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1.
Cell ; 143(4): 628-38, 2010 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-21074052

RESUMO

Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the α2δ family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (α2δ3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, α2δ3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in α2δ3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in α2δ3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.


Assuntos
Canais de Cálcio/genética , Proteínas de Drosophila/genética , Drosophila/genética , Dor/genética , Adulto , Animais , Dor nas Costas/genética , Canais de Cálcio/metabolismo , Proteínas de Drosophila/metabolismo , Técnicas de Silenciamento de Genes , Estudo de Associação Genômica Ampla , Temperatura Alta , Humanos , Camundongos , Polimorfismo de Nucleotídeo Único , Interferência de RNA
2.
Proc Natl Acad Sci U S A ; 119(11): e2118570119, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35263227

RESUMO

SignificanceDespite the identification of neural circuits and circulating hormones in olfactory regulation, the peripheral targets for olfactory modulation remain relatively unexplored. Here we show that dopamine D2 receptor (DRD2) is expressed in the cilia and somata of mature olfactory sensory neurons (OSNs), while nasal dopamine (DA) is mainly released from the sympathetic nerve terminals, which innervate the mouse olfactory mucosa (OM). We further demonstrate that DA-DRD2 signaling in the nose plays important roles in regulating olfactory function using genetic and pharmacological approaches. Moreover, the local DA synthesis in mouse OM is reduced during hunger, which contributes to starvation-induced olfactory enhancement. Altogether, we demonstrate that nasal DA and DRD2 receptor can serve as the potential peripheral targets for olfactory modulation.


Assuntos
Dopamina , Neurônios Receptores Olfatórios , Receptores de Dopamina D2 , Animais , Dopamina/metabolismo , Antagonistas dos Receptores de Dopamina D2/farmacologia , Humanos , Camundongos , Neurônios Receptores Olfatórios/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Transdução de Sinais , Olfato
3.
BMC Musculoskelet Disord ; 25(1): 521, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970016

RESUMO

BACKGROUND: Previous studies have implicated rheumatoid arthritis as an independent risk factor for bone density loss. However, whether there is a causal relationship between rheumatic diseases and bone mineral density (BMD) and fractures is still controversial. We employed a bidirectional Mendelian analysis to explore the causal relationship between rheumatic diseases and BMD or fractures. METHODS: The rheumatic diseases instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Analyses were performed for the three rheumatic diseases: ankylosing spondylitis (AS) (n = 22,647 cases, 99,962 single nucleotide polymorphisms [SNPs]), rheumatoid arthritis (RA) (n = 58,284 cases, 13,108,512 SNPs), and systemic lupus erythematosus (SLE) (n = 14,267 cases, 7,071,163 SNPs). Two-sample Mendelian randomization (MR) analyses were carried out by using R language TwoSampleMR version 0.5.7. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to analyze the causal relationship between rheumatic diseases and BMD or fracture. RESULTS: The MR results revealed that there was absence of evidence for causal effect of AS on BMD or fracture. However, there is a positive causal relationship of RA with fracture of femur (95% CI = 1.0001 to 1.077, p = 0.046), and RA and fracture of forearm (95% CI = 1.015 to 1.064, p = 0.001). SLE had positive causal links for fracture of forearm (95% CI = 1.004 to 1.051, p = 0.020). Additionally, increasing in heel bone mineral density (Heel-BMD) and total bone mineral density (Total-BMD) can lead to a reduced risk of AS without heterogeneity or pleiotropic effects. The results were stable and reliable. There was absence of evidence for causal effect of fracture on RA (95% CI = 0.929 to 1.106, p = 0.759), and fracture on SLE (95% CI = 0.793 to 1.589, p = 0.516). CONCLUSIONS: RA and SLE are risk factors for fractures. On the other hand, BMD increasing can reduce risk of AS. Our results indicate that rheumatic diseases may lead to an increased risk of fractures, while increased BMD may lead to a reduced risk of rheumatic diseases. These findings provide insight into the risk of BMD and AS, identifying a potential predictor of AS risk as a reduction in BMD.


