Management of Pulmonary Mucormycosis After Orthotopic Heart Transplant: A Case Series.

Invasive pulmonary mucormycosis is a potentially fatal infection that can occur in immunosuppressed patients such as those who have undergone orthotopic heart transplant (OHT). High-dose intravenous antifungal agents, including amphotericin B, are generally accepted as the first-line medical treatment, with prompt surgical resection of lesions if feasible. The body of evidence guiding treatment decisions, however, is sparse, particularly regarding adjustment of immunosuppression during acute infection and long-term recovery. We present 2 cases of patients with pulmonary mucormycosis occurring within the first 6 months after OHT, both of whom successfully recovered after appropriate medical and surgical treatment, and we highlight differences in immunosuppression management strategies for this life-threatening condition.

Microgel encapsulated nanoparticles for glucose-responsive insulin delivery.

An insulin delivery system that self-regulates blood glucose levels has the potential to limit hypoglycemic events and improve glycemic control. Glucose-responsive insulin delivery systems have been developed by coupling glucose oxidase with a stimuli-responsive biomaterial. However, the challenge of achieving desirable release kinetics (i.e., insulin release within minutes after glucose elevation and duration of release on the order of weeks) still remains. Here, we develop a glucose-responsive delivery system using encapsulated glucose-responsive, acetalated-dextran nanoparticles in porous alginate microgels. The nanoparticles respond rapidly to changes in glucose concentrations while the microgels provide them with protection and stability, allowing for extended glucose-responsive insulin release. This system reduces blood sugar in a diabetic mouse model at a rate similar to naked insulin and responds to a glucose challenge 3 days after administration similarly to a healthy animal. With 2 doses of microgels containing 60 IU/kg insulin each, we are able to achieve extended glycemic control in diabetic mice for 22 days.

Macrophages with cellular backpacks for targeted drug delivery to the brain.

Most potent therapeutics are unable to cross the blood-brain barrier following systemic administration, which necessitates the development of unconventional, clinically applicable drug delivery systems. With the given challenges, biologically active vehicles are crucial to accomplishing this task. We now report a new method for drug delivery that utilizes living cells as vehicles for drug carriage across the blood brain barrier. Cellular backpacks, 7-10 µm diameter polymer patches of a few hundred nanometers in thickness, are a potentially interesting approach, because they can act as drug depots that travel with the cell-carrier, without being phagocytized. Backpacks loaded with a potent antioxidant, catalase, were attached to autologous macrophages and systemically administered into mice with brain inflammation. Using inflammatory response cells enabled targeted drug transport to the inflamed brain. Furthermore, catalase-loaded backpacks demonstrated potent therapeutic effects deactivating free radicals released by activated microglia in vitro. This approach for drug carriage and release can accelerate the development of new drug formulations for all the neurodegenerative disorders.

The diagnostic challenge of the sequelae of acute pancreatitis on CT imaging: a pictorial essay.

PURPOSE: The purpose of the study was to present a pictorial review of the long-term sequelae of acute pancreatitis on CT imaging as these findings can cause diagnostic confusion in the absence of a proper clinical history and/or prior CT imaging. METHODS: We retrospectively identified 81 patients who had an episode of acute pancreatitis with diagnostic findings on CT and also underwent one or more follow-up CT scans at least 1 month beyond the acute episode. The residual findings on all follow-up CT scans were tabulated, including the time interval since the initial bout of acute pancreatitis. RESULT: Residual inflammatory changes were present in 19.8% of cases, with a median time period lasting 86 days since the initial episode of acute pancreatitis. Residual fluid collections were seen in 27.2% and persisted for a median of 132 days. Three patients had residual solid-appearing inflammatory masses, which could be mistaken for neoplasms. Other long-term sequelae were also tabulated, including pancreatic ductal dilatation, pancreatic atrophy, new or increased pancreatic calcifications, biliary tract dilatation, central portal venous occlusion, and pseudoaneurysm formation. These residual findings and long-term complications are presented as a pictorial essay. CONCLUSION: Recognizing the spectrum of residual findings of acute pancreatitis, some of which can be long term, is important in the correct interpretation of a pancreatic CT. These findings can mimic acute pancreatitis or a pancreatic/peripancreatic neoplasm and often cause diagnostic confusion, especially in the absence of prior CT imaging.

