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1.
J Am Coll Radiol ; 19(11S): S433-S444, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36436968

ABSTRACT

Mesenteric ischemia is a serious medical condition characterized by insufficient vascular supply to the small bowel. In the acute setting, endovascular interventions, including embolectomy, transcatheter thrombolysis, and angioplasty with or without stent placement, are recommended as initial therapeutic options. For nonocclusive mesenteric ischemia, transarterial infusion of vasodilators, such as papaverine or prostaglandin E1, is the recommended initial treatment. In the chronic setting, endovascular means of revascularization, including angioplasty and stent placement, are generally recommend, with surgical options, such as bypass or endarterectomy, considered alternative options. Although the diagnosis of median arcuate ligament syndrome remains controversial, diagnostic angiography can be helpful in rendering a diagnosis, with the preferred treatment option being a surgical release. Systemic anticoagulation is recommended as initial therapy for venous mesenteric ischemia with acceptable rates of recanalization. If anticoagulation fails, transcatheter thrombolytic infusion can be considered with possible adjunctive placement of a transjugular intrahepatic portosystemic shunt to augment antegrade flow. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.


Subject(s)
Mesenteric Ischemia , Radiology , Humans , Mesenteric Ischemia/diagnostic imaging , Mesenteric Ischemia/therapy , Societies, Medical , Evidence-Based Medicine , Anticoagulants/therapeutic use
2.
J Am Coll Radiol ; 19(11S): S445-S461, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36436969

ABSTRACT

This document focuses on imaging in the adult and pregnant populations with right lower quadrant (RLQ) abdominal pain, including patients with fever and leukocytosis. Appendicitis remains the most common surgical pathology responsible for RLQ abdominal pain in the United States. Other causes of RLQ pain include right colonic diverticulitis, ureteral stone, and infectious enterocolitis. Appropriate imaging in the diagnosis of appendicitis has resulted in decreased negative appendectomy rate from as high as 25% to approximately 1% to 3%. Contrast-enhanced CT remains the primary and most appropriate imaging modality to evaluate this patient population. MRI is approaching CT in sensitivity and specificity as this technology becomes more widely available and utilization increases. Unenhanced MRI and ultrasound remain the diagnostic procedures of choice in the pregnant patient. MRI and ultrasound continue to perform best in the hands of the experts. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer-reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer-reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.


Subject(s)
Appendicitis , Pregnancy , Female , Humans , United States , Societies, Medical , Evidence-Based Medicine , Diagnosis, Differential , Abdominal Pain/diagnostic imaging , Magnetic Resonance Imaging/methods
3.
Pancreas ; 51(6): 694-699, 2022 07 01.
Article in English | MEDLINE | ID: mdl-36206471

ABSTRACT

OBJECTIVES: The aim of this study was to determine if the quick Sepsis-Related Organ Failure Assessment (qSOFA) score assessed at and 48 hours after admission is prognostic for alcohol-induced acute pancreatitis (AAP) severity. METHODS: This is a retrospective cohort review study of 161 patients admitted to a single academic hospital in Houston, TX, with the diagnosis of AAP. Receiver operator characteristics analysis and logistic regression were used to assess the diagnostic accuracy and prognostic ability of the qSOFA score. RESULTS: A qSOFA score of 2 or higher at and 48 hours after admission had a specificity of 94% or greater and sensitivity of 33% or higher for pancreatitis severity and need for intensive care admission, intubation, or vasopressors. The qSOFA score at and 48 hours after admission was prognostic of intensive care unit admission by an adjusted odds ratio of 48.5 (95% confidence interval [CI], 6.4-1013.3; P < 0.001) and 18.8 (95% CI, 2.2-467.3; P < 0.05), respectively. The qSOFA score at admission was prognostic of severe pancreatitis by an adjusted odds ratio of 35.3 (95% CI, 7.2-224.3; P < 0.001). CONCLUSIONS: A qSOFA score of 2 or higher is highly specific and prognostic of multiple clinical outcomes both at and 48 hours after admission in patients with AAP.


