Three-dimensional lung tumor segmentation from x-ray computed tomography using sparse field active models.

PURPOSE: Manual segmentation of lung tumors is observer dependent and time-consuming but an important component of radiology and radiation oncology workflow. The objective of this study was to generate an automated lung tumor measurement tool for segmentation of pulmonary metastatic tumors from x-ray computed tomography (CT) images to improve reproducibility and decrease the time required to segment tumor boundaries. METHODS: The authors developed an automated lung tumor segmentation algorithm for volumetric image analysis of chest CT images using shape constrained Otsu multithresholding (SCOMT) and sparse field active surface (SFAS) algorithms. The observer was required to select the tumor center and the SCOMT algorithm subsequently created an initial surface that was deformed using level set SFAS to minimize the total energy consisting of mean separation, edge, partial volume, rolling, distribution, background, shape, volume, smoothness, and curvature energies. RESULTS: The proposed segmentation algorithm was compared to manual segmentation whereby 21 tumors were evaluated using one-dimensional (1D) response evaluation criteria in solid tumors (RECIST), two-dimensional (2D) World Health Organization (WHO), and 3D volume measurements. Linear regression goodness-of-fit measures (r(2) = 0.63, p < 0.0001; r(2) = 0.87, p < 0.0001; and r(2) = 0.96, p < 0.0001), and Pearson correlation coefficients (r = 0.79, p < 0.0001; r = 0.93, p < 0.0001; and r = 0.98, p < 0.0001) for 1D, 2D, and 3D measurements, respectively, showed significant correlations between manual and algorithm results. Intra-observer intraclass correlation coefficients (ICC) demonstrated high reproducibility for algorithm (0.989-0.995, 0.996-0.997, and 0.999-0.999) and manual measurements (0.975-0.993, 0.985-0.993, and 0.980-0.992) for 1D, 2D, and 3D measurements, respectively. The intra-observer coefficient of variation (CV%) was low for algorithm (3.09%-4.67%, 4.85%-5.84%, and 5.65%-5.88%) and manual observers (4.20%-6.61%, 8.14%-9.57%, and 14.57%-21.61%) for 1D, 2D, and 3D measurements, respectively. CONCLUSIONS: The authors developed an automated segmentation algorithm requiring only that the operator select the tumor to measure pulmonary metastatic tumors in 1D, 2D, and 3D. Algorithm and manual measurements were significantly correlated. Since the algorithm segmentation involves selection of a single seed point, it resulted in reduced intra-observer variability and decreased time, for making the measurements.

Texture analysis of carotid artery atherosclerosis from three-dimensional ultrasound images.

PURPOSE: To quantitatively evaluate local carotid arterial statin effects in 3D US images using multiclassifier image texture analysis tools. METHODS: Texture analysis tools were used to evaluate the effect of 80 mg atorvastatin administered daily to patients with carotid stenosis compared to those treated with placebo. Using three-dimensional carotid ultrasound images, 270 texture features from seven texture techniques were extracted from manually segmented carotid arteries based on the intima-media boundary [vessel wall (VW)]. Individual texture features were compared to the previously determined changes in VW volume (VWV) using the distance between classes, the Wilcoxon rank sum test, and accuracy of the classifiers. Texture features that resulted in maximal classification accuracy from each texture technique were selected using Pudil's sequential floating forward selection (SFFS) as a method of ranking each technique. Finally, SFFS-selected texture features from all texture techniques were used in combination with 24 classifier fusion techniques to improve classification accuracy. RESULTS: Using the measurement of change in VWV, the distance between classes (DBC), Wilcoxon rank sum (WRS) p-value, and median accuracy measures (ACC) were 0.3798, 0.076, and 54.50%, respectively. Texture features improved the detection of statin-related changes using DBC to 0.5199, using WRS to 0.002, and ACC to 63.87%, respectively. The texture techniques that most differentiated between atorvastatin and placebo classes were Fourier power spectrum and Laws texture energy measures. The average classification accuracy between atorvastatin and placebo classes was improved from 57.22 +/- 12.11% using VWV to 97.87 +/- 3.93% using specific texture features. Furthermore, the use of specific texture features resulted in the average area under the receiver-operator characteristic curve (AUC) a value of 0.9988 +/- 0.0069 compared to 0.617 +/- 0.15 using carotid VWV. CONCLUSIONS: Based on DBC, WRS, ACC, and AUC texture features derived from 3D carotid ultrasound were observed to be more sensitive in detecting statin-related changes in carotid atherosclerosis than VWV suggesting that texture classifiers can be used to detect changes in carotid atherosclerosis after therapy.

