Narrative review-focal therapy: are we ready to change the prostate cancer treatment paradigm?

Background and Objective: Prostate cancer (PCa) has seen improved detection methods with a subsequent rise in disease prevalence, making novel prostate cancer treatment options an exciting yet controversial topic. Current treatment modalities encompass traditional approaches, namely surgery (radical prostatectomy) and radiation therapy. While heralded as a standard of care, these modalities may come with significant risk profiles, primarily sexual (erectile dysfunction) and urinary incontinence. Advances in technology and imaging, specifically multi-parametric MRI, have afforded great leaps in targeted focal therapy as a primary treatment option for localized PCa. This review identifies and highlights published data for novel and emerging PCa focal therapy (FT) modalities. Methods: Our study identified and reviewed the current literature for relevant investigations related to primary FT modalities as they apply to the treatment of prostate cancer. After an internal review, relevant studies (published in English, between 2000-April 2022) were included for analysis and summarization. Key Content and Findings: We provide a concise review of several novel focal therapy modalities that offer realistic potential for primary treatment of localized prostate cancer. Our narrative includes studies that primarily include their respective results, specifically focusing on those that reported both oncologic and quality-of-life outcomes after focal therapy. While still in its cumulative infancy, we discuss the current limitations, future directions, and advancements that hopefully push focal therapy into the limelight. Conclusions: While many of the mentioned focal therapies for PCa have shown promising pathologic and quality of life outcomes, further clinical evidence is required to change overall management guidelines and recommendations. The advantages of FT in avoiding sexual and urinary side-effects of radical surgery or radiation are apparent; however, it is necessary to recognize the need for further long-term evidence that is durable over time and comparable to current gold-standard treatment options.

Alternatives to whole gland treatment for localized prostate cancer: a review of novel focal therapies.

PURPOSE OF REVIEW: The mainstays of the management of clinically localized prostate cancer have historically rested upon active surveillance, radiation therapy, or radical prostatectomy. Although both radiation and surgical treatment of localized prostate cancer can achieve excellent oncologic outcomes, the subsequent potential adverse effects of urinary stress incontinence and erectile dysfunction are unappealing to patients. This has led to investigational studies centered upon focal treatment of the cancerous lesion, with the aim to improve quality-of-life outcomes. In this review, we describe numerous novel modalities, including nanoparticle ablation and irreversible electroporation, which are being utilized for the focal treatment of clinically localized prostate cancer. RECENT FINDINGS: Although many of these novel therapies are in their investigational infancy, several have revealed very promising results both in their post-treatment pathologic outcomes as well as objective quality-of-life measures. SUMMARY: Initial data regarding novel focal therapy for prostate cancer treatment show promising short-term outcomes in regards to oncologic and quality-of-life assessments. Further investigational studies are needed to determine inclusion criteria for the selection of optimal candidates.

Microorganisms Move a Short Distance into an Almond Orchard from an Adjacent Upwind Poultry Operation.

Over a 2-year period, drag swabs of orchard soil surface and air, soil, and almond leaf samples were collected in an almond orchard adjacent to (35 m from the first row of trees) and downwind from a poultry operation and in two almond orchards (controls) that were surrounded by other orchards. Samples were evaluated for aerobic plate count, generic Escherichia coli, other coliforms, the presence of Salmonella, bacterial community structure (analyzed through sequencing of the 16S rRNA gene), and amounts of dry solids (dust) on leaf surfaces on trees 0, 60, and 120 m into each orchard. E. coli was isolated from 41 of 206 (20%) and 1 of 207 (0.48%) air samples in the almond-poultry and control orchards, respectively. Salmonella was not isolated from any of the 529 samples evaluated. On average, the amount of dry solids on leaves collected from trees closest to the poultry operation was more than 2-fold greater than from trees 120 m into the orchard or from any of the trees in the control orchards. Members of the family Staphylococcaceae-often associated with poultry-were, on average, significantly (P < 0.001) more abundant in the phyllosphere of trees closest to the poultry operation (10% of relative abundance) than in trees 120 m into the orchard (1.7% relative abundance) or from any of the trees in control orchards (0.41% relative abundance). Poultry-associated microorganisms from a commercial operation transferred a short distance into an adjacent downwind almond orchard.IMPORTANCE The movement of microorganisms, including foodborne pathogens, from animal operations into adjacent plant crop-growing environments is not well characterized. This study provides evidence that dust and bioaerosols moved from a commercial poultry operation a short distance downwind into an almond orchard and altered the microbiome recovered from the leaves. These data provide growers with information they can use to assess food safety risks on their property.