Subject(s)
Pancreatitis, Alcoholic , Sepsis , Acute Disease , Hospital Mortality , Humans , Intensive Care Units , Organ Dysfunction Scores , Pancreatitis, Alcoholic/complications , Pancreatitis, Alcoholic/diagnosis , Prognosis , ROC Curve , Retrospective Studies , Sepsis/complications , Sepsis/diagnosis
4.
BMC Gastroenterol ; 22(1): 412, 2022 Sep 05.
Article in English | MEDLINE | ID: mdl-36064325

ABSTRACT

BACKGROUND: This analysis characterized changes in sodium levels in patients receiving the 1 L polyethylene glycol-based preparation NER1006. METHODS: Data were pooled from three phase III, randomized clinical trials. A post hoc subanalysis included adults who received a 2-day split-dose (evening/morning) NER1006 regimen, a 1-day split-dose (morning only) regimen, or evening-before regimen and had an increase in sodium concentrations from normal to above the upper limit of normal (143-148 mmol/L) at ≥ 1 of three post-treatment visits. Blood samples were collected at baseline, day of colonoscopy (visit 2), 2 ± 1 days post-colonoscopy (visit 3), and 7 ± 1 days post-colonoscopy (visit 4). RESULTS: A total of 214 of 1028 patients were included. Of the 214 patients, sodium concentration increased from a mean baseline value of 141.8 mmol/L to a mean of 147.1 mmol/L (median increase from baseline of approximately 5 mmol/L). The mean sodium concentration was within normal range at visit 3 (142.3 mmol/L) and visit 4 (142.4 mmol/L), as was the median sodium concentration. Overall, ~ 90% of patients had a normal serum concentration at visits 3 and 4. Based on day of colonoscopy test results, there were four adverse events involving hypernatremia (0.4% of 1028), which were mild and did not require medical intervention; sodium levels returned to normal range by visit 3. CONCLUSION: NER1006 was associated with small, transient increases in sodium levels that were not considered clinically significant. Trial registration NOCT (ClinicalTrials.gov: NCT02254486 [registered October 2, 2014]), MORA (ClinTrials.gov: NCT02273167 [registered October 23, 2014]; EudraCT number: 2014-002185-78 [registered August 13, 2014]), DAYB (ClinicalTrials.gov: NCT02273141 [registered October 23, 2014]; EudraCT Number: 2014-002186-30 [registered August 12, 2014]).


Subject(s)
Colonoscopy , Laxatives , Adult , Colonoscopy/methods , Humans , Polyethylene Glycols/adverse effects , Sodium
6.
J Am Coll Radiol ; 19(5S): S208-S222, 2022 05.
Article in English | MEDLINE | ID: mdl-35550803

ABSTRACT

Preoperative imaging of rectal carcinoma involves accurate assessment of the primary tumor as well as distant metastatic disease. Preoperative imaging of nonrectal colon cancer is most beneficial in identifying distant metastases, regardless of primary T or N stage. Surgical treatment remains the definitive treatment for colon cancer, while organ-sparing approach may be considered in some rectal cancer patients based on imaging obtained before and after neoadjuvant treatment. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Subject(s)
Colonic Neoplasms , Rectal Neoplasms , Diagnostic Imaging/methods , Humans , Neoadjuvant Therapy , Societies, Medical , United States
8.
RSC Adv ; 10(10): 5919-5929, 2020 Feb 04.
Article in English | MEDLINE | ID: mdl-35497420

ABSTRACT

We examine the role of water and urea in cellulose solubility in tetrabutylammonium hydroxide (TBAH). Molecular dynamics simulations were performed for several different solvent compositions with a fixed cellulose fraction. For each composition, two simulations were carried out with cellulose fixed in each of the crystalline and the dissolved states. From the enthalpy and the entropy of the two states, the difference in Gibbs free energy (ΔG) and hence the spontaneity is determined. A comparison with solubility experiments showed a strong correlation between the calculated ΔG and the experimental measurements. A breakdown of the enthalpic and entropic contributions reveals the roles of water and urea in solubility. At high water concentration, a drop in solubility is attributed to both increased enthalpy and decreased entropy of dissolution. Water displaces strong IL-cellulose interactions for weaker water-cellulose interactions, resulting in an overall enthalpy increase. This is accompanied by a strong decrease in entropy, which is primarily attributed to both water and the entropy of mixing. Adding urea to TBAH(aq) increases solubility by an addition to the mixing term and by reducing losses in solvent entropy upon dissolution. In the absence of urea, the flexible [TBA]+ ions lose substantial degrees of freedom when they interact with cellulose. When urea is present, it partially replaces [TBA]+ and to a lesser extent OH- near cellulose, losing less entropy because of its rigid structure. This suggests that one way to boost the dissolving power of an ionic liquid is to limit the number of degrees of freedom from the outset.

