Differential early diagnosis of benign versus malignant lung cancer using systematic pathway flux analysis of peripheral blood leukocytes.

Early diagnosis of lung cancer is critically important to reduce disease severity and improve overall survival. Newer, minimally invasive biopsy procedures often fail to provide adequate specimens for accurate tumor subtyping or staging which is necessary to inform appropriate use of molecular targeted therapies and immune checkpoint inhibitors. Thus newer approaches to diagnosis and staging in early lung cancer are needed. This exploratory pilot study obtained peripheral blood samples from 139 individuals with clinically evident pulmonary nodules (benign and malignant), as well as ten healthy persons. They were divided into three cohorts: original cohort (n = 99), control cohort (n = 10), and validation cohort (n = 40). Average RNAseq sequencing of leukocytes in these samples were conducted. Subsequently, data was integrated into artificial intelligence (AI)-based computational approach with system-wide gene expression technology to develop a rapid, effective, non-invasive immune index for early diagnosis of lung cancer. An immune-related index system, IM-Index, was defined and validated for the diagnostic application. IM-Index was applied to assess the malignancies of pulmonary nodules of 109 participants (original + control cohorts) with high accuracy (AUC: 0.822 [95% CI: 0.75-0.91, p < 0.001]), and to differentiate between phases of cancer immunoediting concept (odds ratio: 1.17 [95% CI: 1.1-1.25, p < 0.001]). The predictive ability of IM-Index was validated in a validation cohort with a AUC: 0.883 (95% CI: 0.73-1.00, p < 0.001). The difference between molecular mechanisms of adenocarcinoma and squamous carcinoma histology was also determined via the IM-Index (OR: 1.2 [95% CI 1.14-1.35, p = 0.019]). In addition, a structural metabolic behavior pattern and signaling property in host immunity were found (bonferroni correction, p = 1.32e - 16). Taken together our findings indicate that this AI-based approach may be used for "Super Early" cancer diagnosis and amend the current immunotherpay for lung cancer.

Slow Recovery from Critical Coronavirus Disease 2019 Pneumonia in an Immunosuppressed Renal Transplant Recipient with Early Acute Cardiorenal Syndrome.

With the global spread of SARS-Cov-2 infections, increasing numbers of COVID-19 cases have been reported in transplant recipients. However, reports are lacking concerning the treatment and prognosis of COVID-19 pneumonia in renal transplant recipients with acute cardiorenal syndrome. We report here the complete clinical course of a renal transplant recipient with critical COVID-19 pneumonia. In the early phase of SARS-Cov-2 infection, the patient exhibited extensive lung lesions and significant acute kidney and heart injuries, which required treatment in the ICU. After correcting the arrhythmia and heart failure, the patient recovered quickly from the acute kidney injury with a treatment of intensive diuresis and strict control of fluid intake. Without cessation of oral immunosuppressive agents, the patient presented a delayed and low antibody response against SARS-Cov-2 and reappeared positive for the virus twice after being discharged. Nevertheless, the patient's pneumonia continued to improve and he fully recovered in 69 days. This effectively treated case may be meaningful and referable for the treatment of COVID-19 pneumonia in other transplant recipients with acute cardiorenal syndrome.

Coronavirus Disease 2019 Pneumonia in Immunosuppressed Renal Transplant Recipients: A Summary of 10 Confirmed Cases in Wuhan, China.

BACKGROUND: Previous studies on coronavirus disease 2019 (COVID-19) have focused on populations with normal immunity, but lack data on immunocompromised populations. OBJECTIVE: To evaluate the clinical features and outcomes of COVID-19 pneumonia in kidney transplant recipients. DESIGN, SETTING, AND PARTICIPANTS: A total of 10 renal transplant recipients with laboratory-confirmed COVID-19 pneumonia were enrolled in this retrospective study. In addition, 10 of their family members diagnosed with COVID-19 pneumonia were included in the control group. INTERVENTION: Immunosuppressant reduction and low-dose methylprednisolone therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The clinical outcomes (the severity of pneumonia, recovery rate, time of virus shedding, and length of illness) were compared with the control group by statistical analysis. RESULTS AND LIMITATIONS: The clinical symptomatic, laboratory, and radiological characteristics of COVID-19 pneumonia in the renal transplant recipients were similar to those of severe COVID-19 pneumonia in the general population. The severity of COVID-19 pneumonia was greater in the transplant recipients than in the control group (five severe/three critical cases vs one severe case). Five patients developed transient renal allograft damage. After a longer time of virus shedding (28.4 ± 9.3 vs 12.2 ± 4.6 d in the control group) and a longer course of illness (35.3 ± 8.3 vs 18.8 ± 10.5 d in the control group), nine of the 10 transplant patients recovered successfully after treatment. One patient developed acute renal graft failure and died of progressive respiratory failure. CONCLUSIONS: Kidney transplant recipients had more severe COVID-19 pneumonia than the general population, but most of them recovered after a prolonged clinical course and virus shedding. Findings from this small group of cases may have important implications for the treatment of COVID-19 pneumonia in immunosuppressed populations. PATIENT SUMMARY: Immunosuppressed transplant recipients with coronavirus disease 2019 infection had more severe pneumonia, but most of them still achieved a good prognosis after appropriate treatment.

Simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) imaging: Comparison with contrast-enhanced MR angiography for measuring carotid stenosis.

PURPOSE: To evaluate in a proof-of-concept study the feasibility of Simultaneous Noncontrast Angiography and intraPlaque hemorrhage (SNAP) imaging as a clinical magnetic resonance angiography (MRA) technique for measuring carotid stenosis. There is a growing interest in detecting intraplaque hemorrhage (IPH) during the clinical management of carotid disease, yet luminal stenosis has remained indispensable during clinical decision-making. SNAP imaging has been proposed as a novel IPH imaging technique that provides carotid MRA with no added scan time. Flowing blood shows negative signal on SNAP because of phase-sensitive inversion recovery. MATERIALS AND METHODS: In all, 58 asymptomatic subjects with 16-79% stenosis on ultrasound were scanned at 3T by SNAP with 0.8 mm isotropic resolution and 16 cm longitudinal coverage. Two readers measured luminal stenosis of bilateral carotid arteries (n = 116) on minimum intensity projections of SNAP using the NASCET criteria. In the subset (48 arteries) with contrast-enhanced (CE) MRA available for comparison, luminal stenosis was also measured on maximum intensity projections of CE-MRA. RESULTS: Intraclass correlation coefficients (ICCs) with 95% confidence intervals were 0.94 (0.90-0.96) and 0.93 (0.88-0.96) for intra- and interreader agreement on stenosis measurements, respectively. Corresponding kappas for grading stenosis (0-29%, 30-69%, 70-99%, and 100%) were 0.79 (0.67-0.89) and 0.80 (0.68-0.90). Agreement between SNAP and CE-MRA was high (ICC: 0.95 [0.90-0.98]; kappa: 0.82 [0.71-0.93]). CONCLUSION: As a dedicated IPH-imaging sequence, SNAP also provided carotid stenosis measurement that showed high intra- and interreader consistency and excellent agreement with CE-MRA. Further comparisons with digital subtraction angiography and other noninvasive techniques are warranted. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1045-1052.

Magnetic resonance susceptibility weighted imaging in detecting intracranial calcification and hemorrhage.

BACKGROUND: Computed tomography (CT) is better than routine magnetic resonance imaging (MRI) in detecting intracranial calcification. This study aimed to assess the value of MR susceptibility weighted imaging (SWI) in the detection and differentiation of intracranial calcification and hemorrhage. METHODS: Enrolled in this study were 35 patients including 13 cases of calcification demonstrated by CT and 22 cases of intracerebral hemorrhage. MR sequences used in all the subjects included axial T1WI, T2WI and SWI. The phase shift (PS) of calcification and hemorrhage on SWI was calculated and their signal features on corrected phase images were compared. The sensitivity of T1WI, T2WI and SWI in detecting intracranial calcification and hemorrhage was analyzed statistically. RESULTS: The detection rate of SWI for cranial calcification was 98.2%, significantly higher than that of T1WI and T2WI. It was not significantly different from that of CT (P > 0.05). There were 49 hemorrhagic lesions at different stages detected on SWI, 30 on T2WI and 18 on T1WI. The average PS of calcification and hemorrhage was +0.734 +/- 0.073 and -0.112 +/- 0.032 respectively (P < 0.05). The PS of calcification was positive and presented as a high signal or the mixed signal dominated by a high signal on the corrected phase images, whereas the PS of hemorrhage was negative and presented as a low signal or the mixed signal dominated by a low signal. CONCLUSIONS: SWI can accurately demonstrate intracranial calcification, not dependant on CT. Being more sensitive than routine MRI in detecting micro-hemorrhage, SWI may play an important role in differentiating cerebral diseases associated with calcification or hemorrhage.