Effect of anaemia and iron deficiency in heart failure with mildly reduced ejection fraction.

OBJECTIVE: The present study aims to clarify the prevalence and prognostic impact of anaemia and iron deficiency in patients with heart failure with mildly reduced ejection fraction (HFmrEF). BACKGROUND: The prognostic impact of anaemia and iron deficiency in HFmrEF has not yet been clarified. METHODS: Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. Patients with anaemia (i.e. haemoglobin <13 g/dL in males and < 12 g/dL in females) were compared to patients without, respectively patients with or without iron deficiency. The primary endpoint was all-cause mortality at 30 months (median follow-up), secondary endpoints comprised HF-related rehospitalisation. RESULTS: Two thousand one hundred and fifty four patients with HFmrEF with a median haemoglobin level of 12.2 g/dL were included. Anaemia was present in 52% of patients with HFmrEF and associated with a higher risk of all-cause mortality (44% vs. 18%; HR = 3.021; 95% CI 2.552-3.576; p =.001) and HF-related rehospitalisation (18% vs. 8%; HR = 2.351; 95% CI 1.819-3.040; p =.001) at 30 months, which was confirmed after multivariable adjustment. Although iron status was infrequently assessed in anaemics with HFmrEF (27%), the presence of iron deficiency was associated with higher risk of rehospitalisation for worsening HF (25% vs. 15%; HR = 1.746; 95% CI 1.024-2.976; p =.038), but not all-cause mortality (p =.279) at 30 months. CONCLUSION: Anaemia and iron deficiency are very common in atleast half of patients with HFmrEF and independently associated with adverse long-term prognosis.

Cerebrospinal fluid-related tissue damage in multiple sclerosis patients with iron rim lesions.

BACKGROUND: In multiple sclerosis (MS), iron rim lesions (IRLs) are associated with pronounced tissue damage, higher disease severity and have been suggested as an imaging marker of chronic active inflammation behind the blood-brain barrier indicating progression. Furthermore, chronic intrathecal compartmentalized inflammation has been suggested to be a mediator of a cerebrospinal fluid (CSF)-related tissue damage. OBJECTIVE: To investigate CSF markers of intrathecal inflammation in patients with at least one IRL compared to patients without IRLs and to investigate tissue damage in lesions and normal-appearing white matter (NAWM) with proximity to CSF spaces. METHODS: A total of 102 patients (51 with at least 1 IRL and 51 age-/sex-matched patients without IRL) scanned with the same 3T magnetic resonance imaging (MRI) and having CSF analysis data were included. RESULTS: Patients with at least one IRL had higher disability scores, higher lesion volumes, lower brain volumes and a higher intrathecal immunoglobulin G (IgG) synthesis. Apparent diffusion coefficient (ADC) values in IRLs were higher compared to non-IRLs. We observed a negative linear correlation of ADC values in all tissue classes and distance to CSF, which was stronger in patients with high IgG quotients. CONCLUSION: IRLs are associated with higher intrathecal IgG synthesis. CSF-mediated intrathecal smouldering inflammation could explain a CSF-related gradient of tissue damage.

Diagnostic and prognostic role of platelets in patients with sepsis and septic shock.

Studies investigating the prognostic role of platelets commonly include critically ill patients, whereas data regarding the prognostic impact of platelet count in patients admitted with sepsis and septic shock is limited. Therefore, the study investigates the prognostic role of platelet count in patients with sepsis and septic shock. Consecutive patients with sepsis and septic shock from 2019 to 2021 were included monocentrically. Blood samples were retrieved from the day of disease onset (day 1), days 2, 3, 5, 7 and 10. Firstly, the diagnostic value of platelet count was tested for septic shock compared to sepsis. Secondly, the prognostic value of platelet count was tested for 30-day all-cause mortality. Statistical analyses included univariable t-test, Spearman's correlation, C-statistics, Kaplan-Meier analyses, as well as multivariable mixed analysis of variance (ANOVA), Cox proportional regression analyses and propensity score matching. A total of 358 patients with sepsis and septic shock were included with a median platelet count of 176 × 106/ml. The presence of thrombocytopenia (i.e. <150 × 106/ml) was associated with increased risk of 30-day mortality (HR = 1.409; 95% CI 1.057-1.878; p = .019), which was still demonstrated after propensity score matching. During the course of sepsis, a nadir was observed on sepsis day 5 with a decrease in the mean platelet count by 21.5%. Especially serum lactate, mean arterial pressure and the presence of malignancies were found to predict platelet decline during the course of sepsis/septic shock. The presence of platelet decline >25% was associated with an increased risk of 30-day all-cause mortality (HR = 1.484; 95% CI 1.045-2.109; p = .028). Following platelet decline, recovery was observed from day 5 to day 10 (mean increase 7.5%). However, platelet recovery was not found to be associated with 30-day all-cause mortality (HR = 1.072; 95% CI 0.567-2.026; p = .832). In conclusion, both thrombocytopenia and platelet decline during the course of sepsis were associated with an increased risk of 30-day all-mortality in patients admitted with sepsis or septic shock.