9.
RSC Adv ; 11(50): 31328-31338, 2021 Sep 21.
Article in English | MEDLINE | ID: mdl-35496850

ABSTRACT

Binary mixtures of hydrocarbons and a thermally robust ionic liquid (IL) incorporating a perarylphosphonium-based cation are investigated experimentally and computationally. Experimentally, it is seen that excess toluene added to the IL forms two distinct liquid phases, an "ion-rich" phase of fixed composition and a phase that is nearly pure toluene. Conversely, n-heptane is observed to be essentially immiscible in the neat IL. Molecular dynamics simulations capture both of these behaviours. Furthermore, the simulated composition of the toluene-rich IL phase is within 10% of the experimentally determined composition. Additional simulations are performed on the binary mixtures of the IL and ten other small hydrocarbons having mixed aromatic/aliphatic character. It is found that hydrocarbons with a predominant aliphatic character are largely immiscible with the IL, while those with a predominant aromatic character readily mix with the IL. A detailed analysis of the structure and energetic changes that occur on mixing reveals the nature of the ion-rich phase. The simulations show a bicontinuous phase with hydrocarbon uptake akin to absorption and swelling by a porous absorbent. Aromatic hydrocarbons are driven into the neat IL via dispersion forces with the IL cations and, to a lesser extent, the IL anions. The ion-ion network expands to accommodate the hydrocarbons, yet maintains a core connective structure. At a certain loading, this network becomes stretched to its limit. The energetic penalty associated with breaking the core connective network outweighs the gain from new hydrocarbon-IL interactions, leaving additional hydrocarbons in the neat phase. The spatially alternating charge of the expanded IL network is shown to interact favourably with the stacked aromatic subphase, something not possible for aliphatic hydrocarbons.

10.
BMC Gastroenterol ; 22(1): 105, 2022 Mar 07.
Article in English | MEDLINE | ID: mdl-35255832

ABSTRACT

BACKGROUND: A randomized, placebo-controlled clinical trial (FDREST) of a novel formulation of caraway oil and L-menthol (COLM-SST) demonstrated symptom relief in patients with functional dyspepsia (FD). Two follow-up studies were conducted to evaluate patient satisfaction, self-regulated dosing, and long-term safety data: FDACT, Functional Dyspepsia Adherence and Compliance Trial, and FDSU36, Functional Dyspepsia Safety Update at 36 months. METHODS: A patient reported outcomes (PRO) questionnaire was designed and distributed online to assess real-world satisfaction and dosing frequency of open-label COLM-SST in patients with FD. A separate study analyzing voluntary safety surveillance data evaluated the frequency and severity of reported adverse events (AEs). RESULTS: A total of 600 FD patients were enrolled in the PRO study. Ninety five percent of respondents reported a major or moderate improvement in their FD symptoms and 91.7% indicated a major or moderate improvement in quality of life (QOL) using COLM-SST. Between 1 and 4 capsules were consumed daily by 91.2% of respondents, with 56.2% taking them before meals. Symptom relief was rapid, with 86.4% of respondents indicating relief within 2 h of taking COLM-SST. Few adverse events (AEs) were reported (0.0187%) by patients using COLM-SST. No serious AEs were identified. CONCLUSION: COLM-SST is safe, well tolerated, and provides rapid relief of FD symptoms. These findings, demonstrated in the FDREST trial, were further supported by a large prospective PRO study evaluating self-regulated dosing frequency, symptom improvement, and QOL. COLM-SST was well-tolerated based on review of AE data at 36 months.


Subject(s)
Dyspepsia , Menthol , Dyspepsia/diagnosis , Dyspepsia/drug therapy , Humans , Menthol/therapeutic use , Plant Oils , Prospective Studies , Quality of Life , Treatment Outcome
11.
Pulmonology ; 2022 Feb 09.
Article in English | MEDLINE | ID: mdl-35151622

