RESUMEN
Objective: Coagulopathy score has been applied as a new prognostic indicator for sepsis, heart failure and acute respiratory failure. However, its ability to forecast intensive care unit (ICU) mortality in patients with an acute cerebral hemorrhage (ICH) has not been assessed. The purpose of this study was to clarify the relationship between ICU mortality and early coagulation problem score. Methods: Data from the Medical Information Mart for Intensive Care (MIMIC-IV) (v2.0) database were used in this retrospective cohort analysis. The association between the coagulation disorder score and ICU mortality was examined using multivariate logistic regression. Furthermore, the impact of additional variables on the results was investigated by a subgroup analysis. Results: 3174 patients (57.3 % male) were enrolled in total. The ICU mortality reached 18.2 %. After adjusting for potential confounders, the ICU mortality of patients rose with the increase of coagulation disorder score. The ROC curve revealed the predictive accuracy of coagulation dysfunction score to mortality in patients with ICU. The coagulation disorder score had a lower AUC value (0.601, P < 0.001) than the SAPSII(AUCs of 0.745[95 % CI, 0.730-0.761]) and the combined indicators(AUCs of 0.752[95 % CI, 0.737-0.767]), but larger than single indicators platelet, INR and APTT. In the subgroup analysis, most subgroups showed no significant interaction, but only age showed significant interaction in the adjusted model. Conclusion: The coagulopathy score and ICU mortality were found to be strongly positively correlated in this study, and its ability to predict ICU mortality was better than that of a single measure (platelet, INR, or APTT), but worse than that of the SAPSII score, GCS system.
RESUMEN
The colloidal borescope, using colloidal particle motion, is used to monitor the flow velocities and directions of groundwater. It integrates advanced techniques such as microscopy, high-speed photography, and big data computing and enjoys high sensitivity at the micron level. However, In the same well, the groundwater flow velocity monitored by colloidal hole mirror is varies greatly from that obtained by conventional hydrogeological monitoring, such as pumping test. In order to solve this problem, the stability catcher and stratified packer are designed to control the interference of the vertical flow in drilling, and to monitor the flow velocity and direction of groundwater velocity at the target aquifer and target fracture. Five wells with different aquifers and different groundwater types were selected for monitoring in south-central China. The instantaneous velocity and direction are converted into east-west component and north-south component, the average velocity and direction is calculated according to the time of 10 min, and the particle trajectory diagram is established. Based on these results, it proposed a concept of cumulative flow velocity. Using curve-fitting equations, the limits of cumulative flow velocities as the monitoring time tends to infinity were then calculated as the actual flow velocities of the groundwater. The permeability coefficient of aquifer is calculated by using the fissure ratio of aquifer, hydraulic slope and flow velocity, and compared with the permeability coefficient obtained by pumping test. The results are as follows: (1) The variation coefficient of the instantaneous flow velocity measured at the same depth in the same well at different times is greater than that of the time average flow velocity and greater than that of the cumulative flow velocity. The variation coefficient of the actual velocity is the smallest, indicating that the risk of using the actual flow velocity is lower. (2) The variation coefficient of the flow rate monitored at different depths in the same well is mainly controlled by the properties of the aquifer. The more uniform water storage space in the aquifer, the smaller the variation coefficient. (3) The comparison between the permeability coefficient obtained by monitoring and the permeability coefficient obtained by pumping test shows that the flow of structural fissure water controlled by planar fissure is more surface flow, and the results are consistent. When the groundwater flow is controlled by pores and solution gaps, the flow channel is complicated, which is easy to produce turbulent flow, and the result consistency is poor. (4) According to different research accuracy requirements, different monitoring and calculation methods can be selected for different aquifers and groundwater types. Researches show that, the permeability coefficient calculated for the actual flow velocity in well DR01 is the same as that calculated for the pumping test. The aquifer characteristics reflected by the coefficient of variation of the actual flow velocity in the same aquifer are more realistic. The pumping test method obtains the comprehensive parameters of a certain aquifer, and this method can be used to monitor a certain fissure. In this paper, the new technology developed for monitoring, and the new algorithm established for data processing, can accurately obtain the flow velocity and direction of groundwater, using capsule hole mirror monitoring method. The key parameters of hydrogeology can be obtained by using one well, which can reduce the time and cost input and improve the work efficiency.