Assuntos
Artrite Reumatoide , Densidade Óssea , Fraturas Ósseas , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Densidade Óssea/genética , Fraturas Ósseas/genética , Fraturas Ósseas/epidemiologia , Artrite Reumatoide/genética , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Doenças Reumáticas/genética , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/complicações , Fatores de Risco , Espondilite Anquilosante/genética , Espondilite Anquilosante/complicações , Espondilite Anquilosante/epidemiologia , Predisposição Genética para Doença
4.
Molecules ; 29(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38542856

RESUMO

Coordination cages sustained by metal-ligand interactions feature polyhedral architectures and well-defined hollow structures, which have attracted significant attention in recent years due to a variety of structure-guided promising applications. Sulfonylcalix[4]arenes-based coordination cages, termed metal-organic supercontainers (MOSCs), that possess unique multi-pore architectures containing an endo cavity and multiple exo cavities, are emerging as a new family of coordination cages. The well-defined built-in multiple binding domains of MOSCs allow the efficient encapsulation of guest molecules, especially for drug delivery. Here, we critically discuss the design strategy, and, most importantly, the recent advances in research surrounding cavity-specified host-guest chemistry and biomedical applications of MOSCs.

5.
Clin Exp Rheumatol ; 41(2): 261-266, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36377563

RESUMO

OBJECTIVES: Inclusion body myositis (IBM) is the most common idiopathic inflammatory myopathy (IIM) above the age of 50 with a distinct clinical phenotype of progressive, painless, asymmetric weakness predominantly involving the long finger flexors and quadriceps. In this study, we compared comorbidities in IBM with other IIMs (i.e., dermatomyositis (DM) and polymyositis (PM)) from the United States National Inpatient Sample Database. METHODS: We identified patients with a primary diagnosis of IBM or IIM from the National Inpatient Sample (NIS) from 2012 to 2018. We then compared the rate of common inpatient comorbidities between the IBM and IIM. RESULTS: There were 18,819 admissions for patients with either IBM or IIM. IBM patients were older (72.9±10.7 years vs. 59.3±18.4 years for IIM, p<0.001), predominantly men (65.0% vs. 31.2% for IIM, p<0.001), and White Caucasians (82.5% vs. 58.4% for IIM, p<0.001). IBM patients had significantly more frequent events of aspiration pneumonia, atrial fibrillation, falls, and sepsis. The rate of PEG tube placement was also significantly higher. When performing multivariable logistic regression, we found that IBM is a risk factor for aspiration pneumonia (OR 3.03), PEG tube placement (OR 2.91), falls (OR 2.05), and sepsis (OR 1.30) but not for significant cardiovascular events. CONCLUSIONS: IBM increases a patient's risk for dysphagia, falls, and infection as compared to other IIM patients. Further population-based studies are warranted to better elucidate the impact of these comorbidities in patients with IBM.


Assuntos
Dermatomiosite , Miosite de Corpos de Inclusão , Miosite , Pneumonia Aspirativa , Polimiosite , Humanos , Dermatomiosite/diagnóstico , Miosite/diagnóstico
6.
Phys Chem Chem Phys ; 25(11): 8144-8152, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36877127

RESUMO

Z-scheme van der Waals heterojunctions are very attractive photocatalysts attributed to their excellent reduction and oxidation abilities. In this paper, we designed InN/XS2 (X = Zr, Hf) heterojunctions and explored their electronic structure properties, photocatalytic performance, and light absorption systematically using first-principles calculations. We found that the valence-band maximum (VBM) and conduction-band minimum (CBM) of the InN/XS2 (X = Zr, Hf) heterojunctions are contributed by InN and XS2, respectively. Photo-generated carriers transferring along the Z-path can accelerate the recombination of interlayer electron-hole pairs. Therefore, the photogenerated electrons in the CBM of the InN layer can be maintained making the hydrogen evolution reaction occur continuously, while photogenerated holes in the VBM of the Ti2CO2 layer make the oxygen evolution reaction occur continuously. The band edge positions of heterojunctions can straddle the required water redox potentials, while pristine InN and XS2 (X = Zr, Hf) can only be used for photocatalytic hydrogen evolution or oxygen evolution, respectively. Furthermore, the HER barriers can be tuned by transition metal doping. With Cr doping, the hydrogen evolution reaction (HER) barriers decrease to -0.12 for InN/ZrS2 and -0.05 eV for InN/HfS2, very close to the optimal value (0 eV). In addition, the optical absorption coefficient is as high as 105 cm-1 in the visible and ultraviolet regions. Therefore, the InN/XS2 (X = Zr, Hf) heterojunctions are expected to be excellent photocatalysts for water splitting.

