Prospective Cohort Study

Importance The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations. Objective To study the neurologic manifestations of patients with COVID-19. Design, Setting, and Participants This is a retrospective, observational case series. Data were collected from January 16, 2020, to February 19, 2020, at 3 designated special care centers for COVID-19 (Main District, West Branch, and Tumor Center) of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. The study included 214 consecutive hospitalized patients with laboratory-confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection. Main Outcomes and Measures Clinical data were extracted from electronic medical records, and data of all neurologic symptoms were checked by 2 trained neurologists. Neurologic manifestations fell into 3 categories: central nervous system manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), and skeletal muscular injury manifestations. Results Of 214 patients (mean [SD] age, 52.7 [15.5] years; 87 men [40.7%]) with COVID-19, 126 patients (58.9%) had nonsevere infection and 88 patients (41.1%) had severe infection according to their respiratory status. Overall, 78 patients (36.4%) had neurologic manifestations. Compared with patients with nonsevere infection, patients with severe infection were older, had more underlying disorders, especially hypertension, and showed fewer typical symptoms of COVID-19, such as fever and cough. Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]), and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). Conclusions and Relevance Patients with COVID-19 commonly have neurologic manifestations. During the epidemic period of COVID-19, when seeing patients with neurologic manifestations, clinicians should suspect severe acute respiratory syndrome coronavirus 2 infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and lose the chance to treat and prevent further transmission.

https://jamanetwork.com/journals/jamaneurology/articlepdf/2764549/jamaneurology_mao_2020_oi_200025.pdf

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China.

Chest CT had higher sensitivity for diagnosis of COVID-19 as compared with initial reverse-transcription polymerase chain reaction from swab samples in the epidemic area of China.

https://pubs.rsna.org/doi/pdf/10.1148/radiol.2020200642

Correlation of Chest CT and RT-PCR Testing for Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases.

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Importance In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited. Objective To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy. Design, Setting, and Participants Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020. Exposures SARS-CoV-2 infection confirmed by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcomes and Measures Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network. Results Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2was greater than 50% in 89% of patients. The median Pao2/Fio2was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0];P = .94). Median Fio2was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, −10% [95% CI, −14% to 6%];P = .006), and median Pao2/Fio2was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, −8 to 22];P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68];P  Conclusions and Relevance In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.

/pdf/baseline-characteristics-and-outcomes-of-1591-patients-4y6nwx3pu4.pdf

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy.

Myeloid-derived suppressor cells (MDSCs) is a heterogeneous population of immature myeloid cells, inhibiting both the innate and adaptive immunity. Recent studies validated that MDSCs caused immune suppression and promoted cancer progression through various mechanisms. However, the prognostic value of MDSCs in cancer remains controversial. Here, we performed this meta-analysis to evaluate the prognostic value of MDSCs in various types of cancer. The electric databases, such as Pubmed, Embase and Web of Science, were searched for relevant publications. Hazards ratios (HRs) with the corresponding 95% confidence intervals (95%CIs) were calculated to evaluate the prognostic role of MDSCs in cancer. A total of 16 studies with 1864 patients were enrolled in our meta-analysis. Elevated MDSCs frequency was shown to be associated with shorter overall survival (OS) (HR = 2.46, 95%CI: 1.87–3.23), and poor disease-free survival / recurrence-free survival (DFS / RFS) (HR = 3.26, 95%CI: 2.10–5.04) after treatment. Furthermore, similar results were also observed in the stratified subgroup analysis, which included the analysis by region, sample size, cancer type, NOS scores, subtype and cut-off value of MDSCs. High MDSCs might be related to poor clinical outcomes of patients with cancer, that is, MDSCs might be a potential prognostic biomarker in cancer.

/pdf/prognostic-role-of-myeloid-derived-suppressor-cells-in-vkztnah7jp.pdf

Prognostic role of myeloid-derived suppressor cells in cancers: a systematic review and meta-analysis

Video prediction is a pixel-wise dense prediction task to infer future frames based on past frames. Missing appearance details and motion blur are still two major problems for current models, leading to image distortion and temporal inconsistency. We point out the necessity of exploring multi-frequency analysis to deal with the two problems. Inspired by the frequency band decomposition characteristic of Human Vision System (HVS), we propose a video prediction network based on multi-level wavelet analysis to uniformly deal with spatial and temporal information. Specifically, multi-level spatial discrete wavelet transform decomposes each video frame into anisotropic sub-bands with multiple frequencies, helping to enrich structural information and reserve fine details. On the other hand, multilevel temporal discrete wavelet transform which operates on time axis decomposes the frame sequence into sub-band groups of different frequencies to accurately capture multifrequency motions under a fixed frame rate. Extensive experiments on diverse datasets demonstrate that our model shows significant improvements on fidelity and temporal consistency over the state-of-the-art works. Source code and videos are available at https://github.com/Bei-Jin/STMFANet.