Na/K-ATPase signaling regulates collagen synthesis through microRNA-29b-3p in cardiac fibroblasts.

Chronic kidney disease (CKD) is accompanied by cardiac fibrosis, hypertrophy, and dysfunction, which are commonly referred to as uremic cardiomyopathy. Our previous studies found that Na/K-ATPase ligands or 5/6th partial nephrectomy (PNx) induces cardiac fibrosis in rats and mice. The current study used in vitro and in vivo models to explore novel roles for microRNA in this mechanism of cardiac fibrosis formation. To accomplish this, we performed microRNA profiling with RT-qPCR based arrays on cardiac tissue from rats subjected to marinobufagenin (MBG) infusion or PNx. The analysis showed that a series of fibrosis-related microRNAs were dysregulated. Among the dysregulated microRNAs, microRNA (miR)-29b-3p, which directly targets mRNA of collagen, was consistently reduced in both PNx and MBG-infused animals. In vitro experiments demonstrated that treatment of primary cultures of adult rat cardiac fibroblasts with Na/K-ATPase ligands induced significant increases in the fibrosis marker, collagen protein, and mRNA expression compared with controls, whereas miR-29b-3p expression decreased >50%. Transfection of miR-29b-3p mimics into cardiac fibroblasts inhibited cardiotonic steroids-induced collagen synthesis. Moreover, a specific Na/K-ATPase signaling antagonist, pNaKtide, prevented ouabain-induced increases in collagen synthesis and decreases in miR-29b-3p expression in these cells. In conclusion, these data are the first to indicate that signaling through Na/K-ATPase regulates miRNAs and specifically, miR-29b-3p expression both in vivo and in vitro. Additionally, these data indicate that miR-29b-3p expression plays an important role in the formation of cardiac fibrosis in CKD.

CT of acute perianal abscesses and infected fistulae: a pictorial essay.

Computed tomography (CT) is an effective, readily available diagnostic imaging tool for evaluation of the emergency room (ER) patients with the clinical suspicion of perianal abscess and/or infected fistulous tract (anorectal sepsis). These patients usually present with perineal pain, fever, and leukocytosis. The diagnosis can be easy if the fistulous tract or abscess is visible on inspection of the perianal skin. If the tract or abscess is deep, then the clinical diagnosis can be difficult. Also, the presence of complex tracts or supralevator extension of the infection cannot be judged by external examination alone. Magnetic resonance imaging (MRI) is the best imaging test to accurately detect fistulous tracts, especially when they are complex (Omally et al. in AJR 199:W43-W53, 2012). However, in the acute setting in the ER, this imaging modality is not always immediately available. Endorectal ultrasound has also been used to identify perianal abscesses, but this modality requires hands-on expertise and can have difficulty localizing the offending fistulous tract. It may also require the use of a rectal probe, which the patient may not be able to tolerate. Contrast-enhanced CT is a very useful tool to diagnose anorectal sepsis; however, this has not received much attention in the recent literature (Yousem et al. in Radiology 167(2):331-334, 1988) aside from a paper describing CT imaging following fistulography (Liang et al. in Clin Imaging 37(6):1069-1076, 2013). An infected fistula is indicated by a fluid-/air-filled soft tissue tract surrounded by inflammation. A well-defined round to oval-shaped fluid/air collection is indicative of an abscess. The purpose of this article is to demonstrate the usefulness of contrast-enhanced CT in the diagnosis of acute anorectal sepsis in the ER setting. We will discuss the CT appearance of infected fistulous tracts and abscesses and how CT imaging can guide the ER physician in the clinical management of these patients.

Spatial control of cell gene expression by siRNA gradients in biodegradable hydrogels.

