Development of a computed tomography-based radiomics nomogram for prediction of transarterial chemoembolization refractoriness in hepatocellular carcinoma

BACKGROUND Some patients with hepatocellular carcinoma(HCC)are more likely to experience disease progression despite continuous transarterial chemoembolization(TACE),which is called TACE refractoriness.At present,it is still difficult to predict TACE refractoriness,although some models/scoring systems have been developed.At present,radiological-based radiomics models have been successfully applied to predict cancer patient prognosis.AIM To develop and validate a computed tomography(CT)-based radiomics nomogram for the pre-treatment prediction of TACE refractoriness.METHODS This retrospective study consisted of a training dataset(n=137)and an external validation dataset(n=81)of patients with clinically/pathologically confirmed HCC who underwent repeated TACE from March 2009 to March 2016.Radiomics features were retrospectively extracted from preoperative CT images of the arterial phase.The pre-treatment radiomics signature was generated using least absolute shrinkage and selection operator Cox regression analysis.A CT-based radiomics nomogram incorporating clinical risk factors and the radiomics signature was built and verified by calibration curve and decision curve analyses.The usefulness of the CT-based radiomics nomogram was assessed by Kaplan-Meier curve analysis.We used the concordance index to conduct head-to-head comparisons of the radiomics nomogram with the other four models(Assessment for Retreatment with Transarterial Chemoembolization score;α-fetoprotein,Barcelona Clinic Liver Cancer,Child-Pugh,and Response score;CT-based radiomics signature;and clinical model).All analyses were conducted according to the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis statement.RESULTS The median duration of follow-up was 61.3 mo(interquartile range,25.5-69.3 mo)for the training cohort and 67.1 mo(interquartile range,32.4-71.3 mo)for the validation cohort.The median number of TACE sessions was 4(range,3-7)in both cohorts.Eight radiomics features were chosen from 869 candidate features to build a radiomics signature.The CT-based radiomics nomogram included the radiomics score(hazard ratio=3.9,95%confidence interval:3.1-8.8,P<0.001)and four clinical factors and classified patients into high-risk(score>3.5)and low-risk(score≤3.5)groups with markedly different prognoses(overall survival:12.3 mo vs 23.6 mo,P<0.001).The accuracy of the nomogram was considerably higher than that of the other four models.The calibration curve and decision curve analyses verified the usefulness of the CT-based radiomics nomogram for clinical practice.CONCLUSION The newly constructed CT-based radiomics nomogram can be used for the pretreatment prediction of TACE refractoriness,which may provide better guidance for decision making regarding further TACE treatment.     

Clinical outcomes of COVID-19 treated with remdesivir across the continuum of care

Introduction

During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined.

Methods

Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals.

Results

Among 3029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended 5-day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06–0.32, p < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27–2.79, p = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45–2.95, p < 0.001).

Conclusions

This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir.     

COVID-19 hospitalization outcomes in adults by HIV status; a nation-wide register-based study

Objectives

To assess the outcome of patients hospitalized with COVID-19 by HIV status and risk factors for severe COVID-19 in people living with HIV (PWH), we performed a nationwide cohort study using register data.

Methods

All people aged ≥18 years hospitalized with a primary COVID-19 diagnosis (U07.1 or U07.2) in Sweden between February 2020 and October 2021 were included. The primary outcome was severe COVID-19 [intensive care unit (ICU) admission or 90-day mortality]. Secondary outcomes were days in hospital and ICU, complications in hospital, and risk factors for severe COVID-19 in PWH. Regression analyses were performed to assess severe COVID-19 by HIV status and risk factors.

Results

Data from 64 815 hospitalized patients were collected, of whom 121 were PWH (0.18%). PWH were younger (p < 0.001), and larger proportions were men (p = 0.014) and migrants (p < 0.001). Almost all PWH had undetectable HIV-RNA (93%) and high CD4 T-cell counts (median = 560 cells/μL, interquartile range: 376–780). In an unadjusted model, PWH had statistically significant lower odds of severe COVID-19 compared with patients without HIV [odds ratio (OR) = 0.6, 95% confidence interval (CI): 0.34–0.94], but there was no significant difference after adjusting for age and comorbidity (adjusted OR = 0.7, 95% CI: 0.43–1.26). A statistically significant lower proportion of PWH (8%, 95% CI: 5–15%) died within 90 days compared with those without HIV (16%, 95% CI: 15–16%, p = 0.024). There was no statistically significant difference in days in hospital and complications during the hospital stay between PWH and patients without HIV.

