With both in vivo and in vitro experiments, the present study was conducted to investigate the effect of regulatory T cell (Treg) on promoting T-lymphocyte apoptosis and its regulatory mechanism through transforming growth factor-beta (TGF-b1) signaling in mice. A murine model of polymicrobial sepsis was reproduced by cecal ligation and puncture (CLP); PC61 and anti-TGF-b antibodies were used to decrease counts of CD4 + CD25 +Tregs and inhibit TGF-b activity, respectively. Splenic CD4 + CD25 + Tregs and CD4 + CD25 -T cells were isolated. Phenotypes, including cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), forkhead/winged helix transcription factor p3 (Foxp3), and TGFb1 m + , as well as the apoptotic rate of CD4 + CD25 -T cell, were analyzed by flow cytometry. Real-time reverse transcription-polymerase chain reaction was performed to determine mRNA expression of TGF-b1, and the expressions of Smad2/Smad3, Bcl-2 superfamily members of Bcl-2/Bim, cytochrome C, the mitochondrial membrane potential, and caspases in CD4 + CD25 -T cells were simultaneously determined. After treatment with PC61 or anti-TGF-b antibody, CTLA-4, Foxp3, and TGFb1 m + expressions of CD4 + CD25 + Tregs were markedly decreased in comparison to that of the CLP group and the apoptosis rate of CD4 + CD25 -T cells was significantly positively correlated with the expression of TGF-b1. Meanwhile, levels of P-Smad2/P-Smad3, proapoptotic protein Bim, cytochrome C, and activity of caspase-3, -8, -9 were downregulated, whereas the mitochondrial membrane potential and antiapoptotic protein Bcl-2 expression were restored. Taken together, our data indicated that the TGF-b1 signal could be partly involved in the apoptosis of CD4 + CD25 -T cells promoted by CD4 + CD25 + Tregs, therefore inhibition of TGF-b1 expression may provide a novel strategy for the improvement of host immunosuppression following sepsis.

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Purpose In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. Methods We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. Results 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp . (20.3%), Escherichia coli (15.8%), and Pseudomonas spp . (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28. Conclusions HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-022-06944-2.

PurposeTo evaluate the quality of life among survivors after sepsis in 2 years, comparing with critical patients without sepsis and the general people, analyze the changes and the predictors of quality of life among septic survivors.MethodsThis prospective case-control study screened the intensive care unit (ICU) patients in Tianjin Third Central Hospital from January 2014 to October 2017, and the Chinese general population in the previous studies was also included. According to inclusion criteria and exclusion criteria, 306 patients with sepsis were enrolled as the observation group, and another 306 patients without sepsis in ICU during the same period, whose ages, gender and Charlson Comorbidity Index matched with observation group, were enrolled as the control group. At 3 mo, 12 mo, and 24 mo after discharge, the Mos 36-item Short Form Health Survey (SF-36), the Euroqol-5 dimension (EQ-5D), and the activities of daily living (ADL) were evaluated in face-to-face for the quality of life among survivors.ResultsThere were 210 (68.6%) septic patients and 236 (77.1%) non-septic critically ill patients surviving. At 3 months after discharge, the observation and control groups had the similar demographic characteristics (age: 58.8 ± 18.1years vs. 57.5 ± 17.6 years, p = 0.542; male: 52.0% vs. 51.4%, p = 0.926). However, the observation group had higher acute physiology and chronic health evaluation II (APACHEII) scores, higher sequential organ failure assessment (SOFA) scores, longer hospital stay, and longer ICU stay than the control group did (p < 0.05). There were no significant differences in the eight dimensions of the SF36 scale, the EQ-5D health utility scores, and the activities of daily life scores between septic survivors and non-septic survivors (p > 0.05). In addition, compared with the quality of life of the Chinese general population (aged 55–64 years), the quality of life of septic patients were significantly lower at 3 months after discharge (p < 0.05). Comparing the quality of life of the ill patients who had been discharged at 3 mo and 24 mo, the general health improved statistically (p = 0.000) and clinically (score improvement > 5 points). Older age (OR, 1.050; 95% CI, 1.022–1.078, p = 0.000), female (OR, 3.375; 95% CI, 1.434–7.941, p = 0.005) and longer mechanical ventilation time (OR, 3.412; 95% CI, 1.413, 8.244, p = 0.006) were the risk factors for the quality of life of septic survivors.ConclusionThe long-term quality of life of septic survivors was similar to that of non-sepsis critically ill survivors. After discharge, the general health of sepsis improved overtime. Age, female and mechanical ventilation time (>5 days) were the predictors of the quality of life after sepsis.

