OBJECTIVETo investigate the spectrum of bacteria and fungi in different sites in severe acute pancreatitis (SAP).

METHODSThe prospective study was performed in 205 patients with SAP treated from January 2000 to December 2008. The Infection rate of bacteria and fungi was observed prospectively in pancreatic necrosis and(or) pus form abdomen, body fluids and deep vein catheter in SAP. Body fluids and pancreatic necrosis were cultured twice a week. Central venous catheter was cultured when it had been placed for two weeks. Blood was cultured for bacteria and fungi when body temperature was more than 39 degrees C. Constituent ratio of bacteria and fungi was observed in different sites and in all sites within 28 days after onset of SAP.

RESULTSThere were 937 pathogens, among which infection rates of gram-negative bacteria was higher than gram-positive bacteria and fungi (P < 0.05), the infection rates of gam-positive bacteria and fungi were similar. Infection rates of gram-negative bacteria in pancreatic necrosis (55.2%), bile (55.4%), blood (68.1%) and central venous catheter (44.4%) were increased significantly (P < 0.05) compared with gram-positive bacteria and (30.2%, 33.9%, 23.4%, 38.9%) and fungi (14.6%, 10.7%, 8.5%, 16.7%); however, infection rate of fungi (59.6%) was increased significantly (P < 0.05) compared with gram-negative bacteria (24.0%) and gram-positive bacteria (16.3%) in urine; infection rate of gram-negative bacteria (53.2%) was significantly higher (P < 0.05) than that of fungi (27.1%) and gram-positive bacteria (19.7%) in sputum. Infection rate of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia) in gram-negative bacteria in pancreatic necrosis, bile, blood, central venous catheter and sputum was significantly higher than that of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae) (P < 0.01); infection rate of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli) was higher significantly (P < 0.01) than that of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii). Infection rate of staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus was significantly higher (P < 0.05) than that of Enterococcus faecalis and Enterococcus faecium in pancreatic necrosis and sputum;but infection rate of Enterococcus faecium in bile and urine was significantly higher than other gram-positive bacteria (P < 0.05). There was not difference among gram-positive bacteria;however, infection rate of Staphylococcus epidermidis in central venous catheter was increased significantly (P < 0.05). Infection rate of candida mycoderma in pancreatic necrosis, bile, urine and sputum was significantly higher than that of tricho bacteria (P < 0.05). The peak of infection rate of microbes in body fluid was within 2 to 3 weeks.

CONCLUSIONSConstituent ratio in gram-negative, gram-positive bacteria and fungi as well as their species in different sites is diverse. The peak of infection rate of microbes is 2 to 3 weeks after onset of the disease.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteria ; isolation & purification ; Female ; Fungi ; isolation & purification ; Humans ; Male ; Middle Aged ; Pancreatitis ; microbiology ; Prospective Studies ; Young Adult

BACKGROUNDA satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel "human-source" model of human breast cancer skeletal metastasis.

METHODSHuman breast cancer stem-like cells, the CD44+/CD24-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1 x 10(5), 1 x 10(6) human breast cancer stem-like cells, and 1 x 10(6) parental MDA-MB-231 cells, respectively. A positive control group (D) without implantation of human bone was also injected with 1 x 10(6) MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 (CXCR4), and osteopontin (OPN). mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction (PCR).

RESULTSOur results demonstrated that cells in implanted human bones of group B, which received 1 x 10(6) cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis (77.8%, P = 0.0230) and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest.

CONCLUSIONSIn the novel "human source" model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.

Animals ; Bone Neoplasms ; secondary ; Breast Neoplasms ; pathology ; CD24 Antigen ; analysis ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Hepatocyte Growth Factor ; pharmacology ; Humans ; Hyaluronan Receptors ; analysis ; Immunohistochemistry ; Mice ; Neoplastic Stem Cells ; pathology ; Osteopontin ; analysis ; Phenotype ; Receptors, CXCR4 ; analysis

OBJECTIVETo investigate the strategy of controlling fluid resuscitation for severe acute pancreatitis (SAP) in acute phase.