RESUMEN
BACKGROUND: The purpose of this study was to analyze myopic regression after corneal refractive surgery (CRS) in civilian pilots and to explore the factors that may cause long-term myopic regression. METHODS: We included civilian pilots who had undergone CRS to correct their myopia and who had at least 5 years of follow-up. We collected retrospective data and completed eye examinations and a questionnaire to assess their eye habits. RESULTS: A total of 236 eyes were evaluated in this study. 211 eyes had Intrastromal ablations (167 eyes had laser in situ keratomileusis, LASIK, 44 eyes had small incision lenticule extraction, SMILE) and 25 eyes had subepithelial ablations (15 eyes had laser epithelial keratomileusis, LASEK and 10 eyes had photorefractive keratectomy, PRK). The mean preoperative spherical equivalent (SE) was - 2.92 ± 1.11 D (range from - 1.00 to -5.00 D). A total of 56 eyes (23.6%) suffered from myopic regression after CRS. Comparisons of individual and eye characteristics between the regression and non-regression groups revealed statistically significant differences in age, cumulative flight time, postoperative SE (at 6 months and current), uncorrected visual acuity (UCVA), accommodative amplitude (AA), positive relative accommodation (PRA), postoperative period, types of CRS and eye habits. Generalized propensity score weighting (GPSW) was used to balance the distribution of covariates among different age levels, types of CRS, cumulative flying time, postoperative period and continuous near-work time. The results of GPS weighted logistic regression demonstrated that the associations between age and myopic regression, types of CRS and myopic regression, continuous near-work time and myopic regression were significant. Cumulative flying time and myopic regression, postoperative period and myopic regression were no significant. Specifically, the odds ratio (OR) for age was 1.151 (P = 0.022), and the OR for type of CRS was 2.769 (P < 0.001). The OR for continuous near-work time was 0.635 with a P value of 0.038. CONCLUSIONS: This is the first report to analyze myopic regression after CRS in civilian pilots. Our study found that for each year increase in age, the risk of civilian pilots experiencing myopic regression was increased. Intrastromal ablations had a lower risk of long-term myopia regression than subepithelial ablations. There is a higher risk of myopic progression with continuous near-work time > 45 min and poor accommodative function may be related factors in this specific population.
Asunto(s)
Queratomileusis por Láser In Situ , Miopía , Queratectomía Fotorrefractiva , Humanos , Lactante , Estudios Retrospectivos , Córnea/cirugía , Queratectomía Fotorrefractiva/métodos , Agudeza Visual , Refracción Ocular , Queratomileusis por Láser In Situ/métodos , Láseres de Excímeros/uso terapéutico , Miopía/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Albumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, undergoing kidney replacement therapy, or experiencing complications of cirrhosis. STUDY DESIGN AND METHODS: Cochairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception through November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development, and Evaluation methodology. The guidelines were revised after public consultation. RESULTS: The panel made 14 recommendations on albumin use in adult critical care (three recommendations), pediatric critical care (one recommendation), neonatal critical care (two recommendations), cardiovascular surgery (two recommendations), kidney replacement therapy (one recommendation), and complications of cirrhosis (five recommendations). Of the 14 recommendations, two recommendations had moderate certainty of evidence, five recommendations had low certainty of evidence, and seven recommendations had very low certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin for patients with cirrhosis undergoing large-volume paracentesis or with spontaneous bacterial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide variety of clinical situations where albumin commonly is transfused. INTERPRETATION: Currently, few evidence-based indications support the routine use of albumin in clinical practice to improve patient outcomes. These guidelines provide clinicians with actionable recommendations on the use of albumin.
Asunto(s)
Albúminas , Humanos , Albúminas/administración & dosificación , Cirrosis Hepática/terapia , Cirrosis Hepática/complicaciones , Cuidados Críticos/normas , Cuidados Críticos/métodos , Medicina Transfusional , Terapia de Reemplazo Renal/métodos , Terapia de Reemplazo Renal/normas , Guías de Práctica Clínica como Asunto , Administración IntravenosaRESUMEN
Sickle cell disease (SCD) is a type of hemoglobinopathy due to an autosomal recessive genetic defect, causing significant red cell sickling, multi-organ damage and long-term severe morbidities. Due to its complicated care and the impact on quality of life, a curative treatment for SCD is highly desirable. In recent years, gene therapy is emerging as a curative option for SCD, where autologous haematopoietic stem cells are collected from SCD patients and genetically modified ex vivo to reduce its sickling tendency before reinfusion. Although still largely investigational, a limited number of gene therapy options have been recently granted approval for SCD patients. Published data are still currently limited, but early studies have so far demonstrated the intended outcomes of less vaso-occlusive crisis and haemolysis. Nonetheless, despite its curative potential, larger clinical trials and longer follow-up period are still necessary to evaluate the safety of this treatment option, especially the risk of unintended genetic modifications. Furthermore, SCD patients frequently have limited access to specialty care; hence, the issues of affordability and accessibility to SCD gene therapy must also be addressed for it to benefit the appropriate patient population.