7.
Phys Chem Chem Phys ; 25(13): 9548-9558, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36939192

RESUMO

The rapid rise of two-dimensional (2D) materials has aroused increasing interest in the fields of microelectronics and optoelectronics; various types of 2D van der Waals heterostructures (vdWHs), especially those based on MoS2, have been widely investigated in theory and experiment. However, the interfacial properties of MoS2 and the uncommon crystal surface of traditional three-dimensional (3D) metals are yet to be explored. In this paper, we studied heterostructures composed of MoS2 and metal(001) slabs, based on the first-principles calculations, and we uncovered that MoS2/Au(001) and MoS2/Ag(001) vdWHs reveal Schottky contacts, and MoS2/Cu(001) belongs to Ohmic contact and possesses ultrahigh electron tunneling probability at the equilibrium distance. Thus, the MoS2/Cu(001) heterostructure exhibits the best contact performance. Further investigations demonstrate that external longitudinal strain can modulate interfacial contact to engineer the Schottky-Ohmic contact transition and regulate interfacial charge transport. We believe that it is a general strategy to exploit longitudinal strain to improve interfacial contact performance to design and fabricate a multifunctional MoS2-based electronic device.

8.
BMC Public Health ; 23(1): 1862, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752456

RESUMO

BACKGROUND: In previous studies, sun-protective behaviors increased cardiovascular incidence. Our present article is to further analyze the potential relationship between sun-protective behaviors (staying in the shade, wearing long-sleeved clothing, and applying sunscreen) and hypertension. METHOD: The present cross-sectional study evaluated 8,613 participants (aged 20-60 years) from the National Health and Nutrition Examination Survey (NHANES) obtained between 2009 and 2014. We performed multiple logistic regression analysis to examine the relationship between sun-protective behaviors and hypertension. Subgroup analysis was then performed. Multiple linear regression analysis was utilized to examine the relationship of sun-protective behaviors and each sun-protective behavior with systolic and diastolic blood pressure, stratified by sex and race. RESULTS: A total of 8,613 participants (weighted n = 127,909,475) were applied in our study, including 1,694 hypertensive subjects. Our study demonstrated that sun-protective behaviors of the 2-3 category were associated with increased risk of hypertension, but not with higher systolic and diastolic blood pressure. In subgroup analysis, men, Mexican American, and 25 < BMI ≤ 30 who reported sun-protective behaviors (2-3) were prone to hypertension. Multiple linear regression models showed that non-Hispanic white men with sun-protective behaviors (2-3) were positively associated with systolic and diastolic blood pressure. The association between other-Hispanic men with frequent wearing long-sleeved clothing and diastolic blood pressure was positively correlated. CONCLUSION: Sun-protective behaviors of the 2-3 category could increase the incidence of hypertension, but not increase systolic and diastolic blood pressure. We only found that non-Hispanic white men who reported sun-protective behaviors (2-3) were positively associated with systolic and diastolic blood pressure. These findings suggested that excessive sun-protective behaviors should be avoided.


Assuntos
Hipertensão , Neoplasias Cutâneas , Masculino , Humanos , Inquéritos Nutricionais , Estudos Transversais , Comportamentos Relacionados com a Saúde , Hipertensão/epidemiologia , Hipertensão/prevenção & controle , Hipertensão/tratamento farmacológico , Protetores Solares/uso terapêutico
9.
J Anaesthesiol Clin Pharmacol ; 39(3): 385-391, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38025551

RESUMO

Background and Aims: Glucocorticoids are commonly utilised as adjuvants to enhance nerve block quality and prolong the analgesic duration. Its systemic effects, after a single-injection adductor canal block (ACB) followed by a continuous infusion, are unclear. The aim of the study was to assess the systemic effects of a single dose of dexamethasone sodium phosphate (DEX), or a combination of DEX and methylprednisolone acetate (MPA), on fasting blood glucose (FBG) and white blood cell count (WBC) when administered perineurally via ACB. Material and Methods: A single-center retrospective study on total knee arthroplasty (TKA) was performed and a total of 95 patients were included in the final analysis. Patients were divided into three groups based on adjuvants received in ACB: Control group (N = 41) and two treatment groups, DEX group (N = 33) and DEX/MPA group (N = 21). Our primary outcomes were the change of FBG from its preoperative baseline value on postoperative day (POD) 2. The secondary outcomes included change of FBG on POD 0 and POD 1, and change of WBC on POD 0, POD 1, and POD 2. Results: The FBG change from baseline in the DEX group was significantly higher than that in the control group (difference = 14.04, 95% CI: 1.3 to 26.77), P = 0.031) on POD 0. The WBC change from baseline in the DEX/MPA group was statistically significant higher than control on POD 0 (2.62 (1.52 to 3.37), P < 0.0001). No significant differences between DEX and DEX/MPA group were found on any given postoperative days for FBG and WBC. Conclusion: This study provided preliminary safety data on the use of a combination of glucocorticoids with hydrophilic (DEX) and lipophilic (MPA) properties as local anesthetic adjuvants in ACB, which induced similar levels of changes on FBG and WBC as those from both control and DEX alone group.