What is the context? Despite improved treatment strategies in intensive care medicine, sepsis and septic shock represent one of the major causes of death at intensive care units worldwide.Although it is known that platelets are associated with prognosis, most studies included "critically illness" patients and were not restricted to patients admitted with sepsis or septic shock. Furthermore, studies focusing on patients with sepsis were predominantly published prior to the sepsis-3 criteria. Specifically, the course of the platelet count during ICU hospitalization needs further investigation.What is new? The present study suggests that the platelet count reflects a reliable tool for the diagnosis of septic shock during the first week of ICU hospitalization.Furthermore, platelet count and the platelet-to-white-blood-cell-ratio are predictive for 30-day all-cause mortality in the presence of sepsis or septic shock.Especially, a decrease in platelet count during the first 5 days of ICU hospitalizations was associated with an increased risk of 30-day all-cause mortality in patients with sepsis and septic shock, whereas the platelet recovery was not found to be associated with a worse prognosis.What is the impact? This study provides further evidence that the platelet count represents a reliable tool for the diagnosis of septic shock and furthermore predicts short-term prognosis in patients admitted with sepsis or septic shock during the first 10 days of ICU hospitalization.

D-Dimer Levels and the Risk of 30-Day All-Cause Mortality in Cardiogenic Shock Stratified by Etiology.

BACKGROUND: The study investigates the prognostic impact of D-dimer levels in patients with cardiogenic shock (CS). Although D-dimer levels were found to be associated with prognosis in various clinical settings such as heart failure or acute myocardial infarction (AMI), the prognostic role of D-dimer levels in CS patients has not yet been clarified. METHODS: Consecutive CS patients with and without concomitant AMI were prospectively included from 2019 to 2021. The prognostic impact of D-dimer levels was tested for 30-day all-cause mortality within the entire study cohort and stratified by the presence or absence of AMI. Statistical analyses included C-statistics, Kaplan-Meier, and multivariate Cox regression analyses. RESULTS: One hundred and twenty-three consecutive CS patients were included with an overall all-cause mortality at 30 days of 55%. The median D-dimer level on admission was 8.44 mg/L, whereas D-dimer levels were higher in 30-day non-survivors compared to survivors (median 13.0 vs. 5.2 mg/L; p = 0.011). D-dimer levels above the median were associated with an increased risk of 30-day all-cause mortality compared to patients with lower D-dimer levels (66% vs. 54%, log rank p = 0.050; HR = 1.594; 95% CI 0.979 - 2.594; p = 0.061), especially in patients with non-AMI-related CS (65% vs. 30%, log rank p = 0.010). The prognostic value of D-dimer levels was still demonstrated after multivariate adjustment (HR = 1.024; 95% CI 1.004 - 1.045; p = 0.020). CONCLUSIONS: D-dimer measurement may be a reliable biomarker to predict the risk of 30-day mortality in CS patients, especially in patients with non-AMI related CS.

The Neutrophil-to-Lymphocyte-Ratio as Diagnostic and Prognostic Tool in Sepsis and Septic Shock.

BACKGROUND: Studies investigating the diagnostic and prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in sepsis or septic shock commonly included preselected subgroups of patients or were published prior to the current sepsis-3 criteria. Therefore, this study investigates the diagnostic and prognostic impact of the NLR in patients with sepsis and septic shock. METHODS: Consecutive patients with sepsis and septic shock from 2019 to 2021 from the prospective "MARSS-registry" were included monocentrically. First, the diagnostic value of the NLR compared to established sepsis scores was tested for septic shock compared to sepsis. Second, the diagnostic value of the NLR with regard to positive blood cultures was tested. Thereafter, the prognostic value of the NLR was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman´s correlations, C-statistics, Kaplan-Meier analyses, Cox proportional regression analyses as well as uni- and multivariate logistic regression models. RESULTS: A total of 104 patients were included, of which 60% were admitted with sepsis and 40% with septic shock. The overall rate of all-cause mortality at 30 days was 56%. With an area under the curve (AUC) of 0.492, the NLR was shown to have a poor diagnostic value with regard to the diagnosis of septic shock compared to sepsis. However, the NLR was shown to be a reliable parameter to discriminate between patients with negative and positive blood cultures when admitted with septic shock (AUC = 0.714). This was still evident after multivariable adjustment (OR = 1.025; 95% CI 1.000 - 1.050; p = 0.048). In contrast, the NLR revealed a poor prognostic accuracy (AUC = 0.507) with regard to 30-day all-cause mortality. Finally, a higher NLR was not associated with an increased risk of 30-day all-cause mortality (log rank p-value = 0.775). CONCLUSIONS: The NLR was a reliable diagnostic tool for the identification of patients with blood culture confirmed sepsis. Yet, the NLR was not a reliable parameter to discriminate between patients with sepsis and septic shock nor between 30-day survivors and non-survivors.