METHODSFrom March 2001 to January 2006, 83 patients meeting for experimental criteria were included in this clinical trial. They were divided into early fluid expansion group (Group I, within 24 h after admission, 21 patients), middle fluid expansion group (Group II, within 25 - 48 h, 35 patients) and late fluid expansion group (Group III, within 49 - 72 h, 27 patients). Parameters of treatment of fluid therapy within 4 d after admission were observed. Serum lactic level was measured on admission and on meeting for criteria of fluid expansion. APACHEII scores, operation rate within 2 weeks, rate of mechanical ventilation, rate of ACS and survival rate were observed.

RESULTSTime interval for meeting fluid expansion criteria in Group I, Group II, Group III was (13 +/- 6) h, (38 +/- 5) h and (61 +/- 8) h, respectively. And there was statistical significance among them (P < 0.05). HCT (%) in Group I (33 +/- 6)% was lower than that of Group II (40 +/- 6)% and Group III (42 +/- 11)% significantly (P < 0.01) at the first day after admission; and there was no statistical significance between Group II and Group III. The amount of crystal and colloid infused in Group I (4014 +/- 2887) ml and (1220 +/- 705) ml at the day of admission was more than those of Group II (2366 +/- 1959) ml and (821 +/- 600) ml and Group III (2615 +/- 1574) ml and (701 +/- 585) ml (P < 0.01); but there was not different between Group II and Group III (P > 0.05). The ratio of colloid and crystal in Group III at the day of admission was lower than those of Group I and Group II (P < 0.05). The total amount of fluid infused was not different among 3 groups for the 4 d (P > 0.05). And infusion rate at the day of admission in Group I was more rapid than those of Group II and Group III (P < 0.05); and there was no difference between Group II and Group III (P > 0.05). The total amount of fluid sequestration in Group II for the 4 d was lower than those of Group I and Group III (P < 0.05); and there was no statistical significance between Group I and Group III (P > 0.05). At the first to the third day after admission APACHEII scores in Group I were higher than those of Group II and Group III (P < 0.05); and at the second and third day, APACHEII scores in Group III were higher than those of Group II (P < 0.05). Rate of mechanical ventilation in Group I (85.7%) was higher than those of Group II (37.1%) and group III (63.0%) (P < 0.05); and rate of ACS was most lowest in Group II (37.1%) (P < 0.05). Survival rate in Group I (38.1%) was lower than those of Group II (85.7%) and Group III (66.7%) (P < 0.05); and Group III was lower than that of Group II (P = 0.075).

CONCLUSIONSWithin 72 h after onset of the disease, survival rate is improved significantly through controlling fluid resuscitation and prevention of body fluid sequestration.

APACHE ; Adult ; Aged ; Female ; Fluid Therapy ; methods ; Humans ; Male ; Middle Aged ; Pancreatitis, Acute Necrotizing ; mortality ; pathology ; therapy ; Resuscitation ; methods ; Severity of Illness Index ; Survival Rate ; Treatment Outcome

OBJECTIVETo investigate strategy of treatment of hemofiltration on severe acute pancreatitis (SAP) and fulminant acute pancreatitis (FAP).

METHODSOne hundred and thirty patients with SAP and eighty-one patients with FAP treated with hemofiltration (HF) were prospectively observed from March 1997 to December 2008. Indications for HF, variables (time interval for hemofiltration), mode, therapeutic dosage, blood rate, heparin dosage and components of hemofiltration, therapeutic efficacy (time of disapearance of abdominal pain, intra-abdominal pressure and survival rate) and complications (incidence of bleeding and blood infection).

RESULTSAll patients underwent high volume hemofiltration (HVHF) or hemodialysis-filtration (HDF) within 72 hours after onset of the disease. Dose of SAP and FAP was (53 +/- 6) mlxkg(-1)xh(-1) and (59 +/- 10) mlxkg(-1)xh(-1) (P < 0.05), respectively. Rate of short veno-venous hemofiltration in SAP (76.9%) was higher than that of FAP (38.3%) (P < 0.05); however, rate of continuous veno-venous hemofiltration (23.1%) was lower than that of FAP (37.0%) (P < 0.05). Rate of HDF was much higher in FAP than that of SAP. Low molecular weight heparin and heparin were both available to anticoagualte;but dosage required in patients with FAP was much higher than that of SAP (P < 0.05). Time intervals for amelioration of abdominal pain in SAP and FAP were (9 +/- 6) h and (15 +/- 10) h, respectively. Itra-abdominal pressure was decreased significantly at the end of hemofiltration compared to prior to hemofiltration in SAP and FAP (P < 0.05). Level of serum triglyceride decreased abruptly after adsorption (P < 0.05). Rate of operation within 28 days in SAP (73.8%) was lower than FAP (87.7%). The in-hospital survival rates in SAP and FAP were 88.5% and 67.9%, respectively. Amount of platelet decreased in patients with blood flow rate less than 240 ml/min was higher than that of more than 240 ml/min (P < 0.05). And incidence of blood stream infection and bleeding increased significantly (P < 0.05).