ABSTRACT

INTRODUCTION AND OBJECTIVES: Unsupervised PA interventions might have a role in the management of chronic obstructive pulmonary disease (COPD) but their effectiveness is largely unknown. Thus, we aimed to identify and synthesise data on the effects of unsupervised PA interventions in people with COPD. MATERIAL AND METHODS: Databases were systematically searched in April 2020, with weekly updates until September 2021. Randomised controlled trials and quasi-experimental studies comparing unsupervised PA with usual care, were included. Primary outcomes were dyspnoea, exercise capacity and physical activity. The effect direction plot was performed to synthesise results. Meta-analysis with forest plots were conducted for the Chronic Respiratory Disease questionnaire - dyspnoea domain (CRQ-D), 6-minute walk distance (6MWD) and incremental shuttle walk distance (ISWD). RESULTS: Eleven studies with 900 participants with COPD (68±10 years; 58.8% male, FEV1 63.7±15.8% predicted) were included. All interventions were conducted at home, most with daily sessions, for 8-12 weeks. Walking was the most common component. The effect direction plot showed that unsupervised PA interventions improved emotional function, fatigue, health-related quality of life, muscle strength and symptoms of anxiety and depression. Meta-analysis showed statistical, but not clinical, significant improvements in dyspnoea (CRQ-D, MD=0.12, 95% CI 0.09-0.15) and exercise capacity, measured with 6MWD (MD=13.70, 95% CI 3.58-23.83). Statistical and clinical significant improvements were observed in exercise capacity, measured with ISWD (MD=58.59, 95% CI 5.79-111.39). None to minor adverse events and a high adherence rate were found. CONCLUSIONS: Unsupervised PA interventions benefits dyspnoea and exercise capacity of people with COPD, are safe and present a high adherence rate. Unsupervised PA interventions should be considered for people with COPD who cannot or do not want to engage in supervised PA interventions or as a maintenance strategy of PA levels.

12.
IEEE Trans Ultrason Ferroelectr Freq Control ; 69(4): 1428-1441, 2022 04.
Article in English | MEDLINE | ID: mdl-35143395

ABSTRACT

Peripheral artery disease (PAD) affects more than 200 million people globally. Minimally invasive endovascular procedures can provide relief and salvage limbs while reducing injury rates and recovery times. Unfortunately, when a calcified chronic total occlusion is encountered, ~25% of endovascular procedures fail due to the inability to advance a guidewire using the view provided by fluoroscopy. To enable a sub-millimeter, robotically steerable guidewire to cross these occlusions, a novel single-element, dual-band transducer is developed that provides simultaneous multifrequency, forward-viewing imaging with high penetration depth and high spatial resolution while requiring only a single electrical connection. The design, fabrication, and acoustic characterization of this device are described, and proof-of-concept imaging is demonstrated in an ex vivo porcine artery after integration with a robotically steered guidewire. Measured center frequencies of the developed transducer were 16 and 32 MHz, with -6 dB fractional bandwidths of 73% and 23%, respectively. When imaging a 0.2-mm wire target at a depth of 5 mm, measured -6 dB target widths were 0.498 ± 0.02 and 0.268 ± 0.01 mm for images formed at 16 and 32 MHz, respectively. Measured SNR values were 33.3 and 21.3 dB, respectively. The 3-D images of the ex vivo artery demonstrate high penetration for visualizing vessel morphology at 16 MHz and ability to resolve small features close to the transducer at 32 MHz. Using images acquired simultaneously at both frequencies as part of an integrated forward-viewing, guidewire-based imaging system, an interventionalist could visualize the best path for advancing the guidewire to improve outcomes for patients with PAD.


Subject(s)
Robotic Surgical Procedures , Acoustics , Animals , Arteries , Equipment Design , Humans , Phantoms, Imaging , Swine , Transducers
13.
Gastroenterol Clin North Am ; 51(1): 93-105, 2022 03.
Article in English | MEDLINE | ID: mdl-35135667

ABSTRACT

Spinal cord injury and neurogenic bowel dysfunction (NBD) are life-changing events for affected patients. The clinical manifestations of NBD vary depending on the level and severity of the spinal cord lesion. Managing patients with NBD can be complicated by comorbidities, such as immobility, bladder dysfunction, progressive neurologic decline, psychological factors, loss of independence, and social withdrawal, and ideally involves a multimodal, multidisciplinary approach. Evaluation and management should be individualized, depending on the residual neurologic capabilities of the patient and their predominant gastrointestinal symptoms, and commonly involves lifestyle modifications, physical therapy, laxative medications, and surgical interventions.