D-Dimer Levels and the Disseminated Intravascular Coagulation Score to Predict Severity and Outcomes in Sepsis or Septic Shock.

BACKGROUND: Studies investigating the diagnostic and prognostic value of D-dimer levels and the disseminated intravascular coagulation (DIC) score in sepsis or septic shock commonly include preselected subgroups of patients or were published prior to the current sepsis-3 criteria. Therefore, this study investigates the diagnostic and prognostic impact of D-dimer levels and the DIC score in patients with sepsis and septic shock. METHODS: Consecutive patients with sepsis and septic shock enrolled in the prospective and monocentric "MARSS" registry from 2019 to 2021 were included. First, the diagnostic value of D-dimer levels was compared to the DIC score to discriminate patients with septic shock from patients with sepsis without shock. Thereafter, the prognostic value of D-dimer levels and the DIC score was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman´s correlations, C-statistics, Kaplan-Meier, as well as uni- and multivariable cox regression analyses. RESULTS: One hundred patients were included (n = 63 with sepsis and n = 37 with septic shock). The overall rate of all-cause mortality at 30 days was 51%. With an area under the curve (AUC) of 0.710 and 0.739, both D-dimer level and the DIC score revealed reliable diagnostic accuracy for the discrimination of septic shock. However, D-dimer levels and the DIC scores were shown to have poor to moderate prognostic accuracy (AUC 0.590 - 0.610) with regard to 30-day all-cause mortality. Specifically, very high D-dimer levels (i.e., > 30 mg/L) (HR = 2.648; 95% CI 1.147 - 6.112; p = 0.023) and a DIC scores ≥ 3 (HR = 2.095; 95% CI 1.095 - 4.009; p = 0.0258) were associated with highest risk of 30-day all-cause mortality. Finally, both higher D-dimer levels (HR = 1.032; 95% CI 1.005 - 1.060; p = 0.021) and DIC scores (HR = 1.313; 95% CI 1.106 - 1.559; p = 0.002) were associated with increased risk of 30-day all-cause mortality after multivariable adjustment. CONCLUSIONS: Both D-dimer levels and the DIC scores revealed reliable diagnostic accuracy for the discrimination of septic shock, but a poor to moderate prognostic value for the discrimination of 30-day all-cause mortality. Especially very high D-dimer levels (i.e., > 30 mg/L) and a DIC score ≥ 3 were associated with highest risk of 30-day all-cause mortality.

Diagnostic and Prognostic Performance of Plasma Albumin and Cholinesterase in Patients with Sepsis and Septic Shock.

OBJECTIVE: Despite improved risk stratification tools and identification of novel biomarkers for the diagnosis and prognosis in patients with sepsis, sepsis-related mortality has not significantly improved during the past years. This study investigates the diagnostic and prognostic role of the plasma albumin and cholinesterase (ChE) in patients with sepsis and septic shock. METHODS: Consecutive patients with sepsis and septic shock from 2019 to 2021 were included at one institution. Blood samples were obtained on the day of disease onset (day 1), and on days 2, 3, 5, and 7 thereafter. The diagnostic value of ChE for the diagnosis of a septic shock was compared to albumin and the prognostic value of the albumin and the ChE for 30-day all-cause mortality was tested. RESULTS: 239 patients were included with a median albumin level of 21.4 g/dL and a median ChE of 5004 U/L on admission. With an area under the curve (AUC) of 0.641-0.762 on days 3 and 5, the ChE was associated with moderate but better diagnostic discrimination between sepsis and septic shock than albumin. Furthermore, ChE was able to discriminate between 30-day non-survivors and survivors (range of AUC 0.612-0.686). Patients with a ChE below the median had higher rates of 30-days all-cause mortality in comparison to patients with a ChE above the median (65 vs. 42%, log rank p = 0.001; HR = 1.820; 95% CI = 1.273-2.601; p = 0.001), which was still demonstrated after multivariable adjustment. CONCLUSION: The level of ChE was associated with moderate diagnostic and prognostic accuracy in patients with sepsis and septic shock, whereas albumin was not.