Asunto(s)
Anemia de Células Falciformes , Terapia Genética , Anemia de Células Falciformes/terapia , Anemia de Células Falciformes/genética , Humanos , Terapia Genética/métodos , Trasplante de Células Madre Hematopoyéticas/métodosRESUMEN
Plants are associated with a large diversity of microbes, and these complex plant-associated microbial communities are critical for plant health. Welsh onion (Allium fistulosum L.) is one of the key and oldest vegetable crops cultivated in Taiwan. The leaf of the Welsh onion is one of the famous spices in Taiwanese cuisine, thus, it is crucial to control foliar diseases. In recent years, Welsh onion cultivation in Taiwan has been severely threatened by the occurrence of leaf blight disease, greatly affecting their yield and quality. However, the overall picture of microbiota associated with the Welsh onion plant is still not clear as most of the recent etiological investigations were heavily based on the isolation of microorganisms from diseased plants. Therefore, studying the diversity of fungal communities associated with the leaf blight symptoms of Welsh onion may provide information regarding key taxa possibly involved in the disease. Therefore, this investigation was mainly designed to understand the major fungal communities associated with leaf blight to identify key taxa potentially involved in the disease and further evaluate any shifts in both phyllosphere and rhizosphere mycobiome assembly due to foliar pathogen infection by amplicon sequencing targeting the Internal Transcribed Spacer (ITS) 1 region of the rRNA. The alpha and beta-diversity analyses were used to compare the fungal communities and significant fungal groups were recognized based on linear discriminant analyses. Based on the results of relative abundance data and co-occurrence networks in symptomatic plants we revealed that the leaf blight of Welsh onion in Sanxing, is a disease complex mainly involving Stemphylium and Colletotrichum taxa. In addition, genera such as Aspergillus, Athelia and Colletotrichum were abundantly found associated with the symptomatic rhizosphere. Alpha-diversity in some fields indicated a significant increase in species richness in the symptomatic phyllosphere compared to the asymptomatic phyllosphere. These results will broaden our knowledge of pathogens of Welsh onion associated with leaf blight symptoms and will assist in developing effective disease management strategies to control the progress of the disease.
RESUMEN
BACKGROUND AND OBJECTIVES: Solid organ transplant surgeries including liver transplants constitute a substantial risk of bleeding complications and given frequent national blood shortages, supporting D-negative transplant recipients with D-negative red blood cell products perioperatively can be difficult for the transfusion services. This study was designed to compare the incidence of alloimmunization after D-mismatched red cell transfusions between patients with and without a history of solid organ transplant at a single tertiary care hospital. The patients undergoing solid organ transplants are on strong immunosuppressive regimens perioperatively to help reduce the risk of rejection. We hypothesized that the use of these immunosuppressive agents makes these patients very less likely to mount an immune response and form anti-D antibodies when exposed to the D-positive red blood cell products perioperatively. STUDY DESIGN AND METHODS: At our center, D-negative patients who received ≥1 unit of D-positive red blood cell products were identified using historical transfusion records. Antibody testing results were examined to determine the incidence of the formation of anti-D and any other red cell alloantibodies after transfusion and these results were compared between patients with and without a history of solid organ transplant. RESULTS: We were able to identify a total of 22 patients over 10 years with D-negative phenotype who had undergone a solid organ transplant and had received D-positive red blood cell products during the transplant surgeries. We also identified a second group of 54 patients with D-negative phenotype who had received D-positive red blood cell products for other indications including medical and surgical. A comparison of the data showed no new anti-D formation among patients with a history of D mismatched transfusion during solid organ transplant surgeries. CONCLUSION: Among our limited study population, we observed a very low likelihood of D alloimmunization among solid organ transplant recipients. A larger, prospective study could help further evaluate the need for prophylactic D matching for red cell transfusions during solid organ transplant surgeries.