The extracellular environment exposes cells to numerous biochemical and physical signals that regulate their behavior. Strategies for generating continuous gradients of signals in biomaterials may allow for spatial control and patterning of cell behavior, and ultimately aid in the engineering of complex tissues. Short interfering RNA (siRNA) can regulate gene expression by silencing specific mRNA molecules post-transcriptionally, which may be valuable when presented in a continuous gradient for regenerative or therapeutic applications. Here, a biodegradable hydrogel system containing a gradient of siRNA is presented, and its capacity to regulate protein expression of encapsulated cells in a spatially continuous manner is demonstrated. Photocross-linkable dextran hydrogels containing a gradient of siRNA have been successfully fabricated using a dual-programmable syringe pump system, and differential gene silencing in incorporated cells that is sustained over time has been shown using green fluorescent protein as a reporter. This platform technology may be applied in tissue engineering to spatially control biologically relevant cellular processes.

The use of argon beam coagulation in treating vulvar intraepithelial neoplasia III: a retrospective review.

UNLABELLED: Argon beam coagulation (ABC) has unique properties which make it suitable for the local treatment of superficial epithelial disorders such as vulvar intraepithelial neoplasia (VIN III). OBJECTIVE: To evaluate argon beam coagulation in treating multifocal VIN III. METHODS: Argon beam coagulation was used in twenty-nine patients. ABC was set at 80 W, 7 L/min. All patients were given 1% silvadene cream to apply to vulva. Patients had follow-up appointments two weeks and six weeks postoperatively. Patients were followed every three to six months for the subsequent year. RESULTS: 2 of 29 (6.8%) experienced moderate pain within the first two weeks postoperatively requiring prescriptions for perocet. 2 of 29 (6.8%) had yeast infection requiring diflucan. Mean follow-up time was 34.9 months (11.7-37.4). 15 of 29 (51.7%) had no recurrence within the follow-up period. 14 of 29 (48.3%) recurred within the follow-up period. The mean time to recurrence is 23.2 months. CONCLUSION: This small retrospective review is the first to evaluate argon beam coagulation in treating multifocal VIN III. This review indicates that ABC is comparable to other vulva organ conserving therapies. ABC retains cosmesis, and form of the vulva. This is a major advantage over surgery. Repeat treatments are also possible, which is important in a condition such as VIN, which tends to be multifocal and recurrent.

Evaluation of exposures to healthcare personnel from cisplatin during a mock demonstration of intra-operative intraperitoneal chemotherapy administration.

UNLABELLED: Ovarian cancer is the leading cause of death from gynecologic malignancies in the United States. In 2006, the National Cancer Institute released an announcement supporting the use of intraperitoneal (IP) chemotherapy in advanced ovarian cancer. It remains unanswered how many cycles of IP chemotherapy are required to maintain a survival advantage. There may be a benefit with as few as three IP cycles and possibly as few as one IP chemotherapy cycle. OBJECTIVE: In preparation for a clinical trial in which chemotherapy would be administered intra-operatively, the question of exposure to healthcare personnel arose, therefore, the purpose of this study was to perform an evaluation of healthcare personnel exposure to cisplatin during a mock demonstration of intraperitoneal chemotherapy administration. MATERIALS AND METHODS: The National Institute of Occupational Safety and Health (NIOSH), the Women's Cancer Center of Nevada, and the staff of the University Medical Center, Las Vegas, participated in this mock demonstration. Employees wore personal protective equipment recommended by NIOSH. Wipe, area, and breathing zone air samples were taken from the pharmacy and operating room, and during sterilization of equipment. RESULTS: All samples were negative for cisplatin, except for one surface wipe from the floor of the operating room (OR) after the mock procedure. Upon sanitization of the OR, no cisplatin was detected on the floor. CONCLUSION: This was the first study evaluating the exposure of healthcare personnel to the administration of cisplatin intra-operatively. NIOSH endorsed this practice so long as the employees adhere to using the recommended personal protective equipment.

Vitamin d and the risk of uterine fibroids.

