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1.
J Med Virol ; 95(1): e28337, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36418241

RESUMO

Viral reactivation is widespread in patients with severe pneumonia, yet the landscape of viral reactivation in the lungs is not well-known. This study aims to assess the landscape and clinical features of viral reactivation in the early onset of severe pneumonia in ICU patients. The clinical data from 97 patients were collected retrospectively from the intensive care units of five teaching hospitals between June 2018 and July 2021. Metagenomic next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid (BALF) was performed at the onset of severe pneumonia. Cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), and Epstein-Barr virus (EBV) were the most common reactivated viruses in the lower respiratory tract of patients with severe pneumonia. After adjusting for the risk of confounding and competition of age, sex, sequential organ failure assessment, acute physiology chronic health assessment II and immunosuppression status, viral reactivation resulted in an overall 2.052-fold increase in 28-day all-cause mortality (95% CI: 1.004-4.194). This study showed that CMV, HSV-1, and EBV were the most common reactivated viruses in the lungs of patients with severe pneumonia. The existence of viral reactivations was associated with an increased risk of mortality. The simultaneous reactivation of multiple viruses needs to be considered in the design of clinical trials.


Assuntos
Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 1 , Pneumonia Viral , Pneumonia , Humanos , Estudos Retrospectivos , Herpesvirus Humano 4/fisiologia , Citomegalovirus/fisiologia , Pulmão
2.
BMC Infect Dis ; 23(1): 199, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013474

RESUMO

BACKGROUND: vasopressin is commonly used as a second-line vasopressor for patients with septic shock, but the optimal timing of initiation is uncertain. This study was designed to investigate when vasopressin initiation may be beneficial for 28-day mortality in septic shock patients. METHODS: This was a retrospective observational cohort study from the MIMIC-III v1.4 and MIMIC-IV v2.0 databases. All adults diagnosed with septic shock according to Sepsis-3 criteria were included. Patients were stratified into two groups based on norepinephrine (NE) dose at the time of vasopressin initiation, defined as the low doses of NE group (NE<0.25 µg/kg/min) and the high doses of NE group (NE ≥ 0.25 µg/kg/min). The primary end-point was 28-day mortality after diagnosis of septic shock. The analysis involved propensity score matching (PSM), multivariable logistic regression, doubly robust estimation, the gradient boosted model, and an inverse probability-weighting model. RESULTS: A total of 1817 eligible patients were included in our original cohort (613 in the low doses of NE group and 1204 in the high doses of NE group). After 1:1 PSM, 535 patients from each group with no difference in disease severity were included in the analysis. The results showed that vasopressin initiation at low doses of NE was associated with reduced 28-day mortality (odds ratio [OR] 0.660, 95% confidence interval [CI] 0.518-0.840, p < 0.001). Compared with patients in the high doses of NE group, patients in the low doses of NE group received significantly shorter duration of NE, with less intravenous fluid volume on the first day after initiation of vasopressin, more urine on the second day, and longer mechanical ventilation-free days and CRRT-free days. Nevertheless, there were no significant differences in hemodynamic response to vasopressin, duration of vasopressin, and ICU or hospital length of stay. CONCLUSIONS: Among adults with septic shock, vasopressin initiation when low-dose NE was used was associated with an improvement in 28-day mortality.


Assuntos
Choque Séptico , Adulto , Humanos , Choque Séptico/tratamento farmacológico , Estudos de Coortes , Vasoconstritores/uso terapêutico , Vasoconstritores/efeitos adversos , Vasopressinas/uso terapêutico , Vasopressinas/efeitos adversos , Norepinefrina/uso terapêutico , Norepinefrina/efeitos adversos , Estudos Retrospectivos
3.
Crit Care ; 27(1): 248, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353839