Adherence to the evidence-based guidelines in the management of acute biliary pancreatitis: A case series.

BACKGROUND: Acute pancreatitis (AP) is considered one of the most common gastrointestinal disorders; the annual worldwide incidence for AP is 4.9-73.4 cases / 100,000 people and the total mortality rate is 4-8%, increasing to 33% in patients with infected necrosis. This study aims to assess the outcome of providing standardized evidence-based care to patients with acute biliary pancreatitis. METHODS: Thirty patients diagnosed with acute biliary pancreatitis, were enrolled in this study and managed according to the Japanese guidelines, 2015 with a complementary scope on other recent guidelines. RESULTS: Out of 30 patients in the study, 60% were females. Twenty-five cases were presented in the early phase of the disease while the rest presented in the late phase. Gallstones were the commonest cause (80%). The complications encountered were a systemic complication in one case, organ failure in three cases, and the local complications in the form of fluid collections in (43.3%) of cases.Out of 30 patients, 6 patients had an intervention. The main approach was minimally invasive techniques (4 cases), Open approach was performed in 2 cases. The total mortality rate was 10%. Most mild cases were discharged within one week from admission. Cases readmitted with recurrent attacks of acute pancreatitis were 3 cases, one male and 2 females. CONCLUSION: By applying guidelines in the management of acute biliary pancreatitis, we can reduce disease-related morbidity and mortality. Besides, we can reduce the costs of medical services with the proper investment of healthcare resources.

Trends in Renal Function Among Heart Transplant Recipients of Donor-Derived Hepatitis C Virus.

Donor-derived hepatitis C (dd-HCV) infection may increase the risk of renal impairment (RI) among heart transplantation (HT) recipients. Sofosbuvir, an integral component of HCV direct-acting antivirals (DAAs) has also been linked to RI. To date, no study has examined the trends in renal function for HT recipients of dd-HCV infection and assessed safety and efficacy of Sofosbuvir-based DAAs. Between September 2016 and June 2018, 46 HCV-naive patients and one patient with a history of HCV treated pretransplant, underwent HT from HCV-positive donors (follow-up available through October 10, 2018). Patients were treated with Ledipasvir-Sofosbuvir (genotype 1) or Sofosbuvir-Velpatasvir (genotype 3) for 12 or 24 weeks; no dose adjustments were made for renal function. Data on renal function were available for 23 patients who achieved a sustained virologic response at 12 weeks after the treatment (SVR12; cohort A) and 18 patients who completed 1 year of follow-up (cohort B). Treatment of dd-HCV infection was initiated at a median of 6 weeks post-HT. In both cohorts, a nonsignificant reduction in median estimated glomerular filtration rate (eGFR; ml/min/1.73 m) was noted (cohort A: pretransplant eGFR: 62 [interquartile range {IQR}: 1-84] to SVR12 eGFR: 49 [IQR: 37-82]; p = 0.43; cohort B: pretransplant eGFR: 65 [IQR: 54-84] to 1 year post-HT eGFR: 56 [IQR: 39-75]; p = 0.29). Pretreatment renal function had no significant impact on changes in renal function during treatment. All patients tolerated DAAs well with 100% completion rate to the assigned therapy and duration and 100% success at achieving SVR12. In this first and largest reported case series to date of HT recipients with dd-HCV infection, we observed that neither the dd-HCV infection nor its treatment with Sofosbuvir-based DAAs increased the risk of RI. Sofosbuvir-based DAAs appear safe, tolerable, and effective for HCV treatment even in presence of severe RI.

Expanding Heart Transplant in the Era of Direct-Acting Antiviral Therapy for Hepatitis C.

