Utility of routine left ventricular ejection fraction measurement before anthracycline-based chemotherapy in patients with diffuse large B-cell lymphoma.

PURPOSE: Despite the lack of evidence, routine left ventricular ejection fraction (LVEF) measurement in diffuse large B-cell lymphoma (DLBCL) before anthracycline-based chemotherapy (ABC) is recommended by practice guidelines and required in DLBCL trials in the United States. METHODS: We determined the frequency of the following in 197 consecutive patients with newly diagnosed DLBCL treated at our institution: one, LVEF measurement before ABC; two, finding of asymptomatic LV dysfunction (ALVD); and three, modification in treatment strategy as a result of LVEF measurement. RESULTS: The median age was 71 years, and 54% of patients were men. LVEF was measured in 128 patients (65%) pretreatment, including in 15 with prior congestive heart failure (CHF). The reasons for not measuring LVEF were: clinically low risk for ALVD (n = 32), medical frailty (n = 15), palliative care (n = 3), ABC not standard therapy (n = 12), and prior CHF (n = 7). Among patients without prior CHF who had LVEF assessed (n = 113), ALVD was detected in four (4%), with LVEF ranging from 41% to 48%. Four patients were not treated despite normal LVEF because of comorbidities and anticipated toxicities. In contrast, all four patients with ALVD received ABC. No patient had a modification in treatment strategy as a result of LVEF measurement. After a median follow-up of 60 months, among those who remained alive, CHF developed in 15% versus 6% of patients receiving ABC who did and did not have LVEF measured, respectively (P = .246). CONCLUSION: Our findings challenge the utility of routine LVEF measurement in patients with DLBCL before ABC. Potential cost savings to our health care system could be substantial.

Contralateral testicular relapse after prophylactic radiation in a patient with primary testicular diffuse large B-cell lymphoma.

Prophylactic radiation to the contralateral uninvolved testicle has become a standard practice in the treatment of primary testicular lymphoma. While it is generally felt to be very effective, its failure rate is unknown. We describe a patient with primary testicular diffuse large B-cell lymphoma, who developed recurrent disease in the contralateral testicle despite receiving prophylactic testicular radiation, central nervous system prophylaxis, and anthracycline-based chemo-immunotherapy. Review of the literature shows that the testicular failure rate after prophylactic radiation may be unexpectedly high at 10% or more. We put forward hypotheses on testicular relapse and discuss potential alternative preventive strategies.

The genome of Heliobacterium modesticaldum, a phototrophic representative of the Firmicutes containing the simplest photosynthetic apparatus.

Despite the fact that heliobacteria are the only phototrophic representatives of the bacterial phylum Firmicutes, genomic analyses of these organisms have yet to be reported. Here we describe the complete sequence and analysis of the genome of Heliobacterium modesticaldum, a thermophilic species belonging to this unique group of phototrophs. The genome is a single 3.1-Mb circular chromosome containing 3,138 open reading frames. As suspected from physiological studies of heliobacteria that have failed to show photoautotrophic growth, genes encoding enzymes for known autotrophic pathways in other phototrophic organisms, including ribulose bisphosphate carboxylase (Calvin cycle), citrate lyase (reverse citric acid cycle), and malyl coenzyme A lyase (3-hydroxypropionate pathway), are not present in the H. modesticaldum genome. Thus, heliobacteria appear to be the only known anaerobic anoxygenic phototrophs that are not capable of autotrophy. Although for some cellular activities, such as nitrogen fixation, there is a full complement of genes in H. modesticaldum, other processes, including carbon metabolism and endosporulation, are more genetically streamlined than they are in most other low-G+C gram-positive bacteria. Moreover, several genes encoding photosynthetic functions in phototrophic purple bacteria are not present in the heliobacteria. In contrast to the nutritional flexibility of many anoxygenic phototrophs, the complete genome sequence of H. modesticaldum reveals an organism with a notable degree of metabolic specialization and genomic reduction.

Niche adaptation and genome expansion in the chlorophyll d-producing cyanobacterium Acaryochloris marina.

Acaryochloris marina is a unique cyanobacterium that is able to produce chlorophyll d as its primary photosynthetic pigment and thus efficiently use far-red light for photosynthesis. Acaryochloris species have been isolated from marine environments in association with other oxygenic phototrophs, which may have driven the niche-filling introduction of chlorophyll d. To investigate these unique adaptations, we have sequenced the complete genome of A. marina. The DNA content of A. marina is composed of 8.3 million base pairs, which is among the largest bacterial genomes sequenced thus far. This large array of genomic data is distributed into nine single-copy plasmids that code for >25% of the putative ORFs. Heavy duplication of genes related to DNA repair and recombination (primarily recA) and transposable elements could account for genetic mobility and genome expansion. We discuss points of interest for the biosynthesis of the unusual pigments chlorophyll d and alpha-carotene and genes responsible for previously studied phycobilin aggregates. Our analysis also reveals that A. marina carries a unique complement of genes for these phycobiliproteins in relation to those coding for antenna proteins related to those in Prochlorococcus species. The global replacement of major photosynthetic pigments appears to have incurred only minimal specializations in reaction center proteins to accommodate these alternate pigments. These features clearly show that the genus Acaryochloris is a fitting candidate for understanding genome expansion, gene acquisition, ecological adaptation, and photosystem modification in the cyanobacteria.

The complete genome sequence of Roseobacter denitrificans reveals a mixotrophic rather than photosynthetic metabolism.

Purple aerobic anoxygenic phototrophs (AAPs) are the only organisms known to capture light energy to enhance growth only in the presence of oxygen but do not produce oxygen. The highly adaptive AAPs compose more than 10% of the microbial community in some euphotic upper ocean waters and are potentially major contributors to the fixation of the greenhouse gas CO2. We present the complete genomic sequence and feature analysis of the AAP Roseobacter denitrificans, which reveal clues to its physiology. The genome lacks genes that code for known photosynthetic carbon fixation pathways, and most notably missing are genes for the Calvin cycle enzymes ribulose bisphosphate carboxylase (RuBisCO) and phosphoribulokinase. Phylogenetic evidence implies that this absence could be due to a gene loss from a RuBisCO-containing alpha-proteobacterial ancestor. We describe the potential importance of mixotrophic rather than autotrophic CO2 fixation pathways in these organisms and suggest that these pathways function to fix CO2 for the formation of cellular components but do not permit autotrophic growth. While some genes that code for the redox-dependent regulation of photosynthetic machinery are present, many light sensors and transcriptional regulatory motifs found in purple photosynthetic bacteria are absent.