BACKGROUND: Uterine leiomyomata (also known as fibroids) are benign tumors of uterine smooth muscle that are characterized by overproduction of extracellular matrix. Fibroids are the leading indication for hysterectomy in the United States. The active metabolite of vitamin D has been shown to inhibit cell proliferation and extracellular matrix production in fibroid tissue culture and to reduce fibroid volume in the Eker rat. No previous study has examined whether vitamin D is related to fibroid status in women. METHODS: The National Institute of Environmental Health Sciences Uterine Fibroid Study enrolled randomly selected 35- to 49-year-old women who were members of an urban health plan during 1996-1999. Fibroid status was determined by ultrasound screening of premenopausal women (620 blacks, 416 whites). Vitamin D status was assessed in stored plasma by radioimmunoassay of 25-hydroxyvitamin D (25(OH)D) and questionnaire data on sun exposure. Associations were evaluated with logistic regression, controlling for potential confounders. RESULTS: Only 10% of blacks and 50% of whites had levels of 25(OH)D regarded as sufficient (>20 ng/ml). Women with sufficient vitamin D had an estimated 32% lower odds of fibroids compared with those with vitamin D insufficiency (adjusted odds ratio [aOR] = 0.68, 95% confidence interval [CI] = 0.48-0.96). The association was similar for blacks and whites. Self-reported sun exposure ≥ 1 hour per day (weather permitting) was also associated with reduced odds of fibroids (aOR = 06. [0.4-0.9]), with no evidence of heterogeneity by ethnicity. CONCLUSIONS: The consistency of findings for questionnaire and biomarker data, the similar patterns seen in blacks and whites, and the biological plausibility provide evidence that sufficient vitamin D is associated with a reduced risk of uterine fibroids.

Ultrasound is superior to computed tomography for assessment of medullary nephrocalcinosis in hypoparathyroidism.

CONTEXT: Nephrocalcinosis is a complication of hypoparathyroidism and other metabolic disorders. Imaging modalities include ultrasonography (US) and computed tomography (CT). Few studies have compared these modalities, and standard clinical practice is not defined. OBJECTIVE: The objective of the study was to determine the preferred method for assessing nephrocalcinosis. DESIGN: The design of the study was a retrospective, blinded analysis. SETTING: The study was conducted at a clinical research center. PATIENTS: Twenty-two hypoparathyroid subjects and 7 controls participated in the study. INTERVENTIONS: Contemporaneous renal US and CT images were reviewed in triplicate by 4 blinded radiologists. Nephrocalcinosis was classified using a 0-3 scale with 0 meaning no nephrocalcinosis and 3 meaning severe nephrocalcinosis. MAIN OUTCOME MEASURES: Intraobserver, interobserver, and interdevice agreements were measured. RESULTS: Intraobserver agreement was high, with an overall weighted kappa of 0.83 for CT and 0.89 for US. Interobserver agreement was similar between modalities, with kappas of 0.74 for US and 0.70 for CT. Only moderate agreement was found between US and CT scores, with an intermodality kappa of 0.47 and 60% concordance. Of discordant pairs, 81% had higher US scores and only 19% had higher CT scores. Of nephrocalcinosis seen on US and not CT, 45%, 46%, and 9% were grades 1, 2, and 3, respectively. Overall, US scores were higher than CT with a cumulative odds ratio (95% confidence interval) of 5.97 (2.60, 13.75) (P < .01). In controls, 100% of US ratings were 0, and 95% of CT ratings were 0. CONCLUSIONS: US is superior to CT for assessment of mild to moderate nephrocalcinosis in patients with hypoparathyroidism. This finding, in combination with its low cost, lack of radiation, and portability, defines US as the preferred modality for assessment of nephrocalcinosis.

Biodegradable photo-crosslinked alginate nanofibre scaffolds with tuneable physical properties, cell adhesivity and growth factor release.