Importance: For patients awaiting heart transplant, hepatitis C-positive donors offer an opportunity to expand the donor pool, shorten wait times, and decrease wait-list mortality. While early reported outcomes among few heart transplant recipients have been promising, knowledge of 1-year outcomes in larger cohorts of patients is critical to shared decision-making with patients about this option. Objective: To better define the association of hepatitis C-positive donors with heart transplant volumes, wait-list duration, the transmission and cure of donor-derived hepatitis C, and morbidity and mortality at 1 year. Design, Setting, and Participants: This was a prospective, single-center observational study of 80 adult (age 18 years or older) patients who underwent heart transplant using hearts from hepatitis C-positive donors between September 2016 and April 2019 at a large academic medical center. Among donors, who were considered hepatitis C-positive if results from hepatitis C antibody and/or nucleic acid testing were positive, 70 had viremia and 10 were seropositive but did not have viremia. Follow-up was available through May 15, 2019. Comparisons were drawn with patients who underwent transplant with hearts from hepatitis C-negative donors during the same period. Exposures: In addition to standard posttransplant management, transplant recipients who developed donor-derived hepatitis C infection were treated with direct-acting antivirals. Main Outcomes and Measures: The main outcomes included wait-list duration and 1-year survival in all patients, and for those who developed donor-derived hepatitis C, the response to direct-acting antiviral treatment. Results: Of 80 patients, 57 (71.3%) were men, 55 (68.7%) were white, and 17 (26.3%) were black; the median age at transplant was 54.5 years (interquartile range, 46-62 years). Following consent to accept hearts from hepatitis C-exposed donors, the median days to heart transplant was 4 (interquartile range, 1-18). No recipients of donors with negative nucleic acid testing results (10 [12.5%]) developed donor-derived hepatitis C. Of 70 patients who were recipients of donors with positive nucleic acid testing results, 67 (95.7%) developed donor-derived hepatitis C over a median follow-up of 301 days (interquartile range, 142-617). Treatment with direct-acting antivirals was well tolerated and yielded sustained virologic responses in all treated patients. Within the cohort with infection, 1-year patient survival was 90.4%, which was not significantly different compared with the cohort without infection or with patients who received transplants from hepatitis C-negative donors during the same period. Conclusions and Relevance: In the era of direct-acting antivirals, hepatitis C-positive donors are a viable option to expand the donor pool, potentially reducing wait-list duration and mortality. In heart transplant recipients with donor-derived hepatitis C, infection is well-tolerated and curable, and 1-year survival is equivalent to that in recipients of hepatitis C-negative donors.

Three-dimensional therapy needle applicator segmentation for ultrasound-guided focal liver ablation.

PURPOSE: Minimally invasive procedures, such as microwave ablation, are becoming first-line treatment options for early-stage liver cancer due to lower complication rates and shorter recovery times than conventional surgical techniques. Although these procedures are promising, one reason preventing widespread adoption is inadequate local tumor ablation leading to observations of higher local cancer recurrence compared to conventional procedures. Poor ablation coverage has been associated with two-dimensional (2D) ultrasound (US) guidance of the therapy needle applicators and has stimulated investigation into the use of three-dimensional (3D) US imaging for these procedures. We have developed a supervised 3D US needle applicator segmentation algorithm using a single user input to augment the addition of 3D US to the current focal liver tumor ablation workflow with the goals of identifying and improving needle applicator localization efficiency. METHODS: The algorithm is initialized by creating a spherical search space of line segments around a manually chosen seed point that is selected by a user on the needle applicator visualized in a 3D US image. The most probable trajectory is chosen by maximizing the count and intensity of threshold voxels along a line segment and is filtered using the Otsu method to determine the tip location. Homogeneous tissue mimicking phantom images containing needle applicators were used to optimize the parameters of the algorithm prior to a four-user investigation on retrospective 3D US images of patients who underwent microwave ablation for liver cancer. Trajectory, axis localization, and tip errors were computed based on comparisons to manual segmentations in 3D US images. RESULTS: Segmentation of needle applicators in ten phantom 3D US images was optimized to median (Q1, Q3) trajectory, axis, and tip errors of 2.1 (1.1, 3.6)°, 1.3 (0.8, 2.1) mm, and 1.3 (0.7, 2.5) mm, respectively, with a mean ± SD segmentation computation time of 0.246 ± 0.007 s. Use of the segmentation method with a 16 in vivo 3D US patient dataset resulted in median (Q1, Q3) trajectory, axis, and tip errors of 4.5 (2.4, 5.2)°, 1.9 (1.7, 2.1) mm, and 5.1 (2.2, 5.9) mm based on all users. CONCLUSIONS: Segmentation of needle applicators in 3D US images during minimally invasive liver cancer therapeutic procedures could provide a utility that enables enhanced needle applicator guidance, placement verification, and improved clinical workflow. A semi-automated 3D US needle applicator segmentation algorithm used in vivo demonstrated localization of the visualized trajectory and tip with less than 5° and 5.2 mm errors, respectively, in less than 0.31 s. This offers the ability to assess and adjust needle applicator placements intraoperatively to potentially decrease the observed liver cancer recurrence rates associated with current ablation procedures. Although optimized for deep and oblique angle needle applicator insertions, this proposed workflow has the potential to be altered for a variety of image-guided minimally invasive procedures to improve localization and verification of therapy needle applicators intraoperatively.