CONCLUSIONSHVHF and HDF used in SAP and FAP patients underwent conservative treatment within 72 hours, respectively, can increase survival rate significantly.

Acute Disease ; Hemofiltration ; Humans ; Pancreatitis ; therapy ; Survival Rate

BACKGROUNDFluid therapy for severe acute pancreatitis (SAP) should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has not a strategy for fluid therapy dedicated to SAP. So, this study was aimed to investigate the effects of fluid therapy treatment on prognosis of SAP.

METHODSSeventy-six patients were admitted prospectively according to the criteria within 72 hours of SAP onset. They were randomly assigned to a rapid fluid expansion group (Group I, n = 36) and a controlled fluid expansion group (Group II, n = 40). Hemodynamic disorders were either quickly (fluid infusion rate was 10 - 15 ml x kg(-1) x h(-1), Group I) or gradually improved (fluid infusion rate was 5 - 10 ml x kg(-1) x h(-1), Group II) through controlling the rate of fluid infusion. Parameters of fluid expansion, blood lactate concentration were obtained when meeting the criteria for fluid expansion. And APACHE II scores were obtained serially for 72 hours. Rate of mechanical ventilation, incidence of abdominal compartment syndrome (ACS), sepsis, and survival rate were obtained.

RESULTSThe two groups had statistically different (P < 0.05) time intervals to meet fluid expansion criteria (Group I, 13.5 +/- 6.6 hours; Group II, (24.0 +/- 5.4) hours). Blood lactate concentrations were both remarkably lower as compared to the level upon admission (P < 0.05) and reached the normal level in both groups upon treatment. It was only at day 1 that hematocrit was significantly lower in Group I (35.6% +/- 6.8%) than in Group II (38.5% +/- 5.4%) (P < 0.01). Amount of crystalloid and colloid in group I ((4028 +/- 1980) ml and (1336 +/- 816) ml) on admission day was more than those of group II ((2472 +/- 1871) ml and (970 +/- 633) ml). No significant difference was found in the total amount of fluids within four days of admission between the two groups (P > 0.05). Total amount of fluid sequestration within 4 days was higher in Group I ((5378 +/- 2751) ml) than in Group II ((4215 +/- 1998) ml, P < 0.05). APACHE II scores were higher in Group I on days 1, 2, and 3 (P < 0.05). Rate of mechanical ventilation was higher in group I (94.4%) than in group II (65%, P < 0.05). The incidences of abdominal compartment syndrome (ACS) and sepsis were significantly lower in Group II (P < 0.05). Survival rate was remarkably lower in Group I (69.4%) than in Group II (90%, P < 0.05).

CONCLUSIONSControlled fluid resuscitation offers better prognosis in patients with severe volume deficit within 72 hours of SAP onset.

Acute Disease ; Adult ; Female ; Fluid Therapy ; methods ; Humans ; Male ; Middle Aged ; Pancreatitis ; pathology ; therapy

OBJECTIVETo investigate therapeutic strategy of fulminant acute pancreatitis (FAP) in acute response stage.

METHODSSixty-four patients were divided into Death group (27 patients) and Survival group (37 patients). The time course of shock and recovery of enteral function, parameters of fluid resuscitation, PaO(2)/FiO(2) and AaDO(2) at 24 hours prior to mechanical ventilation, rate of continuous venovenous hemofiltration (CVVH) and abdominal compartment syndrome (ACS), severity of the disease in the acute response stage were investigated. And the effect of surgical manner and time on the prognosis was also analyzed.

