High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis

RATIONALE: High-resolution computed tomography (HRCT) is an integral aspect of the evaluation of patients with suspected idiopathic pulmonary fibrosis (IPF). However, few studies have evaluated its use in a large cohort. OBJECTIVES: To describe HRCT features in patients with mild to moderate IPF, compare diagnostic evaluations by a radiology core (three thoracic radiologists) with those by study-site radiologists, correlate baseline clinical and physiologic variables with HRCT findings, and evaluate their association with mortality. METHODS: We assessed HRCT scans from patients with IPF (n = 315) enrolled in a randomized controlled study evaluating IFN-gamma1b. MEASUREMENTS AND MAIN RESULTS: There was concordance between study-site and core radiologists regarding the diagnosis of IPF in 86% of cases. Diffusing capacity of carbon monoxide (DLCO) was the physiologic characteristic most highly correlated with HRCT findings. Multivariate analysis identified three independent predictors of mortality: a higher extent of fibrosis score increased the risk of death (p < 0.0001), whereas a higher percent-predicted DLCO (p = 0.004) and treatment assignment to IFN-gamma1b rather than placebo (p = 0.04) reduced the risk of death. CONCLUSIONS: A study-site diagnosis of IPF on HRCT was regularly confirmed by core radiologists. Extent of reticulation and honeycombing on HRCT is an important independent predictor of mortality in patients with IPF.     

l‐Methionine anti‐biofilm activity against Pseudomonas aeruginosa is enhanced by the cystic fibrosis transmembrane conductance regulator potentiator,ivacaftor

Background

Biofilms may contribute to refractory chronic rhinosinusitis (CRS), as they lead to antibiotic resistance and failure of effective clinical treatment. l ‐Methionine is an amino acid with reported biofilm‐inhibiting properties. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator with mild antimicrobial activity via inhibition of bacterial DNA gyrase and topoisomerase IV. The objective of this study was to evaluate whether co‐treatment with ivacaftor and l ‐methionine can reduce the formation of Pseudomonas aeruginosa biofilms.

Methods

P aeruginosa (PAO‐1 strain) biofilms were studied in the presence of l ‐methionine and/or ivacaftor. For static biofilm assays, PAO‐1 was cultured in a 48‐well plate for 72 hours with stepwise combinations of these agents. Relative biofilm inhibitions were measured according to optical density of crystal violet stain at 590 nm. Live/dead assays (BacTiter‐Glo? assay, Promega) were imaged with laser scanning confocal microscopy. An agar diffusion test was used to confirm antibacterial effects of the drugs.

Results

l ‐Methionine (0.5 μM) significantly reduced PAO‐1 biofilm mass (32.4 ± 18.0%; n = 4; p < 0.001) compared with controls. Low doses of ivacaftor alone (4, 8, and 12 μg/mL) had no effect on biofilm formation. When combined with ivacaftor (4 μg/mL), a synergistic anti‐biofilm effect was noted at 0.05 μM and 0.5 μM of l ‐methionine (two‐way analysis of variane, p = 0.0415) compared with corresponding concentrations of l ‐methionine alone.

Conclusion

Ivacaftor enhanced the anti‐biofilm activity of l ‐methionine against the PAO‐1 strain of P aeruginosa. Further studies evaluating the efficacy of ivacaftor/l ‐methionine combinations for P aeruginosa sinusitis are planned.

     

The Perceived Relationship Knowledge Scale: An Initial Validation

The rationale, development, and initial validation of the Perceived Relationship Knowledge Scale (PRKS), a brief six‐item instrument designed to measure central aspects of perceptions of relationship knowledge, are described in this article. To test the instrument's psychometric properties, two studies were conducted: an exploratory study with a small clinical sample (n = 54; Study 1), and the second with a sample of participants in a statewide relationship education initiative (n = 2,183; Study 2). In both studies, exploratory factor analyses yielded a single‐factor structure. Maximum‐likelihood confirmatory factor analyses in Study 2 indicated good internal consistency and good model fit. Analyses of construct validity in both studies indicated that the PRKS measures relationship knowledge in psychometrically expected ways, and that the instrument discriminates low versus high levels of perceived relationship knowledge. The use of the instrument is described and research implications are discussed.     

Evaluating the size criterion for PI-RADSv2 category 5 upgrade: is 15 mm the best threshold?