Conclusions

In this nationwide study including well-treated PWH, HIV was not a risk factor in hospitalized patients for developing severe COVID-19.     

Treatment limitations and clinical outcomes in critically ill frail patients with and without COVID-19 pneumonitis

Background

The presence of treatment limitations in patients with frailty at intensive care unit (ICU) admission is unknown. We aimed to evaluate the presence and predictors of treatment limitations in patients with and without COVID-19 pneumonitis in those admitted to Australian and New Zealand ICUs.

Methods

This registry-based multicenter, retrospective cohort study included all frail adults (≥16 years) with documented clinical frailty scale (CFS) scores, admitted to ICUs with admission diagnostic codes for viral pneumonia or acute respiratory distress syndrome (ARDS) over 2 years between January 01, 2020 and December 31, 2021. Frail patients (CFS ≥5) coded as having viral pneumonitis or ARDS due to COVID-19 were compared to those with other causes of viral pneumonitis or ARDS for documented treatment limitations.

Results

884 frail patients were included in the final analysis from 129 public and private ICUs. 369 patients (41.7%) had confirmed COVID-19. There were more male patients in COVID-19 (55.3% vs 47.0%; p = 0.015). There were no differences in age or APACHE-III scores between the two groups. Overall, 36.0% (318/884) had treatment limitations, but similar between the two groups (35.8% [132/369] vs 36.1% [186/515]; p = 0.92). After adjusting for confounders, increasing frailty (OR = 1.72; 95%-CI 1.39–2.14), age (OR = 1.05; 95%-CI 1.04–1.06), and presence of chronic respiratory condition (OR = 1.58; 95%-CI 1.10–2.27) increased the likelihood of instituting treatment limitations. However, the presence of COVID-19 by itself did not influence treatment limitations (odds ratio [OR] = 1.39; 95%-CI 0.98–1.96).

Conclusions

The proportion of treatment limitations was similar in patients with frailty with or without COVID-19 pneumonitis at ICU admission.     

Analysis of the humoral and cellular response after the third COVID-19 vaccination in patients with autoimmune hepatitis

Background & aims

To explore the humoral and T-cell response to the third COVID-19 vaccination in autoimmune hepatitis (AIH).

Methods

Anti-SARS-CoV-2 antibody titers were prospectively determined in 81 AIH patients and 53 healthy age- and sex-matched controls >7 days (median 35) after the first COVID-19 booster vaccination. The spike-specific T-cell response was assessed using an activation-induced marker assay (AIM) in a subset of patients.

Results

Median antibody levels were significantly lower in AIH compared to controls (10 908 vs. 25 000 AU/ml, p < .001), especially in AIH patients treated with MMF (N = 14, 4542 AU/ml, p = .004) or steroids (N = 27, 7326 AU/ml, p = .020). Also, 48% of AIH patients had antibody titers below the 10% percentile of the healthy controls (9194 AU/ml, p < .001). AIH patients had a high risk of failing to develop a spike-specific T-cell response (15/34 (44%) vs. 2/16 (12%), p = .05) and showed overall lower frequencies of spike-specific CD4 + T cells (median: 0.074% vs 0.283; p = .01) after the booster vaccination compared to healthy individuals. In 34/81 patients, antibody titers before and after booster vaccination were available. In this subgroup, all patients but especially those without detectable/low antibodies titers (<100 AU/ml) after the second vaccination (N = 11/34) showed a strong, 148-fold increase.

Conclusion

A third COVID-19 vaccination efficiently boosts antibody levels and T-cell responses in AIH patients and even seroconversion in patients with the absent immune response after two vaccinations, but to a lower level compared to controls. Therefore, we suggest routinely assessing antibody levels in AIH patients and offering additional booster vaccinations to those with suboptimal responses.     