10.
Diabetologia ; 65(5): 895-905, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247067

RESUMO

AIMS/HYPOTHESIS: We have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by 1H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA1c normalise intracerebral glucose levels. METHODS: Eight individuals (two men, six women) with poorly controlled type 2 diabetes and mean ± SD age 44.8 ± 8.3 years, BMI 31.4 ± 6.1 kg/m2 and HbA1c 84.1 ± 16.2 mmol/mol (9.8 ± 1.4%) underwent 1H MRS scanning at 4 Tesla during a hyperglycaemic clamp (~12.21 mmol/l) to measure changes in cerebral glucose at baseline and after a 12 week intervention that improved glycaemic control through the use of continuous glucose monitoring, diabetes regimen intensification and frequent visits to an endocrinologist and nutritionist. RESULTS: Following the intervention, mean ± SD HbA1c decreased by 24.3 ± 15.3 mmol/mol (2.1 ± 1.5%) (p=0.006), with minimal weight changes (p=0.242). Using a linear mixed-effects regression model to compare glucose time courses during the clamp pre and post intervention, the pre-intervention brain glucose level during the hyperglycaemic clamp was significantly lower than the post-intervention brain glucose (p<0.001) despite plasma glucose levels during the hyperglycaemic clamp being similar (p=0.266). Furthermore, the increases in brain glucose were correlated with the magnitude of improvement in HbA1c (r = 0.71, p=0.048). CONCLUSION/INTERPRETATION: These findings highlight the potential reversibility of cerebral glucose transport capacity and metabolism that can occur in individuals with type 2 diabetes following improvement of glycaemic control. Trial registration ClinicalTrials.gov NCT03469492.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Adulto , Glicemia/metabolismo , Automonitorização da Glicemia , Encéfalo/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Cinética , Masculino , Pessoa de Meia-Idade
11.
Vasc Med ; 27(3): 251-257, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35485400

RESUMO

BACKGROUND: Multiple frailty screening tools are implemented; however, it is unclear whether they perform in a comparable way for both frailty detection and prediction of perioperative outcomes in patients undergoing lower-extremity revascularization. METHODS: Patients undergoing lower-extremity revascularization were identified from the Vascular Quality Initiative (VQI) national database. Two cohorts were established based on the revascularization type (percutaneous vascular interventions (PVI) or lower-extremity bypass). Frailty was assessed by the 5-item modified frailty index (mFI-5) and the VQI-derived risk analysis index (RAI). RESULTS: Out of 134,081 patients undergoing PVI, frailty was identified in 67% by mFI-5 and 28% by RAI. Similarly, out of 41,316 patients in the bypass cohort, frailty was identified in 69% by mFI-5 and 16% by RAI. There was little agreement between the two frailty tools for both vascular cohorts (PVI: kappa: 0.17; bypass: kappa: 0.13). In an adjusted analysis, frailty as assessed by mFI-5 and RAI was associated with higher odds of mortality in both cohorts (p < 0.001). A significant association between frailty and unplanned amputations was only noted in the bypass cohort when RAI was applied (OR: 1.50, p < 0.01). The addition of frailty to traditional PAD risk factors marginally improved model performance to predict mortality and unplanned major amputations. CONCLUSION: There was significant variation in frailty detection by mFI-5 and RAI. Although frailty was associated with mortality, the predictive value of these tools in predicting outcomes in PAD was limited. Future research should focus on designing new frailty screening tools specific to the PAD population.