Conditions at the time of inoculation influence survival of attenuated Escherichia coli O157:H7 on field-inoculated lettuce.

The impact of plant development, environmental conditions at the time of inoculation, and inoculum concentration on survival of attenuated BSL1 Escherichia coli O157:H7 strain ATCC 700728 on field-grown romaine lettuce was evaluated over 3 years. E. coli 700728 was inoculated onto 4- and 6-week-old romaine lettuce plants in the Salinas Valley, CA, at night or the next morning with either low (5 log) or high (7 log) cell numbers per plant to simulate a single aqueous contamination event. At night, when leaf wetness and humidity levels were high, E. coli cell numbers declined by 0.5 log CFU/plant over the first 8-10 h. When applied in the morning, E. coli populations declined up to 2 log CFU/plant within 2 h. However, similar numbers of E. coli were retrieved from lettuce plants at 2 and 7 days. E. coli cell numbers per plant were significantly lower (P < 0.05) 7 days after application onto 4-week-old compared to 6-week-old plants. E. coli 700728 could be recovered by plating or enrichment from a greater proportion of plants for longer times when inoculated at high compared with low initial concentrations and after inoculation of 6-week-old plants compared with 4-week-old plants, even at the low initial inoculum. A contamination event near harvest or when leaf wetness and humidity levels are high may enhance survivability, even when low numbers of E. coli are introduced.

Draft Genome Sequence of Enterococcus plantarum Strain TRW2, Isolated from Lettuce.

We report the draft genome sequence for Enterococcus plantarum strain TRW2, isolated from the phyllosphere of romaine lettuce. The draft sequence consists of 3,383,441 bp, with a G+C content of 35.8% and 3,218 protein-coding genes. None of the 22,190 known antibiotic resistance genes were detected.

Effects of Exogenous Yeast and Bacteria on the Microbial Population Dynamics and Outcomes of Olive Fermentations.

In this study, we examined Sicilian-style green olive fermentations upon the addition of Saccharomyces cerevisiae UCDFST 09-448 and/or Pichia kudriazevii UCDFST09-427 or the lactic acid bacteria (LAB) Lactobacillus plantarum AJ11R and Leuconostoc pseudomesenteroides BGM3R. Olives containing S. cerevisiae UCDFST 09-448, a strain able to hydrolyze pectin, but not P. kudriazevii UCDFST 09-427, a nonpectinolytic strain, exhibited excessive tissue damage within 4 weeks. DNA sequencing of fungal internal transcribed spacer (ITS) regions and comparisons to a yeast-specific ITS sequence database remarkably showed that neither S. cerevisiae UCDFST 09-448 nor P. kudriazevii UCDFST 09-427 resulted in significant changes to yeast species diversity. Instead, Candida boidinii constituted the majority (>90%) of the total yeast present, independent of whether S. cerevisiae or P. kudriazevii was added. By comparison, Lactobacillus species were enriched in olives inoculated with potential starter LAB L. plantarum AJ11R and L. pseudomesenteroides BGM3R according to community 16S rRNA gene sequence analysis. The bacterial diversity of those olives was significantly reduced and resembled control fermentations incubated for a longer period of time. Importantly, microbial populations were highly dynamic at the strain level, as indicated by the large variations in AJ11R and BGM3R cell numbers over time and reductions in the numbers of yeast isolates expressing polygalacturonase activity. These findings show the distinct effects of exogenous spoilage and starter microbes on indigenous communities in plant-based food fermentations that result in very different impacts on product quality. IMPORTANCE Food fermentations are subject to tremendous selective pressures resulting in the growth and persistence of a limited number of bacterial and fungal taxa. Although these foods are vulnerable to spoilage by unintended contamination of certain microorganisms, or alternatively, can be improved by the deliberate addition of starter culture microbes that accelerate or beneficially modify product outcomes, the impact of either of those microbial additions on community dynamics within the fermentations is not well understood at strain-specific or global scales. Herein, we show how exogenous spoilage yeast or starter lactic acid bacteria confer very different effects on microbial numbers and diversity in olive fermentations. Introduced microbes have long-lasting consequences and result in changes that are apparent even when levels of those inoculants and their major enzymatic activities decline. This work has direct implications for understanding bacterial and fungal invasions of microbial habitats resulting in pivotal changes to community structure and function.