Impact of age on the prognosis of patients with ventricular tachyarrhythmias and aborted cardiac arrest.

BACKGROUND: This study evaluated the prognostic impact of age on patients presenting with ventricular tachyarrhythmias (VTA) and aborted cardiac arrest. MATERIAL AND METHODS: The present registry-based, monocentric cohort study included all consecutive patients presenting at the University Medical Center Mannheim (UMM) between 2002 and 2016 with ventricular tachycardia (VT), ventricular fibrillation (VF) and aborted cardiac arrest. Middle-aged (40-60 years old) were compared to older patients (> 60 years old). Furthermore, age was analyzed as a continuous variable. The primary endpoint was all-cause mortality at 2.5 years. The secondary endpoints were cardiac death at 24 h, all-cause mortality at index hospitalization, all-cause mortality after index hospitalization and the composite endpoint at 2.5 years of cardiac death at 24 h, recurrent VTA, and appropriate implantable cardioverter defibrillator (ICD) treatment. RESULTS: A total of 2259 consecutive patients were included (28% middle-aged, 72% older). Older patients were more often associated with all-cause mortality at 2.5 years (27% vs. 50%; hazard ratio, HR = 2.137; 95% confidence interval, CI 1.809-2.523, p = 0.001) and the secondary endpoints. Even patient age as a continuous variable was independently associated with mortality at 2.5 years in all types of VTA. Adverse prognosis in older patients was demonstrated by multivariate Cox regression analyses and propensity score matching. Chronic kidney disease (CKD), systolic left ventricular dysfunction (LVEF) < 35%, cardiopulmonary resuscitation (CPR) and cardiogenic shock worsened the prognosis for both age groups, whereas acute myocardial infarction (STEMI/NSTEMI) and the presence of an ICD improved prognosis. CONCLUSION: The results of this study suggest that increasing age is associated with increased mortality in VTA patients. Compared to the middle-aged, older patients were associated with higher all-cause mortality at 2.5 years and the secondary endpoints.

Lyve-1 deficiency enhances the hepatic immune microenvironment entailing altered susceptibility to melanoma liver metastasis.

BACKGROUND: Hyaluronan receptor LYVE-1 is expressed by liver sinusoidal endothelial cells (LSEC), lymphatic endothelial cells and specialized macrophages. Besides binding to hyaluronan, LYVE-1 can mediate adhesion of leukocytes and cancer cells to endothelial cells. Here, we assessed the impact of LYVE-1 on physiological liver functions and metastasis. METHODS: Mice with deficiency of Lyve-1 (Lyve-1-KO) were analyzed using histology, immunofluorescence, microarray analysis, plasma proteomics and flow cytometry. Liver metastasis was studied by intrasplenic/intravenous injection of melanoma (B16F10 luc2, WT31) or colorectal carcinoma (MC38). RESULTS: Hepatic architecture, liver size, endothelial differentiation and angiocrine functions were unaltered in Lyve-1-KO. Hyaluronan plasma levels were significantly increased in Lyve-1-KO. Besides, plasma proteomics revealed increased carbonic anhydrase-2 and decreased FXIIIA. Furthermore, gene expression analysis of LSEC indicated regulation of immunological pathways. Therefore, liver metastasis of highly and weakly immunogenic tumors, i.e. melanoma and colorectal carcinoma (CRC), was analyzed. Hepatic metastasis of B16F10 luc2 and WT31 melanoma cells, but not MC38 CRC cells, was significantly reduced in Lyve-1-KO mice. In vivo retention assays with B16F10 luc2 cells were unaltered between Lyve-1-KO and control mice. However, in tumor-free Lyve-1-KO livers numbers of hepatic CD4+, CD8+ and regulatory T cells were increased. In addition, iron deposition was found in F4/80+ liver macrophages known to exert pro-inflammatory effects. CONCLUSION: Lyve-1 deficiency controlled hepatic metastasis in a tumor cell-specific manner leading to reduced growth of hepatic metastases of melanoma, but not CRC. Anti-tumorigenic effects are likely due to enhancement of the premetastatic hepatic immune microenvironment influencing early liver metastasis formation.