RESULTSCompared with Survival group, the time course of shock and recovery of enteral function in Death group were prolonged significantly (P < 0.05). Between the groups, there was no difference in the amount of crystal fluid infused from admission to 72 hours after, but the amount of colloid fluid infused and ratio of amount of colloid and crystal fluid in Survival group were higher (P < 0.05). The amount of fluid retention in third space from admission to 72 hours after in Death group was higher than that of Survival group significantly (P < 0.05). The fluid infusing rate in Survival group in the first day of admission was faster than Death group (P < 0.05). PaO(2)/FiO(2) and AaDO(2) in 24 hours prior to mechanical ventilation in Death group were negatively changed significantly. Within 72 hours after the onset of the disease, the rate of CVVH in Survival group was higher than Death group. Incidence rate of ACS and the APACHEII scores within 72 hours after admission in Death group were higher than in Survival group. The cure rate of the patients operated in the day 7 to day 14 after admission was higher than that of patients operated prior and post this period. Time for the first operation in operated patients was earlier than patients received minimally invasive drainage (MID) and its cure rate was lower than that of MID Group.

CONCLUSIONSIt is the key point to shorten the time course of ischemia, to control persistent systemic inflammatory response syndrome (SIRS) and to adopt reasonable surgical intervention in acute response stage for FAP.

Acute Disease ; Adult ; Combined Modality Therapy ; Female ; Humans ; Male ; Middle Aged ; Pancreatitis ; complications ; mortality ; therapy ; Resuscitation ; methods ; Retrospective Studies

Background: A patient’s infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. Methods: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients’ oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. Results: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0–62.0) years were analyzed. After in-hospital treatment, patients’ inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0–11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients’ stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0–16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0–4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients’ urine specimens after throat swabs were negative. Using a multiple linear regression model (F=2.669, P=0.044, and adjusted R²=0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients’ stools (t=-2.699, P=0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs 8.0 days, respectively; t=2.550, P=0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs 11 days, respectively; t=4.631, P <0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P >0.05). Conclusions In brief, as the clearance of viral RNA in patients’ stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.

BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.
Adult ; Aged ; Betacoronavirus ; genetics ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; genetics ; rehabilitation ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; genetics ; rehabilitation ; RNA, Viral ; genetics ; Real-Time Polymerase Chain Reaction ; Retrospective Studies

The coronavirus disease 2019(COVID-19) is raging in China and more than 20 other countries and regions since the middle of December 2019. Currently, there is no specific drug or vaccine besides symptomatic supportive therapy. Taking full advantage of the clinical experience of traditional Chinese medicine(TCM) in preventing and controlling major epidemics such as SARS, it is an important mission for TCM to propose effective formula with immediate response and solid evidence by using modern biomedical knowledge and techniques(molecular docking assisted TCM formulation for short). In view of the high homology between the gene sequences of the novel coronavirus and SARS virus, and the similarities between the two in terms of pathogenic mechanism and clinical manifestations, our team established a rapid screening and optimization model for the prevention and treatment of the novel coronavirus based on clinical experience and molecular docking technology. Firstly, the clinical team and the research team pre-developed and screened TCM formula by using "back-to-back" manner. Then, the formula was optimized and determined by comparing and analyzing the results of the two groups. The results showed that the research team screened out 46 active ingredients from candidate TCMs that could act on the novel coronavirus S-protein-binding site of human ACE2 protein, which were mainly attributed to 7 herbs such as Lonicerae Japonicae Flos and Mori Folium. The result was largely consistent with the formula raised by the clinical group, verifying and supporting its rationality. This provides evidence for the scientific and potential efficacy of the TCM prescription from the perspective of treatment target analysis, and also suggests that the TCM prescription has the potential to directly inhibit viral infection in addition to improving clinical symptoms or syndromes. Based on this, our team optimized and formed a new anti-coronavirus TCM prescription "Keguan Yihao", immediately providing the TCM prescription with certain clinical experience and objective evidence support for the prevention and treatment of new emergent infectious diseases in our hospital. The TCM prescription was combined with modern medicine symptomatic supportive treatment for clinical treatment, preliminary results showed better effect than symptomatic supportive therapy alone. This research has innovated the method mode in clinical practice and basic research integration of traditional Chinese medicine for the prevention and control of new emerging infectious diseases. It is of great significance to further improve the rapid response mechanism of TCM in face of major epidemics, and further improve the capability level of TCM to prevent and treat new emerging infectious diseases.
Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/pharmacology* ; Betacoronavirus ; COVID-19 ; China ; Coronavirus Infections/drug therapy* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pandemics ; Peptidyl-Dipeptidase A/chemistry* ; Pneumonia, Viral/drug therapy* ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/chemistry* ; COVID-19 Drug Treatment

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate