most common form of resistance detected among new cases followed by multidrug resistance, with a categorical agreement between the two methods above 90% for all tested drugs. CONCLUSIONS: MODS assay is an attractive option once standardized for second line susceptibility testing and GeneXpert assay is of high sensitivity for rapid detection of MTB and RIF resistance especially in treatment naive cases.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Humanos , Isoniazida , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/genética , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico
15.
J Clin Microbiol ; 58(5)2020 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-32132191

RESUMEN

Pyrazinamide (PZA) is considered the pivot drug in all tuberculosis treatment regimens due to its particular action on the persistent forms of Mycobacterium tuberculosis However, no drug susceptibility test (DST) is considered sufficiently reliable for routine application. Although molecular tests are endorsed, their application is limited to known PZA resistance associated mutations. Microbiological DSTs for PZA have been restricted by technical limitations, especially the necessity for an acidic pH. Here, for the first time, MODS culture at neutral pH was evaluated using high PZA concentrations (400 and 800 µg/ml) to determine PZA susceptibility directly from sputum samples. Sputum samples were cultured with PZA for up to 21 days at 37°C. Plate reading was performed at two time points: R1 (mean, 10 days) and R2 (mean, 13 days) for each PZA concentration. A consensus reference test, composed of MGIT-PZA, pncA sequencing, and the classic Wayne test, was used. A total of 182 samples were evaluated. The sensitivity and specificity for 400 µg/ml ranged from 76.9 to 89.7 and from 93.0 to 97.9%, respectively, and for 800 µg/ml ranged from 71.8 to 82.1 and from 95.8 to 98.6%, respectively. Compared to MGIT-PZA, our test showed a similar turnaround time (medians of 10 and 12 days for PZA-sensitive and -resistant isolates, respectively). In conclusion, MODS-PZA is presented as a fast, simple, and low-cost DST that could complement the MODS assay to evaluate resistance to the principal first-line antituberculosis drugs. Further optimization of test conditions would be useful in order to increase its performance.


Asunto(s)
Mycobacterium tuberculosis , Preparaciones Farmacéuticas , Tuberculosis Resistente a Múltiples Medicamentos , Amidohidrolasas/genética , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Humanos , Concentración de Iones de Hidrógeno , Pruebas de Sensibilidad Microbiana , Mutación , Pirazinamida/farmacología , Esputo , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico
16.
Crit Care ; 24(1): 545, 2020 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-32887651

RESUMEN

BACKGROUND: Severe critical illness-induced immune suppression, termed immunoparalysis, is associated with longer duration of organ dysfunction in septic children. mRNA studies have suggested differential benefit of hydrocortisone in septic children based on their immune phenotype, but this has not been shown using a functional readout of the immune response. This study represents a secondary analysis of a prospectively conducted immunophenotyping study of pediatric severe sepsis to test the hypothesis that hydrocortisone will be differentially associated with clinical outcomes in children with or without immunoparalysis. METHODS: Children with severe sepsis/septic shock underwent blood sampling within 48 h of sepsis onset. Immune function was measured by quantifying whole blood ex vivo LPS-induced TNFα production capacity, with a TNFα response < 200 pg/ml being diagnostic of immunoparalysis. The primary outcome measure was number of days in 14 with MODS. Univariate and multivariable negative binomial regression models were used to examine associations between hydrocortisone use, immune function, and duration of MODS. RESULTS: One hundred two children were enrolled (age 75 [6-160] months, 60% male). Thirty-one subjects received hydrocortisone and were more likely to be older (106 [52-184] vs 38 [3-153] months, p = 0.04), to have baseline immunocompromise (32 vs 8%, p = 0.006), to have higher PRISM III (13 [8-18] vs 7 [5-13], p = 0.0003) and vasoactive inotrope scores (20 [10-35] vs 10 [3-15], p = 0.0002) scores, and to have more MODS days (3 [1-9] vs 1 [0-3], p = 0.002). Thirty-three subjects had immunoparalysis (TNFα response 78 [52-141] vs 641 [418-1047] pg/ml, p < 0.0001). Hydrocortisone use was associated with longer duration of MODS in children with immunoparalysis after adjusting for covariables (aRR 3.7 [1.8-7.9], p = 0.0006) whereas no association with MODS duration was seen in children without immunoparalysis (aRR 1.2 [0.6-2.3], p = 0.67). CONCLUSION: Hydrocortisone use was independently associated with longer duration of MODS in septic children with immunoparalysis but not in those with more robust immune function. Prospective clinical trials using a priori immunophenotyping are needed to understand optimal hydrocortisone strategies in this population.


Asunto(s)
Hidrocortisona/efectos adversos , Insuficiencia Multiorgánica/clasificación , Sepsis/tratamiento farmacológico , Factores de Tiempo , Adolescente , Antiinflamatorios/efectos adversos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Hidrocortisona/farmacología , Hidrocortisona/uso terapéutico , Huésped Inmunocomprometido/efectos de los fármacos , Huésped Inmunocomprometido/inmunología , Lactante , Tiempo de Internación/estadística & datos numéricos , Masculino , Insuficiencia Multiorgánica/etiología , Pediatría/métodos , Estudios Prospectivos , Sepsis/complicaciones
17.
Crit Care ; 24(1): 518, 2020 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-32831133