A case series of severe breakthrough infections observed in nine patients with COVID-19 in a southwestern German university hospital.

PURPOSE: Vaccination is the key element for protection against COVID-19. Increased vaccination breakthroughs raise the question of whether additional prevention is necessary in case of individual risk factors for a severe course with hospitalization or death despite vaccination. METHODS: Since July 13, 2021, there is an extended reporting requirement by German law. We analyzed our hospitalized patients with vaccine breakthrough infection during the first 8 weeks. RESULTS: Nine of 67 patients (13.4%) hospitalized for COVID-19 (median age 75 years) were fully vaccinated. Five of these patients received intensive care; two patients died. All had received two doses of BNT162b2 vaccines (Pfizer-BioNTech). There was a median of 99 days between complete immunization and symptom onset. All patients suffered from ≥ three comorbidities. Six patients (66.7%) showed a negative Anti-SARS-CoV-2-N titer at the time of vaccine breakthrough, five of these also had Anti-SARS-CoV-2-S titers < 100 U/ml. All determinable cases were Delta variant B.1.617.2. CONCLUSION: Advanced age, underlying cardiorespiratory disease, and the Delta variant of SARS-CoV-2 were associated with hospitalization of our patients, suffering from vaccine breakthrough infection. Avoidance of face masks, lack of immunization of close contacts, and travel to high-risk areas have been observed as modifiable behavioural circumstances. Consistent personal protective measures, vaccination of close caregivers, and increased awareness might be effective measures in addition to COVID-19 booster vaccination for patients at a high risk to suffer a severe course of infection.

SARS-CoV-2 Antibody Testing - How to Increase the Positive Predictive Value.

BACKGROUND: Despite increasing COVID-19 infection rates, low overall prevalence resulting in a poor positive predictive value (PPV) of serological tests requires strategies to increase specificity. We therefore investigated a dual diagnostic strategy and evaluated the correlation between the severity of a SARS-CoV-2 infection and the detectable immune-response. METHODS: Participants were systematically categorized into positive and control cohorts and a probability score of COVID-19 was calculated based on clinical symptoms. Six hundred eighty-two serum samples were analyzed using a highly specific high-throughput system. Combining the serological test result and probability score was performed as a dual diagnostic strategy. RESULTS: Specificity of 99.61% and sensitivity of 86.0% were the basis of our approach. A dual diagnostic strategy led to increased pre-test probability and thus to a test specificity of 100%. In a flu-like symptomatic population, we estimated a COVID-prevalence of 4.79%. Moreover, we detected significantly higher antibody values in patients with fever than without fever. CONCLUSIONS: Based on sensitivity and specificity results of our study being in line with previous findings, we demonstrated a dual assessment strategy including a symptom-based probability score and serological testing to increase the PPV. Moreover, the presence of fever seems to trigger a stronger immune-response.

Hypokalemia but not Hyperkalemia is Associated with Recurrences of Ventricular Tachyarrhythmias in ICD Recipients.

BACKGROUND: Only few data evaluating the prognostic impact of blood-derived potassium levels (K) on arrhythmic endpoints in patients with implantable cardioverter-defibrillators (ICD) is available. Therefore, this study evaluates the prognostic impact of potassium levels on recurrences of ventricular tachyarrhythmias in consecutive ICD recipients. METHODS: A large retrospective registry was used including all consecutive patients presenting with ventricular tachyarrhythmias on admission from 2002 to 2016 at one institution. Patients were divided into three subgroups: hypokalemia (i.e., K < 3.3 mmol/L), normokalemia (i.e., K 3.3 - 4.5 mmol/L), and hyperkalemia (i.e., K > 4.5 mmol/L). Kaplan-Meier and Cox regression analyses were applied for the evaluation of the primary endpoint of first recurrences of ventricular tachyarrhythmias at one year. Secondary endpoints comprised of first appropriate ICD therapy, first cardiac rehospitalization, and all-cause mortality at one year. RESULTS: Five hundred and thirty ICD recipients with a median potassium level of 4.23 mmol/L were included (67%: normokalemia, 27%: hyperkalemia, and 6%: hypokalemia). Whereas hyperkalemia was not associated with increasing risk of recurrent ventricular tachyarrhythmias, hypokalemia was associated with decreasing freedom from recurrent ventricular tachyarrhythmias (HR = 2.135; 95% CI 1.158 - 3.937; p = 0.015), even after mul-tivariable adjustment (HR = 2.577; 95% CI 1.236 - 5.372; p = 0.012). Higher risk of recurrences was especially attributed to higher rates of electrical storm in the presence of hypokalemia (15% vs. 3 - 4%). Negative impact of hypokalemia was mainly attributed to secondary preventive ICD (HR = 2.637; 95% CI 1.325 - 5.248; p = 0.006). Moreover, hypokalemia was associated with increasing risk of appropriate ICD therapies (HR = 1.920; 95% CI 0.912 - 4.042; statistical trend: p = 0.086), which was still demonstrated after multivariable adjustment. In contrast, risk of first cardiac rehospitalization and all-cause mortality were not affected by potassium levels. CONCLUSIONS: In consecutive ICD recipients with ventricular tachyarrhythmias at index, hypokalemia - but not hyperkalemia - was associated with increasing risk of recurrent ventricular tachyarrhythmias and appropriate ICD therapies.

