Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir–ritonavir, and ...ribavirin for treating patients with COVID-19.
This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688.
Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3–7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days IQR 5–11) than the control group (12 days 8–15; hazard ratio 4·37 95% CI 1·86–10·24, p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir–ritonavir because of biochemical hepatitis. No patients died during the study.
Early triple antiviral therapy was safe and superior to lopinavir–ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted.
The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.
Abstract Sepsis is the commonest cause of acute kidney injury in critically ill patients. Its pathophysiology is complex and not well understood. Until recently, it was believed that kidney ...hypoperfusion is the major contributor of septic acute kidney injury. However, recent publications have improved our understanding on this topic. We now know that its mechanisms included the following: (1) renal macrocirculatory and microcirculatory disturbance, (2) surge of inflammatory markers and oxidative stress, (3) coagulation cascade activation, and (4) bioenergetics adaptive response with controlled cell-cycle arrest aiming to prevent cell death. Uncovering these complicated mechanisms may facilitate the development of more appropriate therapeutic measures in the future.
Abstract
The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and red cell distribution width (RDW) are emerging biomarkers to predict ...outcomes in general ward patients. However, their role in the prognostication of critically ill patients with pneumonia is unclear. A total of 216 adult patients were enrolled over 2 years. They were classified into viral and bacterial pneumonia groups, as represented by influenza A virus and
Streptococcus pneumoniae,
respectively. Demographics, outcomes, and laboratory parameters were analysed. The prognostic power of blood parameters was determined by the respective area under the receiver operating characteristic curve (AUROC). Performance was compared using the APACHE IV score. Discriminant ability in differentiating viral and bacterial aetiologies was examined. Viral and bacterial pneumonia were identified in 111 and 105 patients, respectively. In predicting hospital mortality, the APACHE IV score was the best prognostic score compared with all blood parameters studied (AUC 0.769, 95% CI 0.705–0.833). In classification tree analysis, the most significant predictor of hospital mortality was the APACHE IV score (adjusted P = 0.000, χ
2
= 35.591). Mechanical ventilation was associated with higher hospital mortality in patients with low APACHE IV scores ≤ 70 (adjusted P = 0.014, χ
2
= 5.999). In patients with high APACHE IV scores > 90, age > 78 (adjusted P = 0.007, χ
2
= 11.221) and thrombocytopaenia (platelet count ≤ 128, adjusted P = 0.004, χ
2
= 12.316) were predictive of higher hospital mortality. The APACHE IV score is superior to all blood parameters studied in predicting hospital mortality. The single inflammatory marker with comparable prognostic performance to the APACHE IV score is platelet count at 48 h. However, there is no ideal biomarker for differentiating between viral and bacterial pneumonia.
The main mechanism of virulence in
Klebsiella pneumoniae
is the acquisition of
K. pneumoniae
virulence plasmids (KpVPs), which include two dominant types, namely, KpVP-1 (carrying
iuc
1,
iro
1,
rmpA
..., and
rmpA2
) and KpVP-2 (carrying
iuc
2,
iro
2, and
rmpA
). Both are non-conjugative and associated with different hypervirulent clones. In contrast to KpVP-1 reported in K1, K2, and other serotypes of
K. pneumoniae
, KpVP-2 was only reported in K2 strains and rarely characterized. In this study, we identified a conjugative KpVP-2-type virulence plasmid from a clinical hypervirulent
K. pneumoniae
strain. This plasmid was generated by the integration of conjugative transfer genes into the KpVP-2-type plasmid Kp52.145 II and could be readily conjugated to
Escherichia coli
strain EC600 and
K. pneumoniae
strains of various types which are clinically existing, mediating hypervirulence. Furthermore, this kind of conjugative KpVP-2-type virulence plasmid has been disseminated in clinical settings in Hong Kong and other regions of the world. The generation of conjugative virulence plasmid may promote its transmission and explain the evolution of this type of virulence plasmid.
...the finding that CR-HvKP was detected among CRKP stains, accounting for up to three (42%) of seven CRKP isolates (unpublished), was notable. Because of the high transmissibility of these strains, ...more extensive molecular epidemiological studies are required to assess the potential threat that this newly emerged strain might pose for the health-care system in Hong Kong in the future. Number of Klebsiella pneumoniae isolates Number of CRKP isolates (%) Number of HvKP isolates (%) Number of CR-HvKP isolates (%) QMH 65 7 (11%) 7 (11%) 3 (5%) PYNEH 22 0 9 (41%) 0 Total 87 7 (8%) 16 (18%) 3 (3%) 1 D Gu, N Dong, Z Zheng, Klebsiella pneumoniae, in a Chinese hospital: a molecular epidemiological study, Lancet Infect Dis, 2017, published online Aug 29. 2 L Zhan, S Wang, Y Guo, Klebsiella pneumoniae, ST11 isolates with carbapenem resistance in a tertiary hospital in China, Front Cell Infect Microbiol, Vol. 7, 2017, 182 3 C Shankar, LE Nabarro, NK Devanga Ragupathi, Klebsiella pneumoniae, isolates from bacteremia, Genome Announc, Vol. 4, 2016, e01081-e01116 4 R Zhang, D Lin, EW Chan, D Gu, GX Chen, S Chen, Klebsiella pneumoniae, strains in China, Antimicrob Agents Chemother, Vol. 60, 2015, 709-711 5 Y Zhang, J Zeng, W Liu, Klebsiella pneumoniae, isolate from clinical infections in China, J Infect, Vol. 71, 2015, 553-560
Purpose The objective of this study is to examine the incidence, clinical characteristics, and outcome (90-day mortality) of critically ill Chinese patients with septic AKI. Methods Patients admitted ...to the ICU of a regional hospital from 1 January 2011 to 31 December 2013 were included, excluding those on chronic renal replacement therapy. AKI was defined using KDIGO criteria. Patients were followed till 90 days from ICU admission or death, whichever occurred earlier. Demographics, diagnosis, clinical characteristics, and outcome were analyzed. Results In total, 3687 patients were included and 54.7% patients developed AKI. Sepsis was the most common cause of AKI (49.2%). Compared to those without AKI, AKI patients had higher disease severity, more physiological and biochemical disturbance, and carried significant co-morbidities. Ninety-day mortality increased with severity of AKI (16.7, 27.5, and 48.3% for KDIGO stage 1, 2, and 3 AKI, p < 0.001). Full renal recovery was achieved in 71.6% of AKI patients. Compared with non-septic AKI, septic AKI was associated with higher disease severity and required more aggressive support. Non-recovery of renal function occurred in 2.5% of patients with septic AKI, compared with 6.4% in non-septic AKI (p < 0.001). Cox regression analysis showed that age, emergency ICU admission, post-operative cases, admission diagnosis, etiology of AKI, disease severity score, mechanical ventilation, vasopressor support, and blood parameters (like albumin, potassium and pH) independently predicted 90-day mortality. Conclusions AKI, especially septic AKI is common in critically ill Chinese patients and is associated with poor patient outcome. Etiology of AKI has a significant impact on 90-day mortality and may affect renal outcome.