Assuntos
Fragilidade , Doença Arterial Periférica , Fragilidade/diagnóstico , Humanos , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
Nutr Neurosci ; 25(1): 64-69, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31900092

RESUMO

Background: Glutamine synthetase (GS) is the only enzyme known to synthesize significant amounts of glutamine in mammals, and loss of GS in the hippocampus has been implicated in the pathophysiology of medication refractory mesial temporal lobe epilepsy (MTLE). Moreover, loss-of-function mutations of the GS gene causes severe epileptic encephalopathy, and supplementation with glutamine has been shown to normalize EEG and possibly improve the outcome in these patients. Here we examined whether oral glutamine supplementation is an effective treatment for MTLE by assessing the frequency and severity of seizures after supplementation in a translationally relevant model of the disease.Methods: Male Sprague Dawley rats (380-400 g) were allowed to drink unlimited amounts of glutamine in water (3.6% w/v; n = 8) or pure water (n = 8) for several weeks. Ten days after the start of glutamine supplementation, GS was chronically inhibited in the hippocampus to induce MTLE. Continuous video-intracranial EEG was collected for 21 days to determine the frequency and severity of seizures.Results: While there was no change in seizure frequency between the groups, the proportion of convulsive seizures was significantly higher in glutamine treated animals during the first three days of GS inhibition.Conclusion: The results suggest that oral glutamine supplementation transiently increases seizure severity in the initial stages of an epilepsy model, indicating a potential role of the amino acid in seizure propagation and epileptogenesis.


Assuntos
Epilepsia do Lobo Temporal/fisiopatologia , Glutamina/administração & dosagem , Convulsões/induzido quimicamente , Índice de Gravidade de Doença , Animais , Suplementos Nutricionais , Modelos Animais de Doenças , Epilepsia do Lobo Temporal/etiologia , Glutamato-Amônia Ligase/antagonistas & inibidores , Glutamato-Amônia Ligase/metabolismo , Hipocampo/enzimologia , Masculino , Ratos , Ratos Sprague-Dawley
13.
J Foot Ankle Surg ; 61(1): 37-42, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34253433

RESUMO

We conducted a prospective randomized controlled trial to compare the radiological and clinical outcomes of Sanders type III calcaneal fractures treated with percutaneous prodding reduction and K-wire fixation via a sinus tarsi approach (PPRKF) versus open reduction and internal fixation (ORIF). Fifty-one patients with closed, unilateral, Sanders type III calcaneal fractures were randomly assigned to the PPRKF group (n = 26) or the ORIF group (n = 25). The clinical outcomes evaluated were time to surgery, blood loss, operative time, hospital stay, wound healing time, wound complications, and Maryland foot score. Radiological results were evaluated on lateral and axial X-rays and computed tomography images and included Böhler's angle, Gissane's angle, and calcaneal width. Compared with the ORIF group, the PPRKF group had shorter time to surgery, shorter operative time, less blood loss, shorter hospital stay, shorter wound healing time, and fewer wound complications (p < .001). The postoperative Böhler's angle, Gissane's angle, and calcaneal width in both groups were significantly better than those measured preoperatively (p < .001) and did not differ between the PPRKF group and ORIF group (p> .05). Regarding clinical results, there was no significant difference in Maryland foot score between the two groups at 12 months after surgery (p > .05). Both PPRKF and ORIF can result in satisfactory clinical function. PPRKF is superior to ORIF in reducing the time to surgery, operative time, blood loss, hospital stay, wound healing time, and wound complications.


Assuntos
Calcâneo , Fraturas Ósseas , Fraturas Intra-Articulares , Calcâneo/diagnóstico por imagem , Calcâneo/cirurgia , Fixação Interna de Fraturas , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Calcanhar , Humanos , Redução Aberta , Resultado do Tratamento
14.
Eur Respir J ; 58(3)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33632796

RESUMO

BACKGROUND: The optimal oxygenation in mechanically ventilated critically ill patients remains unclear. METHODS: We performed a systematic review of randomised controlled trials (RCTs) with the aim to classify oxygenation goals and investigate their relative effectiveness. RCTs investigating different oxygenation goal-directed mechanical ventilation in critically ill adult patients were eligible for the analysis. The trinary classification classified oxygenation goals into conservative (partial pressure of arterial oxygen (P aO2 ) 55-90 mmHg), moderate (P aO2 90-150 mmHg) and liberal (P aO2 >150 mmHg). The quadruple classification further divided the conservative goal from the trinary classification into far-conservative (P aO2 55-70 mmHg) and conservative (P aO2 70-90 mmHg) goals. The primary outcome was 30-day mortality. The secondary outcomes included intensive care unit, hospital and 90-day mortalities. The effectiveness was estimated by the relative risk and 95% credible interval (CrI) using network meta-analysis and visualised using surface under the cumulative ranking curve (SUCRA) scores and survival curves. RESULTS: We identified eight eligible studies involving 2532 patients. There were no differences between conservative and moderate goals (relative risk 1.08, 95% CrI 0.85-1.36; moderate quality), between moderate and liberal goals (relative risk 0.83, 95% CrI 0.61-1.10; low quality) or between conservative and liberal goals (relative risk 0.89, 95% CrI 0.61-1.30; low quality) based on the trinary classification. There were no differences in secondary outcomes among the different goals. The results were consistent between the trinary and quadruple classifications. The SUCRA scores and survival curves suggested that the moderate goal in the trinary and quadruple classifications and the conservative goal in the quadruple classification may be superior to the liberal and far-conservative goals. CONCLUSIONS: Different oxygenation goals do not lead to different mortalities in mechanically ventilated critically ill patients. The potential superiority of maintaining P aO2 in the range 70-150 mmHg remains to be validated.