Subject(s)
Fecal Incontinence , Neurogenic Bowel , Spinal Cord Injuries , Central Nervous System , Constipation/etiology , Constipation/therapy , Fecal Incontinence/etiology , Fecal Incontinence/therapy , Humans , Neurogenic Bowel/etiology , Neurogenic Bowel/therapy , Spinal Cord Injuries/complications , Spinal Cord Injuries/therapy
14.
Ultrasound Med Biol ; 48(3): 530-545, 2022 03.
Article in English | MEDLINE | ID: mdl-34972572

ABSTRACT

Contrast-enhanced ultrasound imaging allows vascular imaging in a variety of diseases. Radial modulation imaging is a contrast agent-specific imaging approach for improving microbubble detection at high imaging frequencies (≥7.5 MHz), with imaging depth limited to a few centimeters. To provide high-sensitivity contrast-enhanced ultrasound imaging at high penetration depths, a new radial modulation imaging strategy using a very low frequency (100 kHz) ultrasound modulation wave in combination with imaging pulses ≤5 MHz is proposed. Microbubbles driven at 100 kHz were imaged in 10 successive oscillation states by manipulating the pulse repetition frequency to unlock the frame rate from the number of oscillation states. Tissue background was suppressed using frequency domain radial modulation imaging (F-RMI) and singular value decomposition-based radial modulation imaging (S-RMI). One hundred-kilohertz modulation resulted in significantly higher microbubble signal magnitude (63-88 dB) at the modulation frequency relative to that without 100-kHz modulation (51-59 dB). F-RMI produced images with high contrast-to-tissue ratios (CTRs) of 15 to 22 dB in a stationary tissue phantom, while S-RMI further improved the CTR (19-26 dB). These CTR values were significantly higher than that of amplitude modulation pulse inversion images (11.9 dB). In the presence of tissue motion (1 and 10 mm/s), S-RMI produced high-contrast images with CTR up to 18 dB; however, F-RMI resulted in minimal contrast enhancement in the presence of tissue motion. Finally, in transcranial ultrasound imaging studies through a highly attenuating ex vivo cranial bone, CTR values with S-RMI were as high as 23 dB. The proposed technique demonstrates successful modulation of microbubble response at 100 kHz for the first time. The presented S-RMI low-frequency radial modulation imaging strategy represents the first demonstration of real-time (20 frames/s), high-penetration-depth radial modulation imaging for contrast-enhanced ultrasound imaging.


Subject(s)
Contrast Media , Microbubbles , Phantoms, Imaging , Ultrasonic Waves , Ultrasonography/methods
15.
IEEE Trans Ultrason Ferroelectr Freq Control ; 69(3): 1064-1076, 2022 03.
Article in English | MEDLINE | ID: mdl-34971531

ABSTRACT

Coronary artery disease (CAD) is a leading cause of death globally. Computed tomography coronary angiography (CTCA) is a noninvasive imaging procedure for diagnosis of CAD. However, CTCA requires cardiac gating to ensure that diagnostic-quality images are acquired in all patients. Gating reliability could be improved by utilizing ultrasound (US) to provide a direct measurement of cardiac motion; however, commercially available US transducers are not computed tomography (CT) compatible. To address this challenge, a CT-compatible 2.5-MHz cardiac phased array transducer is developed via modeling, and then, an initial prototype is fabricated and evaluated for acoustic and radiographic performance. This 92-element piezoelectric array transducer is designed with a thin acoustic backing (6.5 mm) to reduce the volume of the radiopaque acoustic backing that typically causes arrays to be incompatible with CT imaging. This thin acoustic backing contains two rows of air-filled, triangular prism-shaped voids that operate as an acoustic diode. The developed transducer has a bandwidth of 50% and a single-element SNR of 9.9 dB compared to 46% and 14.7 dB for a reference array without an acoustic diode. In addition, the acoustic diode reduces the time-averaged reflected acoustic intensity from the back wall of the acoustic backing by 69% compared to an acoustic backing of the same composition and thickness without the acoustic diode. The feasibility of real-time echocardiography using this array is demonstrated in vivo, including the ability to image the position of the interventricular septum, which has been demonstrated to effectively predict cardiac motion for prospective, low radiation CTCA gating.