Asunto(s)
Transfusión Sanguínea , Trasplante de Órganos , Globulina Inmune rho(D) , Humanos , Estudios Prospectivos , Incidencia , Eritrocitos , IsoanticuerposRESUMEN
OBJECTIVES: To observe the effects of zhongfeng cutong moxibustion (moxibustion therapy for unblocking and treating stroke) on the motor function and the structure of corticospinal tract (CST) in the patients with motor dysfunction during the recovery period of cerebral infarction, and to explore the central mechanism of this moxibustion therapy for improving the motor function. METHODS: Fifty patients with motor dysfunction during the recovery period of cerebral infarction were randomly divided into an observation group (25 cases, 1 case dropped out) and a control group (25 cases, 1 case dropped out). The patients in both groups underwent the conventional basic treatment. In the control group, acupuncture was applied to Baihui (GV 20) and Shuigou (GV 26), as well as Chize (LU 5), Neiguan (PC 6), Weizhong (BL 40) and Sanyinjiao (SP 6) etc. on the affected side. Besides the intervention of the control group, in the observation group, zhongfeng cutong moxibustion therapy was combined at Baihui (GV 20), Shenque (CV 8) and bilateral Zusanli (ST 36). Both acupuncture and moxibustion therapies were delivered once daily, 5 times a week, for 2 weeks. The scores of Fugl-Meyer assessment scale (FMA) and National Institutes of Health stroke scale (NIHSS) were compared between the two groups before and after treatment. The diffusion tensor imaging technique was used to observe the fractional anisotropy (FA) of CST at the bilateral whole segment, the cerebral cortex, the posterior limb of the internal capsule and the cerebral peduncle before and after treatment in the two groups. RESULTS: The scores of the upper and the lower limbs of FMA, as well as the total FMA score swere increased after treatment when compared with those before treatment in the two groups (P<0.05), the upper limb FMA score and the total FMA score in the observation group were higher than those in the control group (P<0.05), and NIHSS scores of the two groups were dropped compared with those before treatment (P<0.01). FA of CST at the bilateral sides of the posterior limb of the internal capsule and the whole segment on the focal side was improved in comparison with that before treatment in the observation group (P<0.05), and FA of CST at the healthy side of the whole segment was higher than that before treatment in the control group (P<0.05). CONCLUSIONS: Zhongfeng cutong moxibustion improves motor function and reduces neurological deficits in the patients with motor dysfunction during the recovery period of cerebral infarction, which may be related to enhancing the remodeling of white matter fiber bundles in the corticospinal tract on the focal side of the whole segment and the bilateral posterior limb of the internal capsule.
Asunto(s)
Terapia por Acupuntura , Moxibustión , Accidente Cerebrovascular , Humanos , Tractos Piramidales , Imagen de Difusión Tensora , Infarto Cerebral/terapia , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Puntos de Acupuntura , Resultado del TratamientoRESUMEN
Objective: Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of neonatal hyperbilirubinemia. The aim of this study is to evaluate the risk factors associated with hyperbilirubinemia in infants from the western part of Guangdong Province, and to assess the contribution of G6PD deficiency to neonatal jaundice. Methods: The term infants with neonatal hyperbilirubinemia in People's Hospital of Yangjiang from June 2018 to July 2022 were recruited for the retrospective analysis. All the infants underwent quantitative detection of the G6PD enzyme. The etiology was determined through laboratory tests and clinical manifestations. Results: Out of 1,119 term infants, 435 cases presented with jaundice. For the etiology analysis, infection was responsible for 16.09% (70/435), G6PD deficiency accounted for 9.66% (42/435), of which 3 were complicated with acute bilirubin encephalopathy), bleeding accounted for 8.05% (35/435), hemolytic diseases accounted for 3.45% (15/435), and breast milk jaundice accounted for 2.53% (11/435). One case (0.23%) was attributed to congenital hypothyroidism, multiple etiologies accounted for 22.3% (97/435), and 35.63% (155/435) were of unknown etiology. Of the jaundiced infants, 19.54% (85/435) had G6PD deficiency, while only 10.23% (70/684) of non-jaundiced infants had G6PD deficiency; this difference was found to be statistically significant (P < 0.001). Furthermore, the hemoglobin levels in the jaundiced infants with G6PD deficiency (146.85 ± 24.88â g/L) were lower than those without G6PD deficiency (156.30 ± 22.07â g/L) (P = 0.001). 65 jaundiced infants with G6PD deficiency underwent G6PD mutation testing, and six different genotypes were identified, including c.95A > G, c.392G > T, c.1024C > T, c.1311C > T, c.1376G > T, c.1388G > A, c.871G > A/c.1311C > T, c.392G > T/c.1388G > A, and c.1376G > T/c.1311C > T.65iciency. Conclusion: In newborns in Yangjiang, G6PD deficiency, infection, and neonatal hemolytic disease were identified as the main causes of hyperbilirubinemia and acute bilirubin encephalopathy. Specifically, Hemolytic factors in infants with G6PD deficiency may lead to reduced hemoglobin and increased bilirubin levels in jaundiced infants.