Assuntos
Estado Terminal , Objetivos , Adulto , Estado Terminal/terapia , Humanos , Unidades de Terapia Intensiva , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial
15.
Anesthesiology ; 135(6): 1076-1090, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34597362

RESUMO

BACKGROUND: Mortality in critically ill COVID-19 patients remains high. Although randomized controlled trials must continue to definitively evaluate treatments, further hypothesis-generating efforts to identify candidate treatments are required. This study's hypothesis was that certain treatments are associated with lower COVID-19 mortality. METHODS: This was a 1-yr retrospective cohort study involving all COVID-19 patients admitted to intensive care units in six hospitals affiliated with Yale New Haven Health System from February 13, 2020, to March 4, 2021. The exposures were any COVID-19-related pharmacologic and organ support treatments. The outcome was in-hospital mortality. RESULTS: This study analyzed 2,070 patients after excluding 23 patients who died within 24 h after intensive care unit admission and 3 patients who remained hospitalized on the last day of data censoring. The in-hospital mortality was 29% (593 of 2,070). Of 23 treatments analyzed, apixaban (hazard ratio, 0.42; 95% CI, 0.363 to 0.48; corrected CI, 0.336 to 0.52) and aspirin (hazard ratio, 0.72; 95% CI, 0.60 to 0.87; corrected CI, 0.54 to 0.96) were associated with lower mortality based on the multivariable analysis with multiple testing correction. Propensity score-matching analysis showed an association between apixaban treatment and lower mortality (with vs. without apixaban, 27% [96 of 360] vs. 37% [133 of 360]; hazard ratio, 0.48; 95% CI, 0.337 to 0.69) and an association between aspirin treatment and lower mortality (with vs. without aspirin, 26% [121 of 473] vs. 30% [140 of 473]; hazard ratio, 0.57; 95% CI, 0.41 to 0.78). Enoxaparin showed similar associations based on the multivariable analysis (hazard ratio, 0.82; 95% CI, 0.69 to 0.97; corrected CI, 0.61 to 1.05) and propensity score-matching analysis (with vs. without enoxaparin, 25% [87 of 347] vs. 34% [117 of 347]; hazard ratio, 0.53; 95% CI, 0.367 to 0.77). CONCLUSIONS: Consistent with the known hypercoagulability in severe COVID-19, the use of apixaban, enoxaparin, or aspirin was independently associated with lower mortality in critically ill COVID-19 patients.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19/mortalidade , Estado Terminal/mortalidade , Estado Terminal/terapia , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anticoagulantes/administração & dosagem , Antivirais/administração & dosagem , Estudos de Coortes , Inibidores do Fator Xa/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estudos Retrospectivos , Resultado do Tratamento
16.
Br J Anaesth ; 127(4): 620-628, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34446224

RESUMO

BACKGROUND: Previous studies on the association between renal tissue desaturation and acute kidney injury (AKI) in infant cardiac surgery are limited by small sample sizes and inconsistent results. This prospective study aimed to determine the association between renal desaturation and AKI in infants undergoing surgical repair of an isolated ventricular septal defect (VSD). METHODS: Infants undergoing VSD repair involving cardiopulmonary bypass participated in this prospective cohort study. The exposure of interest was renal tissue desaturation, defined as at least 20% decrease in saturation from baseline for at least 60 consecutive seconds. Intraoperative care was not guided by renal oxygenation, as the anaesthesiologists were blinded to the monitor. The outcome was AKI arising within postoperative Days 1-3. The primary analysis was based on propensity score-matched infants with and without intraoperative renal desaturation. RESULTS: Intraoperative renal desaturation was detected in 38 of 242 infants using near-infrared spectroscopy. This group of infants was matched with 114 infants without intraoperative renal saturation after propensity score matching. Acute kidney injury occurred in 47% (18/38) and 27% (31/114) of infants with or without renal desaturation, respectively. Infants with renal desaturation had higher odds of developing AKI than infants without renal desaturation based on conditional logistic regression (odds ratio 2.79; 95% confidence interval: 1.21-6.44; P=0.016). The cumulative time of renal desaturation correlated moderately with the ratio of postoperative peak creatinine to preoperative baseline creatinine (r=0.51; P<0.001). CONCLUSIONS: Intraoperative renal desaturation is associated with increased odds of developing AKI after surgical repair of an isolated VSD involving cardiopulmonary bypass in infants. CLINICAL TRIAL REGISTRATION: NCT03941015.


