Utility of echocardiogram in neutropenic patients with gram positive bacteremia - a retrospective study.

INTRODUCTION: Hemato-oncology patients are vulnerable to bloodstream infections due to immunocompromised state and use of intravascular catheters. Data regarding risk of infective endocarditis (IE) among those with gram positive bacteremia is limited. We aimed to evaluate the incidence of IE among neutropenic hemato-oncology patients, and to explore the yield of echocardiogram in this population. METHODS: we conducted a single retrospective study of all hospitalized hemato-oncology neutropenic patients with gram positive blood cultures between 2007 and 2021. Data regarding Patients' characteristics, blood cultures and echocardiogram was collected. RESULTS: Study included 241 patients, with 283 isolates. Coagulase negative staphylococcus (CONS) were the most commonly isolates found, followed by streptococcus viridans. Trans thoracic echocardiography (TTE) was performed in 45% of patients overall, of which 5.8% had additional Trans esophageal echocardiogram (TEE). Only a single case of IE was identified; 47 y/o multiple myeloma patient with neutropenic fever, streptococcus viridans bacteremia, and stroke caused by septic emboli. TTE and TEE failed to demonstrate valvular pathology consistent with IE. Conclusion In our experience, the yield of echocardiogram in hemato-oncological neutropenic patients with bacteremia is extremely low, owing to reduced probability of IE in this population, and thus could be avoided in most cases.

Clinical efficacy and safety of high dose trivalent influenza vaccine in adults and immunosuppressed populations - A systematic review and meta-analysis.

OBJECTIVES: Influenza is associated with significant morbidity and mortality, especially in older and immunocompromised patients. Few data are available on the clinical benefit of high dose trivalent influenza vaccine (TIV). We aimed to assess the clinical efficacy and safety of high dose TIV. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), evaluating high dose versus standard dose TIV for prevention of seasonal influenza in adult population. Primary outcome was laboratory-confirmed influenza. Subgroups analyses included older adults and immunocompromised patients. RESULTS: We included 16 trials, 47,857 patients; 10 included older adults and three immunocompromised patients. Laboratory confirmed influenza was significantly reduced with high dose TIV (relative risk 0.76, 95% confidence interval 0.64 to 0.9). This outcome stemmed mainly from one trial in older adults. Specifically, A(H3N2) laboratory confirmed influenza, but not A(H1N1) or B lineages, was reduced. No difference in mortality or hospitalizations was demonstrated. Immunological response was significantly higher with high dose vaccine. Serious adverse events were significantly less common in the high dose group. CONCLUSIONS: High dose TIV lowers the rates of laboratory confirmed influenza, mainly A (H3N2), in older adults vs. standard dose. Further studies should address immunocompromised patients and report clinical outcomes.

Desmoplasia in Lymph Node Metastasis of Pancreatic Adenocarcinoma Reveals Activation of Cancer-Associated Fibroblasts Pattern and T-helper 2 Immune Cell Infiltration.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a peritumoral proliferation of fibroblasts and extracellular matrix production known as desmoplasia. We aimed to study desmoplasia in PDAC lymph node (LN) metastases. METHODS: We evaluated LNs from 66 patients with PDAC and LN metastases. We used immunohistochemistry and real-time polymerase chain reaction to phenotype the desmoplastic response. RESULTS: Desmoplasia was identified in 57% of patients with LN metastases (Des+). Cancer-associated fibroblasts (CAFs) in Des+ expressed α-smooth muscle actin and collagen 11A1. The latter expression was present only in CAFs but not in LN stroma or in LN metastases without desmoplasia (Des-). Desmoplasia was associated with upregulation of transforming growth factor ß messenger RNA. Whereas numbers of CD8+ in tumor vicinity were not different between Des+ and Des- patients (78 [standard deviation {SD}, 57] vs 92 [SD, 52], P = 0.48, respectively), the numbers of GATA-3+ cells, a marker of T-helper 2 immune response was significantly increased (3.7 [SD, 6.3] for Des+ vs 1.3 [SD, 2.7] for Des-, P < 0.05). CONCLUSIONS: Lymph node desmoplasia is associated with CAF pattern activation and Th2 infiltration. Therapeutic modulation of desmoplasia may be relevant in the metastatic phase and influence antitumor immune response.