Normative data for modified Box and Blocks test measuring upper-limb function via motion capture.

Motion analysis is an important tool for examining upper-limb function. Based on previous work demonstrating a modified Box and Blocks (BB) test with motion capture to assess prosthetic performance, we collected data in 16 nondisabled participants to establish normative kinematics for this test. Four motions of the modified BB test were analyzed to establish kinematic data for upper-limb and trunk motion. The test was repeated for right and left arms in standing and seated positions. Data were compared using a nonparametric Friedman test. No differences were found between right- and left-hand performance other than for task completion time. Small but significant differences were found for standing and seated performance, with slightly greater ranges in standing for axial trunk rotation, medial-lateral sternum displacement, and anterior-posterior hand displacement. The kinematic trajectories, however, were very consistent. The consistency in our nondisabled data suggests that normative kinematic trajectories can be defined for this task. This motion capture procedure may add to the understanding of movement in upper-limb impairment and may be useful for measuring the effect of interventions to improve upper-limb function.

Phyllosphere microbiota composition and microbial community transplantation on lettuce plants grown indoors.

UNLABELLED: The aerial surfaces of plants, or phyllosphere, are microbial habitats important to plant and human health. In order to accurately investigate microbial interactions in the phyllosphere under laboratory conditions, the composition of the phyllosphere microbiota should be representative of the diversity of microorganisms residing on plants in nature. We found that Romaine lettuce grown in the laboratory contained 10- to 100-fold lower numbers of bacteria than age-matched, field-grown lettuce. The bacterial diversity on laboratory-grown plants was also significantly lower and contained relatively higher proportions of Betaproteobacteria as opposed to the Gammaproteobacteria-enriched communities on field lettuce. Incubation of field-grown Romaine lettuce plants in environmental growth chambers for 2 weeks resulted in bacterial cell densities and taxa similar to those on plants in the field but with less diverse bacterial populations overall. In comparison, the inoculation of laboratory-grown Romaine lettuce plants with either freshly collected or cryopreserved microorganisms recovered from field lettuce resulted in the development of a field-like microbiota on the lettuce within 2 days of application. The survival of an inoculated strain of Escherichia coli O157:H7 was unchanged by microbial community transfer; however, the inoculation of E. coli O157:H7 onto those plants resulted in significant shifts in the abundance of certain taxa. This finding was strictly dependent on the presence of a field-associated as opposed to a laboratory-associated microbiota on the plants. Phyllosphere microbiota transplantation in the laboratory will be useful for elucidating microbial interactions on plants that are important to agriculture and microbial food safety. IMPORTANCE: The phyllosphere is a habitat for a variety of microorganisms, including bacteria with significant relevance to plant and human health. Some indigenous epiphytic bacteria might affect the persistence of human food-borne pathogens in the phyllosphere. However, studies on human pathogens are typically performed on plants grown indoors. This study compares the phyllosphere microbiota on Romaine lettuce plants grown in a Salinas Valley, CA, field to that on lettuce plants grown in environmental chambers. We show that phyllosphere microbiota from laboratory-grown plants is distinct from that colonizing plants grown in the field and that the field microbiota can be successfully transferred to plants grown indoors. The microbiota transplantation method was used to examine alterations to the phyllosphere microbiota after Escherichia coli O157:H7 inoculation on lettuce plants in a controlled environment. Our findings show the importance and validity of phyllosphere microbiota transplantation for future phyllosphere microbiology research.

