Effect and sustainability of a stepwise implemented multidisciplinary antimicrobial stewardship programme in a university hospital emergency department.

Objectives: To explore effectiveness and sustainability of guideline adherence and antibiotic consumption after establishing treatment guidelines and initiating antimicrobial stewardship (AMS) ward rounds in a university hospital emergency department (ED). Methods: Data were gathered retrospectively from 2017 to 2021 in the LMU University Hospital in Munich, Germany. Four time periods were compared: P1 (pre-intervention period); P2 (distribution of guideline pocket cards); P3 (reassessment after 3 years); and P4 (refresher of guideline pocket cards and additional daily AMS ward rounds for different medical disciplines). Primary outcome was adherence to guideline pocket cards for community-acquired pneumonia, cystitis, pyelonephritis and COVID-19-associated bacterial pneumonia. Secondary outcomes were reduction in antibiotic consumption and adherence to AMS specialist recommendations. Results: The study included 1324 patients. Guideline adherence increased in P2 for each of the infectious diseases entities. After 3 years (P3), guideline adherence decreased again, but was mostly on a higher level than in P1. AMS ward rounds resulted in an additional increase in guideline adherence (P1/P2: 47% versus 58.6%, P = 0.005; P2/P3: 58.6% versus 57.3%, P = 0.750; P3/P4: 57.3% versus 72.5%, P < 0.001). Adherence increased significantly, not only during workdays but also on weekends/nightshifts. Adherence to AMS specialist recommendations was excellent (91.3%). We observed an increase in use of narrow-spectrum antibiotics and a decrease in the application of fluoroquinolones and cephalosporins. Conclusions: Establishing treatment guidelines in the ED is effective. However, positive effects can be diminished over time. Daily AMS ward rounds are useful, not only to restore but to further increase guideline adherence significantly.

Non-invasive assessment of liver alterations in Senning and Mustard patients.

BACKGROUND: Adults with congenital heart disease and ventricular dysfunction are prone to liver congestion, leading to fibrosis or cirrhosis but little is known about the prevalence of liver disease in atrial switch patients. Liver impairment may develop due to increased systemic venous pressures. This prospective study aimed to assess non-invasively hepatic abnormalities in adults who underwent Senning or Mustard procedures. METHODS: Hepatic involvement was assessed non-invasively clinically by laboratory analysis, hepatic fibrotic markers, sonography, and liver stiffness measurements [transient elastography (TE) and acoustic radiation force impulse imaging (ARFI)]. RESULTS: Overall, 24 adults who had undergone atrial switch operation (13 Senning, 11 Mustard; four female; median age 27.8 years; range 24-45 years) were enrolled. In liver stiffness measurements, only three patients had values within the normal reference. All other patients showed mild, moderate or severe liver fibrosis or cirrhosis, respectively. Using imaging and laboratory analysis, 71% of the subjects had signs of liver fibrosis (46%) or cirrhosis (25%). CONCLUSIONS: Non-invasive screening for liver congestion, fibrosis or cirrhosis could be meaningful in targeted screening for hepatic impairment in patients with TGA-ASO. As expert knowledge is essential, patients should be regularly controlled in highly specialised centres with cooperations between congenital cardiologists and hepatologists.

Cardiotoxicity After Anthracycline Treatment in Survivors of Adult Cancers: Monitoring by USCOM, Echocardiography and Serum Biomarkers.

BACKGROUND: Anthracyclines are agents with a well known documented anti-tumoral activity. Cardiac side effects are the principal toxicity. Here we evaluate and monitor the onset of late anthracycline-induced cardiotoxicity with real-time CW-Doppler ultrasound cardiac output monitoring (USCOM®) and echocardiography in combination with serum biomarkers. METHODS: Fifty-two patients without cardiac disease who had received an anthracycline-based regimen for various cancer types were included in this study. Patients' hemodynamic parameters as stroke volume (SV USCOM (mL)) and ejection fraction (EF ECHOCARDIOGRAPHY (%)) were measured with USCOM and echocardiography and correlated to serum biomarkers (NT-pro-BNP and cTnT). RESULTS: Eighteen patients (34.6%) developed cardiac disease (NYHA I-III). An increasing cumulative anthracycline dose was associated with a decrease of the EF determined by echocardiography as well the SV by USCOM and with a higher NYHA class. Those patients who experienced cardiac disease showed a reduction of the EF and SV and increased serum biomarkers. CONCLUSIONS: Real-time CW-Doppler USCOM, is a fast and reliable method to monitor late hemodynamic changes as a symptom of anthracycline-induced cardiotoxicity comparable to the findings by echocardiography and serum biomarkers.

Mortality of patients with hematological malignancy after admission to the intensive care unit.