Rapid susceptibility testing of multi-drug resistant Escherichia coli and Klebsiella by glucose metabolization monitoring.

Background The increasing number of multi-drug resistant (MDR) bacteria provides enormous challenges for choosing an appropriate antibiotic therapy in the early phase of sepsis. While bacterial identification has been greatly accelerated by the introduction of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), the antibiotic susceptibility testing (AST) remains time-consuming. Here, we present a rapid susceptibility testing method for testing Gram-negative bacteria, exemplarily validated for Escherichia coli and Klebsiella spp. Methods Gram-negative isolates (E. coli and Klebsiella spp.) were either taken as single colonies from agar plates (n=136) or directly extracted and identified from positive blood cultures (n=42) using MALDI-TOF MS. Bacteria were incubated in glucose-supplemented Luria broths (LBs) each containing one antibiotic (ceftazidime, piperacillin, imipenem and ciprofloxacin), routinely used to classify Gram-negative bacteria in Germany. To determine susceptibility the dynamics of glucose utilization in bacterial suspensions were quantitatively measured in the presence or absence of antibiotics designated liquid-AST (L-AST). Results The L-AST can be run on clinical-chemistry analyzers and integrated into laboratory routines. It yields critical resistance information within 90-150 min downstream of a MS-based identification. The results showed a high concordance with routine susceptibility testing, with less than 1% very major errors (VME) and 3.51% major errors (ME) for 178 assessed isolates. Analysis of turnaround time (TAT) for 42 clinical samples indicated that L-AST results could be obtained 34 h earlier than the routine results. Conclusions As exemplified for E. coli and Klebsiella spp., L-AST provides substantial acceleration of susceptibility testing following MALDI-TOF MS identification. The assay is a simple and low-cost method that can be integrated into clinical laboratory to allow for 24/7 AST. This approach could improve antibiotic therapy.

The Impact of Clinical Factors and SARS-CoV-2 Variants on Antibody Production in Vaccinated German Healthcare Professionals Infected Either with the Delta or the Omicron Variant.

BACKGROUND: The aim of the rapid introduction of vaccines during the COVID-19 pandemic was a reduction in SARS-CoV-2 transmission and a less frequent occurrence of severe COVID-19 courses. Thus, we evaluated COVID-19 severity in vaccinated individuals to examine variant-specific symptom characteristics and their clinical impact on the serological immune response. METHODS: A total of 185 individuals previously vaccinated against and infected with the SARS-CoV-2 Delta (B.1.617.2) or Omicron (BA.4 and BA.5) variant, were enrolled for anti-SARS-CoV-2 anti-N- and anti-RBD/S1-Ig level detection. A structured survey regarding medical history was conducted. RESULTS: In 99.5 percent of cases, outpatient treatment was satisfactory. Specific symptoms associated with variants included ageusia and anosmia in patients with Delta infections and throat pain in Omicron infections. Among Delta-infected individuals with specific symptoms, significantly higher levels of anti-N antibodies were observed. CONCLUSION: Our study identified variant-specific differences in the amount of SARS-CoV-2 antibody production and COVID-19 symptoms. Despite this, vaccinated individuals with Omicron or Delta infections generally experienced mild disease courses. Additionally, asymptomatic individuals exhibit lower anti-SARS-CoV-2 antibody levels, indicating a clinical correlation between disease-specific antibodies and distinct symptoms, particularly in the case of the Delta variant. In follow-up studies, exploring post-COVID syndrome and focusing on cognitive symptoms in the acute phase of Omicron infections is crucial as it has the potential to longitudinally impact the lives of those affected.

Predictors and Prognostic Impact of Early Acute Kidney Injury in Cardiogenic Shock: Results from a Monocentric, Prospective Registry.