RESUMEN

BACKGROUND: Sepsis remains a common condition with high mortality when multiple organ failure develops. The evidence for therapeutic plasma exchange (TPE) in this setting is promising but inconclusive. Our study aims to evaluate the efficacy of adjunct TPE for septic shock with multiple organ failure compared to standard therapy alone. METHODS: A retrospective, observational chart review was performed, evaluating outcomes of patients with catecholamine-resistant septic shock and multiple organ failure in intensive care units at a tertiary care hospital in Winston-Salem, NC, from August 2015 to March 2019. Adult patients with catecholamine-resistant septic shock (≥ 2 vasopressors) and evidence of multiple organ failure were included. Patients who received adjunct TPE were identified and compared to patients who received standard care alone. A propensity score using age, gender, chronic co-morbidities (HTN, DM, CKD, COPD), APACHE II score, SOFA score, lactate level, and number of vasopressors was used to match patients, resulting in 40 patients in each arm. RESULTS: The mean baseline APACHE II and SOFA scores were 32.5 and 14.3 in TPE patients versus 32.7 and 13.8 in control patients, respectively. The 28-day mortality rate was 40% in the TPE group versus 65% in the standard care group (p = 0.043). Improvements in baseline SOFA scores at 48 h were greater in the TPE group compared to standard care alone (p = 0.001), and patients receiving adjunct TPE had a more favorable fluid balance at 48 h (p = 0.01). Patients receiving adjunct TPE had longer ICU and hospital lengths of stay (p = 0.003 and p = 0.006, respectively). CONCLUSIONS: Our retrospective, observational study in adult patients with septic shock and multiple organ failure demonstrated improved 28-day survival with adjunct TPE compared to standard care alone. Hemodynamics, organ dysfunction, and fluid balance all improved with adjunct TPE, while lengths of stay were increased in survivors. The study design does not allow for a generalized statement of support for TPE in all cases of sepsis with multiple organ failure but offers valuable information for a prospective, randomized clinical trial.


Asunto(s)
Insuficiencia Multiorgánica/terapia , Intercambio Plasmático/normas , Choque Séptico/terapia , Resultado del Tratamiento , APACHE , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/fisiopatología , Intercambio Plasmático/métodos , Estudios Retrospectivos , Choque Séptico/fisiopatología
18.
Br J Anaesth ; 125(6): 912-925, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32988604

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic has resulted in a significant surge of critically ill patients and an unprecedented demand on intensive care services. The rapidly evolving understanding of pathogenesis, limited disease specific evidence, and demand-resource imbalances have posed significant challenges for intensive care clinicians. COVID-19 is a complex multisystem inflammatory vasculopathy with a significant mortality implication for those admitted to intensive care. Institutional strategic preparation and meticulous intensive care support are essential to maximising outcomes during the pandemic. The significant mortality variation observed between institutions and internationally, despite a single aetiology and uniform presentation, highlights the potential influence of management strategies on outcome. Given that optimal organ support and adjunctive therapies for COVID-19 have not yet been well defined by trial-based outcomes, strategies are predicated on existing literature and experiential learning. This review outlines the relevant pathophysiology and management strategies for critically ill patients with COVID-19, and shares some of the collective learning accumulated in a high volume severe respiratory failure centre in London.


Asunto(s)
Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Cuidados Críticos/métodos , Manejo de la Enfermedad , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/terapia , Neumonía Viral/complicaciones , Neumonía Viral/terapia , COVID-19 , Humanos , Pandemias
19.
Adv Exp Med Biol ; 1238: 195-202, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32323186

RESUMEN

Multiple organ dysfunction syndrome (MODS), also referred to as external challenge-induced multiple organ injury, is characterized by dysfunction of two or more organs during infection or following shock or trauma. The pathogenesis of MODS is multifactorial and involves systemic inflammation and cell stress responses including cell death; sepsis is defined as an infection with MODS. Gut microbiota contributes significantly to organ dysfunction and to the pathobiology of sepsis. However, the relationship between the development of sepsis and the composition of gut microbiota is equivocal and is only now starting to be elucidated. Recent studies by our group and others reveal that enteric microbial composition and function are disrupted during sepsis, and that microbial products can either promote or alleviate the progression of sepsis. Here, we summarize the current research on the functional link between gut microbiota and sepsis, and argue the point that gut microbiota is a potential therapeutic target in the management of sepsis.


Asunto(s)
Microbioma Gastrointestinal , Insuficiencia Multiorgánica/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Inflamación/microbiología , Inflamación/terapia , Insuficiencia Multiorgánica/terapia , Sepsis/microbiología , Sepsis/terapia
20.
Qatar Med J ; 2020(1): 22, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33628712

RESUMEN

Multiorgan dysfunction syndrome (MODS) remains a major complication and challenge to treat patients with critical illness in different intensive care unit settings. The exact mechanism and pathophysiology of MODS is complex and remains unexplored. We reviewed the literature from January 2011 to August 2019 to analyze the underlying mechanisms, prognostic factors, MODS scoring systems, organ systems dysfunctions, and the management of MODS. We used the search engines PubMed, MEDLINE, Scopus, and Google Scholar with the keywords "multiple organ dysfunction syndrome," "intensive care units," "multiorgan failure," "MODS scoring system," and "MODS management." The initial search yielded 3550 abstracts, of which 91 articles were relevant to the scope of the present article. A better understanding of a disease course will help differentiate the signs of an intense inflammatory response from the early onset of sepsis and minimize the inappropriate use of medications. This, in turn, will promote organtargeted therapy and prevent occurrence and progression of MODS.

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