BACKGROUND: The admission of patients with malignancies to an intensive care unit (ICU) still remains a matter of substantial controversy. The identification of factors that potentially influence the patient outcome can help ICU professionals make appropriate decisions. PATIENTS AND METHODS: 90 adult patients with hematological malignancy (leukemia 47.8%, high-grade lymphoma 50%) admitted to the ICU were analyzed retrospectively in this single-center study considering numerous variables with regard to their influence on ICU and day-100 mortality. RESULTS: The median simplified acute physiology score (SAPS) II at ICU admission was 55 (ICU survivors 47 vs. 60.5 for non-survivors). The overall ICU mortality rate was 45.6%. With multivariate regression analysis, patients admitted with sepsis and acute respiratory failure had a significantly increased ICU mortality (sepsis odds ratio (OR) 9.12, 95% confidence interval (CI) 1.1- 99.7, p = 0.04; respiratory failure OR 13.72, 95% CI 1.39-136.15, p = 0.025). Additional factors associated with an increased mortality were: high doses of catecholamines (ICU: OR 7.37, p = 0.005; day 100: hazard ratio (HR) 2.96, p < 0.0001), renal replacement therapy (day 100: HR 1.93, p = 0.026), and high SAPS II (ICU: HR 1.05, p = 0.038; day 100: HR 1.2, p = 0.027). CONCLUSION: The decision for or against ICU admission of patients with hematological diseases should become increasingly independent of the underlying malignant disease.

Anthracycline-induced cardiotoxicity: cardiac monitoring by continuous wave-Doppler ultrasound cardiac output monitoring and correlation to echocardiography.

BACKGROUND: Anthracyclines are agents with a wellknown cardiotoxicity. The study sought to evaluate the hemodynamic response to an anthracycline using realtime continuous-wave (CW)-Doppler ultrasound cardiac output monitoring (USCOM) and echocardiography in combination with serum biomarkers. METHODS: 50 patients (26 male, 24 female, median age 59 years) suffering from various types of cancer received an anthracycline-based regimen. Patients' responses were measured at different time points (T0 prior to infusion, T1 6 h post infusion, T2 after 1 day, T3 after 7 days, and T4 after 3 months) with CW-Doppler ultrasound (T0-T4) and echocardiography (T1, T4) for hemodynamic parameters such as stroke volume (SV; SVUSCOM ml) and ejection fraction (EF; EFechocardiography%) and with NT-pro-BNP and hs-Troponin T (T0-T4). RESULTS: During the 3-month observation period, the relative decrease in the EF determined by echocardiography was -2.1% (▵T0-T4, T0 71 ± 7.8%, T4 69.5 ± 7%, p = 0.04), whereas the decrease in SV observed using CW-Doppler was -6.5% (▵T0-T4, T0 54 ± 19.2 ml, T4 50.5 ± 20.6 ml, p = 0.14). The kinetics for serum biomarkers were inversely correlated. CONCLUSIONS: Combining real-time CW-Doppler USCOM and serum biomarkers is feasible for monitoring the immediate and chronic hemodynamic changes during an anthracycline-based regimen; the results obtained were comparable to those from echocardiography.

Inhibitory molecules that regulate expansion and restoration of HCV-specific CD4+ T cells in patients with chronic infection.

BACKGROUND & AIMS: Inhibitory receptors such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen (CTLA)-4 mediate CD8+ T-cell exhaustion during chronic viral infection, but little is known about roles in dysfunction of CD4+ T cells. METHODS: We investigated the functions of inhibitory molecules on hepatitis C virus (HCV)-, influenza-, and Epstein-Barr virus (EBV)-specific CD4+ T cells in patients with chronic infections compared with patients with resolved HCV infection and healthy donors. Expression of PD-1, CTLA-4, CD305, and CD200R were analyzed on HCV-specific CD4+ T cells, isolated from peripheral blood using major histocompatibility complex class II tetramers. We investigated the effects of in vitro inhibition of various inhibitory pathways on proliferation and cytokine production by CD4+ T cells, and we compared these effects with those from inhibition of interleukin (IL)-10 and transforming growth factor (TGF)-ß1. RESULTS: PD-1 and CTLA-4 were up-regulated on virus-specific CD4+ T cells from patients with chronic HCV infections. PD-1 expression was lower on influenza- than on HCV-specific CD4+ T cells from subjects with chronic HCV infection, whereas CTLA-4 was expressed at similar levels, independent of their specificity. CD305 and CD200R were up-regulated in HCV resolvers. Blockade of PD-L1/2, IL-10, and TGF-ß1 increased expansion of CD4+ T cells in patients with chronic HCV, whereas inhibition of IL-10 and TGF-ß1 was most effective in restoring HCV-specific production of interferon gamma, IL-2, and tumor necrosis factor α. CONCLUSIONS: We characterized expression of inhibitory molecules on HCV-, influenza-, and EBV-specific CD4+ T cells and the effects of in vitro blockade on CD4+ T-cell expansion and cytokine production. Inhibition of PD-1, IL-10, and TGF-ß1 is most efficient in restoration of HCV-specific CD4+ T cells.

Coronary dilatation after heart transplantation.