RESUMO

PURPOSE: The significance of detecting human herpesvirus 7 (HHV-7) in the lower respiratory tract of patients with severe pneumonia is unclear. This study aims to evaluate the clinical characteristics and prognosis of detecting HHV-7 in the lower respiratory tract of patients with severe pneumonia. METHODS: Patients with severe pneumonia requiring invasive mechanical ventilation and underwent commercial metagenomic next-generation sequencing (mNGS) testing of bronchoalveolar lavage fluid from January 2019 to March 2023 were enrolled in 12 medical centers. Clinical data of patients were collected retrospectively, and propensity score matching was used for subgroup analysis and mortality assessment. RESULTS: In a total number of 721 patients, 45 cases (6.24%) were identified with HHV-7 positive in lower respiratory tract. HHV-7 positive patients were younger (59.2 vs 64.4, p = 0.032) and had a higher rate of co-detection with Cytomegalovirus (42.2% vs 20.7%, p = 0.001) and Epstein-Barr virus (35.6% vs 18.2%, p = 0.008). After propensity score matching for gender, age, SOFA score at ICU admission, and days from ICU admission to mNGS assay, there was no statistically significant difference in the 28-day mortality rate between HHV-7 positive and negative patients (46.2% vs 36.0%, p = 0.395). Multivariate Cox regression analysis adjusting for gender, age, and SOFA score showed that HHV-7 positive was not an independent risk factor for 28-day mortality (HR 1.783, 95%CI 0.936-3.400, p = 0.079). CONCLUSION: HHV-7 was detected in the lungs of 6.24% of patients with severe pneumonia. The presence of HHV-7 in patients with severe pneumonia requiring invasive mechanical ventilation is associated with a younger age and co-detected of Cytomegalovirus and Epstein-Barr virus. While HHV-7 positivity was not found to be an independent risk factor for mortality in this cohort, this result may have been influenced by the relatively small sample size of the study.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 7 , Pneumonia , Humanos , Estudos Retrospectivos , Incidência , Herpesvirus Humano 4 , Pneumonia/epidemiologia , Pulmão , Citomegalovirus
4.
Crit Care ; 26(1): 167, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35676730

RESUMO

BACKGROUND: The purpose of this study was to clarify the prognostic value of Pentraxin-3 (PTX3) on the mortality of patients with sepsis. METHODS: Publications published up to January 2021 were retrieved from PubMed, EMBASE, and the Cochrane library. Data from eligible cohort and case-control studies were extracted for the meta-analysis. Multivariate regression analysis was used to evaluate the correlation of the outcomes with sample size and male proportion. RESULTS: A total of 17 studies covering 3658 sepsis patients were included. PTX3 level was significantly higher in non-survivor compared to survivor patients (SMD (95% CI): -1.06 (-1.43, -0.69), P < 0.001). Increased PTX3 level was significantly associated with mortality (HR (95% CI): 2.09 (1.55, 2.81), P < 0.001). PTX3 showed good predictive capability for mortality (AUC:ES (95% CI): 0.73 (0.70, 0.77), P < 0.001). The outcome comparing PTX3 level in non-survivors vs. survivors and the outcome of the association between PTX3 and mortality were associated with sample size but not male proportion. AUC was associated with both sample size and male proportion. CONCLUSIONS: PTX3 level was significantly higher in non-survivor compared to survivor patients with sepsis. Elevated PTX3 level was significantly associated with mortality. Furthermore, the level of PTX3 might predict patient mortality.


Assuntos
Proteína C-Reativa , Sepse , Componente Amiloide P Sérico , Biomarcadores , Proteína C-Reativa/análise , Estudos de Coortes , Humanos , Masculino , Prognóstico , Curva ROC , Sepse/mortalidade , Componente Amiloide P Sérico/análise
5.
J Med Virol ; 93(7): 4446-4453, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33448426

