Avatrombopag-induced lactic acidosis in a patient with severe thrombocytopenia.

A woman in her 60s was admitted for refractory thrombocytopenia, initially presumed to be from immune thrombocytopenia (ITP). She was treated with the thrombopoietin receptor agonist (TPO-RA) avatrombopag, as well as prophylactic ciprofloxacin and fluconazole for neutropenia. She developed an anion gap metabolic acidosis with a significantly elevated lactate level peaking at 7.5 mmol/L. Other causes of lactic acidosis including hypovolaemia, sepsis, ischaemia and diabetic ketoacidosis were ruled out. Avatrombopag was discontinued, with quick resolution of the lactic acidosis. Fluconazole and ciprofloxacin were found to inhibit the metabolism of avatrombopag and were also discontinued. Worsening thrombocytopenia prompted a rechallenge with increased dose avatrombopag and severe lactic acidosis again developed, with subsequent quick resolution after drug discontinuation. We conclude that a dose-dependent lactic acidosis occurred with avatrombopag in this case. While other TPO-RAs including eltrombopag have been associated with lactic acidosis, to our knowledge, this is the first report of avatrombopag-induced lactic acidosis.

Risk Factors for Surgical-Site Infections After Liver Transplant: Does Perioperative Antibiotic Regimen Matter?

BACKGROUND: Surgical-site infections (SSIs) are common in liver transplant recipients. The optimal SSI antimicrobial prophylaxis agent and duration are not established. We aimed to explore risk factors for SSIs after transplant, with a particular interest in the impact of perioperative antibiotic regimen on the development of SSIs. METHODS: Retrospective study of adults undergoing liver transplant across 3 transplant programs between January 1, 2020, and June 01, 2021. RESULTS: Of 557 patients included in the study, 32 (5.7%) were infected or colonized with a multidrug-resistant organism (MDRO) within 1 y before liver transplant. Narrow-spectrum SSI prophylaxis with ceftriaxone or cefazolin alone was administered in 488 of 577 patients (87.6%); the remaining 69 patients (12.4%) received broad-spectrum prophylaxis with vancomycin and aztreonam (n = 40), piperacillin-tazobactam (n = 11), carbapenems (n = 8), ceftriaxone and another antibiotic (n = 7), and others. Patients with pretransplant MDRO were more likely to receive broad-spectrum coverage than those without pretransplant MDROs (28.1% versus 11.4%, P = 0.005). SSIs were identified in 40 patients (7.2%); 25 (62.5%) were organ-space infections, 3 (7.5%) were deep incisional infections, and 12 (30.0%) were superficial incisional infections. The median time from liver transplant to SSIs was 14 d (interquartile range, 10-20.2). MDROs were identified in 12 SSIs (30%). Multivariable analysis revealed no significant association between antimicrobial spectrum and risk of SSIs (P = 0.5), whereas surgical leak (P<0.001) and reoperation (P = 0.017) were independently associated with increased risk of SSIs. SSIs were not significantly associated with composite risk of death or liver allograft failure. CONCLUSIONS: The spectrum of antimicrobial prophylaxis did not impact the development of SSIs in liver transplant recipients.

Grading Pancreatic Neuroendocrine Tumors Via Endoscopic Ultrasound-guided Fine Needle Aspiration: A Multi-institutional Study.

OBJECTIVES: To identify factors associated with concordance between World Health Organization (WHO) grade on cytological analysis (c-grade) and histopathological analysis (h-grade) of surgical specimen in patients with PanNETs and examine trends in utilization and accuracy of EUS-FNA in preoperatively predicting grade. BACKGROUND: WHO grading system is prognostic in pancreatic neuroendo-crine tumors (PanNETs). The concordance between c-grade and h-grade is reported to be between 50% and 92%. METHODS: A multicenter retrospective study was performed on patients undergoing resection for PanNETs at four high-volume centers between 2010 and 2019. Patients with functional or syndrome-associated tumors, and those receiving neoadjuvant therapy were excluded. Factors associated with concordance between c-grade and h-grade and trends of utilization of EUS-FNA were assessed. RESULTS: Of 869 patients included, 517 (59.5%) underwent EUS-FNA; 452 (87.4%) were diagnostic of PanNETs and WHO-grade was reported for 270 (59.7%) patients. The concordance between c-grade and h-grade was 80.4% with moderate concordance ( Kc = 0.52, 95% CI: 0.41-0.63). Significantly higher rates of concordance were observed in patients with smaller tumors (<2 vs. ≥2cm, 81.1% vs. 60.4%, P = 0.005). Highest concordance (98.1%) was observed in patients with small tumors undergoing assessment between 2015-2019 with a near-perfect concordance ( Kc = 0.88, 95% CI: 0.61-1.00). An increase in the utilization of EUS-FNA (56.1% to 64.1%) was observed over the last 2 decades ( P = 0.017) and WHO-grade was more frequently reported (44.2% vs. 77.6%, P < 0.001). However, concordance between c-grade and h-grade did not change significantly (P = 0.118). CONCLUSION: Recently, a trend towards increasing utilization and improved diagnostic accuracy of EUS-FNA has been observed in PanNETs. Concordance between c-grade and h-grade is associated with tumor size with near-perfect agreement when assessing PanNETs <2cm in size.