Purpose Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily infects the lower airways and binds to angiotensin-converting enzyme 2 (ACE2) on alveolar epithelial cells. ACE2 is widely expressed not only in the lungs but also in the cardiovascular system. Therefore, SARS-CoV-2 can also damage the myocardium. This report aimed to highlight decreased heart rate variability (HRV) and cardiac injury caused by SARS-CoV-2. Materials and Methods We evaluated three COVID-19 patients who died. Patients’ data were collected from electronic medical records. We collected patient’s information, including baseline information, lab results, body temperature, heart rate (HR), clinical outcome and other related data. We calculated the HRV and the difference between the expected and actual heart rate changes as the body temperature increased. Results As of March 14, 2020, 3 (2.2%) of 136 patients with COVID-19 in Tianjin died in the early stage of the COVID-19 epidemic. The immediate cause of death for Case 1, Case 2, and Case 3 was cardiogenic shock, cardiac arrest and cardiac arrest, respectively. The HRV were substantially decreased in the whole course of all three cases. The actual increases in heart rate were 5 beats/min, 13 beats/min, and 4 beats/min, respectively, less than expected as their temperature increased. Troponin I and Creatine Kinase MB isoenzyme (CK-MB) were substantially increased only in Case 3, for whom the diagnosis of virus-related cardiac injury could not be made until day 7. In all three cases, decreased in HRV and HR changes occurred earlier than increases in cardiac biomarkers (e.g., troponin I and CK-MB). Conclusions In conclusion, COVID-19 could affect HRV and counteract tachycardia in response to increases in body temperature. The decreases of HRV and HR changes happened earlier than the increases of myocardial markers (troponin I and CK-MB). It suggested the decreases of HRV and HR changes might help predict cardiac injury earlier than myocardial markers in COVID-19, thus its early identification might help improve patient prognosis.

PurposeThis prospective observational study aims to evaluate the accuracy of dead-space fraction derived from the ventilator volumetric capnography (volumetric CO2) or a prediction equation to predict the survival of mechanically ventilated patients with acute respiratory distress syndrome (ARDS).MethodsConsecutive VD/VT measurements were obtained based upon a prediction equation validated by Frankenfield et al for dead-space ventilation fraction: VD/VT = 0.320 + 0.0106 (PaCO2-ETCO2) + 0.003 (RR) + 0.0015 (age) in adult patients who had infection-related severe pneumonia and were confirmed as having ARDS. Here PaCO2 is the arterial partial pressure of carbon dioxide in mmHg; ETCO2, the end-tidal carbon dioxide measurement in mmHg; RR, respiratory rate per minute; and age in years. Once the patient had intubation, positive end expiratory pressure was adjusted and after Phigh reached a steady state, VD/VT was measured and recorded as the data for the first day. VD/VT measurement was repeated on days 2, 3, 4, 5 and 6. Meanwhile we collected dead-space fraction directly from the ventilator volumetric CO2 and recorded it as Vd/Vt. We analyzed the changes in VD/VT and Vd/Vt over the 6-day period to determine their accuracy in predicting the survival of ARDS patients.ResultsOverall, 46 patients with ARDS met the inclusion criteria and 24 of them died. During the first 6 days of intubation, VD/VT was significantly higher in nonsurvivors on day 4 (0.70 ± 0.01 vs 0.57 ± 0.01), day 5 (0.73 ± 0.01 vs. 0.54 ± 0.01), and day 6 (0.73 ± 0.02 vs. 0.54 ± 0.01) (all p = 0.000). Vd/Vt showed no significant difference on days 1–4 but it was much higher in nonsurvivors on day 5 (0.45 ± 0.04 vs. 0.41 ± 0.06) and day 6 (0.47 ± 0.05 vs. 0.40 ± 0.03) (both p = 0.008). VD/VT on the fourth day was more accurate to predict survival than Vd/Vt. The area under the receiver-operating characteristic curve for VD/VT and Vd/Vt in evaluating ARDS patients survival was day 4 (0.974 ± 0.093 vs. 0.701 ± 0.023, p = 0.0024) with the 95% confidence interval being 0.857–0.999 vs. 0.525–0.841.ConclusionCompared with Vd/Vt derived from ventilator volumetric CO2, VD/VT on day 4 calculated by Frankenfield et al's equation can more accurately predict the survival of ARDS patients.

Background The use of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) for cardiorespiratory support is increasing. However, few criteria for hemodynamic management have been described yet in V-A ECMO patients. Method We performed a review of hemodynamic management during V-A ECMO in CS patient based the literature published. We discuss how to optimize hemodynamic management. Results Patients on V-A ECMO require special hemodynamic management. It is crucial to maintain an adequate tissue oxygen supply and demand balance. Hemodynamic optimization is essential to support LV decompression and improve end-organ function and should be initiated immediately after initiating V-A ECMO support, during which more positive fluid balance is associated with worse outcomes. Conclusion The hemodynamic management of CS patients with V-A ECMO are complex and involves various aspect. Clinicians who care for patients on VA ECMO should combined use many availability indicators to guide hemodynamic management.

On March 12, 2020, the World Health Organization (WHO) announced that the coronavirus disease 2019 (COVID-19) outbreak had become a pandemic. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily infects the lower airways and binds to Angiotensin-Converting Enzyme 2 (ACE2) on alveolar epithelial cells. ACE2 is widely expressed, not only in the lungs but also in the cardiovascular system. Therefore, SARS-CoV-2 can also damage the myocardium. We analysed three COVID-19 cases that resulted in death and found that either COVID-19 or antiviral drugs could affect the coupling between the autonomic nervous system and the sinus node, thus affecting heart rate variability and preventing the heart rate from rising in response to the increase in body temperature. Early detection of the preclinical phase of cardiac autonomic dysfunction may help determine patients in need of aggressive treatment and control of cardiovascular risk factors. Antiviral drugs should be used with caution in patients with heart injury.