Prediction of early recurrence of hepatocellular carcinoma after liver transplantation based on computed tomography radiomics nomogram

BackgroundEarly recurrence results in poor prognosis of patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). This study aimed to explore the value of computed tomography (CT)-based radiomics nomogram in predicting early recurrence of patients with HCC after LT.MethodsA cohort of 151 patients with HCC who underwent LT between December 2013 and July 2019 were retrospectively enrolled. A total of 1218 features were extracted from enhanced CT images. The least absolute shrinkage and selection operator algorithm (LASSO) logistic regression was used for dimension reduction and radiomics signature building. The clinical model was constructed after the analysis of clinical factors, and the nomogram was constructed by introducing the radiomics signature into the clinical model. The predictive performance and clinical usefulness of the three models were evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA), respectively. Calibration curves were plotted to assess the calibration of the nomogram.ResultsThere were significant differences in radiomics signature among early recurrence patients and non-early recurrence patients in the training cohort (P < 0.001) and validation cohort (P < 0.001). The nomogram showed the best predictive performance, with the largest area under the ROC curve in the training (0.882) and validation (0.917) cohorts. Hosmer-Lemeshow testing confirmed that the nomogram showed good calibration in the training (P = 0.138) and validation (P = 0.396) cohorts. DCA showed if the threshold probability is within 0.06-1, the nomogram had better clinical usefulness than the clinical model.ConclusionsOur CT-based radiomics nomogram can preoperatively predict the risk of early recurrence in patients with HCC after LT.     

Frequency of delirium and its associated factors among COVID-19 inpatients in Iran

Background and aim

Delirium has been presented as the leading cause of sudden change in the mental state of patients with coronavirus disease 2019 (COVID-19). Given that the delayed diagnosis of such a dysfunction is often associated with excess mortality, it seems essential to devote vastly more attention to this significant clinical characteristic.

Materials and methods

This cross-sectional study was performed on 309 patients [viz. 259 cases hospitalized in general wards and 50 individuals admitted to the intensive care unit (ICU)]. For this purpose, a Demographic-Clinical Information Questionnaire, the Confusion Assessment Method (CAM), the Confusion Assessment Method for the ICU (CAM-ICU), the Richmond Agitation-Sedation Scale (RASS) and face-to-face interviews were completed by a trained senior psychiatry resident. The data analysis was further done with the SPSS Statistics V22.0 software package.

Results

Out of 259 patients admitted to the general wards and 50 cases in the ICU due to COVID-19, 41 (15.8%) and 11 (22%) individuals were diagnosed with delirium, respectively. As well, a significant relationship was observed between the incidence rate of delirium and age (p < 0.001), level of education (p < 0.001), hypertension (HTN) (p = 0.029), a history of stroke (p = 0.025), a history of ischemic heart disease (IHD) (p = 0.007), a history of psychiatric disorders, a history of cognitive impairment (p < 0.001), use of hypnotic and antipsychotic medications (p < 0.001) and a history of substance abuse (p = 0.023). Among 52 patients with delirium, only 20 cases had received psychiatric consultation by consultation-liaison psychiatry service for the possibility of delirium.

Conclusion

In view of the high frequency of delirium among COVID-19 inpatients, their screening for this important mental state should be a priority in clinical settings.     

A UK nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID-19

Aims

To investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission.

Materials and methods

Retrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression.

Results

In total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment.

Conclusions

Hospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA.     

COVID-19 is associated with increased care needs and a decreased likelihood of returning home following a hip fracture: The IMPACT frailty study

Purpose

The primary aim was to evaluate the impact of COVID-19 on frailty in patients surviving a hip fracture. Secondary aims were to assess impact of COVID-19 on (i) length of stay (LoS) and post-discharge care needs, (ii) readmissions, and (iii) likelihood of returning to own home.

Methods

This propensity score-matched case-control study was conducted in a single centre between 01/03/20–30/11/21. A ‘COVID-positive’ group of 68 patients was matched to 141 ‘COVID-negative’ patients. ‘Index’ and ‘current’ Clinical Frailty Scale (CFS) scores were assigned for frailty at admission and at follow-up. Data were extracted from validated records and included: demographics, injury factors, COVID-19 status, delirium status, discharge destination, and readmissions. For subgroup analysis controlling for vaccination availability, the periods 1 March 2020–30 November 2020 and 1 February 2021–30 November 2021 were considered pre-/post-vaccine periods.