RESUMEN
BACKGROUND: The Association for the Advancement of Blood and Biotherapies Clinical Transfusion Medicine Committee (CTMC) composes a summary of new and important advances in transfusion medicine (TM) on an annual basis. Since 2018, this has been assembled into a manuscript and published in Transfusion. STUDY DESIGN AND METHODS: CTMC members selected original manuscripts relevant to TM that were published electronically and/or in print during calendar year 2022. Papers were selected based on perceived importance and/or originality. References for selected papers were made available to CTMC members to provide feedback. Members were also encouraged to identify papers that may have been omitted initially. They then worked in groups of two to three to write a summary for each new publication within their broader topic. Each topic summary was then reviewed and edited by two separate committee members. The final manuscript was assembled by the first and senior authors. While this review is extensive, it is not a systematic review and some publications considered important by readers may have been excluded. RESULTS: For calendar year 2022, summaries of key publications were assembled for the following broader topics within TM: blood component therapy; infectious diseases, blood donor testing, and collections; patient blood management; immunohematology and genomics; hemostasis; hemoglobinopathies; apheresis and cell therapy; pediatrics; and health care disparities, diversity, equity, and inclusion. DISCUSSION: This Committee Report reviews and summarizes important publications and advances in TM published during calendar year 2022, and maybe a useful educational tool.
RESUMEN
Objective: To analyze the clinical characteristics of neonatal infection during the outbreak of COVID-19 omicron variant in Guangdong province of China. Method: The clinical data of neonates infected with COVID-19 omicron variant were collected from three hospitals of Guangdong province, their epidemiological history, clinical manifestation and prognosis were summarized. Results: From December 12, 2022 to January 15, 2023, a total of 52 neonates with COVID-19 infection were identified across three hospitals in Guangdong Province, including 34 males and 18 females. The age of diagnosis was 18.42 ± 6.32 days. 24 cases had clear contact history with adults who were suspected to be infected with COVID-19. The most common clinical manifestation was fever (43/52, 82.7%), the duration of fever was 1-8 days. The other clinical manifestations were cough (27/52, 51.9%), rales (21/52, 40.4%), nasal congestion (10/52, 19.2%), shortness of breath (2/52, 3.8%), and vomiting (4/52, 7.7%). C-reactive protein was only increased in 3 cases. Chest radiological examination was performed in 42 neonates, twenty-three cases showed abnormal chest radiographic findings, including ground-glass opacity and consolidation. Fifty cases were admitted with COVID-19 presentation, two cases were admitted for jaundice. The hospital stay was 6.59 ± 2.77 days. The clinical classification included 3 cases of severe COVID-19 and one critical case. Fifty-one cases were cured and discharged after general treatment, and one critical case with respiratory failure was intubated and transferred to another hospital. Conclusion: The COVID-19 omicron variant infection in neonates is usually mild. The clinical manifestation and laboratory results are not specific, and the short-term prognosis is good.
RESUMEN
BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is an underrecognized and emerging infectious disease that may threaten the safety of donor blood supply in many parts of the world. We sought to elucidate whether our local community blood supply is at increased susceptibility for transmission of transfusion-associated HEV infections. MATERIALS AND METHODS: We screened 10,002 randomly selected donations over an 8-month period between 2017 and 2018 at the Stanford Blood Center for markers of HEV infection using commercial IgM/IgG serological tests and reverse transcriptase quantitative polymerase chain reaction assays (RT-qPCR). Donor demographic information, including gender, age, self-identified ethnicity, location of residence and recent travel, were obtained from the donor database and used to generate multivariate binary logistic regressions for risk factors of IgG seropositivity. RESULTS: A total of 10,002 blood donations from 7507 unique donors were screened, and there was no detectable HEV RNA by RT-qPCR. The overall seropositivity rate was 12.1% for IgG and 0.56% for IgM. Multivariate analysis of unique donors revealed a significantly higher risk of IgG seropositivity with increasing age, White/Asian ethnicities and residence in certain local counties. CONCLUSION: Although HEV IgG seroprevalence in the San Francisco Bay Area is consistent with ongoing infection, the screening of a large donor population did not identify any viraemic blood donors. While HEV is an underrecognized and emerging infection in other regions, there is no evidence to support routine blood screening for HEV in our local blood supply currently; however, periodic monitoring may still be required to assess the ongoing risk.
Asunto(s)
Virus de la Hepatitis E , Hepatitis E , Humanos , Donantes de Sangre , Anticuerpos Antihepatitis , Hepatitis E/epidemiología , Virus de la Hepatitis E/genética , Inmunoglobulina G , Inmunoglobulina M , ARN Viral , Estudios Seroepidemiológicos , Masculino , FemeninoRESUMEN
Maternal exposure to dibutyl phthalate (DBP) induces renal fibrosis in offspring. However, the specific roles of connexin 43 (Cx43) in DBP-induced renal fibrosis remain unknown. Therefore, in this study, we analysed the expression of Cx43 in renal tubular epithelial cells (RTECs) with or without DBP exposure using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. A small interfering RNA against Cx43 was introduced to assess its role in epithelial-mesenchymal transition (EMT) of RTECs caused by 100 µmol/L DBP. Bioinformatics analysis was conducted with AMP-activated protein kinase (AMPK)-α2 and angiotensin (Ang) II inhibitors to determine the mechanisms involved in the expression of Cx43 in HK-2 cells. RT-qPCR and western blotting revealed that DBP increased the expression of Cx43 in vitro. Moreover, Cx43 knockdown significantly alleviated DBP-induced EMT caused by DBP in HK-2 cells. Bioinformatics analysis with AMPKα2 and Ang II inhibitors revealed that DBP upregulated Cx43 expression by activating the Ang II/AMPKα2 signaling pathway. Our findings indicate that DBP induces renal fibrosis by activating Ang II/AMPKα2/Cx43 signaling pathway and EMT in RETCs, suggesting a potential target for the treatment of renal fibrosis.
Asunto(s)
Dibutil Ftalato , Transición Epitelial-Mesenquimal , Humanos , Femenino , Dibutil Ftalato/toxicidad , Conexina 43/genética , Conexina 43/metabolismo , Transducción de Señal , Células Epiteliales/metabolismo , FibrosisRESUMEN
OBJECTIVE: Resolvin D1 (RvD1) has anti-inflammatory properties and may be neuroprotective. This study was designed to assess usability of serum RvD1 as a prognostic biomarker after intracerebral hemorrhage (ICH). METHODS: In this prospective, observational study of 135 patients and 135 controls, serum RvD1 levels were measured. Its relations to severity, early neurologic deterioration (END) and poststroke 6-month worse outcome (modified Rankin Scale scores of 3-6) were determined via multivariate analysis. Predictive effectiveness was evaluated based on area under receiver operating characteristic curve (AUC). RESULTS: Patients had markedly lower serum RvD1 levels than controls (median, 0.69 ng/ml versus 2.15 ng/ml). Serum RvD1 levels were independently correlated with the National Institutes of Health Stroke Scale (NIHSS) [ß, -0.036; 95 % confidence interval (CI), -0.060--0.013; VIF, 2.633; t = -3.025; P = 0.003] and hematoma volume (ß, -0.019; 95 % CI, -0.056--0.009; VIF, 1.688; t = -2.703; P = 0.008). Serum RvD1 levels substantially discriminated risks of END and worse outcome with AUCs at 0.762 (95 % CI, 0.681-0.831) and 0.783 (95 % CI, 0.704-0.850) respectively. A RvD1 cut-off value of 0.85 ng/ml was effective in predicting END with a sensitivity of 95.0 % and specificity of 48.4 % and its levels <0.77 ng/ml distinguished patients at risk of worse outcome with a sensitivity of 84.5 % and specificity of 63.6 %. Under restricted cubic spline, serum RvD1 levels were linearly related to risk of END and worse outcome (both P > 0.05). Serum RvD1 levels and NIHSS scores independently predicted END with odds ratio (OR) values of 0.082 (95 % CI, 0.010-0.687) and 1.280 (95 % CI, 1.084-1.513) respectively. Serum RvD1 levels (OR, 0.075; 95 % CI, 0.011-0.521), hematoma volume (OR, 1.084; 95 % CI, 1.035-1.135) and NIHSS scores (OR, 1.240; 95 % CI, 1.060-1.452) were independently associated with worse outcome. END prediction model containing serum RvD1 levels and NIHSS scores, and prognostic prediction model containing serum RvD1 levels, hematoma volumes and NIHSS scores displayed efficient predictive ability with AUCs at 0.828 (95 % CI, 0.754-0.888) and 0.873 (95 % CI, 0.805-0.924) respectively. Such two models were visually shown via building two nomograms. Using Hosmer-Lemeshow test, calibration curve and decision curve, the models were comparatively stable and had clinical benefit. CONCLUSION: There is a dramatical declination of serum RvD1 levels after ICH, which is tightly related to stroke severity and is independently predictive of poor clinical outcome, implying that serum RvD1 may be of clinical significance as a prognostic marker of ICH.
Asunto(s)
Hemorragia Cerebral , Accidente Cerebrovascular , Humanos , Pronóstico , Estudios Prospectivos , Estudios Longitudinales , Hemorragia Cerebral/diagnóstico , Accidente Cerebrovascular/diagnóstico , HematomaRESUMEN
The stem cell factor (SCF) binds to c-Kit in endothelial cells, thus activating downstream signaling and angiogenesis. Herein, we examined the role of G protein subunit alpha inhibitory (Gαi) proteins in this process. In MEFs and HUVECs, Gαi1/3 was associated with SCF-activated c-Kit, promoting c-Kit endocytosis, and binding of key adaptor proteins, subsequently transducing downstream signaling. SCF-induced Akt-mTOR and Erk activation was robustly attenuated by Gαi1/3 silencing or knockout (KO), or due to dominant negative mutations but was strengthened substantially following ectopic overexpression of Gαi1/3. SCF-induced HUVEC proliferation, migration, and capillary tube formation were suppressed after Gαi1/3 silencing or KO, or due to dominant negative mutations. In vivo, endothelial knockdown of Gαi1/3 by intravitreous injection of endothelial-specific shRNA adeno-associated virus (AAV) potently reduced SCF-induced signaling and retinal angiogenesis in mice. Moreover, mRNA and protein expressions of SCF increased significantly in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. SCF silencing, through intravitreous injection of SCF shRNA AAV, inhibited pathological retinal angiogenesis and degeneration of retinal ganglion cells in DR mice. Finally, the expression of SCF and c-Kit increased in proliferative retinal tissues of human patients with proliferative DR. Taken together, Gαi1/3 mediate SCF/c-Kit-activated signaling and angiogenesis.