Purpose

The purpose of the study was to determine if the ≥ 15 mm threshold currently used to define PIRADS 5 lesions is the optimal size threshold for predicting high likelihood of clinically significant (CS) cancers.

Materials

Three hundred and fifty-eight lesions that may be changed from category 4 to 5 or vice versa on the basis of the size criterion (category 4: n = 288, category 5: n = 70) from 255 patients were evaluated. Kendall’s tau-b statistic accounting for inter-lesion correlation, generalized estimation equation logistic regression, and receiver operating curve analysis evaluated two lesion size-metrics (lesion diameter and relative lesion diameter—defined as lesion diameter/prostate volume) for ability to identify CS (Gleason grade ≥ 3 + 4) cancer at targeted biopsy. Optimal cut-points were identified using the Youden index. Analyses were performed for the whole prostate (WP) and zone-specific sub-cohorts of lesions in the peripheral and transition zones (PZ and TZ).

Results

Lesion diameter showed a modest correlation with Gleason grade (WP: τB = 0.21, p < 0.0001; PZ: τB = 0.13, p = 0.02; TZ: τB = 0.32, p = 0.001), and association with CS cancer detection (WP: AUC = 0.63, PZ: AUC = 0.59, TZ: AUC = 0.74). Empirically derived thresholds (WP: 14 mm, PZ: 13 mm, TZ: 16 mm) performed similarly to the current ≥ 15 mm standard. Lesion relative lesion diameter improved identification of CS cancers compared to lesion diameter alone (WP: τB = 0.30, PZ: τB = 0.24, TZ: τB = 0.42, all p < 0.0001). AUC also improved for WP and PZ lesions (WP: AUC = 0.70, PZ: AUC = 0.68, and TZ: AUC = 0.74).

Conclusions

The current ≥ 15 mm diameter threshold is a reasonable delineator of PI-RADS category 4 and category 5 lesions in the absence of extraprostatic extension to predict CS cancers. Additionally, relative lesion diameter can improve identification of CS cancers and may serve as another option for distinguishing category 4 and 5 lesions.

     

Maximizing gait and balance: behaviors and decision-making processes of persons with multiple sclerosis and physical therapists

Purpose: To describe the behavioral decisions used by persons with multiple sclerosis (MS) and physical therapists to maximize gait and balance following outpatient physical therapy.

Methods: A multi-method case series with seven matched pairs (persons with MS–physical therapists). Quota sampling maximized variability among persons with MS (disease steps score range 3–6). Three of the four physical therapists were MS or neurology certified. Persons with MS completed a phone survey, follow-up interview, and standardized questionnaires. Physical therapists completed an interview. Data were collected 2–8 weeks following discharge. Content and constant comparison analyses were used for thematic development and triangulation.

Results: Core themes arose exemplifying the decision-making processes and actions of persons with MS (challenging self by pushing but respecting limits) and physical therapists (finding the right fit). One overarching theme, keeping their lived world large, or participation in valued life roles, emerged integrating both perspectives driving decision-making.

Conclusions: Participants have a shared goal of maximizing gait and balance so persons with MS can participate in valued life roles. Understanding the differences in the behavioral decisions and optimizing skill sets in shared decision-making and self-management may enhance the therapeutic partnership and engagement in gait- and balance-enhancing behaviors.

• Implications for Rehabilitation

• Persons with MS and physical therapists have a shared goal of maximizing gait and balance so persons with MS can participate in valued activities and life roles, or more poetically, keep their lived world large.

• Knowledge that persons with MS aim to challenge themselves by pushing but respecting limits can provide physical therapists with greater insight in helping persons with MS resolve uncertainty, set meaningful goals, and build the routines and resilience needed for engagement in gait- and balance-enhancing behaviors.

• Enriching skill sets in shared decision-making, behavior change and self-management may optimize the physical therapist toolbox.