INTRODUCTION: The presence of acute kidney injury (AKI) was shown to increase the risk of mortality following acute myocardial infarction; however, data regarding the prognostic impact of early AKI in patients with concomitant cardiogenic shock (CS) is limited. The study investigates predictors and the prognostic impact of AKI in patients with CS. METHODS: Consecutive patients with CS from 2019 to 2021 were included at one institution. Laboratory values were retrieved from day of disease onset (day 1) and days 2, 3, 4, and 8 thereafter. Predictors for AKI (defined as an increase of plasma creatinine >50% within 48 h referring to pre-admission or baseline creatinine on day 1 and/or the need for continuous veno-venous hemodiafiltration [CVVHDF]) and the prognostic impact of early AKI with regard to 30-day all-cause mortality were assessed. Statistical analyses included t test, Spearman's correlation, C-statistics, Kaplan-Meier, and Cox proportional regression analyses. RESULTS: A total of 219 CS patients were included with an incidence of early CS-related AKI of 52%. With an area under the curve of up to 0.689 (p = 0.001), creatine discriminated 30-day mortality in CS. Increasing lactate levels (OR = 1.194; 95% CI: 1.083-1.316; p = 0.001; per increase of 1 mmol/L) was associated with the occurrence of AKI. The presence of AKI was associated with an increased risk of 30-day all-cause mortality (63% vs. 36%; HR = 2.138; 95% CI: 1.441-3.171; p = 0.001), even after multivariable adjustment (HR = 1.861; 95% CI: 1.207-2.869; p = 0.005). Finally, highest risk of all-cause mortality was observed in patients with AKI requiring CVVHDF (75% vs. 44%; log rank p = 0.001; HR = 2.211; 95% CI: 1.315-3.718; p = 0.003). CONCLUSION: Early AKI affects more than half of patients with CS and is independently associated with 30-day all-cause mortality in CS, with highest risk of death among patients with AKI requiring CVVHDF.

Heterologous Vector-mRNA Based SARS-CoV-2 Vaccination Strategy Appears Superior to a Homologous Vector-Based Vaccination Scheme in German Healthcare Workers Regarding Humoral SARS-CoV-2 Response Indicating a High Boosting Effect by mRNA Vaccines.

BACKGROUND: Longitudinal humoral SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) immunity for up to 15 months due to vaccination, the efficacy of vaccination strategies (homologous, vector-vector versus heterologous, vector-mRNA), the influence of vaccination side effects, and the infection rate in German healthcare workers need to be investigated. METHODS: In this study, 103 individuals vaccinated against SARS-CoV-2 were enrolled to examine their anti-SARS-CoV-2 anti-N- and anti-RBD/S1-Ig levels. A total of 415 blood samples in lithium heparin tubes were prospectively obtained, and a structured survey regarding medical history, type of vaccine, and vaccination reactions was conducted. RESULTS: All participants demonstrated a humoral immune response, among whom no values decreased below the positivity cutoff. Five to six months after the third vaccination, three participants showed anti-RBD/S1 antibodies of less than 1000 U/mL. We observed higher levels for heterologous mRNA-/vector-based combinations compared to pure vector-based vaccination after the second vaccination, which is harmonized after a third vaccination with the mRNA-vaccine only in both cohorts. The incidence of vaccine breakthrough in a highly exposed cohort was 60.3%. CONCLUSION: Sustained long-term humoral immunity was observed, indicating the superiority of a heterologous mRNA-/vector-based combination compared to pure vector-based vaccination. There was longevity of anti-RBD/S1 antibodies of at least 4 and up to 7 months without external stimulus. Regarding vaccination reactogenity, the occurrence of local symptoms as pain at the injection site was increased after the first mRNA application compared to the vector-vector cohort with a general decrease in adverse events at later vaccination time points. Overall, a correlation between the humoral vaccination response and vaccination side effects was not observed. Despite the high prevalence of vaccine breakthroughs, these only occurred in the later course of the study when more infectious variants, which are, however, associated with milder courses, were present. These results provide insights into vaccine-related serologic responses, and the study should be expanded using additional vaccine doses and novel variants in the future.

Lightweight Visual Transformers Outperform Convolutional Neural Networks for Gram-Stained Image Classification: An Empirical Study.