Asunto(s)
Células Endoteliales , Transducción de Señal , Animales , Humanos , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Células Endoteliales/metabolismo , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , ARN Interferente Pequeño/metabolismo , Transducción de Señal/genética , Factor de Células Madre/genética , Factor de Células Madre/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismoRESUMEN
BACKGROUND: The clinical significance of serologic reactivity of unidentified specificity (SRUS) in pregnancy is not clear based on available literature. The aim of this study is to determine if SRUS is associated with hemolytic disease of the fetus and newborn (HDFN). STUDY DESIGN AND METHODS: Retrospective data were collected from eight institutions over an 11-year study period (2010-2020), when available (5/8 sites). The outcome of the pregnancies with SRUS-no, mild, moderate, or severe HDFN-was determined. RESULTS: SRUS was demonstrated in 589 pregnancies. After excluding those with incomplete data, a total of 284 pregnancies were included in the primary HDFN outcome analysis. SRUS was detected in 124 (44%) pregnancies in isolation, and none were affected by HDFN. Of 41 pregnancies with SRUS and ABO incompatibility, 37 (90%) were unaffected, and 4 (10%) were associated with mild HDFN. Of 98 pregnancies with SRUS and concurrent identifiable antibody reactivity(s), 80 (81%) were unaffected, and 19 (19%) were associated with mild to severe HDFN. There was 1 case of mild HDFN and 1 case of severe HDFN in the 21 pregnancies with SRUS, ABO incompatibility, and concurrent identifiable antibody reactivity(s), and 19 (90%) were unaffected by HDFN. Among all patients with repeat testing, newly identified alloantibodies or other antibodies were identified in 63 of 212 (30%) patients. Although most were not clinically significant, on occasion SRUS preceded clinically significant antibody(s) associated with HDFN (3%, 5/188). CONCLUSION: The antenatal serologic finding of SRUS in isolation is not associated with HDFN but may precede clinically significant antibodies.
Asunto(s)
Antígenos de Grupos Sanguíneos , Eritroblastosis Fetal , Recién Nacido , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Eritroblastosis Fetal/diagnóstico , Isoanticuerpos , FetoRESUMEN
BACKGROUND: Grafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past. But it has seemed to remain controversial in the last decade, as a result of modified clinical protocols, selected recipients, and advanced technology of organ perfusion and preservation. The present study aimed to examine the impact of older donor age on complications and survival of liver transplant using grafts from donation after circulatory death (DCD). METHODS: A total of 944 patients who received DCD liver transplantation from 2015 to 2020 were included and divided into two groups: using graft from older donor (aged ≥ 65 years, n = 87) and younger donor (age < 65 years, n = 857). Propensity score matching (PSM) was applied to eliminate selection bias. RESULTS: A progressively increased proportion of liver transplants with grafts from older donors was observed from 1.68% to 15.44% during the study period. The well-balanced older donor (n = 79) and younger donor (n = 79) were 1:1 matched. There were significantly more episodes of biliary non-anastomotic stricture (NAS) in the older donor group than the younger donor group [15/79 (19.0%) vs. 6/79 (7.6%); P = 0.017]. The difference did not reach statistical significance regarding early allograft dysfunction (EAD) and primary non-function (PNF). Older livers had a trend toward inferior 1-, 2-, 3-year graft and overall survival compared with younger livers, but these differences were not statistically significant (63.1%, 57.6%, 57.6% vs. 76.9%, 70.2%, 67.7%, P = 0.112; 64.4%, 58.6%, 58.6% vs. 76.9%, 72.2%, 72.2%, P = 0.064). The only risk factor for poor survival was ABO incompatible transplant (P = 0.008) in the older donor group. In the subgroup of ABO incompatible cases, it demonstrated a significant difference in the rate of NAS between the older donor group and the younger donor group [6/8 (75.0%) vs. 3/14 (21.4%); P = 0.014]. CONCLUSIONS: Transplants with grafts from older donors (aged ≥ 65 years) after circulatory death are more frequently associated with inferior outcome compared to those from younger donors. Older grafts from DCD are more likely to develop NAS, especially in ABO incompatible cases.
