Risk of Invasive Fungal Infections in Patients With Chronic Lymphocytic Leukemia Treated With Bruton Tyrosine Kinase Inhibitors: A Case-Control Propensity Score-Matched Analysis.

Background: Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitor (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom a BTKi is now the first-line recommended therapy. Methods: We queried TriNetX, a global research network database, to identify adult patients with CLL using the International Classification of Diseases, Tenth Revision code (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs. Results: Among 5358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi versus 3.5% among patients not on a BTKi at 5 years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of Pneumocystis jirovecii pneumonia (PJP) (0.5% vs 0.3%, P = .02) and invasive candidiasis (3.5% vs 2.7%, P = .012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively. Conclusions: We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are, however, low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKis are required to identify at-risk patients and preventive, cost-effective interventions.

Number Needed to Diagnose in Malignant Ascites: Effects of Volume, Repeating Collection, and Primary Malignancy on Diagnostic Performance in Peritoneal Fluid Cytology.

INTRODUCTION: Volume recommendations of 80-200 mL have been proposed for peritoneal fluid cytology. While cutoffs are impractical when volume is limited by the amount present and disease factors, collections, however, can be repeated. This study addresses adequacy and number needed to diagnose by comparing diagnostic agreement to volumes in single specimens, total volumes collected daily, and within admissions. The diagnostic yield of repeating collection within a single day, admission, and throughout admissions of a patient's lifetime was also investigated. METHODS: Peritoneal fluid cytology specimens over a 27-year period were retrieved and matched by collection date, admission number, and patient number. Case notes were reviewed to establish all cases of malignant ascites. RESULTS: In total, 19,392 specimens from 14,327 admissions and 11,089 patients were retrieved, with 1,531 patients confirmed with malignant ascites. Agreements between cytologic diagnoses within the same day and admission were high (κ > 0.8). Fluid volume increased with grade of cytologic diagnosis (p < 0.001), and greater volume was associated with higher discordance (p < 0.05). Specimens of 60-100 mL showed the best diagnostic concordance. To achieve a 99.5% diagnostic rate, three sequential aliquots, collections from two different days in an admission, or three admissions within a lifetime are required. The diagnostic yield of one aliquot within batches from the same day was only 88.9%. Gastrointestinal (p = 0.040), gynecologic (p = 0.005), and lung (p < 0.001) malignancies required the least repeats for diagnosis. CONCLUSIONS: Omission of any fluid from laboratory submission is strongly discouraged. As a simple rule, three repeats are necessary for excluding malignant ascites.

Outcomes of fracture-related infections - do organism, depth of involvement, and temporality count?

Purpose: To determine mortality and outcomes of patients diagnosed with fracture-related infections (FRIs).Methods: FRI patients treated at a trauma centre between 2001 and 2020 were analysed. The primary outcome was 1-year mortality; mortality associations with FRI organism, depth of involvement, and temporality were investigated with multivariable survival analysis. Healthcare-associated and serological outcomes were reported as secondary outcomes. Results: 311 FRIs with mean age of 67.0 and median Charlson comorbidity index of 0 were analysed. Methicillin-sensitive Staphylococcus aureus (MSSA) (29.9%) was the most frequently implicated organism. The majority of FRIs were deep infections (62.7%). FRIs were diagnosed at a median of 40 (IQR 15-200) days post index surgery. The mean follow-up was 5.9 years. One-year mortality amounted to 17.7%. MSSA FRIs were associated with better survival (adj HR 0.34, 95%CI 0.15-0.76, p = 0.008). There was no difference in survivorship between deep or superficial FRI (adj HR 0.86, 95%CI 0.62-1.19, p = 0.353) or in relation to onset time (adj HR 1.0, 95%CI 0.99-1.00, p = 0.943). Implant removal or debridement alone was performed in 61.7% and 17% respectively. Antibiotics was prescribed for 53 (IQR 23-110) days, and patients were hospitalised for 39 (IQR 19-78) days. CRP and ESR normalised in 70.3% (median 46 days) and 53.8% (median 86 days) patients respectively. Conclusion: Fracture-related infections are associated with significant mortality and morbidity regardless of depth and temporality. Non-MSSA FRIs are associated with inferior survival.

Comparison of PneumID real-time PCR assay with Amplex eazyplex LAMP assay for laboratory diagnosis of Pneumocystis jirovecii Pneumonia.

We compared PneumID PCR with Amplex eazyplex LAMP assay for the diagnosis of Pneumocystis jirovecii pneumonia (PJP). Both assays enable accurate diagnosis of definite PJP. Cut-off cycle threshold of the PneumID assay was < 26.68 while the cut-off time-to-positivity of the eazyplex assay was 16:02 (minutes:seconds). The positive and negative percentage agreement of eazyplex assay with PneumID assay was 75.0% and 100.0% respectively, while the overall agreement was substantial with kappa = 0.80. For both assays, establishment of cut-off values to differentiate probable PJP from colonization was not feasible as results overlapped.

Both PneumID PCR and Amplex eazyplex LAMP assay enable accurate diagnosis of definite Pneumocystis jirovecii pneumonia (PJP). PneumID assay was more sensitive than eazyplex assay for detection of P. jirovecii. However, differentiation between probable PJP from colonization was not feasible.

Systemic Lupus Erythematosus Patients Exhibit Reduced Expression of CLEC16A Isoforms in Peripheral Leukocytes.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with multiple etiological factors. The SLE susceptibility locus on chromosome 16p13 encodes a novel gene CLEC16A and its functional relationship with SLE is unclear. This study aimed to investigate the expression correlation of the two major CLEC16A spliced transcripts with SLE development. Expressions of the long (V1) and short (V2) CLEC16A isoforms in the peripheral blood mononuclear cells (PBMCs) were assayed by quantitative real time PCR and compared between healthy individuals and SLE patients. Correlation of CLEC16A isoform expression levels with SLE susceptibility, disease severity and twelve clinical parameters were also evaluated. Full length transcripts of CLEC16A V1 and V2 isoforms were readily amplified from PBMCs of healthy controls and patients at varying abundance. Compared with healthy controls (n = 86), expression levels of V1 and V2 were significantly reduced by ~two- and four-fold respectively in SLE patients (n = 181). The relative V2/V1 ratio was also significantly reduced by approximately two-fold. With regard to SLE disease parameters, only a weak positive correlation was found between CLEC16A V1 expression levels and SLE disease activity index (SLEDAI) score. Taken together, CLEC16A was found to be a susceptibility factor for SLE, with possible contribution to the development of the disease.