Early outcomes using hepatitis C-positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies.

BACKGROUND: Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors. METHODS: Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent. Patients who acquired HCV were referred to hepatology and treated with direct-acting anti-viral therapies (DAAs). Data collection and analysis were performed with institutional review board approval. RESULTS: At the time of HT, mean age of recipients was 53 ± 10 years, and 8 patients (61.5%) were on left ventricular assist device support. After consent to consider an HCV-positive heart, mean time to HT was 11 ± 12 days. Nine of 13 patients (69%) developed HCV viremia after transplant, including 8 who completed DAA treatment and demonstrated cure, as defined by a sustained virologic response 12 weeks after treatment. One patient died during Week 7 of his treatment due to pulmonary embolism. DAAs were well tolerated in all treated patients. CONCLUSIONS: In the era of highly effective DAAs, the use of HCV-positive donors represents a potential approach to safely expand the donor pool. Additional follow-up is needed to elucidate long-term outcomes.

A three-part intervention to change the use of hormone replacement therapy in response to new evidence.

BACKGROUND: Slow adaptation of new information by providers may result in suboptimal care. OBJECTIVE: To evaluate changes in prescriptions for combination hormone replacement therapy (HRT) after a multicomponent intervention to deliver new information to patients and providers. DESIGN: Quasi-experimental study with multiple baselines. SETTING: Veterans Affairs Tennessee Valley Healthcare System (VA-TVHS). PATIENTS: Female veterans age 50 to 79 years who had a prescription filled at the VA-TVHS for combination HRT between 1 January 2002 and 1 July 2002. MEASUREMENTS: Discontinuation of HRT. INTERVENTION: A 3-part intervention consisted of 1) notifying patients who were using combination HRT of the results of the Women's Health Initiative study (patient education component), 2) sending all providers an e-mail with the Women's Health Initiative study results (provider education component), and 3) placing an electronic alert in each eligible patient's chart (provider care component). The alert asked providers to reevaluate the need for combination HRT. The intervention was implemented at different VA-TVHS sites in a stepwise fashion to differentiate intervention effect from media effect. Study follow-up continued through 31 December 2002. RESULTS: The total rate of discontinuation of combination HRT was 70.3% in 2002. The proportion of discontinuation from time of media release until intervention was 23.3%. After initiation of the intervention, an additional 43% of the original cohort discontinued use of HRT; this percentage represents a 59% relative decrease in HRT use among patients. After adjustment for time, the discontinuation rate per day was 4.9 times higher after the multifacted intervention than after the media release (95% CI, 1.8 to 13.1). LIMITATIONS: A true control group is lacking. CONCLUSION: A multifaceted approach in an integrated health care system with standardized methods of communication is an effective way to implement patient-centered, effective, and timely care with changing medical knowledge.

Urinary F2-isoprostanes in young healthy children at risk for type 1 diabetes mellitus.