Season, irrigation, leaf age, and Escherichia coli inoculation influence the bacterial diversity in the lettuce phyllosphere.

The developmental and temporal succession patterns and disturbance responses of phyllosphere bacterial communities are largely unknown. These factors might influence the capacity of human pathogens to persist in association with those communities on agriculturally-relevant plants. In this study, the phyllosphere microbiota was identified for Romaine lettuce plants grown in the Salinas Valley, CA, USA from four plantings performed over 2 years and including two irrigation methods and inoculations with an attenuated strain of Escherichia coli O157:H7. High-throughput DNA pyrosequencing of the V5 to V9 variable regions of bacterial 16S rRNA genes recovered in lettuce leaf washes revealed that the bacterial diversity in the phyllosphere was distinct for each field trial but was also strongly correlated with the season of planting. Firmicutes were generally most abundant in early season (June) plantings and Proteobacteria comprised the majority of bacteria recovered later in the year (August and October). Comparisons within individual field trials showed that bacterial diversity differed between sprinkler (overhead) and drip (surface) irrigated lettuce and increased over time as the plants grew. The microbiota were also distinct between control and E. coli O157:H7-inoculated plants and between E. coli O157:H7-inoculated plants with and without surviving pathogen cells. The bacterial inhabitants of the phyllosphere therefore appear to be affected by seasonal, irrigation, and biological factors in ways that are relevant for assessments of fresh produce food safety.

Do physician organizations located in lower socioeconomic status areas score lower on pay-for-performance measures?

BACKGROUND: Physician organizations (POs)--independent practice associations and medical groups--located in lower socioeconomic status (SES) areas may score poorly in pay-for-performance (P4P) programs. OBJECTIVE: To examine the association between PO location and P4P performance. DESIGN: Cross-sectional study; Integrated Healthcare Association's (IHA's) P4P Program, the largest non-governmental, multi-payer program for POs in the U.S. PARTICIPANTS: 160 POs participating in 2009. MAIN MEASURES: We measured PO SES using established methods that involved geo-coding 11,718 practice sites within 160 POs to their respective census tracts and weighting tract-specific SES according to the number of primary care physicians at each site. P4P performance was defined by IHA's program and was a composite mainly representing clinical quality, but also including measures of patient experience, information technology and registry use. KEY RESULTS: The area-based PO SES measure ranged from -11 to +11 (mean 0, SD 5), and the IHA P4P performance score ranged from 23 to 86 (mean 69, SD 15). In bivariate analysis, there was a significant positive relationship between PO SES and P4P performance (p < 0.001). In multivariate analysis, a one standard deviation increase in PO SES was associated with a 44% increase (relative risk 1.44, 95%CI, 1.22-1.71) in the likelihood of a PO being ranked in the top two quintiles of performance (p < 0.001). CONCLUSIONS: Physician organizations' performance scores in a major P4P program vary by the SES of the areas in which their practice sites are located. P4P programs that do not account for this are likely to pay higher bonuses to POs in higher SES areas, thus increasing the resource gap between these POs and POs in lower SES areas, which may increase disparities in the care they provide.

Pay for performance: its influence on the use of IT in physician organizations.

The introduction of information technology (IT) in physician organizations and practices is a source of great interest to physician leaders and policy makers. In this article, the authors describe what may be the nation's largest pay-for-performance program, its performance metrics, and incentives for the implementation and use of IT in medical groups and independent physician associations (IPAs). Results include the increased use of electronic clinical data, point-of-care technology, and the generation of more actionable reports for quality improvement. Noteworthy are the efforts by physician organizations to enhance data collection to demonstrate improved clinical performance and earn financial incentives.