A novel tool to predict nodal metastasis in small pancreatic neuroendocrine tumors: A multicenter study.

BACKGROUND: Nonfunctional pancreatic neuroendocrine tumors display a wide range of biological behavior, and nodal disease is associated with metastatic disease and poorer survival. The aim of this study was to develop a tool to predict nodal disease in patients with small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors. METHODS: A multicenter retrospective study was performed on patients undergoing resection for small nonfunctional pancreatic neuroendocrine tumors. Patients with genetic syndromes, metastatic disease at diagnosis, neoadjuvant therapy, or positive resection margin were excluded. Factors associated with nodal disease were identified to develop a predictive model. Internal validation was performed using bootstrap with 1,000 resamples. RESULTS: Nodal disease was observed in 39 (11.1%) of the 353 patients included. Presence of nodal disease was significantly associated with lower 5-year disease-free survival (71.6% vs 96.2%, P < .001). Two predictors were strongly associated with nodal disease: G2 grade (odds ratio: 3.51, 95% confidence interval: 1.71-7.22, P = .001) and tumor size (per mm increase, odds ratio: 1.14, 95% confidence interval: 1.03-1.25, P = .009). Adequate discrimination was observed with an area under the curve of 0.71 (95% confidence interval: 0.63-0.80). Based on risk distribution, 3 risk groups of nodal disease were identified; low (<5%), intermediate (≥5% to <20%), and high (≥20%) risk. The observed mean risk of nodal disease was 3.7% in the low-risk patients, 9.6% in the intermediate-risk patients, and 30.4% in the high-risk patients (P < .001). The 10-year disease-free survival in the low, intermediate, and high-risk groups was 100%, 88.8%, and 50.1%, respectively. CONCLUSION: Our model using tumor grade and size can predict nodal disease in small nonfunctional pancreatic neuroendocrine tumors. Integration of this tool into clinical practice could help guide management of these patients.

Ceftriaxone versus antistaphylococcal antibiotics for definitive treatment of methicillin-susceptible Staphylococcus aureus infections: a systematic review and meta-analysis.

Optimal therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections is unclear. Current standard of care consists of antistaphylococcal antibiotics (ASAs) such as nafcillin, oxacillin and cefazolin. Ceftriaxone has been evaluated due to its advantage as a once-daily outpatient regimen. However, questions remain regarding its efficacy compared with ASAs. We aimed to conduct a review and synthesis of available literature for outcomes of patients treated with ceftriaxone or ASAs for MSSA infections. We searched Cochrane Central Register of Controlled Trials, Embase Ovid, MEDLINE Ovid, Scopus and Web of Science (1990 to June 2021). Risk of bias for cohort studies was assessed by the Newcastle-Ottawa scale. We pooled risk ratios (RRs) using the DerSimonian-Laird random-effects model for outcomes of those receiving ceftriaxone versus ASAs. Heterogeneity was assessed by the I2 index. From 459 identified studies, 7 were included in the quantitative synthesis totalling 1640 patients. Definitive therapy with ceftriaxone was associated with a lower risk of toxicity requiring therapy alteration (RR 0.49, 95% CI 0.27-0.88; I2 = 0%). There was no difference in terms of 90-day all-cause mortality (RR 0.93, 95% CI 0.46-1.88; I2 = 9%), hospital readmission (RR 0.96, 95% CI 0.57-1.64; I2 = 0%) or infection recurrence (RR 1.04, 95% CI 0.63-1.72; I2 =0%). Current evidence suggests there is no difference in efficacy between ceftriaxone and ASAs for MSSA infection, with a lower risk of toxicity with ceftriaxone. Within the limitations of available retrospective studies, ceftriaxone is a consideration for definitive therapy of MSSA infection. [Trial registration: PROSPERO ID: CRD42021259086].

Risk factors for mortality of patients with ceftriaxone resistant E. coli bacteremia receiving carbapenem versus beta lactam/beta lactamase inhibitor therapy.

OBJECTIVE: Extended spectrum ß-lactamases (ESBL) producing Enterobacteriaceae predominantly E. coli and K. pneumoniae bacteremia have limited treatment options and high mortality. The objective was to determine the risk factors for in-hospital mortality particularly treatment with carbapenem versus beta lactam/beta lactamase combination (BL/BLI) in patients with ceftriaxone resistant E. coli bacteremia. A retrospective cohort study was conducted at the Aga Khan University, Karachi, Pakistan. Adult patients with sepsis and monomicrobial ceftriaxone resistant E. coli bacteremia were enrolled. Factors associated with mortality in patients were determined using logistic regression analysis. RESULTS: Mortality rate was 37% in those empirically treated with carbapenem compared to 20% treated with BL/BLI combination therapy (p-value: 0.012) and was 21% in those treated with a carbapenem compared to 13% in patients definitively treated with BL/BLI combination therapy (p-value: 0.152). In multivariable logistic regression analysis, only Pitt bacteremia score of ≥ four was significantly associated with mortality (OR: 7.7 CI 2.6-22.8) while a urinary source of bacteremia was protective (OR: 0.26 CI 0.11-0.58). In-hospital mortality in patients with Ceftriaxone resistant E. coli bacteremia did not differ in patients treated with either a carbapenem or BL/BLI combination. However, Pitt bacteremia score of ≥ 4 was strongly associated with mortality.