Assuntos
Injúria Renal Aguda/etiologia , Procedimentos Cirúrgicos Cardíacos/métodos , Comunicação Interventricular/cirurgia , Complicações Pós-Operatórias/epidemiologia , Injúria Renal Aguda/epidemiologia , Ponte Cardiopulmonar/métodos , Estudos de Coortes , Creatinina/metabolismo , Feminino , Humanos , Lactente , Rim/metabolismo , Masculino , Oxigênio/metabolismo , Estudos Prospectivos , Espectroscopia de Luz Próxima ao Infravermelho
17.
Anesth Analg ; 133(1): 176-186, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33721874

RESUMO

BACKGROUND: The association between cerebral desaturation and postoperative delirium in thoracotomy with one-lung ventilation (OLV) has not been specifically studied. METHODS: A prospective observational study performed in thoracic surgical patients. Cerebral tissue oxygen saturation (Scto2) was monitored on the left and right foreheads using a near-infrared spectroscopy oximeter. Baseline Scto2 was measured with patients awake and breathing room air. The minimum Scto2 was the lowest measurement at any time during surgery. Cerebral desaturation and hypersaturation were an episode of Scto2 below and above a given threshold for ≥15 seconds during surgery, respectively. The thresholds based on relative changes by referring to the baseline measurement were <80%, <85%, <90%, <95%, and <100% baseline for desaturation and >105%, >110%, >115%, and >120% baseline for hypersaturation. The thresholds based on absolute values were <50%, <55%, <60%, <65%, and <70% for desaturation and >75%, >80%, >85%, and >90% for hypersaturation. The given area under the threshold (AUT)/area above the threshold (AAT) was analyzed. Delirium was assessed until postoperative day 5. The primary analysis was the association between the minimum Scto2 and delirium using multivariable logistic regression controlled for confounders (age, OLV time, use of midazolam, occurrence of hypotension, and severity of pain). The secondary analysis was the association between cerebral desaturation/hypersaturation and delirium, and between the AUT/AAT and delirium using multivariable logistic regression controlled for the same confounders. Multiple testing was corrected using the Holm-Bonferroni method. We additionally monitored somatic tissue oxygen saturation on the forearm and upper thigh. RESULTS: Delirium occurred in 35 (20%) of 175 patients (65 ± 6 years old). The minimum left or right Scto2 was not associated with delirium. Cerebral desaturation defined by <90% baseline for left Scto2 (odds ratio [OR], 5.82; 95% confidence interval [CI], 2.12-19.2; corrected P =.008) and <85% baseline for right Scto2 (OR, 4.27; 95% CI, 1.77-11.0; corrected P =.01) was associated with an increased risk of delirium. Cerebral desaturation defined by other thresholds, cerebral hypersaturation, the AUT/AAT, and somatic desaturation and hypersaturation were all not associated with delirium. CONCLUSIONS: Cerebral desaturation defined by <90% baseline for left Scto2 and <85% baseline for right Scto2, but not the minimum Scto2, may be associated with an increased risk of postthoracotomy delirium. The validity of these thresholds needs to be tested by randomized controlled trials.