Nanofibrous scaffolds are of interest in tissue engineering due to their high surface area to volume ratio, interconnected pores, and architectural similarity to the native extracellular matrix. Our laboratory recently developed a biodegradable, photo-crosslinkable alginate biopolymer. Here, we show the capacity of the material to be electrospun into a nanofibrous matrix, and the ability to enhance cell adhesion and proliferation on these matrices by covalent modification with cell adhesion peptides. Additionally, the potential of covalently incorporating heparin into the hydrogels during the photopolymerisation process to sustain the release of a heparin binding growth factor via affinity interactions was demonstrated. Electrospun photo-crosslinkable alginate nanofibrous scaffolds endowed with cell adhesion ligands and controlled delivery of growth factors may allow for improved regulation of cell behaviour for regenerative medicine.

Ultrasound-guided biopsies of the abdomen.

Ultrasound is the most useful imaging technique for guiding biopsies and fine-needle aspirations that are performed percutaneously. It is a safe and accurate method to guide needles using real-time imaging into abdominal and pelvic organs and masses. Its advantages over computed tomography-guided biopsies are that it can be done portably, is less expensive, and does not use ionizing radiation. Even lesions as small as 1 cm can be biopsied assuming the procedure can be performed safely and the mass can be visualized sonographically.This review article discusses the different components of performing percutaneous biopsies in adult patients including review of the patients imaging studies, coagulation status, and medications. We explain when and how we do core biopsies versus fine-needle aspirations to obtain a diagnosis depending on the suspected diagnosis and organ/mass being biopsied. We also describe how we take care of the patient after biopsy.Ultrasound can be used safely and successfully to perform biopsies and fine-needle aspirations in solid organs of the abdomen and pelvis including the retroperitoneum and abdominal wall. This technique allows adequate tissue sampling with real-time monitoring during placement of the biopsy needle. Postprocedure complications are extremely rare with the vast majority of our patients requiring only a short recovery time of 2 hours following the biopsy.

Quantification of in vitro and in vivo angiogenesis stimulated by ovine forestomach matrix biomaterial.

Ovine forestomach matrix (OFM) biomaterial acts as a biomimetic of native extracellular matrix (ECM) by providing structural and functional cues to orchestrate cell activity during tissue regeneration. The ordered collagen matrix of the biomaterial is supplemented with secondary ECM-associated macromolecules that function in cell adhesion, migration and communication. As angiogenesis and vasculogenesis are critical processes during tissue regeneration we sought to quantify the angiogenic properties of the OFM biomaterial. In vitro studies demonstrated that soluble OFM components stimulated human umbilical vein endothelial cell (HUVEC) migration and increased vascular sprouting from an aorta. Blood vessel density and branch points increased in response to OFM in an ex ovo chicken chorioallantoic membrane (CAM) assay. The OFM biomaterial was shown to undergo remodeling in a porcine full-thickness excisional model and gave rise to significantly more blood vessels than wounds treated with small intestinal submucosa decellularized ECM or untreated wounds.

Potential risk factors associated with subtypes of uterine leiomyomata.

OBJECTIVE: To compare potential risk factors for uterine leiomyomata (UL) subtypes among premenopausal African American and Caucasian women. METHODS: This cross-sectional study included 986 premenopausal women, aged 35 to 49 years old, from the National Institute of Environmental Health Sciences (NIEHS) Uterine Fibroid Study (UFS). Uterine leiomyomata were subtyped as submucosal, intramural/subserosal, and diffuse, based on ultrasound examinations. RESULTS: For both ethnic groups, age, age at menarche, body mass index, and current physical activity had similar associations across the 3 UL subtypes. Inverse associations with pregnancies after age 24 appeared to be stronger for the submucosal subtype. Current smoking was associated only with diffuse UL (adjusted odds ratio [aOR] = 1.97, 95% CI: 1.11, 3.51 in African Americans, aOR = 3.00, 95% CI: 1.07, 8.38 in Caucasians). CONCLUSIONS: Although the 2 focal UL subtypes had similar risk factor profiles, the diffuse UL subtype appeared to have a distinctive risk profile with regard to current smoking. Further study of the diffuse heterogeneity seen with uterine ultrasound is needed.