BACKGROUND: The angiographic incidence of coronary dilatation (CD) in the nontransplant population is approximately 0.2% to 5%. The endothelial-dependent and -independent causes for CD are postulated. So far, the incidence and prognosis of CD after heart transplantation is unknown. METHODS: We retrospectively analyzed the annual coronary angiographies of 688 heart transplant recipients regarding the incidence of CD (defined as ≥1.5-fold localized increased vessel diameter or diffuse dilatation involving more than 50% of the coronary artery). A subgroup analysis of coronary epicardial (quantitative angiography) and microvascular (doppler flow measurement) vasomotor function in response to acetylcholine (endothelial dependent) and adenosine (endothelial independent) as well as intravascular ultrasound was performed in 177 patients. RESULTS: CD was detectable in 26 patients (3.8%) and was associated with stenosing coronary artery disease in 27% of the patients. Segments with CD tended to have less intimal hyperplasia compared with nondilated segments. A diffuse dilatation (type I-II) was present in 63% of the recipients. The right coronary artery was always involved. The patients with CD (5 of 177) showed a 31% reduced flow velocity in the dilated coronaries compared with the nondilated coronary arteries (P=0.03). Microvascular endothelial-independent function was impaired in CD by -29% (coronary flow reserve mean 1.9 vs. 2.7; P=0.04), whereas endothelial-dependent response was unchanged. Epicardial endothelial-dependent and -independent responses were not different between the groups. Incidence of CD was not associated with limited survival. CONCLUSION: The incidence of CD in the nontransplant population is similar to that in the transplanted population. However, the latter shows a more diffuse extent. Heart transplantation patients with CD had microvascular endothelial-independent functional limitations and flow deceleration, whereas survival was not affected.

Long-term follow-up of patients with metastatic breast cancer: results of a retrospective, single-center analysis from 2000 to 2005.

Recent epidemiological studies suggest that chemotherapy for metastatic breast cancer (MBC) has not contributed to a marked improvement in the patient outcome during the last decades. Randomized trials that investigated the efficacy of a first-line schedule for MBC, observed a median survival of 18-24 months. This study aimed to analyze patients with MBC who have been treated in a single university outpatient clinic for survival. Patients with MBC who had received their complete anticancer treatment in our outpatient clinic between 2000 and 2005 were analyzed for treatment schedules and survival. A total of 232 patients [median age, 53 years; range, 27-87 years; estrogen receptor and/or progesterone-positive hormone receptor, n=174 (75%); human epidermal growth factor receptor 2 overexpression (human epidermal growth factor receptor 2 positive), n=79 (34%)] were included in this analysis, of which 43.7% of hormone receptor-positive patients received 1-2, 28.3% received 3-4, and 1.7% received more than four hormonal regimens. In addition, 53.4% of all patients received up to three chemotherapeutic agents in palliative intent, whereas four to six regimens were applied in 22.1, and 12.9% received more than six subsequent regimens. An increased number of regimens were associated with an improvement in survival. The median overall survival was 44 months (95% confidence interval: 39-49). HR positivity, bone only, or single-site metastases were associated with an improved survival. An improved survival was also shown in patients who underwent locoregional procedures for oligometastatic disease (n=31; median overall survival >50 months), whereas triple-negative breast cancer was related to worse outcome (16 months; 95% confidence interval: 7-25). These data collected from a selective patient population of a single center support the hypothesis that the sequential use of all treatment modalities for MBC to its full potential may result in an increased survival. Whether innovative medicine, a step-by-step escalation of all treatment modalities according to standard guidelines and individualized clinical requirements, and a multidisciplinary treatment approach contribute to these good outcomes is debatable.

Is anal carcinoma a HAART-related problem?

BACKGROUND: There is evidence that frequency of AIN/AC rises in HIV+ individuals treated with HAART whilst frequency of most other opportunistic neoplasms declines with immune reconstitution. METHOD: 1472 patients were screened 3655 times for ACA as a strong risk factor for AIN/AC. The periods 1985 to 1995 (before introduction of PI in Germany) and 1996 to 2001 were compared. In addition, 10 cases of AC are described. Time between HIV-infection and AC as well as time between ACA and AC is assessed, pre-treatment with HAART, age, CD4-cell count and CDC-stage at timepoint of diagnosis of AC is mentioned. RESULTS: There are significantly higher numbers of ACA+ screens in the years after 1996 (p<0.001) independent of number of CD4+ T-lymphocytes. AIN/AC occurs more often in HIV+ individuals, preferably in advanced disease stages, at younger age and within a shorter time after first signs of ACA than in HIV-negative population. AC occurs more likely in patients pretreated with HAART, AC tumor stage is ACIS in most cases. - CONCLUSION: Analogical to AIN/AC, frequency of ACA seems to rise under HAART (regimen including PI) although risk for opportunistic diseases usually decreases under HAART. Similarity of AC to ICC in HIV+ women is striking and AC could become part of the list of AIDS-indicator diseases. According to pre-existing cost-effectiveness calculations [6], screening for AC (including physical examination, proctoscopy, cytology and biopsy of all suspect lesions) should be performed every 2-3 years in patients with CD4+ T-lymphocytes >500/microl and yearly in patients with CD4+ T-lymphocytes <500/microl. Existing ACA should be treated thoroughly. The role of serum HIV load in development and progression of ACA [20], and in consequence of AIN/AC needs further investigation.