Outcomes in transcatheter aortic valve replacement (TAVR) patients requiring red blood cell transfusion: A nationwide perspective.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) can be complicated by anemia due to periprocedural bleeding, hemolysis, vascular events, or significant bleeding associated with antiplatelet therapy. OBJECTIVE: We used the National Inpatient Sample (NIS) database to study the outcomes of patients who underwent TAVR and developed significant anemia requiring red blood cell (RBC) transfusion. METHODS: This is a retrospective cohort study utilizing the NIS database from 2016 to 2017. We identified patients who underwent TAVR and required RBC transfusion using ICD-10 and PCS-10 codes. The primary outcome was all-cause inpatient mortality, and the secondary outcomes were the cost of hospitalization and length of stay (LOS). Student t-test, Chi-square, and ANOVA were utilized for statistical analysis where applicable. Multivariate logistic regression was used to adjust for potential confounders. STATA 15.0 was utilized for data analysis. RESULTS: A total of 18,325 patients underwent TAVR in 2016-2017. Among them, 6.7 % of patients required RBC transfusion. Patients were relatively older in the transfusion group (81 yrs vs 79 yrs; p < 0.001). The mean cost of hospitalization was higher in the transfusion group (283,153 USD vs 208,939 USD; p < 0.001). The mean length of stay (LOS) was higher in the transfusion group (9.0 days vs 4.3 days; p < 0.001). Patients in the transfusion group had higher inpatient all-cause mortality compared to patients without transfusion (6.1 % vs 1.3 %; odds ratio 4.94; p < 0.001, 95 % CI 3.7-6.4). Inpatient mortality and LOS didn't differ by race or sex in the transfusion group. All-cause mortality, LOS, and cost of hospitalization were independently increased by transfusion after adjusting for potential confounders i.e. sex, race, hospital teaching status, hospital region, heart block, pacemaker, arrhythmias, heart failure, diabetes, pulmonary hypertension, CKD, and others using multivariate logistic regression. CONCLUSION: In patients undergoing TAVR, blood transfusion was associated with adverse outcomes including increased mortality, length of stay, and cost of hospitalization. The role of careful patient selection, judicious use of antiplatelets, anticoagulants, and pre-procedural optimization of anemia needs further investigation to optimize patient outcomes.

The genomic trajectory of ovarian high-grade serous carcinoma can be observed in STIC lesions.

Ovarian high-grade serous carcinoma (HGSC) originates in the fallopian tube, with secretory cells carrying a TP53 mutation, known as p53 signatures, identified as potential precursors. p53 signatures evolve into serous tubal intraepithelial carcinoma (STIC) lesions, which in turn progress into invasive HGSC, which readily spreads to the ovary and disseminates around the peritoneal cavity. We recently investigated the genomic landscape of early- and late-stage HGSC and found higher ploidy in late-stage (median 3.1) than early-stage (median 2.0) samples. Here, to explore whether the high ploidy and possible whole-genome duplication (WGD) observed in late-stage disease were determined early in the evolution of HGSC, we analysed archival formalin-fixed paraffin-embedded (FFPE) samples from five HGSC patients. p53 signatures and STIC lesions were laser-capture microdissected and sequenced using shallow whole-genome sequencing (sWGS), while invasive ovarian/fallopian tube and metastatic carcinoma samples underwent macrodissection and were profiled using both sWGS and targeted next-generation sequencing. Results showed highly similar patterns of global copy number change between STIC lesions and invasive carcinoma samples within each patient. Ploidy changes were evident in STIC lesions, but not p53 signatures, and there was a strong correlation between ploidy in STIC lesions and invasive ovarian/fallopian tube and metastatic samples in each patient. The reconstruction of sample phylogeny for each patient from relative copy number indicated that high ploidy, when present, occurred early in the evolution of HGSC, which was further validated by copy number signatures in ovarian and metastatic tumours. These findings suggest that aberrant ploidy, suggestive of WGD, arises early in HGSC and is detected in STIC lesions, implying that the trajectory of HGSC may be determined at the earliest stages of tumour development. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

In vitro activity of cefiderocol against carbapenem-resistant Acinetobacter baumannii carrying various ß-lactamase encoding genes.