Oxidative stress has been linked to many diseases, but little information exists on biomarkers of oxidative stress in healthy children. The purpose of this study was to describe factors that correlate with urinary F2-isoprostanes, an indicator of oxidative stress, and to establish normal concentrations of F2-isoprostanes in children at risk to develop type 1 diabetes mellitus. Creatinine-adjusted urinary F2-isoprostanes were assessed in 342 Denver children under the age of 7 years, from whom we had collected data during 769 clinic visits from August 1997 through January 2001 (mean 2.3 visits per child). Children were identified by newborn screening for HLA-markers, of varying degrees of prediction, for the development of type 1 diabetes. Plasma antioxidants and carotenoids, age at clinic visit, vitamin supplement use, exposure to environmental tobacco smoke, gender, and race were evaluated as correlates to the degree of oxidative stress, using mixed models for longitudinal data. F2-isoprostane levels were highest in infancy and decreased nonlinearly until 7 years. Female gender, HLA-DR3/4 genotype, higher plasma gamma-tocopherol:total lipids ratio, and lower alpha-carotene:total lipids ratio correlated with higher F2-isoprostane levels. Normal values in this healthy population can be used as the basis for future studies of disease mechanisms involving oxidative stress.

Survival and quality of life after organ transplantation in veterans and nonveterans.

BACKGROUND: Some previous studies suggested that transplantation performed in Department of Veterans Affairs (VA) patients was associated with a higher rate of complications and poorer outcomes. We examined more than a decade of experience with solid organ transplantation at a single center and compared VA patients with nonveteran patients to assess long-term patient and graft survival and health-related quality of life (HRQOL). METHODS: Demographic, clinical, and survival data were extracted from a database that included all transplants from January 1990 through December 2002 at Vanderbilt University Medical Center (non-VA) and the Nashville VA Medical Center (VA). The HRQOL was assessed in a subset of patients using the Karnofsky functional performance (FP) index and the Short-Form-36 self-report questionnaire. Data were analyzed by Kaplan-Meier survival and analysis of variance methods. RESULTS: One thousand eight hundred nine adult patients receiving solid organ transplants (1,896 grafts) between 1990 and 2002 were reviewed: 380 VA patients (141 liver, 54 heart, 183 kidney, 2 lung) and 1429 non-VA patients (280 liver, 246 heart, 749 kidney, 154 lung). Mean follow-up time was 46 +/- 1 months. Five-year graft survival for VA and non-VA patients, respectively, was liver 65% +/- 5% versus 69% +/- 3% (P = 0.97); heart 73% +/- 8% versus 73% +/- 3% (P = 0.67); and kidney 76% +/- 5% versus 77% +/- 2% (P = 0.84). Five-year patient survival was liver 75% +/- 5% versus 78% +/- 3% (P = 0.94); heart 73% +/- 8% versus 74% +/- 3% (P = 0.75); and kidney 84% +/- 4% versus 87% +/- 2% (P = 0.21) for VA and non-VA, respectively. In the first 3 years after transplant, the FP scores for VA versus non-VA patients were 85 +/- 2 versus 87 +/- 1 (P = 0.50). The SF-36 mental component scales were 47 +/- 3 versus 49 +/- 1 (P = 0.39); and the SF-36 physical component scales were 37 +/- 2 versus 38 +/- 1 (P = 0.59), respectively. Longer-term (through year 7) HRQOL scores for VA versus non-VA patients were FP 85 +/- 1 versus 88 +/- 1 (P = 0.17); mental component scales 47 +/- 2 versus 49 +/- 1 (P = 0.29); and physical component scales 35 +/- 2 versus 39 +/- 1 (P = 0.05), respectively. CONCLUSIONS: The veteran patients have similar graft and patient survival as the nonveteran patients. Overall quality of life is similar between veterans and nonveterans during the first three years after transplantation. A trend toward a later decline in the veterans' perception of their physical functioning may stem from the increased prevalence of hepatitis C virus among VA liver transplant recipients, a known factor reducing late HRQOL.

Validating methods of urine collection: a pilot study.

In this pilot study of 21 adults, direct collection versus cotton-ball collection of urine was studied. Results showed the use of cotton balls for collecting urine is a safe and effective method for measuring antioxidants and markers of oxidative stress for clinical and research use.

Case of fulminant hepatic failure due to unrecognized peripartum cardiomyopathy.

