Letermovir for Cytomegalovirus Prevention in Adolescent Patients Following Hematopoietic Cell Transplantation.

There are limited data for letermovir as primary cytomegalovirus (CMV) prophylaxis in patients less than 18 years of age. We report 9 adolescent patients who received letermovir following hematopoietic cell transplantation. No patients developed clinically significant CMV while taking letermovir. Letermovir was well tolerated and efficacious in preventing CMV infections.

Seasonal Dynamics of Methanotrophic Bacteria in a Boreal Oil Sands End Pit Lake.

Base Mine Lake (BML) is the first full-scale demonstration end pit lake for the oil sands mining industry in Canada. We examined aerobic methanotrophic bacteria over all seasons for 5 years in this dimictic lake. Methanotrophs comprised up to 58% of all bacterial reads in 16S rRNA gene amplicon sequencing analyses (median 2.8%), and up to 2.7 × 104 cells mL-1 of water (median 0.5 × 103) based on qPCR of pmoA genes. Methanotrophic activity and populations in the lake water were highest during fall turnover and remained high through the winter ice-covered period into spring turnover. They declined during summer stratification, especially in the epilimnion. Three methanotroph genera (Methylobacter, Methylovulum, and Methyloparacoccus) cycled seasonally, based on both relative and absolute abundance measurements. Methylobacter and Methylovulum populations peaked in winter/spring, when methane oxidation activity was psychrophilic. Methyloparacoccus populations increased in the water column through summer and fall, when methane oxidation was mesophilic, and also predominated in the underlying tailings sediment. Other, less abundant genera grew primarily during summer, possibly due to distinct CH4/O2 microniches created during thermal stratification. These data are consistent with temporal and spatial niche differentiation based on temperature, CH4 and O2. This pit lake displays methane cycling and methanotroph population dynamics similar to natural boreal lakes. IMPORTANCE The study examined methanotrophic bacteria in an industrial end pit lake, combining molecular DNA methods (both quantitative and descriptive) with biogeochemical measurements. The lake was sampled over 5 years, in all four seasons, as often as weekly, and included sub-ice samples. The resulting multiseason and multiyear data set is unique in its size and intensity, and allowed us to document clear and consistent seasonal patterns of growth and decline of three methanotroph genera (Methylobacter, Methylovulum, and Methyloparacoccus). Laboratory experiments suggested that one major control of this succession was niche partitioning based on temperature. The study helps to understand microbial dynamics in engineered end pit lakes, but we propose that the dynamics are typical of boreal stratified lakes and widely applicable in microbial ecology and limnology. Methane-oxidizing bacteria are important model organisms in microbial ecology and have implications for global climate change.

Sentinel lymph node biopsy in patients with endometrial cancer and an indocyanine green or iodinated contrast reaction - A proposed management algorithm.

OBJECTIVE: To describe the incidence of adverse reactions to indocyanine green (ICG) administered during sentinel lymph node (SLN) biopsy for endometrial cancer, and to propose an ICG management algorithm for these patients. METHODS: All patients who underwent surgery for endometrial cancer with SLN biopsy using ICG from 1/2017 to 8/2020 were identified using a single-institution prospective database. Surgical adverse events (SAEs) related to the procedure were identified. A review of the literature was performed. RESULTS: In all, 1414 patients met inclusion criteria and were evaluated. Sixty-seven (4.7%) patients had a history of either an iodine or contrast allergy. No patients had a history of documented ICG allergy. Among patients with an iodine or contrast allergy, 65 (97%) received a corticosteroid with or without diphenhydramine prior to ICG administration. One hundred five patients (7.4%) experienced 116 SAEs. Among these patients, 3 experienced potentially allergic SAEs possibly related to ICG administration. After thorough chart review, however, the likelihood these SAEs were due to ICG appeared low. No patients experienced an anaphylactic response after ICG admission. CONCLUSION: There were no anaphylactic reactions to ICG intracervical administration during 1414 consecutive SLN biopsies, including in patients with a documented iodine or contrast allergy. Intracervical injection of ICG is safe, and premedication using corticosteroids with or without diphenhydramine prior to SLN biopsy is a reasonable strategy in patients with iodinated contrast allergy.

Management of Patients with Acute Methotrexate Nephrotoxicity with High-Dose Leucovorin.

BACKGROUND: Acute kidney injury complicating high-dose methotrexate (HDMTX) therapy increases the risk for severe mucositis, myelosuppression, and death. It is unclear whether high-dose leucovorin and supportive therapy without the use of glucarpidase can reduce toxicity from HDMTX. STUDY DESIGN: The charts of all patients at Memorial Sloan Kettering Cancer Center whose methotrexate (MTX) drug levels at 48 or 72 hours after administration were 10 times or more the toxic level were reviewed between January 2000 and December 2011. RESULTS: Eighty-eight patients (median age 51 years, range 9-90 years) who received 100 courses of HDMTX were identified. Serum creatinine increased by 2-fold from baseline (median, range 1- to 10-fold), but all patients recovered kidney function. Serum levels of MTX were 69 µmol/L (median, range 2.2-400), 6.9 µmol/L (1.3-64), and 2.0 µmol/L (0.05-26) at 24, 48, and 72 hours, respectively, after administration. A statistically significant correlation existed between MTX levels at 48, 72, 96, and 120 hours after administration but not between 24 and 72 hours or subsequent time points. High-dose leucovorin was given in 81% of courses in accordance with institutional protocols in most cases. Myelosuppression was present in 42%; grade III or higher neutropenia in 29%, and thrombocytopenia in 25%. Infectious complications, oral mucositis, and diarrhea occurred in 21%, 17%, and 6% of patients, respectively. Five deaths occurred, none directly attributed to complications from MTX administration. Seven additional patients received glucarpidase at the discretion of a treating physician during the study period, and results are reported separately. CONCLUSION: Patients who had 100 episodes of HDMTX-associated acute kidney injury were treated with a strategy that only included usual supportive measures and high-dose leucovorin. No deaths were directly attributed to complications related to HDMTX. Glucarpidase, an expensive drug, may not be necessary for a significant number of patients.