Subject(s)
Acoustics , Transducers , Equipment Design , Humans , Prospective Studies , Reproducibility of Results , Tomography , Tomography, X-Ray Computed
16.
J Cutan Pathol ; 49(5): 426-433, 2022 May.
Article in English | MEDLINE | ID: mdl-34877687

ABSTRACT

BACKGROUND: Acquired lymphangioma circumscriptum of the vulva is rare and can occur subsequent to malignancies of the anogenital and pelvic region. We sought to investigate the clinicopathologic characteristics of malignancy-associated acquired vulvar lymphangioma circumscriptum (AVLC). METHODS: We identified all cases of AVLC within our institution with history of prior malignancy between 2005 and 2021. A similar search was performed in the PubMed database to identify published cases to date. The clinical and histopathologic information was recorded. RESULTS: A total of 71 cases were identified. The most common preceding malignancy was cervical carcinoma (71.8%, 51/71). Radiation therapy was given to 91.4% (64/70) of the patients and lymph node dissection was made on 70.2% (40/57). Median interval between the diagnosis of malignancy and the AVLC was 10 years (range 0-32 years). AVLC frequently presented as vesicular (31.6%, 18/57) or verrucous (28.1%, 16/57) lesions clinically. Common treatments for AVLC included excision (53.1%, 26/49) and laser therapy (16.3%, 8/49), with an overall recurrence rate of 42.9% (24/56) at a median follow-up interval of 1.8 years (range 0.04-32.3 years). CONCLUSION: AVLC is a rare, late complication of anogenital and pelvic malignancies causing debilitating physical symptoms and psychological stress. Further studies are warranted to determine the most effective treatment modalities to mitigate recurrence.


Subject(s)
Laser Therapy , Lymphangioma , Vulvar Neoplasms , Female , Humans , Laser Therapy/adverse effects , Lymphangioma/pathology , Treatment Outcome , Vulva/pathology , Vulvar Neoplasms/pathology
17.
Ann Clin Lab Sci ; 51(5): 678-685, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34686510

ABSTRACT

OBJECTIVE: To elucidate the reasons for the decreased effectiveness of Vedolizumab (VDZ) treatment in patients with Crohn's disease (CD) previously treated (CD-T) with anti-TNF-α biologics. METHODS: Immunohistochemical staining was performed on sections of formalin-fixed paraffin-embedded ileocolonic biopsies using antibodies for the mucosal addressin molecule (MAdCAM-1) and Etrolizumab. RESULTS: The mean number of MAdCAM-1 positive capillaries (MAdCAM-1-C) was 3 in controls, 8.5 in CD, 5.37 in CD-T, 5.7 in ulcerative colitis (UC), and 3.1 in lymphocytic colitis (LC) (p=0.0032). When all biopsies with inflammatory bowel disease (IBD) in this series were considered together, the number of MAdCAM-1-C increased with an increased histologic activity score (HAS) (p<0.001). The mean MAd-CAM-1-C was lower in CD-T than CD (5.37 vs. 8.5, p=0.0362), even in cases with high HAS (6.46 vs. 9.5, p=0.073). Two of 6 (33%) controls, 4 of 6 (67%) CD, 9 of 16 (56%) CD-T, 6 of 7 (86%) UC, and 0 of 8 (0%) LC showed Etrolizumab-positive lymphocytes (E-Ly, p=0.0106). IBD biopsies positive for E-Ly were associated with higher HAS (p=0.0546). MAdCAM-1-C was heterogenous in some IBD cases. CONCLUSIONS: Our results suggest that treatment with anti-TNF-α reduces the number of MAdCAM-1-C in CD, even in biopsies with high HAS. This suggests that high inflammation in such cases obviously failed to respond to anti-TNF-α, may be less dependent on the migration of a4b7-lymphocytes to the inflamed mucosa, and therefore may not optimally respond to VDZ treatment.Presented in part at the Digestive Diseases Week meeting, San Diego, CA, May 2019. Supported by Takeda Pharmaceuticals.


Subject(s)
Capillaries/drug effects , Cell Adhesion Molecules/metabolism , Crohn Disease/drug therapy , Integrins/metabolism , Mucoproteins/metabolism , Tumor Necrosis Factor Inhibitors/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Biological Products/pharmacology , Capillaries/metabolism , Capillaries/pathology , Case-Control Studies , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/pathology , Crohn Disease/metabolism , Crohn Disease/pathology , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Humans , Ileum/drug effects , Ileum/metabolism , Lymphocytes/drug effects , Lymphocytes/metabolism , Lymphocytes/pathology , Tumor Necrosis Factor Inhibitors/therapeutic use
18.
Langmuir ; 37(35): 10439-10449, 2021 Sep 07.
Article in English | MEDLINE | ID: mdl-34427450