Goals and objectives for an integrated, graduated curriculum in abdominal radiology.

The Residency Review Committee of the American Council of Graduate Medical Education has designated abdominal radiology as one of the subspecialty areas required for radiology residency training. Because it spans both gastrointestinal and genitourinary organ systems and multiple modalities, a graduated, integrated abdominal radiology curriculum, which is based on the General Competencies, was developed.

The correlation between elevated cardiac troponin I and pulmonary artery obstruction index in ED patients with pulmonary embolism.

OBJECTIVES: The aim of this study is to investigate the correlation between cardiac troponin I (cTnI) values and the pulmonary artery obstruction index assessed with spiral computed tomography (CT) scan in emergency department (ED) patients with pulmonary embolism (PE). METHODS: This is a retrospective cohort study of all 179 ED patients diagnosed with PE between December 2004 and January 2007. Study population consisted of 104 (58.1%) of 179 patients with PE in whom both cTnI was measured and a contemporaneously performed CT scan was available for review. In these patients, the levels of cTnI measured in the ED were correlated with the degree of pulmonary vascular obstruction determined by applying the modified Computed Tomography Obstruction Index to the spiral CT scan performed in the ED. RESULTS: Troponin values were elevated in 20 (19.2%) of 104 patients (95% confidence interval [CI], 11.6-26.8) with a mean cTnI concentration of 0.38 +/- 0.44 microg/L. Elevated cTnI value had a significant correlation with main pulmonary arteries involvement using the modified Computed Tomography Obstruction Index score (P = .0001). Elevated ED cTnI value had 53.8% (95% CI, 37.6-66) sensitivity and 92.3% (95% CI, 87-96.4) specificity, 70% (95% CI, 49-86) PPV, and 85.7% (95% CI, 80.7-90) NPV for predicting main pulmonary artery obstruction on CT. Increased cTnI values were highly correlated to intensive care unit admission of patients with PE (RR, 12.83; 95% CI, 3.87-42.4). CONCLUSIONS: Measuring cTnI value might be considered in ED patients who are suspected of having PE. Elevated cTnI should raise the clinician's concern for the possibility of central pulmonary vascular obstruction.

Uterine leiomyomata in relation to insulin-like growth factor-I, insulin, and diabetes.

BACKGROUND: Insulin-like growth factor-I (IGF-I) and insulin stimulate cell proliferation in uterine leiomyoma (fibroid) tissue. We hypothesized that circulating levels of these proteins would be associated with increased prevalence and size of uterine fibroids. METHODS: Participants were 35-49-year-old, randomly selected members of an urban health plan who were enrolled in the study in 1996-1999. Premenopausal participants were screened for fibroids with ultrasound. Fasting blood samples were collected. Associations between fibroids and diabetes, plasma IGF-I, IGF binding protein 3 (BP3), and insulin were evaluated for blacks (n = 585) and whites (n = 403) by using multiple logistic regression. RESULTS: IGF-I showed no association with fibroids in blacks, but in whites the adjusted odds ratios (aORs) for both mid and upper tertiles compared with the lowest tertile were 0.6 (95% confidence intervals [CI] = 0.3-1.0 and 0.4-1.1, respectively). Insulin and diabetes both tended to be inversely associated with fibroids in blacks. The insulin association was with large fibroids; aOR for the upper insulin tertile relative to the lowest was 0.4 (0.2-0.9). The aOR for diabetes was 0.5 (0.2-1.0). Associations of insulin and diabetes with fibroids were weak for whites. Binding protein 3 showed no association with fibroids. CONCLUSIONS: Contrary to our hypothesis, high circulating IGF-I and insulin were not related to increased fibroid prevalence. Instead, there was suggestion of the opposite. The inverse association with diabetes, although based on small numbers, is consistent with previously reported findings. Future studies might investigate vascular dysfunction as a mediator between hyperinsulinemia or diabetes and possible reduced risk of fibroids.