Investigating the effect of forestry on leaf-litter arthropods (Algonquin Park, Ontario, Canada).

Arthropods are the most diverse taxonomic group of terrestrial eukaryotes and are sensitive to physical alterations in their environment such as those caused by forestry. With their enormous diversity and physical omnipresence, arthropods could be powerful indicators of the effects of disturbance following forestry. When arthropods have been used to measure the effects of disturbance, the total diversity of some groups is often found to increase following forestry. However, these findings are frequently derived using a coarse taxonomic grain (family or order) to accommodate for various taxonomic impediments (including cryptic diversity and poorly resourced taxonomists). Our intent with this work was to determine the diversity of arthropods in and around Algonquin Park, and how this diversity was influenced by disturbance (in this case, forestry within the past 25 years). We used DNA barcode-derived diversity estimates (Barcode Index Number (BIN) richness) to avoid taxonomic impediments and as a source of genetic information with which we could conduct phylogenetic estimates of diversity (PD). Diversity patterns elucidated with PD are often, but not always congruent with taxonomic estimates-and departures from these expectations can help clarify disturbance effects that are hidden from richness studies alone. We found that BIN richness and PD were greater in disturbed (forested) areas, however when we controlled for the expected relationship between PD and BIN richness, we found that cut sites contained less PD than expected and that this diversity was more phylogenetically clustered than would be predicted by taxonomic richness. While disturbance may cause an evident increase in diversity, this diversity may not reflect the full evolutionary history of the assemblage within that area and thus a subtle effect of disturbance can be found decades following forestry.

Pandemic preparedness in Hawaii: a multicenter verification of real-time RT-PCR for the direct detection of influenza virus types A and B.

OBJECTIVE: We integrated multicenter, real-time (RTi) reverse transcription polymerase chain reaction (RT-PCR) screening into a statewide laboratory algorithm for influenza surveillance and response. METHODS: Each of three sites developed its own testing strategy and was challenged with one randomized and blinded panel of 50 specimens previously tested for respiratory viruses. Following testing, each participating laboratory reported its results to the Hawaii State Department of Health, State Laboratories Division for evaluation and possible discrepant analysis. RESULTS: Two of three laboratories reported a 100% sensitivity and specificity, resulting in a 100% positive predictive value and a 100% negative predictive value (NPV) for influenza type A. The third laboratory showed a 71% sensitivity for influenza type A (83% NPV) with 100% specificity. All three laboratories were 100% sensitive and specific for the detection of influenza type B. Discrepant analysis indicated that the lack of sensitivity experienced by the third laboratory may have been due to the analyte-specific reagent probe used by that laboratory. Use of a newer version of the product with a secondary panel of 20 specimens resulted in a sensitivity and specificity of 100%. CONCLUSIONS: All three laboratories successfully verified their ability to conduct clinical testing for influenza using diverse nucleic acid extraction and RTi RT-PCR platforms. Successful completion of the verification by all collaborating laboratories paved the way for the integration of those facilities into a statewide laboratory algorithm for influenza surveillance and response.

Direct comparison of hepatitis C virus genotypes tested by INNO-LiPA HCV II and TRUGENE HCV genotyping methods.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. It is associated with the development of end-stage liver disease and hepatocellular carcinoma. Studies have shown that patients infected with different genotypes of HCV may respond to interferon-ribavirin therapy differently and thus HCV genotype information is very important in helping physicians to better managing their patients. OBJECTIVES: Compare the end results of HCV typing of the two commercially available tests. STUDY DESIGN: TRUGENE Genotyping test (Visible Genetics) was used to analyze clinical specimens obtained from North America. The 5' NC was amplified with the Roche COBAS Amplicor HCV Monitor Test. Amplification products were blinded and genotyped by the TRUGENE HCV 5'NC method. Genotype results were compared with those obtained by the reverse hybridization based INNO-LiPA HCV II (Innogenetics) assay. Additional sequencing of the NS5B region was done to resolve discrepancies. RESULTS AND CONCLUSIONS: Among the total of 110 consecutively collected serum specimens submitted for HCV genotyping, 108/110 could be typed by the sequencing method and 107/110 were typable by LiPA HCV II method. Our experiences with the tests suggest that at type level, HCV genotype results are 100% concordant between the two tests studied for those 106 specimens successfully typed by both methods. More sensitive amplification, such as qualitative PCR, is needed to test specimens with viral load lower than 20000 IU/ml. Both tests can be easily adapted by a clinical diagnostic laboratory.