OBJECTIVE: To describe a postpartum patient who presented with fulminant hepatic failure and hepatic coma as a result of unrecognized peripartum cardiomyopathy. DESIGN: Case report. SETTING: Medical intensive care unit of a tertiary care academic medical center. PATIENT: A 35-yr-old woman 5 wks postpartum from an uneventful spontaneous vaginal delivery who was transferred to our institution with fulminant hepatic failure and worsening hepatic encephalopathy of unknown etiology for consideration of liver transplantation. INTERVENTIONS: An echocardiogram was obtained as part of an evaluation for refractory shock and the patient was found to have severe global hypokinesis with an ejection fraction of approximately 15%. She was diagnosed with peripartum cardiomyopathy and treatment with digoxin and afterload reduction was initiated. MEASUREMENTS AND MAIN RESULTS: After initiation of appropriate treatment for dilated cardiomyopathy, the patient's hepatic failure resolved and she made a full recovery. CONCLUSIONS: Congestive heart failure is one of the few treatable causes of fulminant hepatic failure. Congestive heart failure must always be included in the differential diagnosis of fulminant hepatic failure of unknown pathogenesis.

Prospective multicenter study of eligibility for antiviral therapy among 4,084 U.S. veterans with chronic hepatitis C virus infection.

BACKGROUND: Many veterans may not be candidates for hepatitis C virus (HCV) treatment due to contraindications to therapy. The aims of this study were to determine the proportion of HCV-infected veterans who were eligible for interferon alfa and ribavirin therapy and to evaluate barriers to HCV treatment. METHODS: We prospectively enrolled 4,084 veterans who were referred for HCV treatment over a 1-yr period at 24 Veterans Affairs (VA) Medical Centers. Treatment candidacy was assessed using standardized criteria and the opinion of the treating clinician. RESULTS: Overall, 32.2% (95% CI, 30.8-33.7%) were candidates for HCV treatment according to standardized criteria, whereas 40.7% (95% CI, 39.2-42.3%) were candidates in the opinion of the treating clinician. Multivariable analysis identified ongoing substance abuse (OR = 17.68; 95% CI, 12.24-25.53), comorbid medical disease (OR = 9.62; 95% CI, 6.85-13.50), psychiatric disease (OR = 9.45; 95% CI, 6.70-13.32), and advanced liver disease (OR = 8.43; 95% CI, 4.42-16.06) as the strongest predictors of not being a treatment candidate. Among patients who were considered treatment candidates, 76.2% (95% CI, 74.0-78.3%) agreed to be treated and multivariable analysis showed that persons >/=50 yr of age (OR = 1.37; 95% CI, 1.07-1.76) and those with >50 lifetime sexual partners (OR = 1.44; 95% CI, 1.08-1.93) were more likely to decline treatment. CONCLUSIONS: The majority of veteran patients are not suitable candidates for HCV treatment because of substance abuse, psychiatric disease, and comorbid medical disease, and many who are candidates decline therapy. Multidisciplinary collaboration is needed to overcome barriers to HCV therapy in this population.

Adequacy of representation of the National Drug File Reference Terminology Physiologic Effects reference hierarchy for commonly prescribed medications.

The National Drug File Reference Terminology contains a novel reference hierarchy to describe physiologic effects (PE) of drugs. The PE reference hierarchy contains 1697 concepts arranged into two broad categories; organ specific and generalized systemic effects. This investigation evaluated the appropriateness of the PE concepts for classifying a random selection of commonly prescribed medications. Ten physician reviewers classified the physiologic effects of ten drugs and rated the accuracy of the selected term. Inter reviewer agreement, overall confidence, and concept frequencies were assessed and were correlated with the complexity of the drug's known physiologic effects. In general, agreement between reviewers was fair to moderate (kappa 0.08-0.49). The physiologic effects modeled became more disperse with drugs having and inducing multiple physiologic processes. Complete modeling of all physiologic effects was limited by reviewers focusing on different physiologic processes. The reviewers were generally comfortable with the accuracy of the concepts selected. Overall, the PE reference hierarchy was useful for physician reviewers classifying the physiologic effects of drugs. Ongoing evolution of the PE reference hierarchy as it evolves should take into account the experiences of our reviewers.