Report from the American Society of Transplantation on frailty in solid organ transplantation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148387/1/ajt15198_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148387/2/ajt15198.pd

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Mycobacterium abscessus disease in lung transplant recipients: Diagnosis and management

Mycobacterium abscessus complex (MAbsC) disease in lung transplant recipients is increasingly being recognized as an important cause of graft function decline and suboptimal outcomes. Lung transplant recipients appear to be at the highest risk of MAbsC among solid organ transplant recipients, as they have more intense immunosuppression, and the organisms preferentially inhabit the lungs. MAbsC is the most resistant species of rapidly growing mycobacteria and difficult to treat, causing considerable mortality and morbidity in immunocompetent and immunosuppressed patients. Herein we describe the risk factors, epidemiology, clinical features, diagnostics, and treatment strategies of MAbsC in lung transplant candidates and recipients. Keywords: Mycobacterial abscessus complex, Lung transplant, Lung infectio

Characterization of a Novel ADAM Protease Expressed by Pneumocystis carinii▿ †

Pneumocystis species are opportunistic fungal pathogens that cause severe pneumonia in immunocompromised hosts. Recent evidence has suggested that unidentified proteases are involved in Pneumocystis life cycle regulation. Proteolytically active ADAM (named for “a disintegrin and metalloprotease”) family molecules have been identified in some fungal organisms, such as Aspergillus fumigatus and Schizosaccharomyces pombe, and some have been shown to participate in life cycle regulation. Accordingly, we sought to characterize ADAM-like molecules in the fungal opportunistic pathogen, Pneumocystis carinii (PcADAM). After an in silico search of the P. carinii genomic sequencing project identified a 329-bp partial sequence with homology to known ADAM proteins, the full-length PcADAM sequence was obtained by PCR extension cloning, yielding a final coding sequence of 1,650 bp. Sequence analysis detected the presence of a typical ADAM catalytic active site (HEXXHXXGXXHD). Expression of PcADAM over the Pneumocystis life cycle was analyzed by Northern blot. Southern and contour-clamped homogenous electronic field blot analysis demonstrated its presence in the P. carinii genome. Expression of PcADAM was observed to be increased in Pneumocystis cysts compared to trophic forms. The full-length gene was subsequently cloned and heterologously expressed in Saccharomyces cerevisiae. Purified PcADAMp protein was proteolytically active in casein zymography, requiring divalent zinc. Furthermore, native PcADAMp extracted directly from freshly isolated Pneumocystis organisms also exhibited protease activity. This is the first report of protease activity attributable to a specific, characterized protein in the clinically important opportunistic fungal pathogen Pneumocystis

Frailty and Clinical Outcomes in Chronic Obstructive Pulmonary Disease

RationaleFrailty represents an increased vulnerability to adverse health outcomes. The frailty phenotype conceptual model (three or more patient attributes of wasting, exhaustion, low activity, slowness, and weakness) is associated with increased morbidity and mortality in geriatric populations.ObjectivesOur objective was to describe the risks associated with frailty in patients with chronic obstructive pulmonary disease.MethodsData from the National Emphysema Treatment Trial (NETT) were retrospectively analyzed. The frailty phenotype conceptual model was operationalized as three or more frailty parameters (a body mass index decrease of ≥5% over 12 months, self-reported exhaustion, low 6-minute walk distance, or physical activity or respiratory muscle strength in the lowest quartile). Frail participants were compared with participants with two or fewer frailty parameters. Participants were followed starting 12 months after NETT randomization (to minimize surgical effect) for 24 months. Univariate, multivariate, Kaplan-Meier, and Cox proportional hazard analyses were performed, adjusting for treatment arm, age, modified Medical Research Council dyspnea scale, sex, and baseline forced expiratory volume in 1 second (FEV1). Multiple imputation was used for missing values.ResultsThe participants (N = 902) were predominantly white (94.5%) males (59.5%), with a median age of 67 years (interquartile range, 63-70 yr) and a median FEV1% predicted of 26 (interquartile range, 20-33). Six percent of the participants (95% confidence interval [CI], 4.5 to 7.6) were frail. The incidence rate of frailty was 6.4 per 100 person-years. Frail participants reported significantly worse disease-specific and overall quality of life by St. George's Respiratory Questionnaire total score (mean difference of 11.6; 95% CI, 7.6 to 15.6; P < 0.001), mental composite on Medical Outcomes Survey Short Form-36 (mean difference -6.8; 95% CI, -10.0 to -3.6; P < 0.001), and physical composite scores on Medical Outcomes Survey Short Form-36 (mean difference -16.7; 95% CI, -21.3 to -12.1; P = 0.001). Frail participants had an increased rate of hospitalization (adjusted hazard ratio, 1.6; 95% CI, 1.1 to 2.5; P = 0.02) and an adjusted increase in hospital use of 8.0 days (95% CI, 4.4 to 11.6; P < 0.001) compared with nonfrail participants. Frail participants had a higher mortality rate (adjusted hazard ratio, 1.4; 95% CI, 0.97 to 2.0; P = 0.07).ConclusionsAmong adults with chronic obstructive pulmonary disease, our measure of frailty (modified from the Fried frailty phenotype) was associated with incident and longer-duration hospitalization, and with poor quality of life

Management and diagnosis of tuberculosis in solid organ transplant candidates and recipients: Expert survey and updated review,

Background: Optimal screening and management of latent tuberculosis infection (LTBI) and active tuberculosis (TB) in solid organ transplant (SOT) candidates and recipients is necessary to prevent morbidity and mortality.Methods: We conducted a cross-sectional survey of TB and transplant experts across the United States reviewing the clinical practice preferences on key management issues related to LTBI and TB in SOT candidates and recipients.Results: Thirty TB and 13 SOT experts were surveyed (response rate = 53.8%). Both groups agreed that tuberculin skin test (TST) and chest x-ray screening in SOT candidates was useful (78.6% and 84.6%, respectively). TST after SOT was not useful for most transplant experts and TB experts (0% vs. 32.1%, respectively), but both groups were split on usefulness of interferon gamma release assays (IGRA) in SOT recipients (42.9% TB experts vs. 46.2% SOT experts). Most experts recommend LTBI treatment prior to SOT if close monitoring is assured (82.1% TB experts vs. 76.9% transplant experts). LTBI treatment with isoniazid was preferred for patients on calcineurin inhibitors. Evaluation for suspected TB in SOT recipients varied, but most TB experts favored sputum testing (88.9%) whereas most transplant experts favored bronchoscopic testing (69.2%). Preferred TB treatment regimens in SOT recipients were similar to regimens recommended for immunocompetent patients.Conclusions: Most TB and transplant experts recommend evaluation and treatment for LTBI in SOT candidates. Liver transplant candidates, however, should only be treated if close monitoring can be assured and after consulting with a hepatologist. Practice preferences varied regarding the initial diagnostic approach for suspected TB in SOT recipients; however, most experts agreed that SOT recipients should receive similar treatments as immunocompetent patients. Keywords: Tuberculosis, Transplantation, Surve