RESUMO

This study aims to comparatively analyze the therapeutic efficacy upon multiple medication plans over lopinavir/ritonavir (LPV/r), arbidol (ARB), and methylprednisolone on patients with coronavirus disease 2019 (COVID-19). Totally, 75 COVID-19 patients admitted to The First Affiliated Hospital, Zhejiang University School of Medicine from January 22, 2020 to February 29, 2020 were recruited and grouped based on whether or not LPV/r and ARB were jointly used and whether or not methylprednisolone was used. Indexes including body temperature, time for nucleic acid negative conversion, hospital stays, and laboratory indexes were examined and compared. For all patients, there were no significant differences in the change of body temperature, the time for negative conversion, and hospital stays whether LPV/r and ARB were jointly used or not. While for severe and critically severe patients, methylprednisolone noticeably reduced the time for negative conversion. Meanwhile, the clinical efficacy was superior on patients receiving methylprednisolone within 3 days upon admission, and the duration of hospital stays was much shorter when methylprednisolone was given at a total dose of 0-400 mg than a higher dose of >400 mg if all patients received a similar dose per day. Nonetheless, no significant changes across hepatic, renal, and myocardial function indexes were observed. LPV/r combined with ARB produced no noticeably better effect on COVID-19 patients relative to the single-agent treatment. Additionally, methylprednisolone was efficient in severe and critically severe cases, and superior efficacy could be realized upon its early, appropriate, and short-term application.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Indóis/uso terapêutico , Lopinavir/uso terapêutico , Metilprednisolona/uso terapêutico , Ritonavir/uso terapêutico , China , Combinação de Medicamentos , Feminino , Febre/tratamento farmacológico , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/efeitos dos fármacos
6.
Emerg Infect Dis ; 26(6): 1335-1336, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32134381

RESUMO

A woman with coronavirus disease in her 35th week of pregnancy delivered an infant by cesarean section in a negative-pressure operating room. The infant was negative for severe acute respiratory coronavirus 2. This case suggests that mother-to-child transmission is unlikely for this virus.


Assuntos
Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Adulto , Betacoronavirus , COVID-19 , Cesárea , China , Infecções por Coronavirus/terapia , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Masculino , Pandemias , Pneumonia Viral/terapia , Gravidez , SARS-CoV-2
7.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 240-244, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32391671

RESUMO

OBJECTIVE: To analyze the clinical characteristics and pregnancy outcomes of pregnant women complicated with coronavirus disease 2019 (COVID-19). METHODS: The clinical data of 3 pregnant women with COVID-19 admitted to the First Affiliated Hospital of Zhejiang University School of Medicine from January 19 to February 10, 2020 were retrospectively analyzed. RESULTS: There was one case in the first-trimester pregnancy (case 1), one in the second-trimester pregnancy (case 2) and one in third-trimester pregnancy (case 3). Cough, fever, fatigue, lung imaging changes were the main manifestations. The white cell count, lymphocyte percentage had no significantly changes in case 1 and case 3, while the levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-6 and IL-10 elevated. The lymphocyte count and lymphocyte percentage decreased and the inflammatory indicators significantly increased in case 2. All patients were treated with antiviral, antitussive, oxygen inhalation; case 3 received glucocorticoids, case 2 with severe illness received glucocorticoids and additionally gamma globulin. All three cases were cured and discharged. Case 1 with early pregnancy chose to terminate pregnancy after discharge; case 2 chose to continue pregnancy without obstetric complications; and case 3 had cesarean section delivery due to abnormal fetal heart monitoring. CONCLUSIONS: The report shows that COVID-19 in pregnancy women could be cured with active treatment, and the maternal and fetal outcomes can be satisfactory.


Assuntos
Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Complicações Infecciosas na Gravidez , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , COVID-19 , Cesárea , Infecções por Coronavirus/tratamento farmacológico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Oxigênio/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/patologia , Resultado da Gravidez , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento , gama-Globulinas/uso terapêutico
8.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 158-169, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32391659

RESUMO

Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on Diagnosis and treatment of novel coronavirus pneumonia (trial version 6), and Management of COVID-19: the Zhejiang experience, we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.


Assuntos
Infecções por Coronavirus , Tratamento Farmacológico , Pandemias , Pneumonia Viral , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Estado Terminal , Humanos , Apoio Nutricional , Pneumonia Viral/tratamento farmacológico , Probióticos/administração & dosagem , SARS-CoV-2
9.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 232-239, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32391670

RESUMO

Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19). Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical ill COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial ow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO2) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.


Assuntos
Infecções por Coronavirus/terapia , Oxigênio , Pneumonia Viral/terapia , Idoso , Betacoronavirus/isolamento & purificação , COVID-19 , Cânula , Humanos , Oxigênio/administração & dosagem , Pandemias , SARS-CoV-2
10.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 147-157, 2020 02 21.
Artigo em Chinês | MEDLINE | ID: mdl-32391658

RESUMO

The current epidemic situation of coronavirus disease 2019 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance" strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinary personalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in 10%patients' blood samples at acute period and 50%of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifying cytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance" strategy effectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviral effects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favored the balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short period of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as Lactobacillus and Bifidobacterium, so nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore,we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.


Assuntos
Infecções por Coronavirus , Gerenciamento Clínico , Pandemias , Pneumonia Viral , Betacoronavirus/isolamento & purificação , COVID-19 , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Diagnóstico Precoce , Fezes/virologia , Humanos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , SARS-CoV-2 , Escarro/virologia
13.
Zhonghua Nei Ke Za Zhi ; 55(2): 121-6, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-26875581

RESUMO

OBJECTIVE: To explore the clinical manifestations, antimicrobial therapy, and risk factors of mortality in patients with Acinetobacter baumannii bloodstream infection. METHODS: Clinical data of 153 patients with Acinetobacter baumannii bloodstream infection hospitalized in First Affiliated Hospital of Zhejiang University from January 2013 to September 2014 were analyzed retrospectively.According to the 28-day survival after diagnosis, the patients were divided into death group (n=76) and survival group (n=77). Data related to demographic and clinical characteristics, underlying diseases, treatment, invasive procedures, bacterial resistance to antibiotics, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ )scores at onset, and antimicrobial therapy were collected.The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis. RESULTS: This study included 153 patients with Acinetobacter baumannii bloodstream infection. The 28-day mortality was 49.7%. The independent risk factors of mortality were APACHE Ⅱ score ≥ 22 at onset (OR=15.7, 95%CI 5.1-48.1, P<0.001), septic shock(OR=6.3, 95%CI 1.9-21.3, P=0.003), and administration of steroids(OR=3.6, 95%CI 1.0-12.3, P=0.043). Compared with subjects treated with non-cefoperazone-sulbactam-based regimen , those treated with cefoperazone-sulbactam for multidrug-resistant Acinetobacter baumannii(MDR-AB) had significantly lower mortality on day7, day14 and day28(8.9% vs 59.2%, 31.1% vs 65.8%, 44.4% vs 72.4% respectively). CONCLUSIONS: The patients with Acinetobacter baumannii bloodstream infection have high mortality within one month. Administration of steroids and septic shock are associated with poor prognosis. APACHEⅡ score ≥ 22 at onset predicts adverse outcome. Cefoperazone-sulbactam-based antimicrobial therapy improves patients' survival.


Assuntos
Infecções por Acinetobacter/patologia , Bacteriemia/patologia , APACHE , Infecções por Acinetobacter/diagnóstico , Infecções por Acinetobacter/mortalidade , Acinetobacter baumannii , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/mortalidade , Cefoperazona/uso terapêutico , Humanos , Estudos Retrospectivos , Fatores de Risco , Choque Séptico/diagnóstico , Choque Séptico/patologia , Sulbactam/uso terapêutico
15.
Zhonghua Yi Xue Za Zhi ; 95(3): 210-3, 2015 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-25877033

RESUMO

OBJECTIVE: To explorer the efficacies of continuous high volume hemofiltration (CHVHF) in severe sepsis patients with multiple organ dysfunction syndrome (MODS). METHODS: A total of 80 cases of severe sepsis patients with MODS treated at our center from 2011 January to 2013 October were selected and assigned to receive CHVHF (n = 42) and continuous volume hemofiltration (CVHF, n = 38). The changes of vital signs, acute physiology & chronic health evaluationII (APACHEII) scores, MODS evaluation scores, hemodynamics, liver & kidney function parameters, arterial blood lactate and procalcitonin (PCT) were observed before and after treatment. RESULTS: After treatment, their temperatures and heart rates improved and the scores of APACHEIIand MODS were significantly lower (P < 0.05). Hemodynamics significantly improved at 48 and 72 h post-treatment. The values of mean arterial pressure (MAP), cardiac index (CI), stroke volume index (SVI) and systemic vascular resistance index (SVRI) became stabilized as compared with pre-treatment. There were significant differences (P < 0.05). The parameters of liver and kidney function gradually improved after CHVHF. And arterial blood lactate and PCT returned to normal at 24, 48 and 72 h post-treatment (P < 0.05). CONCLUSION: CHVHF may stabilize vital signs and improve hemodynamics, organ function and tissue perfusion in septic patients with MODS.