Exploring Spatial-Temporal Multi-Frequency Analysis for High-Fidelity and Temporal-Consistency Video Prediction

Semantic scene completion predicts volumetric occupancy and object category of a 3D scene, which helps intelligent agents to understand and interact with the surroundings. In this work, we propose a disentangled framework, sequentially carrying out 2D semantic segmentation, 2D-3D reprojection and 3D semantic scene completion. This three-stage framework has three advantages: (1) explicit semantic segmentation significantly boosts performance; (2) flexible fusion ways of sensor data bring good extensibility; (3) progress in any subtask will promote the holistic performance. Experimental results show that regardless of inputing a single depth or RGB-D, our framework can generate high-quality semantic scene completion, and outperforms state-of-the-art approaches on both synthetic and real datasets.

/pdf/see-and-think-disentangling-semantic-scene-completion-2eok4jrowv.pdf

See and Think: Disentangling Semantic Scene Completion

The CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has been widely proved effective on relapsed and refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL). Meanwhile, CAR-T therapy-related toxicities, including cytokine release syndrome (CRS) and neurological toxicities, are drawing researchers’ attention. In addition, our research team notices that coagulopathy and even disseminated intravascular coagulation (DIC) are common problems during CAR-T therapy. In our phase 1/2 clinical trial (NCT02965092), 53 r/r B-ALL patients underwent leukapheresis on day − 11 and received lymphodepleting chemotherapy on day − 7 to day − 5. Finally, they received split infusions of anti-CD19 CAR-T cells on day 0 to day 2. Plasma concentrations of tissue factor (TF) and platelet endothelial cell adhesion molecular-1 (PECAM-1) were also measured to identify the mechanism of coagulation disorders. The overall 1-month remission rate of the 53 patients was 88.7%. During the treatment course, 19 patients experienced grade 3–4 CRS, 8 patients developed grade 2–3 neurological toxicities. Beyond that, 30 patients (30/53, 56.6%) suffered from coagulation disorders, and half of them should be diagnosed as DIC. Benefiting from replacement and anticoagulant therapy, 14 patients successfully got out of the conditions of DIC. Remarkably, the severity of coagulopathy was positively correlated with CRS grade. What is more, plasma TF and PECAM-1 levels indicated that vascular endothelial factors played key roles in the process of CRS-related coagulopathy. To conclude, coagulation disorders frequently happen during CAR-T therapy. TF and PECAM-1 are of great importance in the etiology and pathogenesis of coagulation problems. Early and proper interventions targeted at CRS-related coagulopathy contribute a lot to the control of side effects in CAR-T therapy.

/pdf/improving-the-safety-of-car-t-cell-therapy-by-controlling-xitjfadr1v.pdf

Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy

Red blood cell distribution width (RDW), a biomarker for discrimination of anemia, has been recently identified as a prognostic factor in various types of cancer. Here we performed a meta-analysis in order to assess the correlation between RDW and the survival outcomes in patients with hematologic malignances. We systematically searched PubMed, Embase, and ISI Web of Science for relevant studies, to investigate the prognostic significance of RDW in hematological malignancies. Odds ratios or hazards ratios (HRs) with corresponding 95% confidence intervals (CIs) are pooled to estimate the association between RDW and clinicopathological parameters of patients with hematologic malignances. Seven trials with 1031 patients suffering from hematological malignancies were included in the meta-analysis, and the results indicated that increased pretreatment RDW predicted poor overall survival (HR = 2.35, 95% CI 1.70–3.24), poor progress-free survival (HR = 2.44, 95% CI 1.70–3.49) and poor event-free survival (EFS) (HR = 3.15, 95% CI 1.59–6.25). Furthermore, the similar results were observed in subgroup analysis stratified by cancer type, such as multiple myeloma, and diffuse large B cell lymphoma, etc. As for hematologic malignances, patients with higher RDW are more likely to have poorer prognosis than those with lower RDW.

/pdf/prognostic-role-of-rdw-in-hematological-malignancies-a-26f65eu7cm.pdf

Yu Hu

Papers

Prognostic role of myeloid-derived suppressor cells in cancers: a systematic review and meta-analysis

Exploring Spatial-Temporal Multi-Frequency Analysis for High-Fidelity and Temporal-Consistency Video Prediction

See and Think: Disentangling Semantic Scene Completion

Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy

Prognostic role of RDW in hematological malignancies: a systematic review and meta-analysis.