Asunto(s)
Trasplante de Hígado , Obtención de Tejidos y Órganos , Humanos , Incidencia , Supervivencia de Injerto , Hígado , Donantes de Tejidos , Trasplante de Hígado/métodos , Estudios Retrospectivos , Muerte , Muerte EncefálicaRESUMEN
The shallow-water hydrothermal vent system of Kueishan Island has been described as one of the world's most acidic and sulfide-rich marine habitats. The only recorded metazoan species living in the direct vicinity of the vents is Xenograpsus testudinatus, a brachyuran crab endemic to marine sulfide-rich vent systems. Despite the toxicity of hydrogen sulfide, X. testudinatus occupies an ecological niche in a sulfide-rich habitat, with the underlying detoxification mechanism remaining unknown. Using laboratory and field-based experiments, we characterized the gills of X. testudinatus that are the major site of sulfide detoxification. Here sulfide is oxidized to thiosulfate or bound to hypotaurine to generate the less toxic thiotaurine. Biochemical and molecular analyses demonstrated that the accumulation of thiosulfate and hypotaurine is mediated by the sodium-independent sulfate anion transporter (SLC26A11) and taurine transporter (Taut), which are expressed in gill epithelia. Histological and metagenomic analyses of gill tissues demonstrated a distinct bacterial signature dominated by Epsilonproteobacteria. Our results suggest that thiotaurine synthesized in gills is used by sulfide-oxidizing endo-symbiotic bacteria, creating an effective sulfide-buffering system. This work identified physiological mechanisms involving host-microbe interactions that support life of a metazoan in one of the most extreme environments on our planet.
Asunto(s)
Braquiuros , Respiraderos Hidrotermales , Animales , Tiosulfatos , Sulfuros/toxicidad , Braquiuros/fisiología , BacteriasRESUMEN
Therapeutic plasma exchange (TPE) has traditionally been used to selectively remove pathologic contents including autoantibodies, abnormal proteins, immune complexes, or toxins from a patient's plasma. In addition to the removal of molecular contributors to disease, fluid replacement and infusion of beneficial plasma constituents including albumin can be tapered based on the pathophysiologic mechanisms of the offending disease. This treatment modality has shown efficacy in symptomatic relief and slowing of disease progression for various neurologic, immunologic, and hematologic diseases. This review outlines the rationale for TPE in the treatment of Alzheimer's Disease (AD) through a potential mechanism leveraging the concentration gradient of amyloid ß peptides and the infusion of albumin, and critically reviews the clinical evidence for treatment of AD using TPE and albumin replacement. This review also highlights potential sources of bias that must be considered in conjunction with the evidence of efficacy for the use of TPE in AD.
Asunto(s)
Enfermedad de Alzheimer , Intercambio Plasmático , Humanos , Albúminas/uso terapéutico , Enfermedad de Alzheimer/terapia , Péptidos beta-Amiloides/metabolismo , PlasmaféresisRESUMEN
STUDY DESIGN: Cross-sectional study. OBJECTIVE: Recently, there has been a rise in children and adolescents developing low back pain and/or sciatica. Degenerative lumbar spine MRI phenotypes can occur in this population but reports have been sporadic and the true incidence of such spine changes remains debatable. As such, the study aimed to address the epidemiology of MRI phenotypes of the lumbar spine in this young population. METHODS: 597 children and adolescents with lumbar MRIs were included in the study. T1- and T2-weighted lumbar images from L1/2 to L5/S1 were analyzed in axial and sagittal planes. Global phenotype assessment was performed of each level and based on established nomenclature protocols. RESULTS: The cohort consisted of 57.3% (342) boys and 42.7% (255) girls, with a mean age of 10.75 ± 5.25 years (range: 0 to 18 years). The prevalence of imaging findings of lumbar disc degeneration (LDD) and lumbar disc herniation (LDH) were 2.2% (95% CI: 0.93-3.43) and 5.8% (95%CI: 2.58-8.99), respectively. There was significant difference between each disc segment from L1/2 to L5/S1 for both LDD and LDH. Schmorl's nodes were noted in 16 cases (2.7%, youngest case as 15 years), with 11 boys (68.8%) and most frequent segment as L3/4. Modic changes and high-intensity zones were absent in this cohort. CONCLUSIONS: LDD can emerge as early as the first decade of life with Schmorl's nodes, without additional specific phenotypes, including Modic changes and high-intensity zones. The study provides valuable information of a unique age group that is often under-represented but equally important as adults.