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Id Subject Object Predicate Lexical cue
T1 0-84 Sentence denotes Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia
T2 86-98 Sentence denotes Dear Editor,
T3 99-228 Sentence denotes Since last December, the outbreak of 2019-nCoV in Wuhan has caused ever-increasing attention and public panic all over the world.
T4 229-374 Sentence denotes Up to February 9, 2020, 40,171 patients had been diagnosed with 2019-nCoV infection, including 6484 (16.14%) severe cases and 908 deaths (2.27%).
T5 375-522 Sentence denotes Compared to SARS and MERS, 2019-nCoV appears to be much more contagious but less lethal, as most patients have mild symptoms and good prognosis1,2.
T6 523-793 Sentence denotes However, according to the Chinese government’s daily report, 13.2–21.3% of patients with 2019-nCoV infection developed into severe or fatal illness (Fig. S1a), which is characterized by the rapid development to acute respiratory distress syndrome (ARDS) or septic shock.
T7 794-923 Sentence denotes Along with an increasing number of confirmed cases, the cumulative total of severe patients with 2019-nCoV is growing (Fig. S1b).
T8 924-1021 Sentence denotes Treatment of these critically ill patients is becoming one of the major challenges we are facing.
T9 1022-1133 Sentence denotes Unfortunately, there are still no specific antiviral medicines or vaccines recommended for 2019-nCoV infection.
T10 1134-1246 Sentence denotes For patients with severe clinical manifestations, an effective clinical treatment scheme is of great importance.
T11 1247-1478 Sentence denotes On February 7, 2020, the China’s National Health Commission released the fifth trial version of Diagnosis and Treatment Scheme for Pneumonitis with 2019-nCoV Infection, and provided a systematic treatment strategy for severe cases.
T12 1479-1774 Sentence denotes Remarkably, systematic corticosteroids treatment (methylprednisolone, <1–2 mg per kg body weight, for 3–5 days) was recommended to be an adjuvant therapy3, which immediately raised concerns about whether patients infected with this novel coronavirus could benefit from corticosteroids therapy 4.
T13 1776-1847 Sentence denotes Salvage corticosteroids treatment for critical patients with 2019-nCoV?
T14 1848-2078 Sentence denotes Corticosteroids are widely used to prevent lung injury caused by severe community-acquired pneumonia (sCAP) due to their excellent pharmacological effects on the suppression of exuberant and dysfunctional systematic inflammation5.
T15 2079-2369 Sentence denotes Some scholars may not support the corticosteroids treatment for novel coronavirus pneumonia (NCP), because observational studies and systematic reviews have indicated inconclusive clinical evidence on the effect of corticosteroids therapy for viral pneumonias (such as SARS, MERS and H1N1).
T16 2370-2518 Sentence denotes Additionally, pulse-dose therapy or long-term administration to high dose of corticosteroids in early stage were reported to be possibly harmful6–8.
T17 2519-2830 Sentence denotes However, these conclusions obscured the clinical benefits of corticosteroids on some subgroups of patients, particularly those with severe symptoms, as the clinical effects might be related to the indication (severities of illness), the timing of intervention, the dose and duration of corticosteroids therapy9.
T18 2831-3194 Sentence denotes Of note, as documented in a series of randomized clinical trials (RCT), low or physiologic dose of corticosteroids treatment did not reduce mortality from septic shock caused by primary lung infections, but it could bring clinical benefits to secondary outcomes, such as earlier reversal of shock, shorter duration to exit from ICU and mechanical ventilation9,10.
T19 3195-3508 Sentence denotes Besides, salvage corticosteroids treatment for severe patients with advanced ARDS could alleviate the pulmonary fibrosis and prevent progressive pathological deterioration11, which provides a good framework for explaining why some critical patients with SARS infection benefit from rescue corticosteroids therapy.
T20 3509-3646 Sentence denotes More importantly, mortality benefit favored the severe HIN1-illness in the adjunctive treatment group with low dose of corticosteroids12.