Results

Median age was 83.0 years, 155/209 (74.2%) were female and median follow-up was 479 days (interquartile range [IQR] 311). There was an equivalent median increase in CFS in both groups (+1.00 [IQR 1.00–2.00, p = 0.472]). However, adjusted analysis demonstrated COVID-19 was independently associated with a greater magnitude change (Beta coefficient [β] 0.27, 95% confidence interval [95% CI] 0.00–0.54, p = 0.05). COVID-19 in the post-vaccine availability period was associated with a smaller increase versus pre-vaccine (β −0.64, 95% CI −1.20 to −0.09, p = 0.023). COVID-19 was independently associated with increased acute LoS (β 4.40, 95% CI 0.22–8.58, p = 0.039), total LoS (β 32.87, 95% CI 21.42–44.33, p < 0.001), readmissions (β 0.71, 95% CI 0.04–1.38, p = 0.039), and a four-fold increased likelihood of pre-fracture home-dwelling patients failing to return home (odds ratio 4.52, 95% CI 2.08–10.34, p < 0.001).

Conclusions

Hip fracture patients that survived a COVID-19 infection had increased frailty, longer LoS, more readmissions, and higher care needs. The health and social care burden is likely to be higher than prior to the COVID-19 pandemic. These findings should inform prognostication, discharge-planning, and service design to meet the needs of these patients.     

A single-center review of pre-exposure prophylaxis with tixagevimab–cilgavimab in solid organ transplant recipients

Background

Coronavirus disease 2019 (COVID-19) continues to negatively impact solid organ transplant recipients (SOTr). Data on the use of tixagevimab–cilgavimab (tix-cil) in vaccinated SOTr during circulation of Omicron and its subvariants are limited. Therefore, this single-center review was conducted to evaluate tix-cil efficacy in multiple organ transplant groups during a study period where Omicron B.1.1.529, BA.2.12.1, and BA.5 predominated.

Methods

In this single-center retrospective study, we evaluated the incidence of COVID-19 infection in adult SOTr who did or did not receive pre-exposure prophylaxis (PrEP) with tix-cil. SOTr were included if they were at least 18 years of age and met emergency use authorization criteria for tix-cil use. The primary outcome analyzed was the incidence of COVID-19 infection.

Results

Ninety SOTr met inclusion criteria and comprised of two groups, tix-cil PrEP (n = 45) and no tix-cil PrEP (n = 45). Of SOTr who received tix-cil PrEP, three (6.7%) developed COVID-19 infection, compared to eight (17.8%) in the no tix-cil PrEP group (p = .20). Of the 11 SOTr diagnosed with COVID-19, 15 (82.2%) were fully vaccinated against COVID-19 prior to transplantation. Moreover, 18.2% and 81.8% of the COVID-19 cases observed were asymptomatic and mild-to-moderate, respectively.

Discussion

Our study results, which included months when BA.5 was in increased circulation, suggest no significant difference in COVID-19 infection with or without use of tix-cil PrEP in our solid organ transplant groups. As the COVID-19 pandemic continues to evolve, clinical utility of tix-cil should be evaluated against new, emerging strains.

     

Safety and efficacy of one and two booster doses of SARS-CoV-2 mRNA vaccines in kidney transplant recipients: A randomized clinical trial

Background

Kidney transplant recipients are at risk for a severe course of COVID-19 with a high mortality rate. A considerable number of patients remains without a satisfactory serological response after the baseline and adjuvant SARS-CoV-2 vaccination schedule.

Methods

In this prospective, randomized study, we evaluated the efficacy and safety of one and two booster doses of mRNA vaccines (either mRNA-1273 or BNT162b2) in 125 COVID-19 naive, adult kidney transplant recipients who showed an insufficient humoral response (SARS-CoV-2 IgG <10 AU/ml) to the previous 2-dose vaccination schedule. The primary outcome was the difference in the rate of a positive antibody response (SARS-CoV-2 IgG ≥10 AU/ml) between one and two booster doses at 1 month after the final booster dose.

Results

A positive humoral response was observed in 36 (62%) patients receiving two booster doses and in 28 (44%) patients receiving one booster dose (odds ratio [OR], 2.10, 95% confidence interval [CI], 1.02–4.34, p = .043). Moreover, median SARS-CoV-2 IgG levels were higher with two booster doses (p = .009). The number of patients with positive virus neutralizing antibody (VNA) levels was numerically higher with two booster doses compared to one booster dose, but without statistical significance (66% vs. 50%, p = .084). There was no significant difference in positive seroconversions rate and antibody levels between mRNA-1273 and BNT162b2.

Conclusion

A higher number of kidney transplant recipients achieved a positive antibody response after two booster doses compared to one booster dose.

     

Serial chest CT in cryptogenic organizing pneumonia: Evolutional changes and prognostic determinants

Background and objective

Cryptogenic organizing pneumonia (COP) is corticosteroid responsive but residual computed tomography (CT) chest changes are often noted. The present study examined clinical and HRCT features of COP in which there was incomplete resolution.

Methods

We studied 93 patients with histopathologically confirmed COP and serial HRCT imaging. Clinical features were assessed, and serial CT images were analysed. Uni‐ and multivariate analyses were performed to determine clinical or imaging factors related to incomplete resolution on CT.

Results

Complete resolution on CT imaging was seen in 21/93 patients (23%) and residual abnormalities were seen in 72/93 patients (77%). In univariate analysis, total lesion (P = 0.036), degree of consolidation (P = 0.011), treatment duration (P < 0.001) and single‐breath carbon monoxide diffusing capacity of lung (P = 0.021) were significantly associated with residual imaging abnormalities. In multivariate analysis, extent of consolidation (P = 0.018; odds ratio (OR) = 14.92) and treatment duration (P = 0.011; OR = 1.32) remained as significant factors linked to residual abnormalities. CT images in unresolved COP were akin to fibrotic non‐specific interstitial pneumonia (fNSIP) in 53/72 (74%) patients.

Conclusion

Clinical, radiological and lung diffusion measurements were related to incomplete resolution on CT after COP. Imaging abnormalities on CT chest generally resembled fNSIP.

     

Safety,tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure in elderly patients: A sub-analysis of the STRONG-HF randomized clinical trial

Aims

STRONG-HF examined a high-intensity care (HIC) strategy of rapid up-titration of guideline-directed medical therapy (GDMT) and close follow-up after acute heart failure (AHF) admission. We assess the role of age on efficacy and safety of HIC.

Methods and results

Hospitalized AHF patients, not treated with optimal GDMT were randomized to HIC or usual care. The primary endpoint of 180-day death or HF readmission occurred equally in older (>65 years, n = 493, 74 ± 5 years) and younger patients (53 ± 11 years, adjusted hazard ratio [aHR] 1.02, 95% confidence interval [CI] 0.73–1.43, p = 0.89). Older patients received slightly lower GDMT to day 21, but same doses at day 90 and 180. The effect of HIC on the primary endpoint was numerically higher in younger (aHR 0.51, 95% CI 0.32–0.82) than older patients (aHR 0.73, 95% CI 0.46–1.15, adjusted interaction p = 0.30), partially related to COVID-19 deaths. After exclusion of COVID-19 deaths, the effect of HIC was similar in younger (aHR 0.51, 95% CI 0.32–0.82) and older patients (aHR 0.63, 95% CI 0.32–1.02, adjusted interaction p = 0.56), with no treatment-by-age interaction (interaction p = 0.57). HIC induced larger improvements in quality of life to day 90 in younger (EQ-VAS adjusted-mean difference 5.51, 95% CI 3.20–7.82) than in older patients (1.77, 95% CI −0.75 to 4.29, interaction p = 0.032). HIC was associated with similar rates of adverse events in older and younger patients.

Conclusion

High-intensity care after AHF was safe and resulted in a significant reduction of all-cause death or HF readmission at 180 days across the study age spectrum. Older patients have smaller benefits in terms of quality of life.     

Solid organ transplantation from COVID positive donors in the United States: Analysis of United Network for Organ Sharing database

Background

Significant uncertainties remain regarding the utilization of organs for solid organ transplantation (SOT) from donors with coronavirus disease 2019 (COVID-19). The aim of this study was to assess the trends in utilization of organs from donors with COVID-19 and their short-term outcomes.

Methods

Deceased donors between March 2020 and December 2021 with a positive COVID nucleic acid test from respiratory tract within 14 days of transplantation were analyzed using the de-identified United Network for Organ Sharing (UNOS) database. Donor and recipient characteristics of COVID-19 positive (COVID+) organs were compared to COVID-19 negative (COVID−) organs during this period. We analyzed the trends in the utilization of SOT from COVID+ donors across the United States, donor characteristics, and the quality of donor organ and recipient outcomes (length of hospitalization, rates of organ rejection, delayed graft function, 30-day graft/patient survival).

Results

During the study period, 193 COVID+ donors led to the transplantation of 281-kidneys, 106-livers, and 36-hearts in 414 adult recipients. COVID+ patients donated a median of two organs. These donors were younger and had a lower median Kidney Donor Profile Index (0.37 vs. 0.50, p < .001), lower median serum creatinine (0.8 vs. 1.0 mg/dl, p = .003), similar median serum total bilirubin (0.6 mg/dl, p = .46), and similar left ventricular ejection fraction (60%, p = .84) when compared to COVID− donors. Short-term outcomes, including 30-day graft/patient survival, were similar in both groups.

Conclusions

Analysis of short-term outcomes from the UNOS database indicates that a positive COVID test in an otherwise medically suitable donor should not preclude consideration of non-lung solid organ transplantation.

     

Global haemostatic tests demonstrate the absence of parameters of hypercoagulability in non-hypoxic mild COVID-19 patients: a prospective matched study

Severe COVID-19 patients demonstrate hypercoagulability, necessitating thromboprophylaxis. However, less is known about the haemostatic profile in mild COVID-19 patients. We performed an age and gender-matched prospective study of 10 severe and 10 mild COVID-19 patients. Comprehensive coagulation profiling together with Thromboelastography and Clot Waveform Analysis were performed. FBC, PT, APTT, D-dimer, fibrinogen and CWA were repeated every 3 days for both groups and repeat TEG was performed for severe patients up till 15 days. On recruitment, severe patients had markers reflecting hypercoagulability including raised median D-dimer 1.0 μg/mL (IQR 0.6, 1.4) (p?=?0.0004), fibrinogen 5.6 g/L (IQR 4.9, 6.6) (p?=?0.002), Factor VIII 206% (IQR 171, 203) and vWF levels 265.5% (IQR 206, 321). Mild patients had normal values of PT, aPTT, fibrinogen and D-dimer, and slightly elevated median Factor VIII and von Willebrand factor (vWF) levels. Repeated 3-day assessments for both groups showed declining trends in D-dimer and Fibrinogen. CWA of severe COVID-19 group demonstrated hypercoagulability with an elevated median values of aPTT delta change 78.8% (IQR 69.8, 85.2) (p?=?0.001), aPTT clot velocity (min1) 7.8%/s (IQR 6.7, 8.3) (p?=?0.001), PT delta change 22.4% (IQR 19.4, 29.5) (p?=?0.004), PT min1 7.1%/s (IQR 6.3, 9.0) (p?=?0.02), PT clot acceleration (min 2) 3.6%/s² (IQR 3.2, 4.5) (p?=?0.02) and PT clot deceleration (max2) 2.9%/s² (IQR 2.5, 3.5) (p?=?0.02). TEG of severe patients reflected hypercoagulability with significant increases in the median values of CFF MA 34.6 mm (IQR 27.4,38.6) (p?=?0.003), CRT Angle 78.9° (IQR 78.3, 80.0) (p?=?0.0006), CRT A10 67.6 mm (IQR 65.8, 69.6) (p?=?0.007) and CFF A10 32.0 mm (IQR 26.8, 34.0) (p?=?0.003). Mild COVID-19 patients had absent hypercoagulability in both CWA and TEG. 2 severe patients developed thromboembolic events while none occurred in the mild COVID-19 group. Mild COVID-19 patients show absent parameters of hypercoagulability in global haemostatic tests while those with severe COVID-19 demonstrated parameters associated with hypercoagulability on the global haemostatic tests together with raised D-Dimer, fibrinogen, Factor VIII and vWF levels.

