Detection of Scedosporium spp.: Colonizer or pathogen? A retrospective analysis of clinical significance and management in a large tertiary centre

Infections with Scedosporium spp. are emerging in the past two decades and are associated with a high mortality rate. Microbiological detection can be associated with either a colonization or infection. Evolution from colonization into infection is difficult to predict and clinical management upon microbiological detection is complex. Microbiological samples from 2015 to 2021 were retrospectively analyzed in a single tertiary care centre. Classification into colonization or infection was performed upon first microbiological detection. Clinical evolution was observed until July 2023. Further diagnostic procedures after initial detection were analyzed. Among 38 patients with microbiological detection of Scedosporium spp.,10 were diagnosed with an infection at the initial detection and two progressed from colonization to infection during the observation time. The main sites of infections were lung (5/12; 41.6%) followed by ocular sites (4/12; 33.3%). Imaging, bronchoscopy or biopsies upon detection were performed in a minority of patients. Overall mortality rate was similar in both groups initially classified as colonization or infection (30.7% and 33.3% resp. (p=1.0)). In all patients where surgical debridement of site of infection was performed (5/12; 42%); no death was observed. Although death occurred more often in the group without eradication (3/4; 75%) compared with the group with successful eradication (1/8; 12.5%), statistical significance could not be reached (p=0.053). As therapeutic management directly impacts patients' outcome, a multidisciplinary approach upon microbiological detection of Scedosporium spp. should be encouraged. Data from larger cohorts are warranted in order to analyze contributing factors favoring the evolution from colonization into infection

CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell-engaging antibody AMG 330.

Antibody-based immunotherapy represents a promising strategy to target and eliminate chemoresistant leukemic cells. Here, we evaluated the CD33/CD3-bispecific BiTE® antibody (AMG 330) for its suitability as therapeutic agent in AML. We first assessed CD33 expression levels by flow cytometry and found expression in >99% of patient samples (n=621). CD33 was highest expressed in AMLs with NPM1 mutations (p<0.001) and lower in AMLs with complex karyotypes and t(8;21) translocations (p<0.001). Furthermore, leukemic stem cells within the CD34(+)/CD38(-) compartment displayed CD33 at higher levels than healthy donor stem cells (p=0.047). In MS-5 feeder cell-based long-term cultures that supported the growth of primary AML blasts for up to 36 days, AMG 330 efficiently recruited and expanded residual CD3(+)/CD45RA(-)/CCR7(+) memory T-cells within the patient sample. Even at low effector to target ratios, the recruited T-cells lysed autologous blasts completely in the majority of samples and substantially in the remaining samples in a time- dependent manner. This study provides the first correlation of CD33 expression levels with AML genotype in a comprehensive analysis of adult patients. Targeting CD33 ex-vivo using AMG 330 in primary AML samples led to T-cell recruitment and expansion and remarkable antibody-mediated cytotoxicity suggesting efficient therapeutic potential in-vivo

Outcome of catheter ablation of supraventricular tachyarrhythmias in cardiac sarcoidosis

Background: Sarcoidosis is a multisystem granulomatous disease of not sufficiently understood origin. Some patients develop cardiac involvement in course of the disease which is mostly responsible for adverse outcome. In addition to complications like high degree atrioventricular (AV) block or ventricular tachyarrhythmias, there is a certain percentage of patients developing atrial tachyarrhythmias. Data is limited and the role of catheter ablation uncertain. Therefore, we studied sarcoid patients who presented with supraventricular tachyarrhythmias. Hypothesis: Treatment and ablation of supraventricular tachycardia could be hampered by inflammation in patients with cardiac sarcoidosis. Methods: We enrolled 37 consecutive patients with cardiac sarcoidosis who presented with atrial tachyarrhythmias and underwent an electrophysiologic study over a period of 6 years (03/2013-04/2019). In total, 16 catheter ablations for atrial tachyarrhythmias were performed. Mean follow-up duration was 2.5 years. Results: Most common ablation performed was cavo-tricuspid isthmus ablation for typical atrial flutter in seven patients (54%). Pulmonary vein isolation for treatment of atrial fibrillation (AF) was performed in five patients (38%). Two patients received slow-pathway modulation for treatment of recurrent atrioventricular nodal reentry tachycardia (AVNRT). All but two patients with AF had no clinical recurrence during follow-up. Two patients had recurrence of AF but still reported markedly improved european heart rhythm association (EHRA) class. Periprocedural safety was very high. There were no adverse events related to the ablation procedure. One patient died during follow-up in the presence of electrical storm. Conclusion: Catheter ablations of supraventricular tachycardias seem to be safe and effective in patients with cardiac sarcoidosis. Outcome is comparable to patients without inflammatory heart disease, although data from larger patient collectives are mandatory to make recommendations in this special entity

Outcome of catheter ablation in the very elderly-insights from a large matched analysis

Background: Ablation emerged as first line therapy in the treatment of various arrhythmias. Nevertheless, in older patients (pts), decision is often made pro drug treatment as more complications and less benefit are suspected. Hypothesis: We hypothesized that different kind of ablations can be performed safely regardless of the pts age. Methods: We enrolled all pts aged >80 years (yrs) who underwent ablation for three different arrhythmias (atrial flutter [AFL], atrioventricular nodal re-entry tachycardia [AVNRT], ventricular tachycardia [VT]) between August 2002 and December 2018. Procedural data and outcome were compared with matched groups aged 60 to 80 years and 40 to 60 years, respectively. Periprocedural and in-hospital complications were analyzed. Results: The analysis included 1191 patients (397 pts per group: 63% AFL, 23% AVNRT, 14% VT) who underwent ablation. Acute success was high in all types of arrhythmias irrespective of age (>80, 60-80, 40-60 years: AFL 97%/98%/98%, AVNRT 97%/95%/97%, VT 82%/86%/93%). Rate of periprocedural complications were similar in all groups treated for AFL and AVNRT. For VT ablations significant differences were noted between pts > 80 or 60 to 80 years and those aged 40-60 years (16.1%/14.3%/3.6%). Most complications were infections and groin haematoma. No strokes, iatrogenic atrioventricular blocks and deaths related to the ablation occurred. Conclusion: Ablation appears safe in pts > 80 years. Success rates were comparable to matched younger cohorts. A significant difference was observed for VT patients