T21 3647-4000 Sentence denotes Evidently, all these results strongly suggest that proper use of low-dose corticosteroids may bring survival advantages for critically ill patients with 2019-nCoV, but this treatment should be strictly performed on NCP patients with definite clinical indications (such as refractory ARDS, sepsis or septic shock) according to the recommended guidelines.
T22 4002-4090 Sentence denotes Current evidence: clinical benefits of corticosteroids therapy for critical NCP patients
T23 4091-4283 Sentence denotes Over the past month, we collaborated with front-line ICU physicians and firstly evaluated the efficacy of corticosteroids treatment for severe or fatal cases with 2019-nCoV infection in Wuhan.
T24 4284-4452 Sentence denotes From January 1 to January 29, 2020, the first 15 confirmed critical NCP patients with an average age of 61.7 years were admitted to the ICU in Wuhan Pulmonary Hospital.
T25 4453-4653 Sentence denotes Of the 15 patients, 15 (100.0%) showed bilateral pneumonia, hypoxemia and moderate or severe ARDS, 14 (93.3%) had infections, 8 (53.3%) accompanied by shock and 9 (60.0%) with multiple organ injuries.
T26 4654-4852 Sentence denotes All patients had received treatments containing noninvasive oxygen therapy and antibiotics and/or antiviral agents before and after ICU admission, and hypoxemia was not improved by these treatments.
T27 4853-5127 Sentence denotes According to the guidelines, corticosteroids therapy (median hydrocortisone-equivalent dose of 400.0 mg/day) was instantly initiated after ICU admission for an average of 9.5 days, and outcomes for all patients were followed up until February 9, 2020 (Fig. 1a and Fig. S1c).
T28 5128-5455 Sentence denotes Briefly, we observed that ICU mortality of these severe or fatal NCP patients was 46.7% (7/15), closer to that after adjustment for time-varying confounders induced by critically ill patients with MERS without corticosteroids treatment6, suggesting that corticosteroids might not improve ICU mortality in critical NCP patients.
T29 5456-5749 Sentence denotes But meanwhile, systematic corticosteroids therapy in the first 3−5 days could enhance oxygen saturation (SaO2) and arterial oxygen tension (PaO2)/inspiratory oxygen fraction (FiO2), both of which could be further augmented by collaborating with invasive mechanical ventilation (IMV) (Fig. 1b).
T30 5750-5933 Sentence denotes Corticosteroids did not exert any intervention efficacy on survival advantage of NCP patients complicated with both ARDS and shock or multiple organ injury (seven patients, all dead).
T31 5934-6318 Sentence denotes Nevertheless, corticosteroids treatment in the phase of ARDS would effectively inhibit furious inflammatory storm (Fig. 1b) and gain valuable time for controlling infection and preventing secondary multiorgan damage and shock, which implies that corticosteroids have synergistic biological effects when combined with other intensivists’ treatment against severe or fatal NCP patients.
T32 6319-6846 Sentence denotes Fig. 1 Corticosteroids treatment for severely ill patients with 2019-nCoV. a Demographics and baseline characteristics of patients infected with 2019-nCoV according to survival condition. aOf the 14 infections, 12 with identified pathogens, 2 diagnosed by characteristic clinical symptoms without identified pathogens; bN = 7. *P < 0.05, a significant difference between the two groups. b Part of indexes of 15 critically ill patients with 2019-nCoV infection during corticosteroids therapy. *P < 0.05 vs. the indexes on day 1.
T33 6847-7077 Sentence denotes SaO2 oxygen saturation, CS corticosteroids, IMV invasive mechanical ventilation, PaO2/FiO2 ratio of arterial oxygen tension to fractional inspired oxygen concentrations, WBC white blood cell, CRP C-reaction protein, FIB fibrinogen
T34 7078-7260 Sentence denotes Due to the deficiency of sample size and a matched control group, we could not easily draw an accurate conclusion about the role of corticosteroids in patients with 2019-nCoV by now.
