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BackgroundBetter understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. MethodsImmunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1,164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. FindingsThe median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age [≥] 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63-4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. InterpretationIntegration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. FundingNIH RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe did a systematic search of the PubMed database from January 1st, 2020 until April 24th, 2022 using the search terms: "hospitalized" AND "SARS-CoV-2" OR "COVID-19" AND "Pro-spective" AND "Antibody" OR "PCR" OR "long term follow up" and applying the following filters: "Multicenter Study" AND "Observational Study". No language restrictions were applied. While clinical, laboratory, and radiographic features associated with severe COVID-19 in hospitalized adults have been described, description of the kinetics of SARS-CoV-2 specific assays available to clinicians (e.g. PCR and binding antibody) and their integration with other variables is scarce for both short and long term follow up. The current literature is comprised of several studies with small sample size, cross-sectional design with laboratory data typically only recorded at a single point in time (e.g., on admission), limited clinical characteristics, variable duration of follow up, single-center setting, retrospective analyses, kinetics of either PCR or antibody testing but not both, and outcomes such as death or, mechanical ventilation that do not allow delineation of variations in clinical course. Added value of this studyIn our large longitudinal multicenter cohort, the description of outcome severity, was not limited to survival versus death, but encompassed a clinical trajectory approach leveraging longitudinal data based on time in hospital, disease severity by ordinal scale based on degree of respiratory illness, and presence or absence of limitations at discharge. Fatal COVID-19 cases had the lowest ratio of antibody to viral load levels over time as compared to non-fatal cases. Integration of PCR cycle threshold and antibody values with demographics, baseline comorbidities, and laboratory/radiographic findings identified additional risk factors for outcome severity over the first 28 days. However, female sex was the only variable associated with persistence of symptoms over time. Persistence of symptoms was not associated with clinical trajectory over the first 28 days, nor with antibody/viral loads from the acute phase. Implications of all the available evidenceThe described calculated ratio (binding IgG/PCR Ct value) is unique compared to other studies, reflecting host pathogen interactions and representing an accessible approach for patient risk stratification. Integration of SARS-CoV-2 viral load and binding antibody kinetics with other laboratory as well as clinical characteristics in hospitalized COVID-19 patients can identify patients likely to have the most severe short-term outcomes, but is not predictive of symptom persistence at one year post-discharge.
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Objective To investigate the prompt value of abnormal vaginal morphology on diagnosing pelvic organ prolapse . Methods Forty eight pelvic organ prolapse female patients diagnosed by pelvic organ prolapse quantification were enrolled in the pelvic organ prolapse group and 51 normal female volunteers were enrolled in the control group in this study. Pelvic MRI T2WI were performed in all cases. The vaginal shape were evaluated according to Delancey Ⅱ level on the transverse images, which were divided into two categories:normal morphology (H-shaped) and abnormal morphology(non H-shaped). The vaginal shape distribution of different prolapse degree(0,Ⅰ,Ⅱ,Ⅲ,Ⅳstage) and types(anterior,middle, posterior pelvic prolapse) were recorded. Chi-square test was used to analyse distribution difference of vaginal shape between the two groups. The ROC curve was used to analyse the diagnostic efficiency of abnormal vaginal morphology for diagnosing pelvic organ prolapse. Results In the control group, there were 40 cases with normal vaginal morphology and 11 cases with abnormal morphology mainly including W-shaped and U-shaped abnormal morphology. In the prolapse group, there were 5 cases with normal vaginal morphology and 43 cases with abnormal morphologymainly including U-shaped (13 cases), W-shaped (26 cases) and O-shaped(4 cases) abnormal morphology. There was significant difference between the two groups(c2=46.137,P<0.01). The area under the curve (AUC) was 0.800. The sensitivity and specificity of abnormal vaginal shape for diagnosing pelvic organ prolapse were 89.6% and 78.4%respectively.The distribution of vaginal morphology in different degrees and types of prolapse were different:vaginal morphology of 0 stage prolapse showed H-typed mainly (40/51, 78.4%), Ⅰ stage prolapse showed W-shaped (16/28 57.1%), Ⅱ,Ⅲ stage prolapse all showed non H-shaped (20/20, 100%), Ⅱstage mainly showed W-shaped (9/14), Ⅲ stage mainly showed O-shaped (3/6). Anterior pelvic organ prolapse were manifested mainly with W-shaped vaginal morphology (4/9) and middle pelvic organ prolapse mainly showed O-shaped vaginal morphology (4/7). Conclusions The abnormal vaginal morphology has the prompt value on diagnosing pelvic organ prolapse.Moreover, the different shape probably indicates the different degrees and types of pelvic organ prolapse.