Efficacy and safety of ceftazidime/avibactam: a systematic review and meta-analysis.

Background: Ceftazidime/avibactam is approved for complicated intra-abdominal and urinary tract infections (UTIs) based on results from randomized controlled trials (RCTs). Data regarding its effectiveness in treating hospital-acquired infections or resistant pathogens have not been systematically compiled. Methods: A systematic review and meta-analysis including RCTs evaluating ceftazidime/avibactam versus comparator for the treatment of any infection. Primary outcome was 30 day all-cause mortality. Subgroups of hospital-acquired infections and specific resistance phenotypes were planned. Results: Seven publications (eight trials, 4093 patients) were included, reporting a baseline ∼25% of ESBL-carrying Enterobacteriaceae. No significant difference between ceftazidime/avibactam and comparator (mostly carbapenem) was demonstrated for 30 day all-cause mortality, late follow-up mortality and clinical response [relative risk (RR) 1.10, 95% CI 0.70-1.72, P = 0.69; RR 1.23, 95% CI 0.87-1.76, P = 0.25; RR 0.98, 95% CI 0.96-1.01, P = 0.21, respectively, without significant heterogeneity]. Higher microbiological response rate was demonstrated with ceftazidime/avibactam in patients with UTI (RR 1.14, 1.0-1.29, P = 0.05, I2 = 51%). No significant difference in clinical response was demonstrated for patients with ceftazidime-resistant pathogens (RR 1.02, 95% CI 0.94-1.10, P = 0.66, I2 = 0%). Results for other subgroups of resistant pathogens or hospital-acquired infection were not available. Serious adverse events (SAEs) were significantly more common with ceftazidime/avibactam (RR 1.24, 95% CI 1.00-1.54, P = 0.05, I2 = 0%). Conclusions: Ceftazidime/avibactam is clinically and microbiologically as effective as carbapenems for treatment of infections in a setting of ∼25% ESBL-carrying Enterobacteriaceae. Safety of the drug should be further evaluated owing to a higher rate of SAEs compared with carbapenems. Further studies should assess the drug's effectiveness in the treatment of carbapenemase-producing Enterobacteriaceae.

T-Helper 1 Immune Response in Metastatic Lymph Nodes of Pancreatic Ductal Adenocarcinoma: A Marker For Prolonged Survival.

BACKGROUND: Although lymph node (LN) metastases is considered a grave prognostic sign in pancreatic ductal adenocarcinoma (PDAC), patients with positive lymph nodes (PLN) constitute a heterogeneous group. Our purpose was to identify morphological and immune parameters in the primary tumor and in PLN of resected PDAC patients, which could further stratify these patients to different subgroups. METHODS: We retrospectively evaluated histological and immunohistochemical characteristics of 66 patients with PDAC who were operated at our institution. These were subsequently correlated to clinical outcome. RESULTS: Mean patient age and number of LN harvested was 65.5 ± 10.3 and 12.3 ± 6.5 years, respectively. Tumor size (T stage) and perineural invasion had no effect on clinical outcome. High-grade tumor was associated with decreased survival [overall survival (OS) = 19.6 ± 2.7 months for poorly differentiated PDAC vs. 31.2 ± 4 for well and moderately differentiated, p = 0.03]. Patients with ≥ 8 PLN had significantly worse outcome (OS = 7.3 ± 0.8 months for PLN ≥ 8 vs. OS = 30.1 ± 3.2 months for PLN < 8, p < 0.0001). T helper (Th) 1 immune response was measured both by its effector cells (CD8+) and expression of its main transcription factor, T-bet. CD8+ high patients had significantly increased OS compared with CD8+ low (OS = 36.8 ± 5.3 months for CD8 + high vs. OS = 24.3 ± 3.5 for CD8 + low, p = 0.03) Similarly, Th1 predominant immune response measured by T-bet expression was associated with improved OS compared with non-Th1 (OS = 32.8 ± 3.2 vs. OS = 19.5 ± 2.9, p < 0.0001). CONCLUSIONS: Our data indicate an association between Th1-type immune response and increased survival. Future research is needed to exploit Th1 immune response as a biological marker for immunotherapy.