     

A potential biomarker based on clinical-radiomics nomogram for predicting survival and adjuvant chemotherapy benefit in resected node-negative,early-stage lung adenocarcinoma

BackgroundWe aimed to construct a clinical-radiomics nomogram to predict disease-free survival (DFS) and the added survival benefit of adjuvant chemotherapy (ACT) for node-negative, early-stage (I–II) lung adenocarcinoma (ADC).MethodsIn this retrospective study including 310 patients from two independent cohorts, the CT-derived radiomics features were selected by least absolute shrinkage and selection operator Cox regression to generate a radiomics signature associated with DFS. The radiomics signature was incorporated to construct a clinical-radiomics nomogram along with the independent clinical risk predictors. The model performance was evaluated with reference to discrimination quantified by Harrell concordance index (C-index), integrated discrimination improvement (IDI) and net reclassification index (NRI), calibration and clinical utility. The risk score (RS) for clinical-radiomics nomogram was calculated. The association between ACT and survival benefit was assessed in high and low RS subgroup.ResultsThe clinical-radiomics nomogram achieved the highest C-index of 0.822 [95% confidence interval (CI): 0.769, 0.876] in training cohort and 0.802 (95% CI: 0.716, 0.888) in validation cohort. The incorporation of radiomics signature into clinical-radiomics nomogram showed an incremental benefit over clinical nomogram according to the improved NRI and IDI. The calibration curves and decision curve analysis further verified the clinical utility of clinical-radiomics nomogram. Further, patients with high RS based on clinical-radiomics nomogram were more prone to benefit from ACT.ConclusionsThe clinical-radiomics nomogram approach can feasibly conduct risk prediction and have potential to identify the beneficiaries of ACT among patients with node-negative, early-stage ADC, which might serve as a helpful tool in informing therapeutic decision-making.     

Extracorporeal membrane oxygenation in immunocompromised patients with acute respiratory failure: A retrospective cohort study

Background

The clinical indications of extracorporeal membrane oxygenation (ECMO) in immunosuppressed patients are not clear. This study aimed to analyse the effectiveness of ECMO and to identify the risk factors for the mortality of ECMO in immunocompromised patients with acute respiratory failure.

Methods

This retrospective, cohort study included 46 confirmed immunocompromised patients with acute hypoxemic respiratory failure treated with ECMO between July 2014 and August 2020. The clinical features and outcomes of the survival group and the non-survival group were statistically analysed.

Results

The mean age of the enrolled patients was 60.0 (50.0, 66.0) years; male patients accounted for 60.9% of patients, and the mean CD4 level was 213 cells/μL (150.3, 325.3). The hospital mortality rate of the cohort was 67.4% (31/46 patients). Patients in the survival group showed a higher rate of receiving awake ECMO (11/15 vs. 4/31; p = 0.006), a lower rate of acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT) (1/15 vs. 12/31; p = 0.035), fewer platelet transfusion units (0/15 vs. 2/31 units; p = 0.039) and a lower rate of ventilator-associated pneumonia (2/15 vs. 19/31; p = 0.006). In a multivariate Cox regression analysis model, intubated ECMO (hazard ratio = 1.77, 95% confidence interval: 1.34–2.32, p < 0.001) and AKI requiring CRRT (1.37, 95% confidence interval: 1.14–1.61, p = 0.003) were identified as independent risk factors for mortality.

Conclusions

In-hospital mortality has remained high in ECMO-treated immunocompromised patients with acute respiratory failure. Intubated ECMO and AKI receiving CRRT during ECMO treatment may predict ECMO failure in immunocompromised patients with ARF. A primarily awake ECMO strategy seems feasible in some selected immunocompromised patients.     

Site of care and factors associated with mortality in unvaccinated Australian aged care residents during COVID-19 outbreaks

Background

Residential InReach presents an alternative to hospital admission for aged care residents swabbed for coronavirus disease 2019 (COVID-19), although relative outcomes remain unknown.

Aims

To compare rates and predictors of 28-day mortality for aged care residents seen by InReach with COVID-19, or ‘suspected COVID-19’ (sCOVID), including hospital versus InReach-based care.

Methods

Prospective observational study of consecutive patients referred to a Victorian InReach service meeting COVID-19 testing criteria between April and October 2020 (prevaccine availability). COVID-19 was determined by positive polymerase chain reaction testing on nasopharyngeal swab. sCOVID-19 was defined as meeting symptomatic Victorian Government testing criteria but persistently swab negative.