     

Biliary strictures after liver transplantation. Predictive factors for response to endoscopic management and long-term outcome

BACKGROUND: Biliary strictures after liver transplantation are frequent. The long-term prognosis and predictive factors of response to endoscopic treatment are not well known. METHODS: The aim of this study was to demonstrate the role of endoscopic treatment, predictive factors of response, and outcome in patients with biliary stricture after liver transplantation. We performed a retrospective review of medical records of all consecutive post-liver transplantation patients who underwent endoscopic retrograde cholangiography in our center during the period from October 2001 to October 2006. RESULTS: Twenty-five of 43 patients referred for endoscopic retrograde cholangiography had biliary stricture. Eighteen had stricture at the area of the anastomosis alone, 2 patients had a stricture at the area of the anastomosis and also another area, and 5 had nonanastomotic biliary strictures. Twenty-one patients had a single stricture and 4 had more than 1 stricture. Initially 19 of 24 patients (79%) responded to endoscopic management with normalization of liver enzymes. Four patients (16%) did not respond clinically despite a successful endoscopic approach. All patients who did not respond to endoscopic dilation had more than 1 area of stricture. There was a significantly better response to endoscopic treatment in patients with an anastomotic stricture versus patients with nonanastomotic strictures 17/19 versus 2/5 (P = 0.042). CONCLUSIONS: In our experience, endoscopic treatment of anastomotic biliary strictures is highly effective with a good long-term outcome. The presence of nonanastomotic and multiple strictures should be considered a factor associated with poor response to endoscopic management.     

What is the role of motor simulation in action and object recognition? Evidence from apraxia

An important issue in contemporary cognitive neuroscience concerns the role of motor production processes in perceptual and conceptual analysis. To address this issue, we studied the performance of a large group of unilateral stroke patients across a range of tasks using the same set of common manipulable objects. All patients (n = 37) were tested for their ability to demonstrate the use of the objects, recognize the objects, recognize the corresponding object-associated pantomimes, and imitate those same pantomimes. At the group level we observed reliable correlations between object use and pantomime recognition, object use and object recognition, and pantomime imitation and pantomime recognition. At the single-case level, we document that the ability to recognize actions and objects dissociates from the ability to use those same objects. These data are problematic for the hypothesis that motor processes are constitutively involved in the recognition of actions and objects and frame new questions about the inferences that are merited by recent findings in cognitive neuroscience.     

Early Neurological Changes and Interpretation of Clinical Grades in Aneurysmal Subarachnoid Hemorrhage

ObjectivesHunt and Hess (HH) and World Federation of Neurological Surgeons (WFNS) grades are commonly used to report clinical severity of aneurysmal subarachnoid hemorrhage (aSAH). We sought to determine the impact of early neurological changes and the timing of clinical grade assignment on the prognostication accuracy.MethodsWe retrospectively reviewed a cohort of consecutive patients with aSAH who were admitted to an academic center. Patients with confirmed aneurysmal cause were included. Relevant clinical data including daily clinical grades, imaging data and functional outcome were analyzed. Favorable outcome was defined as mRS 0 to 3. Early neurological improvement (ENI) and early neurological deterioration (END) were respectively defined as any improvement or deterioration of HH grades from hospital day 1 to the earliest time from hospital day 2 to 5.ResultsOf 310 patients, 24% experienced early neurological changes from hospital day 1 to 3. For each point increase in HH grades from day 1 to day 3, the odds ratio for worse outcome was 2.57 (95% CI [1.74-3.79]) and for each point decrease in HH grades from day 1 to day 3, the odds ratio for worse outcome was 0.28 (95% CI [0.17-0.47]). Receiver Operating Characteristic curve analysis revealed that clinical grades on day 3 had higher accuracy in predicting worse outcome than clinical grades on day 1.ConclusionEarly changes in neurological status can alter trajectory of hospital course and functional outcome. The prognostic accuracy of the clinical grades from hospital day 3 is significantly greater than those on admission.     

To tell or not to tell – what to do about p.C282Y heterozygotes identified by HFE screening

Hereditary hemochromatosis (HH) is a common preventable disorder of iron overload that can result in liver cirrhosis and reduced lifespan. Most HH is due to homozygosity for the HFE p.C282Y substitution. We conducted a study of screening for p.C282Y in high schools where p.C282Y heterozygotes (CY) individuals were informed of their genotype by letter. We studied whether these individuals understood the implications of their genotype, whether this resulted in anxiety or reduced health perception and whether cascade testing was higher in families of CY than wild‐type homozygous (CC) individuals. We found 586 of 5757 (1 in 10) screened individuals were CY. One month after receiving their result, 83% correctly answered that they have one copy of p.C282Y. There was no adverse change in anxiety or health perception from prior to screening to 1 month after receiving results. Significantly more family members of CY individuals than CC individuals were informed about HH and had testing for HH. In conclusion, we found that informing CY individuals of their genotype does not increase anxiety and the implications are generally well understood. This leads to cascade testing in a minority of families. CY individuals should be informed of their genetic status when identified by population screening.