Assuntos
Circulação Cerebrovascular/fisiologia , Delírio/etiologia , Ventilação Monopulmonar/efeitos adversos , Complicações Cognitivas Pós-Operatórias/etiologia , Toracotomia/efeitos adversos , Idoso , Estudos de Coortes , Delírio/diagnóstico , Delírio/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ventilação Monopulmonar/tendências , Complicações Cognitivas Pós-Operatórias/diagnóstico , Complicações Cognitivas Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Toracotomia/tendências
18.
Curr Pain Headache Rep ; 25(5): 34, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33760993

RESUMO

PURPOSE OF REVIEW: Prevalence of chronic low back pain (cLBP) is increasing. Sacroiliac joint (SIJ) is a common source of cLBP, but data behind its diagnosis and treatment is controversial. There is moderate quality evidence for effectiveness of therapeutic SIJ injections. However, there are no studies comparing the two most common steroid preparations, methylprednisolone (MTP) and triamcinolone (TAC) in SIJ injections. RECENT FINDINGS: After institutional IRB approval, a retrospective chart review was conducted to evaluate the effectiveness of SIJ injections in terms of pain relief at 1-month follow-up and compare MTP versus TAC. All injections were performed by a single pain physician with fluoroscopic guidance. RESULTS: Sixty-five percent of patients in the MTP group and 57% patients in the TAC group had >50% pain relief at 1-month follow-up, with no statistical difference between the two groups. Patients in the TAC group had significantly greater BMI and consisted of higher proportion of smokers (72% patients in TAC group versus 39% patients in the MTP group, p-value 0.004). Other sources of pain such as facet joints were unmasked post-procedurally after SIJ injections, with this unmasking being significant for the TAC group. Opiate use decreased in the MTP group from 35% pre-procedurally to 20% post-procedurally, and this difference did not reach statistical significance. Both MTP and TAC are effective in providing pain relief for SIJ pain at 1-month follow-up, with no statistical difference between the two types of steroids. Although not statistically significant, there is a modest reduction in opiate use in the MTP group.


Assuntos
Dor Crônica/tratamento farmacológico , Glucocorticoides/uso terapêutico , Dor Lombar/tratamento farmacológico , Metilprednisolona/uso terapêutico , Articulação Sacroilíaca , Triancinolona/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Am J Otolaryngol ; 42(5): 103128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34216877

RESUMO

OBJECTIVES: Esophageal dilation (ED) may be performed in the office under local anesthesia or in a procedure/operating room under general anesthesia or intravenous (IV) sedation. However, indications for type of anesthesia during these procedures have not been established. The purpose of this review is to assess outcomes of esophageal dilation performed using different types of anesthesia to assess the safety of office-based techniques. METHODS: We conducted a systematic review and meta-analysis comparing the outcomes of anesthesia techniques for ED in adults. Exclusion criteria included reviews, small case series, use of stents, diagnoses with high morbidity, and rare diseases. A comprehensive literature search of the PubMed, CINAHL, and EMBASE databases was performed for articles relating to esophageal dilation. RESULTS: 876 papers were identified of which 164 full text studies were assessed and 25 were included in the analysis using the PRISMA guidelines. Data regarding demographics, dilation technique, and adverse events were extracted. The DerSimonian-Laird random-effect models with inverse-variance weighting were fit to estimate the combined effects. There were no statistically significant differences among mortality, perforation, or bleeding based on anesthetic. CONCLUSIONS: With office-based procedures gaining popularity in laryngology, there is a need to profile their safety. Office-based ED appears to have equivalent safety to general and IV sedation, although further research is necessary to define indications favoring office-based techniques.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Anestesia/efeitos adversos , Anestesia/métodos , Dilatação/efeitos adversos , Dilatação/métodos , Esôfago/cirurgia , Segurança , Anestesia Geral , Anestesia Local , Sedação Profunda , Feminino , Humanos , Masculino , Resultado do Tratamento
20.
Sensors (Basel) ; 21(18)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34577406

RESUMO

Compressive Sensing (CS) has proved to be an effective theory in the field of image acquisition. However, in order to distinguish the difference between the measurement matrices, the CS imaging system needs to have a higher signal sampling accuracy. At the same time, affected by the noise of the light path and the circuit, the measurements finally obtained are noisy, which directly affects the imaging quality. We propose a dual-optical imaging system that uses the bidirectional reflection characteristics of digital micromirror devices (DMD) to simultaneously acquire CS measurements and images under the same viewing angle. Since deep neural networks have powerful modeling capabilities, we trained the filter network and the reconstruction network separately. The filter network is used to filter the noise in the measurements, and the reconstruction network is used to reconstruct the CS image. Experiments have proved that the method we proposed can filter the noise in the sampling process of the CS system, and can significantly improve the quality of image reconstruction under a variety of algorithms.


Assuntos
Compressão de Dados , Processamento de Imagem Assistida por Computador , Algoritmos , Redes Neurais de Computação , Imagens de Fantasmas
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