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Objective To investigate MR T2-mapping in evaluating birth-related levator ani muscle injury.Methods 25 primiparas at 6 weeks after first vaginal delivery as primiparous group and 12 nulliparous volunteers as control group were prospectively studied. All the subjects underwent pelvic MRI including T2-mapping,mDIXON-T2 WI sequences.Levator ani muscle were divided into two subgroups:levator ani muscle injury group and non-injury group according to if there were edema,avulsion,or rupture in each levator ani muscle subdivisions[puborectal muscle(PRM);iliococcygeal muscle(ICM)],which were showed on mDIXON-T2 WI images.Two radiologists evaluated T2 values of PRM,ICM and observed artificial color images respectively.The consistency between two observers for T2 values of PRM,ICM were evaluated using the intraclass correlation coefficient (ICC ),the difference of T2 values in each levator ani muscle subdivisions among control group,non-injury group and muscle injury group were analyzed using ANOVA .Results There were 26 PRM injury cases and 24 non-injury cases in primiparous group on mDIXON-T2 WI images,and no ICM injured cases in our study.Inter-rater reliability for T2 values between two observers were good(ICC >0.75).T2 values in PRM injury group,non-injury group and control group were(62.78±1.23)ms,(49.75±3.17)ms,(49.96±4.37)ms respectively and the difference was significant. There were significant difference between PRM injury group and non-injury group,control group respectively(P =0.000,P =0.000). The T2 values of ICM in PRM injury group,non-injury group and control group were(70.80±6.50)ms,(62.41±7.32)ms,(62.78±6.91)ms and there were significant difference(P =0.000),meanwhile the difference between PRM injury group and non-injury group,control group were significant respectively(P =0.000,P =0.000).The color gradation of PRM in PRM injury group were mixed with blue, green,and yellow,and tone were lightened on T2-mapping artificial color images;ICM color gradation were uneven with green and yellow, a d tone were higher than those of control group and non-injurygroup.Conclusion T2-mapping can quantitatively assess birth-related levator ani muscle injury and T2-mapping artificial color images show the range and degree of levator ani muscle injury visually.It is hopeful to find micro lesions that T2 WI images are difficult to find.
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Objective To investigate MR T2-mapping in evaluating birth-related levator ani muscle injury.Methods 25 primiparas at 6 weeks after first vaginal delivery as primiparous group and 12 nulliparous volunteers as control group were prospectively studied. All the subjects underwent pelvic MRI including T2-mapping,mDIXON-T2 WI sequences.Levator ani muscle were divided into two subgroups:levator ani muscle injury group and non-injury group according to if there were edema,avulsion,or rupture in each levator ani muscle subdivisions[puborectal muscle(PRM);iliococcygeal muscle(ICM)],which were showed on mDIXON-T2 WI images.Two radiologists evaluated T2 values of PRM,ICM and observed artificial color images respectively.The consistency between two observers for T2 values of PRM,ICM were evaluated using the intraclass correlation coefficient (ICC ),the difference of T2 values in each levator ani muscle subdivisions among control group,non-injury group and muscle injury group were analyzed using ANOVA .Results There were 26 PRM injury cases and 24 non-injury cases in primiparous group on mDIXON-T2 WI images,and no ICM injured cases in our study.Inter-rater reliability for T2 values between two observers were good(ICC >0.75).T2 values in PRM injury group,non-injury group and control group were(62.78±1.23)ms,(49.75±3.17)ms,(49.96±4.37)ms respectively and the difference was significant. There were significant difference between PRM injury group and non-injury group,control group respectively(P =0.000,P =0.000). The T2 values of ICM in PRM injury group,non-injury group and control group were(70.80±6.50)ms,(62.41±7.32)ms,(62.78±6.91)ms and there were significant difference(P =0.000),meanwhile the difference between PRM injury group and non-injury group,control group were significant respectively(P =0.000,P =0.000).The color gradation of PRM in PRM injury group were mixed with blue, green,and yellow,and tone were lightened on T2-mapping artificial color images;ICM color gradation were uneven with green and yellow, a d tone were higher than those of control group and non-injurygroup.Conclusion T2-mapping can quantitatively assess birth-related levator ani muscle injury and T2-mapping artificial color images show the range and degree of levator ani muscle injury visually.It is hopeful to find micro lesions that T2 WI images are difficult to find.
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Malic acid is a dicarboxylic acid that is widely used in food, pharmaceutical and chemical industries. We studied the effects of overexpression of carboxylation pathway genes and inactivation of malic enzymes on the aerobic production of malic acid. Over expression of phosphoenolpyruvate (PEP) carboxylase (ppc) generated strain E21, which increased malic acid production from 0.57 g/L to 3.83 g/L. Then pyc gene from Coryenbacterium glutamicus and pck gene from Actinobacillus succinogenes were overexpressed in E21 separately. The resulting strains E21 (pTrcpyc) and E21 (pTrc-A-pck) produced 6.04 and 5.01 g/L malate with a yield of 0.79 and 0.65 mol/mol glucose, respectively. Deleting two malic enzymes (encoded by maeA and maeB) also led to an increase of 36% in malic acid production with a production of 5.21 g/L. However, the combination of malic enzymes deletion and pyc overexpression could not further increase the yield of malic acid. After optimization of fermentation conditions, strain E21 (pTrcpyc) produced 12.45 g/L malic acid with a yield of 0.84 mol/mol which is 63.2% of the theoretical yield.