Assuntos
Hemofiltração , Insuficiência de Múltiplos Órgãos , Sepse , Frequência Cardíaca , Hemodinâmica , Humanos , Ácido Láctico , Diálise Renal , Volume Sistólico
16.
Int Immunopharmacol ; 126: 111241, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37984253

RESUMO

BACKGROUND: Sepsis is a systemic inflammatory syndrome that can lead to multiple organ dysfunction and life-threatening complications. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to be present in half of patients with septic shock, increasing their mortality rate to 70-90%. The pathogenesis of SIMD is complex, and no specific clinical treatment has yet been developed. Caloric restriction mimetics (CRM), compounds that simulate the biochemical and functional properties of CR, can improve cardiovascular injury by activating autophagy. This study investigated the effect of a new type of CRM which can induce hypoxia, the SGLT nonspecific inhibitor phlorizin on SIMD. MATERIALS AND METHODS: In vivo, phlorizin was administered at 1 mg/kg/day intragastrically for 28 days. In vitro, AC16 was treated with 120 µM phlorizin for 48 h. Echocardiography was used to assess cardiac function. Myocardial injury markers were detected in serum and cell supernatant. Western blotting was employed to detect changed proteins associated with apoptosis and autophagy. Immunofluorescence, immunohistochemistry, co-immunoprecipitation, molecular docking, and other methods were also used to illustrate cellular changes. RESULTS: In vivo, phlorizin significantly improved the survival rate and cardiac function after sepsis injury, reduced markers of myocardial injury, inhibited myocardial apoptosis and oxidative stress, and promoted autophagy. In vitro, phlorizin alleviated the apoptosis of AC16, as well as inhibited oxidative stress and apoptotic enzyme activity. Phlorizin acts on autophagy at multiple sites through low energy (activation of AMPK) and hypoxia (release of Beclin-1 by Hif-1α/Bnip3 axis), promoting the formation and degradation of autophagosomes. CONCLUSION: We indicated for the first time that phlorizin could inhibit glucose uptake via GLUT-1 and conforms to the metabolic characteristics of CRM, it can induce the hypoxic transcriptional paradigm. In addition, it inhibits apoptosis and improves SIMD by promoting autophagy generation and unobstructing autophagy flux. Moreover, it affects autophagy by releasing Beclin-1 through the Hif-1α/Bnip3 axis.


Assuntos
Autofagia , Miócitos Cardíacos , Florizina , Sepse , Florizina/farmacologia , Hipóxia , Miócitos Cardíacos/efeitos dos fármacos , Sepse/complicações , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Restrição Calórica , Coração/efeitos dos fármacos , Cardiotônicos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Apoptose
17.
Infect Drug Resist ; 17: 1267-1279, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572421

RESUMO

Introduction: The purpose of this study was to compare the viral shedding time in patients infected with the Omicron variant during Paxlovid therapy and conventional therapy and to analyze the effects of Paxlovid on patients infected with COVID-19. Methods: In this study, the demographic and clinical characteristics and laboratory data of 3159 patients infected with the SARS-CoV-2 Omicron variant treated at Jilin Province People's Hospital were collected and analyzed. A total of 362 patients received Paxlovid therapy, and 2797 patients received conventional therapy. After propensity score matching (PSM), 1086 patients were obtained. Results: The difference in platelet (PLT) count between the two groups was statistically significant but within the normal range (P < 0.05). CT value revealed that the nucleic acid test results became negative more quickly in the Paxlovid therapy group. Analysis of the Paxlovid therapy group showed that IgG and IgM levels were increased after Paxlovid therapy administration. Conclusion: The CT value of the Paxlovid therapy group became negative more quickly. This finding suggests that Paxlovid treatment after early diagnosis of the Omicron variant may achieve good therapeutic efficacy.