Results

There were no significant differences in age, sex, Clinical Frailty Score (CFS) or Charlson Comorbidity Index (CCI) between 152 patients with COVID-19 and 118 patients with sCOVID. Similar results were found for 28-day mortality between patients with COVID-19 (35/152, 23%) and sCOVID (32/118, 27%) (P = 0.4). For the combined cohort, 28-day mortality was associated with initial oxygen saturation (P < 0.001), delirium (P < 0.001), hospital transfer for acuity (P = 0.02; but not public health/facility reasons), CFS (P = 0.04), prior ischaemic heart disease (P = 0.01) and dementia (P = 0.02). For patients with COVID-19, 28-day mortality was associated with initial oxygen saturation (P = 0.02), delirium (P < 0.001) and hospital transfer for acuity (P = 0.01), but not public health/facility reasons.

Conclusion

Unvaccinated aged care residents meeting COVID-19 testing criteria seen by InReach during a pandemic experience high mortality rates, including with negative swab result. Residents remaining within-facility (with InReach) experienced similar adjusted mortality odds to residents transferred to hospital for public health/facility-based reasons, and lower than those transferred for clinical acuity.     

The association between nutrients and occurrence of COVID-19 outcomes in the population of Western Iran: A cohort study

Introduction

The study aimed to determine the association between nutrients (micronutrients, macronutrients, and antioxidants) and the occurrence of COVID-19-related outcomes (morbidity and hospitalization) using a cohort study in Western Iran.

Methods

The basic study information was collected from February 2019 to February 2020 from the baseline phase of the Dehgolan Prospective Cohort Study (DehPCS). The primary outcomes in this study included risk of contracting COVID-19 and hospitalization due to it at a specific time. To compare these outcomes based on different nutritional groups (macronutrients or micronutrients), Kaplan–Meier chart and log rank test were used. Also, univariate and multivariate regression models were used to investigate the association between different nutritional groups and desired outcomes (risk of contracting COVID-19 and hospitalization due to it at a certain time).

Results

The results showed that people having an insufficient intake of selenium (HR: 1.180; % 95 CI: 1.032–2.490; P: 0.042), vitamin A (HR: 1.119; % 95 CI: 1.020–1.442; p: 0.033), and vitamin E (HR: 1.544; % 95 CI: 1.136–3.093; p: 0.039) were significantly more infected with COVID-19 than the ones who had a sufficient intake of these nutrients. Also, the results showed that people having an insufficient intake of selenium (HR: 2.130; % 95 CI: 1.232–3.098; p: 0.018) and vitamin A (HR: 1.200; % 95 CI: 1.000–2.090; p: 0.043) were significantly hospitalized more than the ones who had a sufficient intake of these nutrients.

Conclusion

Insufficient intake of selenium and vitamins A and E can significantly increase the incidence of COVID-19 and hospitalization due to it.     

Multisystem inflammatory syndrome in children during the COVID-19 pandemic in Turkey: first report from the Eastern Mediterranean

Objective

We aimed to describe the typical clinical and laboratory features and treatment of children diagnosed with multisystem inflammatory syndrome in children (MIS-C) and to understand the differences as compared to severe/critical pediatric cases with COVID-19 in an eastern Mediterranean country.

Methods

Children (aged <18 years) who diagnosed with MIS-C and severe/critical pediatric cases with COVID-19 and were admitted to hospital between March 26 and November 3, 2020 were enrolled in the study.

Results

A total of 52 patients, 22 patients diagnosed with COVID-19 with severe/critical disease course and 30 patients diagnosed with MIS-C, were included in the study. Although severe COVID-19 cases and cases with MIS-C share many clinical and laboratory features, MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe cases (p<0.001 for each). Of all, 53.3% of MIS-C cases had the evidence of myocardial involvement as compared to severe cases (27.2%). Additionally, C-reactive protein (CRP) and white blood cell (WBC) are the independent predictors for the diagnosis of MIS-C, particularly in the existence of conjunctival injection and rash. Corticosteroids, intravenous immunoglobulin (IVIG), and biologic immunomodulatory treatments were mainly used in MIS-C cases rather than cases with severe disease course. There were only three deaths among 52 patients, one of whom had Burkitt lymphoma and the two cases with severe COVID-19 of late referral.

Conclusion

Differences between clinical presentations, acute phase responses, organ involvements, and management strategies indicate that MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19. Conjunctival injection and higher CRP and low WBC count are reliable diagnostic parameters for MIS-C cases.