ABSTRACT

The binary adsorption of CO2 and water on an amine-functionalized UiO-66 metal-organic framework (MOF) was studied experimentally and computationally. Grand canonical Monte Carlo simulations were used to investigate three additional UiO-66 MOFs with different functionalized linkers. Each MOF was studied in a defect-free form as well as two additional forms with precise linker defects. Binary adsorption isotherms are presented for CO2 at specific water loadings. While water loading in defect-free MOFs reduces the CO2 uptake, the defects slightly boost the CO2 uptake at low water loadings. It was found that water bridges form between the metal oxide cores, replacing the missing linkers. Effectively, this creates smaller pores that are more welcoming of CO2 adsorption. Experimental measurement of the binary isotherms for UiO-66-NH2 shows a behavior that is consistent with this enhancement.

19.
Parkinsonism Relat Disord ; 90: 52-56, 2021 09.
Article in English | MEDLINE | ID: mdl-34385007

ABSTRACT

INTRODUCTION: Reduced postsynaptic D3 dopaminergic receptor availability has been reported in the ventral striatum of pathological gamblers without Parkinson's disease (PD) and in patients with PD and impulse control disorders (ICD). However, a direct relationship between ventral striatum D3 dopaminergic receptors and the severity of ICD in PD patients has not yet been proven using a validated tool for ICD in PD, such as the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease-Rating Scale (QUIP-RS). In this pilot study, we investigated the relationship between ventral striatum D3 dopamine receptor availability and severity of impulse control disorder (ICD) in Parkinson's disease (PD). METHODS: Twelve patients were assessed with PET and the high affinity dopamine D3 receptor radioligand [11C]-PHNO. Severity of ICD was assessed with the QUIP-RS. RESULTS: We found that lower ventral striatum D3 receptor availability measured with [11C]-PHNO PET was associated with greater severity of ICD, as measured by the QUIP-RS score (rho = -0.625, p = 0.03). CONCLUSION: These findings suggest that the occurrence and severity of ICD in Parkinson's disease may be linked to reductions in ventral striatum dopamine D3 receptor availability. Further studies in larger cohort of patients need to be performed in order to confirm our findings and clarify whether lower ventral striatum D3 receptor may reflect a pharmacological downregulation to higher dopamine release in ventral striatum of patients with ICD or a patients' predisposition to ICD.


Subject(s)
Disruptive, Impulse Control, and Conduct Disorders/metabolism , Parkinson Disease/metabolism , Receptors, Dopamine D3/metabolism , Ventral Striatum/metabolism , Aged , Case-Control Studies , Disruptive, Impulse Control, and Conduct Disorders/etiology , Female , Humans , Impulsive Behavior/physiology , Male , Parkinson Disease/psychology , Pilot Projects , Severity of Illness Index
20.
Adv Healthc Mater ; 10(20): e2100968, 2021 10.
Article in English | MEDLINE | ID: mdl-34369107

ABSTRACT

Vascular atresia are often treated via transcatheter recanalization or surgical vascular anastomosis due to congenital malformations or coronary occlusions. The cellular response to vascular anastomosis or recanalization is, however, largely unknown and current techniques rely on restoration rather than optimization of flow into the atretic arteries. An improved understanding of cellular response post anastomosis may result in reduced restenosis. Here, an in vitro platform is used to model anastomosis in pulmonary arteries (PAs) and for procedural planning to reduce vascular restenosis. Bifurcated PAs are bioprinted within 3D hydrogel constructs to simulate a reestablished intervascular connection. The PA models are seeded with human endothelial cells and perfused at physiological flow rate to form endothelium. Particle image velocimetry and computational fluid dynamics modeling show close agreement in quantifying flow velocity and wall shear stress within the bioprinted arteries. These data are used to identify regions with greatest levels of shear stress alterations, prone to stenosis. Vascular geometry and flow hemodynamics significantly affect endothelial cell viability, proliferation, alignment, microcapillary formation, and metabolic bioprofiles. These integrated in vitro-in silico methods establish a unique platform to study complex cardiovascular diseases and can lead to direct clinical improvements in surgical planning for diseases of disturbed flow.


Subject(s)
Bioprinting , Endothelial Cells , Pulmonary Artery , Anastomosis, Surgical , Hemodynamics , Humans , Models, Cardiovascular , Printing, Three-Dimensional , Pulmonary Artery/surgery , Stress, Mechanical
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