18.
Microbes Infect ; : 105373, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38857786

RESUMO

Gut microbiota dysbiosis increases the susceptibility to Clostridioides difficile infection (CDI). In this study, we monitored C. difficile colonization (CDC) patients from no CDC status (CDN) to CDC status (CDCp) and CDI patients from asymptomatic status before CDI (PRECDI), CDI status (ONCDI), to asymptomatic status after CDI (POSTCDI). Based on metagenomic sequencing, we aimed to investigate the interaction pattern between gut microbiota and C. difficile. There was no significant difference of microbiota diversity between CDN and CDCp. In CDCp, Bacteroidetes and short-chain fatty acid (SCFA)-producing bacteria increased, with a positive correlation between SCFA-producing bacteria and C. difficile colonization. Compared with PRECDI, ONCDI and POSTCDI showed a significant decrease in microbiota diversity, particularly in Bacteroidetes and SCFA-producing bacteria, with a positive correlation between opportunistic pathogen and C. difficile. Fatty acid metabolism, and amino acid biosynthesis were enriched in CDN, CDCp, and PRECDI, while bile secretion was enriched in ONCDI and POSTCDI. Microbiota and metabolic pathways interaction networks in CDN and CDCp were more complex, particularly pathways in fatty acid and bile acid metabolism. Increasing of Bacteroidetes and SCFA-producing bacteria, affecting amino acid and fatty acid metabolism, is associated with colonization resistance to C. difficile and inhibiting the development of CDI.

19.
Infect Dis (Lond) ; : 1-12, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753988

RESUMO

BACKGROUND: There is a critical need for a rapid and sensitive pathogen detection method for septic patients. This study aimed to investigate the diagnostic efficacy of Digital droplet polymerase chain reaction (ddPCR) in identifying pathogens among suspected septic patients. METHODS: We conducted a prospective pilot diagnostic study to clinically validate the multiplex ddPCR panel in diagnosing suspected septic patients. A total of 100 sepsis episodes of 89 patients were included in the study. RESULTS: In comparison to blood culture, the ddPCR panel exhibited an overall sensitivity of 75.0% and a specificity of 69.7%, ddPCR yielded an additional detection rate of 17.0% for sepsis cases overall, with a turnaround time of 2.5 h. The sensitivity of ddPCR in the empirical antibiotic treatment and the non-empirical antibiotic treatment group were 78.6% versus 80.0% (p > 0.05). Antimicrobial resistance genes were identified in a total of 13 samples. Whenever ddPCR detected the genes beta-lactamase-Klebsiella pneumoniae carbapenemase (blaKPC) or beta-lactamase-New Delhi metallo (blaNDM), these findings corresponded to the cultivation of carbapenem-resistant gram-negative bacteria. Dynamic ddPCR monitoring revealed a consistent alignment between the quantitative ddPCR results and the trends observed in C-reactive protein and procalcitonin levels. CONCLUSIONS: Compared to blood culture, ddPCR exhibited higher sensitivity for pathogen diagnosis in suspected septic patients, and it provided pathogen and drug resistance information in a shorter time. The quantitative results of ddPCR generally aligned with the trends seen in C-reactive protein and procalcitonin levels, indicating that ddPCR can serve as a dynamic monitoring tool for pathogen load in septic patients.

20.
Front Immunol ; 14: 1099468, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36825017

RESUMO

Immunosuppressed patients can contract parvovirus B19, and some may experience hemophagocytic lymphohistiocytosis (HLH). Herein, we describe the first report of hemophagocytic lymphohistiocytosis in a heart-lung transplant patient with concomitant parvovirus B19 infection. The patient was treated with intravenous immune globulin (IVIG) and the features of HLH were remission. This instance emphasizes the significance of parvovirus B19 monitoring in transplant patients with anemia; if HLH complicates the situation, IVIG may be an adequate remedy. Finally, a summary of the development in diagnosing and managing parvovirus B19 infection complicated by HLH is provided.


Assuntos
Eritema Infeccioso , Transplante de Coração-Pulmão , Linfo-Histiocitose Hemofagocítica , Infecções por Parvoviridae , Parvovirus B19 Humano , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Eritema Infeccioso/complicações , Imunoglobulinas Intravenosas/uso terapêutico , Transplante de Coração-Pulmão/efeitos adversos , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/diagnóstico
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