T35 7261-7503 Sentence denotes However, our clinical experience and available descriptive data from the therapeutic process of the first 15 critical NCP patients are prone to support corticosteroids treatment for specific subgroup of critically ill patients with 2019-nCoV.
T36 7505-7572 Sentence denotes Precautions of corticosteroids treatment in patients with 2019-nCoV
T37 7573-7675 Sentence denotes There is no fixed clinical guideline for the use of corticosteroids in critically ill patients in ICU.
T38 7676-7788 Sentence denotes The anecdotal experience from SARS and sCAP therapy strongly supports precise corticosteroids management of NCP.
T39 7789-7960 Sentence denotes Personalized medicine strategy should contain, but not limited to, specific indications, timing and duration, as well as therapeutic monitoring of corticosteroids therapy.
T40 7961-8192 Sentence denotes As mentioned above, corticosteroids should be avoided unless there are indications for moderate or severe ARDS, sepsis or septic shock, in part consistent with the recommended clinical guidance from World Health Organization (WHO).
T41 8193-8525 Sentence denotes We also do not suggest the use of corticosteroids for mild or early-stage ARDS, because early corticosteroids application could delay the clearance of virus and increase mortality risk, and corticosteroids are more likely to function on inflammation-mediated lung injury and interstitial fibro-proliferation at late-stage of ARDS11.
T42 8526-8656 Sentence denotes Furthermore, clinical adverse complications in SARS patients with corticosteroids treatment have been reported to be dose-related.
T43 8657-8876 Sentence denotes Over 240 mg of hydrocortisone-equivalent dose or an excessive cumulative dose was considered to be able to generate some side effects, including hyperglycemia, psychosis, and secondary infection, avascular necrosis9,10.
T44 8877-9137 Sentence denotes Hence, lower dose and short duration of corticosteroids treatment (methylprednisolone, <1 mg/kg body weight, no more than 7 days), along with adverse drug reaction monitoring, would be more beneficial in clinical management of critical patients with 2019-nCoV.
T45 9138-9262 Sentence denotes In addition, a long-term follow-up (6 months to 3 years) is essential to identify delayed adverse effects in these patients.
T46 9263-9376 Sentence denotes Of course, the optimal treatment strategy requires constant adjustment as patient’s clinical performance changes.
T47 9377-9503 Sentence denotes In conclusion, Chinese government has taken effective measures to prevent a possible national or worldwide 2019-nCoV pandemic.
T48 9504-9606 Sentence denotes Offering the most reasonable treatment to severe NCP patients could be another challenge we will face.
T49 9607-9850 Sentence denotes We endorse the potential benefits from low-dose corticosteroids treatment in a subset of critically ill patients with 2019-nCoV based on existing studies and clinical experience, despite there is no significant improvement in overall survival.
T50 9851-10099 Sentence denotes Certainly, our ongoing well-designed prospective cohort study with sufficient samples may provide systematic answers to this clinical dilemma—“to use or not to use corticosteroids for the treatment of lung injury with 2019-nCoV”—in the near future.
T51 10101-10126 Sentence denotes Supplementary information
T52 10128-10150 Sentence denotes Supplementary Material
T53 10152-10186 Sentence denotes These authors contributed equally:
T54 10187-10232 Sentence denotes Wei Zhou, Yisi Liu, Dongdong Tian, Cheng Wang
T55 10234-10259 Sentence denotes Supplementary information
T56 10260-10395 Sentence denotes The online version of this article (10.1038/s41392-020-0127-9) contains supplementary material, which is available to authorized users.
T57 10397-10413 Sentence denotes Acknowledgements
T58 10414-10556 Sentence denotes We thank all medical staff working in the Intensive Care Unit of Wuhan Pulmonary Hospital for their essential assistance with case collection.
T59 10557-10660 Sentence denotes The authors acknowledge the National Natural Science Foundation of China for the financial support (no.
T60 10661-10677 Sentence denotes 81630102 and no.
T61 10678-10688 Sentence denotes 81803833).
T62 10690-10709 Sentence denotes Competing interests
T63 10710-10753 Sentence denotes The authors declare no competing interests.