OBJECTIVES: This study aimed to determine the in vitro efficacy of cefiderocol in carbapenem-resistant Acinetobacter baumannii (CRAB) isolates and evaluate the disk-diffusion (DD) method as an alternative method to broth-microdilution (BMD). METHODS: Totally 89 CRAB isolates were included. Cluster analysis was determined by Pulsed-Field Gel Electrophoresis (PFGE). Resistance genes; blaOXA-51, blaOXA-23, blaOXA-24, blaOXA-58,blaPER-1, blaNDM, blaIMP and mcr-1 were screened. Cefiderocol susceptibility testing was performed by both DD and BMD. Interpretation was made according to EUCAST and CLSI. Categorical agreement (CA), minor errors (mEs), major errors (MEs), and very major errors (VMEs) were determined. RESULTS: PFGE revealed 5 distinct pulsotypes; 86 of the isolates were extensively drug-resistant (XDR). All the isolates were negative for blaNDM, blaIMP, mcr-1, while positive for blaOXA-58 and blaOXA51. blaPER-1 was positive for 33.7%; blaOXA-23 for 74.2%; blaOXA-24 for 12.3%. According to CLSI, the MEs rate was 1.85%, mEs was 7.86% and there were no VMEs. According to EUCAST, MEs rate was 3.70%, there were no mEs and VMEs. CA was 91% for CLSI and 97.8% for EUCAST. MICs of cefiderocol against A. baumannii isolates ranged from 0.06 to > 128 mg/L, with MIC50 and MIC90 values of 0.5 and > 128 mg/L, respectively. CONCLUSIONS: Cefiderocol susceptibility was 60.7% in CRAB isolates. MIC50, MIC90 of blaPER-1 positive and blaPER-1 negative groups were > 128/>128 and 0.25/>128 mg/L. A correlation between the presence of blaPER-1 and cefiderocol resistance was observed (p < 0.0001). Among colistin-resistant isolates, the presence of blaPER-1 was 47.1% and 75% of them were resistant to cefiderocol respectively.

Spontaneous coronary artery dissection (SCAD) and takotsubo cardiomyopathy (TCM) - A potential association.

Background: Spontaneous coronary artery dissection and takotsubo cardiomyopathy are increasingly recognized in the last two decades. Case reports have shown both entities can present concomitantly - however, little is known about their association. Methods: In this retrospective study we aimed to explore a potential association between SCAD and TCM using the Nationwide Inpatient Sample. The odds of having TCM among patients with SCAD compared with those who did not have SCAD were calculated as an odds ratio. Conversely, the odds of having SCAD among patients with TCM compared with those who did not have TCM were also calculated. The primary outcome was the odds of TCM among patients with a primary diagnosis of SCAD and vice versa. The secondary endpoint was the odds of in-hospital mortality among patients with SCAD, and/or TCM. Results: Hospitalized patients who had SCAD were 7.12 (95 % CI: 6.28-8.08) times more likely to also have TCM than those who did not have SCAD (p < 0.0001).), while patients with TCM were 6.91 (95 % CI: 6.07-7.85) times more likely to have SCAD compared to those who didn't have TCM adjusted for age, gender, race, hypertension, hyperlipidemia, and diabetes mellitus (p < 0.0001). Conclusion: This data indicate that patients with either SCAD or TCM are seven times more likely to be diagnosed concomitantly with both, compared to the patients without either diagnosis [after adjusting for age, gender, race, hypertension, hyperlipidemia, and diabetes mellitus]. Our data are consistent with the growing body of evidence supporting an association between SCAD and TCM and raise the question of a common pathophysiologic mechanism.

Evaluation of in vitro activity of ceftaroline, ceftobiprole and their combination with trimethoprim/sulfamethoxazole against MRSA isolates: a two center study.

There is an increasing need for new synergistic antimicrobial combinations against multidrug-resistant bacteria. Our objective was to evaluate the activity of ceftaroline, ceftobiprole and their combination with trimethoprim/sulfamethoxazole against methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered at two centers in Turkey. Activities of ceftaroline and ceftobiprole were tested against 100 MRSA isolates using gradient diffusion method. Activities of ceftaroline and ceftobiprole in combination with trimethoprim/sulfamethoxazole against 20 selected isolates (including all isolates that were non-susceptible to ceftaroline or ceftobiprole, and randomly selected isolates) were investigated using MIC:MIC ratio method. Antimicrobial interactions were interpreted using the fractional inhibitory concentration (FIC) index. The MIC50/MIC90 values for ceftaroline and ceftobiprole were 0.75/1 and 1/1.5 mg/L, respectively. Ceftaroline and ceftobiprole susceptibility rates among 100 MRSA isolates were 94% and 96%, respectively. Ceftaroline, ceftobiprole and trimethoprim/sulfamethoxazole MICs of isolates were not increased when ceftaroline or ceftobiprole was combined with trimethoprim/sulfamethoxazole. Ceftobiprole- trimethoprim/sulfamethoxazole combination demonstrated additivity against 35%, whereas ceftaroline- trimethoprim/sulfamethoxazole combination demonstrated additivity against 10% of 20 MRSA isolates. The remaining interactions for MRSA isolates were indifference. Three (75%) of four ceftobiprole-resistant isolates became susceptible to ceftobiprole after adding trimethoprim/sulfamethoxazole. None of the ceftaroline non-susceptible isolates became susceptible to ceftaroline after adding trimethoprim/sulfamethoxazole. Ceftobiprole- trimethoprim/sulfamethoxazole combination may be a better treatment option than ceftaroline- trimethoprim/sulfamethoxazole combination for MRSA infections. Clinical studies are needed to confirm the results of our in vitro study.