We aimed to automate Gram-stain analysis to speed up the detection of bacterial strains in patients suffering from infections. We performed comparative analyses of visual transformers (VT) using various configurations including model size (small vs. large), training epochs (1 vs. 100), and quantization schemes (tensor- or channel-wise) using float32 or int8 on publicly available (DIBaS, n = 660) and locally compiled (n = 8500) datasets. Six VT models (BEiT, DeiT, MobileViT, PoolFormer, Swin and ViT) were evaluated and compared to two convolutional neural networks (CNN), ResNet and ConvNeXT. The overall overview of performances including accuracy, inference time and model size was also visualized. Frames per second (FPS) of small models consistently surpassed their large counterparts by a factor of 1-2×. DeiT small was the fastest VT in int8 configuration (6.0 FPS). In conclusion, VTs consistently outperformed CNNs for Gram-stain classification in most settings even on smaller datasets.

Humoral SARS-CoV-2 Immune Response in COVID-19 Recovered Vaccinated and Unvaccinated Individuals Related to Post-COVID-Syndrome.

BACKGROUND: The duration of anti-SARS-CoV-2-antibody detectability up to 12 months was examined in individuals after either single convalescence or convalescence and vaccination. Moreover, variables that might influence an anti-RBD/S1 antibody decline and the existence of a post-COVID-syndrome (PCS) were addressed. METHODS: Forty-nine SARS-CoV-2-qRT-PCR-confirmed participants completed a 12-month examination of anti-SARS-CoV-2-antibody levels and PCS-associated long-term sequelae. Overall, 324 samples were collected. Cell-free DNA (cfDNA) was isolated and quantified from EDTA-plasma. As cfDNA is released into the bloodstream from dying cells, it might provide information on organ damage in the late recovery of COIVD-19. Therefore, we evaluated cfDNA concentrations as a biomarker for a PCS. In the context of antibody dynamics, a random forest-based logistic regression with antibody decline as the target was performed and internally validated. RESULTS: The mean percentage dynamic related to the maximum measured value was 96 (±38)% for anti-RBD/S1 antibodies and 30 (±26)% for anti-N antibodies. Anti-RBD/S1 antibodies decreased in 37%, whereas anti-SARS-CoV-2-anti-N antibodies decreased in 86% of the subjects. Clinical anti-RBD/S1 antibody decline prediction models, including vascular and other diseases, were cross-validated (highest AUC 0.74). Long-term follow-up revealed no significant reduction in PCS prevalence but an increase in cognitive impairment, with no indication for cfDNA as a marker for a PCS. CONCLUSION: Long-term anti-RBD/S1-antibody positivity was confirmed, and clinical parameters associated with declining titers were presented. A fulminant decrease in anti-SARS-CoV-2-anti-N antibodies was observed (mean change to maximum value 30 (±26)%). Anti-RBD/S1 antibody titers of SARS-CoV-2 recovered subjects boosted with a vaccine exceeded the maximum values measured after single infection by 235 ± 382-fold, with no influence on preexisting PCS. PCS long-term prevalence was 38.6%, with an increase in cognitive impairment compromising the quality of life. Quantified cfDNA measured in the early post-COVID-19 phase might not be an effective marker for PCS identification.

Exploring the Synergistic Potential of Radiomics and Laboratory Biomarkers for Enhanced Identification of Vulnerable COVID-19 Patients.

BACKGROUND: Severe courses and high hospitalization rates were ubiquitous during the first pandemic SARS-CoV-2 waves. Thus, we aimed to examine whether integrative diagnostics may aid in identifying vulnerable patients using crucial data and materials obtained from COVID-19 patients hospitalized between 2020 and 2021 (n = 52). Accordingly, we investigated the potential of laboratory biomarkers, specifically the dynamic cell decay marker cell-free DNA and radiomics features extracted from chest CT. METHODS: Separate forward and backward feature selection was conducted for linear regression with the Intensive-Care-Unit (ICU) period as the initial target. Three-fold cross-validation was performed, and collinear parameters were reduced. The model was adapted to a logistic regression approach and verified in a validation naïve subset to avoid overfitting. RESULTS: The adapted integrated model classifying patients into "ICU/no ICU demand" comprises six radiomics and seven laboratory biomarkers. The models' accuracy was 0.54 for radiomics, 0.47 for cfDNA, 0.74 for routine laboratory, and 0.87 for the combined model with an AUC of 0.91. CONCLUSION: The combined model performed superior to the individual models. Thus, integrating radiomics and laboratory data shows synergistic potential to aid clinic decision-making in COVID-19 patients. Under the need for evaluation in larger cohorts, including patients with other SARS-CoV-2 variants, the identified parameters might contribute to the triage of COVID-19 patients.