Background
Sepsis is an important cause of mortality and morbidity among critically ill patients with underlying malignancy.
Methods
Patients with sepsis admitted to the intensive care unit (ICU) of ...the Pamela Youde Nethersole Eastern Hospital from January 1, 2010 to April 30, 2019 were recruited. Demographics, laboratory parameter, and outcome were analyzed. Those with underlying malignancy were matched with those without malignancy based on their severity of organ failure (defined by the sequential organ failure assessment SOFA score) and septic source.
Results
Two hundred sixty‐three patients with underlying active malignancy were matched with 259 patients without malignancy. Those with malignancy had higher APACHE IV score (89 vs. 83), lower albumin (22.1 vs. 24.4), neutrophil count (6.0 vs. 9.3), hemoglobin (8.0 vs. 9.8), platelet count (113 vs. 133), less use of mechanical ventilation (35.7% vs. 45.9%), renal replacement therapy (22.1% vs. 28.2%) and vasopressor (66.2% vs. 74.9%), higher 30‐day (34.2% vs. 24.3%) ICU (22.4% vs. 18.9%), and 1‐year (62.4% vs. 36.7%) mortality compared with those without malignancy. A higher APACHE IV score and pulmonary sepsis were predictors of 30‐day mortality by Cox regression analysis.
Conclusion
Disease severity and pulmonary sepsis, but not underlying malignancy, predicted short‐term mortality among critically ill septic patients.
Effect of the underlying malignancy on critically ill septic patient’s outcome
Introduction: Significant ventilator-associated pneumonia and mortality were found in COVID-19 patients who required mechanical ventilation which calls for non-invasive means in managing respiratory ...failure.
Methods: We retrospectively reviewed patients admitted to the intensive care unit of Pamela Youde Nethersole Eastern Hospital in Hong Kong with severe acute respiratory syndrome coronavirus 2 infection from 28 November to 15 December 2020. Patients' laboratory, respiratory parameters and outcome data were recorded and analysed.
Results: Eleven received prone ventilation. The median age was 67 (inter-quartile range: 59-72) years, and median COVID-19 GRAM score was 151 (inter-quartile range: 133-181), representing a high-risk group. There were significant improvements 1 h after awake proning in SpO2 (95% vs 92%, p = 0.008), FiO2 (0.4 vs 0.5, p = 0.003), SpO2/FiO2 (240 vs 184, p = 0.005), respiratory rate (19 vs 26, p = 0.006) and respiratory rate - oxygenation index (13.22 vs 7.67, p = 0.003; Table 1). Although not reaching statistical significance, the median PaO2, PaCO2 and PaO2/FiO2 improved after proning. The overall intubation rate was 22% and intensive care unit mortality was 22%, which is in contrast to 65.5% and 27.6%, respectively, in the first three waves. Although did not reach statistical significance, those received prone ventilation tend to have a lower ICU mortality (9.1% vs 42.9%, p = 0.245) and hospital mortality (18.2% vs 42.9%, p = 0.326).
Conclusion: Awake proning potentially minimizes complications from invasive ventilation and provides a low-cost low-risk treatment option in COVID-19 patients with respiratory failure. This is particularly important when healthcare resources are strained at times of a pandemic.
Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in ...hospitalized COVID-19 patients.
We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0).
Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio HR, 6.59; 95% confidence interval CI, 6.1-7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79-8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98-11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9-8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4.
Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients.
NCT04647695.
The aquarium in the right heart Lun, Chung‐Tat; Shum, Hoi‐Ping
Echocardiography (Mount Kisco, N.Y.),
September 2018, 2018-09-00, 20180901, Letnik:
35, Številka:
9
Journal Article
Recenzirano
We presented a case with massive hepatic portovenous gas (HPVG) and gastric emphysema, probably due to increased intraluminal pressure in the stomach after bagging and noninvasive ventilation. There ...are multiple microbubbles in the inferior vena cava, right atrium and right ventricle. There has been only one case report ever published showing the similar features of the “aquarium sign” in the right heart in a patient with intussusception. We believe our case is a good illustration of this extremely rare entity in echocardiography.
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