Hemodynamic Changes during a Deep Inspiration Maneuver Predict Fluid Responsiveness in Spontaneously Breathing Patients

Objective. We hypothesized that the hemodynamic response to a deep inspiration maneuver (DIM) indicates fluid responsiveness in spontaneously breathing (SB) patients. Design. Prospective study. Setting. ICU of a general hospital. Patients. Consecutive nonintubated patients without mechanical ventilation, considered for volume expansion (VE). Intervention. We assessed hemodynamic status at baseline and after VE. Measurements and Main Results. We measured radial pulse pressure (PP) using an arterial catheter and peak velocity of femoral artery flow (VF) using continuous Doppler. Changes in PP and VF induced by a DIM (ΔPPdim and ΔVFdim) were calculated in 23 patients. ΔPPdim and ΔVFdim ≥12% predicted responders to VE with sensitivity of 90% and specificity of 100%. Conclusions. In a restricted population of SB patients with severe sepsis or acute pancreatitis, ΔPPdim and ΔVFdim are accurate indices for predicting fluid responsiveness. These results should be confirmed in a larger population before validating their use in current practice

Intensive care unit-acquired Stenotrophomonas maltophilia: incidence, risk factors, and outcome

INTRODUCTION: The aim of this study was to determine incidence, risk factors, and impact on outcome of intensive care unit (ICU)-acquired Stenotrophomonas maltophilia. METHODS: This prospective observational case-control study, which was a part of a cohort study, was conducted in a 30-bed ICU during a three year period. All immunocompetent patients hospitalised >48 hours were eligible. Patients with non-fermenting Gram-negative bacilli (NF-GNB) at ICU admission were excluded. Patients without ICU-acquired S. maltophilia who developed an ICU-acquired NF-GNB other than S. maltophilia were also excluded. Screening (tracheal aspirate and skin, anal, and nasal swabs) for NF-GNB was performed in all patients at ICU admission and weekly. Univariate and multivariate analyses were performed to determine risk factors for ICU-acquired S. maltophilia and for ICU mortality. RESULTS: Thirty-eight (2%) patients developed an S. maltophilia ICU-acquired colonisation and/or infection and were all successfully matched with 76 controls. Chronic obstructive pulmonary disease (COPD) and duration of antibiotic treatment (odds ratio [OR] [95% confidence interval (CI)] = 9.4 [3 to 29], p < 0.001, and 1.4 [1 to 2.3], p = 0.001, respectively) were independently associated with ICU-acquired S. maltophilia. Mortality rate (60% versus 40%, OR [95% CI] = 1.3 [1 to 1.7, p = 0.037]), duration of mechanical ventilation (23 ± 16 versus 7 ± 11 days, p < 0.001), and duration of ICU stay (29 ± 21 versus 15 ± 17 days, p < 0.001) were significantly higher in cases than in controls. In addition, ICU-acquired infection related to S. maltophilia was independently associated with ICU mortality (OR [95% CI] = 2.8 [1 to 7.7], p = 0.044). CONCLUSION: COPD and duration of antibiotic treatment are independent risk factors for ICU-acquired S. maltophilia. ICU-acquired S. maltophilia is associated with increased morbidity and mortality rates. ICU-acquired infection related to S. maltophilia is an independent risk factor for ICU mortality

Effect of ventilator-associated tracheobronchitis on outcome in patients without chronic respiratory failure: a case–control study

INTRODUCTION: Our objective was to determine the effect of ventilator-associated tracheobronchitis (VAT) on outcome in patients without chronic respiratory failure. METHODS: This was a retrospective observational matched study, conducted in a 30-bed intensive care unit (ICU). All immunocompetent, nontrauma, ventilated patients without chronic respiratory failure admitted over a 6.5-year period were included. Data were collected prospectively. Patients with nosocomial pneumonia, either before or after VAT, were excluded. Only first episodes of VAT occurring more than 48 hours after initiation of mechanical ventilation were studied. Six criteria were used to match cases with controls, including duration of mechanical ventilation before VAT. Cases were compared with controls using McNemar's test and Wilcoxon signed-rank test for qualitative and quantitative variables, respectively. Variables associated with a duration of mechanical ventilation longer than median were identified using univariate and multivariate analyses. RESULTS: Using the six criteria, it was possible to match 55 (87%) of the VAT patients (cases) with non-VAT patients (controls). Pseudomonas aeruginosa was the most frequently isolated bacteria (34%). Although mortality rates were similar between cases and controls (29% versus 36%; P = 0.29), the median duration of mechanical ventilation (17 days [range 3–95 days] versus 8 [3–61 days]; P < 0.001) and ICU stay (24 days [range 5–95 days] versus 12 [4–74] days; P < 0.001) were longer in cases than in controls. Renal failure (odds ratio [OR] = 4.9, 95% confidence interval [CI] = 1.6–14.6; P = 0.004), tracheostomy (OR = 4, 95% CI = 1.1–14.5; P = 0.032), and VAT (OR = 3.5, 95% CI = 1.5–8.3; P = 0.004) were independently associated with duration of mechanical ventilation longer than median. CONCLUSION: VAT is associated with longer durations of mechanical ventilation and ICU stay in patients not suffering from chronic respiratory failure

The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis

The accurate repair of DNA double-strand breaks (DSBs), highly toxic DNA lesions, is crucial for genome integrity and is tightly regulated during the cell cycle. In mitosis, cells inactivate DSB repair in favor of a tethering mechanism that stabilizes broken chromosomes until they are repaired in the subsequent cell cycle phases. How this is achieved mechanistically is not yet understood, but the adaptor protein TOPBP1 is critically implicated in this process. Here, we identify CIP2A as a TOPBP1-interacting protein that regulates TOPBP1 localization specifically in mitosis. Cells lacking CIP2A display increased radio-sensitivity, micronuclei formation and chromosomal instability. CIP2A is actively exported from the cell nucleus in interphase but, upon nuclear envelope breakdown at the onset of mitosis, gains access to chromatin where it forms a complex with MDC1 and TOPBP1 to promote TOPBP1 recruitment to sites of mitotic DSBs. Collectively, our data uncover CIP2A-TOPBP1 as a mitosis-specific genome maintenance complex

SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition

Background Following SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic. Methods The study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA. Results The frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups. Conclusions The antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens

SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition

BackgroundFollowing SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic.MethodsThe study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA.ResultsThe frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups.ConclusionsThe antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens