Automated detection of incidental abdominal aortic aneurysms on computed tomography.

PURPOSE: To detect and assess abdominal aortic aneurysms (AAAs) on CT in a large asymptomatic adult patient population using fully-automated deep learning software. MATERIALS AND METHODS: The abdominal aorta was segmented using a fully-automated deep learning model trained on 66 manually-segmented abdominal CT scans from two datasets. The axial diameters of the segmented aorta were extracted to detect the presence of AAAs-maximum axial aortic diameter greater than 3 cm were labeled as AAA positive. The trained system was then externally-validated on CT colonography scans of 9172 asymptomatic outpatients (mean age, 57 years) referred for colorectal cancer screening. Using a previously-validated automated calcified atherosclerotic plaque detector, we correlated abdominal aortic Agatston and volume scores with the presence of AAA. RESULTS: The deep learning software detected AAA on the external validation dataset with a sensitivity, specificity, and AUC of 96%, (95% CI 89%, 100%), 96% (96%, 97%), and 99% (98%, 99%) respectively. The Agatston and volume scores of reported AAA-positive cases were statistically significantly greater than those of reported AAA-negative cases (p < 0.0001). Using plaque alone as a AAA detector, at a threshold Agatston score of 2871, the sensitivity and specificity were 84% (73%, 94%) and 87% (86%, 87%), respectively. CONCLUSION: Fully-automated detection and assessment of AAA on CT is feasible and accurate. There was a strong statistical association between the presence of AAA and the quantity of abdominal aortic calcified atherosclerotic plaque.

Comparison of MiraLAX and magnesium citrate for bowel preparation at CT colonography.

PURPOSE: To compare MiraLAX, a hypo-osmotic lavage, and magnesium citrate (MgC), a hyper-osmotic agent for bowel preparation at CTC. METHODS: 398 total screening CTC studies were included in this retrospective, single institution study. 297 underwent preparation with a double-dose MgC regimen (mean age, 61 ± 5.5 years; 142 male/155 female) and 101 with 8.3 oz (equivalent to 238 g PEG) of MiraLAX (mean age, 60 ± 9.6 years; 45 male/56 female). Oral contrast for tagging purposes was utilized in both regimens. Studies were retrospectively analyzed for residual fluid volume and attenuation by automated analysis, as well for subjective oral contrast coating of the normal colonic wall and polyps. 50 patients underwent successive CTC studies utilizing each agent (mean, 6.1 ± 1.7 years apart), allowing for intra-patient comparison. Chi-squared, Fisher's exact, McNemar, and t-tests were used for data comparison. RESULTS: Residual fluid volume (as percentage of total colonic volume) and fluid density was 7.2 ± 4.2% and 713 ± 183 HU for the MgC cohort and 8.7 ± 3.8% and 1044 HU ± 274 for the MiraLAX cohort, respectively (p = 0.001 and p < 0.001, respectively). Similar results were observed for the intra-patient cohort. Colonic wall coating negatively influencing interpretation was noted in 1.7% of MgC vs. 6.9% of MiraLAX examinations (p = 0.008). Polyps were detected in 12% of all MgC vs. 16% of all MiraLAX CTCs (p = 0.29). CONCLUSION: CTC bowel preparation with the hypo-osmotic MiraLAX agent appears to provide acceptable diagnostic quality that is comparable to the hyper-osmotic MgC agent, especially when factoring in patient safety and tolerance.

Stercoral colitis: CT imaging findings and clinical risk factors.

PURPOSE: To describe and update stercoral colitis clinical risk factors, relative frequency, location, and CT imaging features correlated with surgical and pathological results. METHODS: CT reports over a 5-year period (05/2017-05/2022) at a single medical center were searched. Main inclusion criteria were luminal distention with formed stool, wall thickening, and surrounding inflammation. Positive cases were graded as mild (early or developing stercoral colitis) versus moderate-to-severe based on CT findings. Medical records were reviewed for risk factors and outcome data in moderate-to-severe cases. P-values were tabulated for comparison. RESULTS: 545 total cases (71 (60, 82) years, 278 males) were identified on CT, including 452 mild (82.9%) and 93 moderate-to-severe cases (17%, 67 (55, 79) years, 48 females). Twenty cases showed evidence of perforation (3.7% total cohort, 22% moderate-to-severe cohort). Diagnosis as an incidental finding was frequent (46.0% of mild cases). Most cases involved the rectum (97.6% of mild cohort and 69% of moderate-to-severe cohort). The sigmoid was involved in 31% of moderate-to-severe cases, but 95% of the perforated subcohort (19/20, 13/20 without rectal involvement). Among the moderate-to-severe cohort, perforation was associated with slightly increased wall thickness (6.4 vs. 5.7 mm, p = 0.03), opioid use (50 vs. 23%, p = 0.04), and disease-specific mortality (11 vs. 0%, p =0.04). Perforation was less associated with major neurocognitive disorders (20 vs. 60%, p = 0.003), institutionalized status (5 vs. 38%, p = 0.005), and a prescribed bowel regimen (30 vs. 63%, p = 0.01). CONCLUSION: Stercoral colitis may be under-reported. Perforation tends to favor sigmoid involvement and a less traditional patient cohort.

Use of Spinal Cord Stimulators in Patients With Pacemakers or Implantable Cardiac Defibrillators: A Review of Documented Accounts of Interference.

OBJECTIVES: To assess the currently available evidence regarding associations between spinal cord stimulator (SCS) lead type, clinical indications for device placement, and interference between SCSs and cardiac pacemakers (CPMs)/implantable cardioverter-defibrillators (ICDs). STUDY DESIGN: Review of case reports and original research studies assessing the interference between SCS and CPM/ICD. MATERIALS AND METHODS: PubMed and Cochrane databases were searched for articles commenting on the interference between SCS and CPM/ICD. The search criteria which generated the greatest number of relevant studies was (spinal cord stimulator AND [pacemaker OR implantable cardioverter defibrillator]). Additional, empiric review was conducted using JSTOR, ScienceDirect, and EBSCOhost databases; however, no additional eligible studies were identified. Data were extracted, summarized into tables, and quantitatively analyzed using LibreTexts and MedCalc software. RESULTS: There was no statistically significant interference observed between SCS and CPM/ICD devices in patients regardless of indication for SCS placement and SCS lead polarity. LIMITATIONS: Limited by variability of patient cases and variability in maximum frequency and amplitude of SCS devices tried in individual cases. Also limited by small sample size and the absence of a standard definition for device interference across studies. CONCLUSIONS: Interference between cardiac devices and SCSs is a rare occurrence. As there are currently no published guidelines, devices should be interrogated on a case-by-case basis in the SCS trial period (if implanted after cardiac device), during permanent implantation, and during scheduled follow-up visits. Peri-operative testing should include increasing the SCS settings to maximally tolerated levels with cardiac device set at its maximum sensitivity.

Intrathecal Drug Delivery for the Treatment of Cancer-Associated Chronic Pain in Children.

OBJECTIVES: Management of refractory cancer-associated pain can be particularly challenging. Regional anesthesia is an alternative modality to treat acute and chronic refractory pain. Intrathecal (IT) drug delivery of opioids and other adjuncts has been used to treat refractory cancer-associated pain. This method has been shown to be relatively safe and effective, often associated with fewer systemic side effects when compared to oral or IV opioid administration. While intrathecal drug delivery systems (IDDS) are regularly used in the adult cancer population for the treatment of refractory, chronic pain, there is limited evidence of similar use in the pediatric setting. MATERIALS AND METHODS: We performed a systematic review using conventional Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology to identify studies reporting IT drug delivery for the treatment of pediatric cancer-related pain. The primary outcome was satisfaction with analgesia categorized as "satisfactory" or "unsatisfactory." Functional benefits, previous systemic pharmaceutical interventions, previous non-IT regional interventions, indication for IT drug delivery, IT drugs used, and method of delivery were collected. RESULTS: A total of 11 studies were identified, describing 16 patients with cancer-related pain treated with IT drug delivery. The average age of the cohort was 12.25 years, with ages ranging from 3 to 19 years. Most patients were adolescent (10/16). All patients had cancer diagnoses, with most patients suffering from solid tumor pain (14/16). Nearly all patients achieved satisfactory analgesia through IT drug delivery (15/16) and most reported functional benefits in addition to analgesia (13/16). Majority received IT drugs via external catheters (9/16). One severe complication of respiratory depression was reported, which resolved following naloxone administration. CONCLUSIONS: There exist children with cancer whose pain is refractory to the standard approaches and may benefit from IT drug delivery. The existing data, although limited and of low tier evidence, suggest that IT drug delivery has been effective in the pediatric cancer population.

Controlled aggregation enhances immunomodulatory potential of mesenchymal stromal cell aggregates.

Human mesenchymal stromal cells (MSCs) are promising candidates for cell therapy due to their ease of isolation and expansion and their ability to secrete antiapoptotic, pro-angiogenic, and immunomodulatory factors. Three-dimensional (3D) aggregation "self-activates" MSCs to augment their pro-angiogenic and immunomodulatory potential, but the microenvironmental features and culture parameters that promote optimal MSC immunomodulatory function in 3D aggregates are poorly understood. Here, we generated MSC aggregates via three distinct methods and compared them with regard to their (a) aggregate structure and (b) immunomodulatory phenotype under resting conditions and in response to inflammatory stimulus. Methods associated with fast aggregation kinetics formed aggregates with higher cell packing density and reduced extracellular matrix (ECM) synthesis compared to those with slow aggregation kinetics. While all three methods of 3D aggregation enhanced MSC expression of immunomodulatory factors compared to two-dimensional culture, different aggregation methods modulated cells' temporal expression of these factors. A Design of Experiments approach, in which aggregate size and aggregation kinetics were systematically covaried, identified a significant effect of both parameters on MSCs' ability to regulate immune cells. Compared to small aggregates formed with fast kinetics, large aggregates with slow assembly kinetics were more effective at T-cell suppression and macrophage polarization toward anti-inflammatory phenotypes. Thus, culture parameters including aggregation method, kinetics, and aggregate size influence both the structural properties of aggregates and their paracrine immunomodulatory function. These findings underscore the utility of engineering strategies to control properties of 3D MSC aggregates, which may identify new avenues for optimizing the immunomodulatory function of MSC-based cell therapies.

Radiotherapy-Specific Chronic Pain Syndromes in the Cancer Population: An Evidence-Based Narrative Review.

While radiation therapy is increasingly utilized in the treatment paradigm of many solid cancers, the chronic effects of radiation therapies are poorly characterized. Notably, understanding radiation-specific chronic pain syndromes is paramount given that the diagnosis and management of these conditions can serve to prevent long-standing functional impairments, optimize quality of life, and even allow for continued radiotherapy candidacy. These radiation-specific chronic pain phenomena include dermatitis, mucositis, enteritis, connective tissue fibrosis, lymphedema, and neuropathic pain syndromes. It is necessary to maintain a low threshold of suspicion for appropriately diagnosing these conditions as there exists a variance in when these symptoms arise after radiation. However, we present key epidemiological data delineating vulnerable cancer populations for each pain syndrome along with the available evidence for the management for each specific condition.

Interventional Radiofrequency Treatment for the Sympathetic Nervous System: A Review Article.

INTRODUCTION: Interventional techniques such as radiofrequency (RF) treatment can be used to interrupt pain signals transmitted through the sympathetic nervous system (SNS). RF treatments including the pulsed (PRF) and continuous (CRF) modalities show enhanced control over lesion size and enhanced ability to confirm accurate positioning compared to other interventional methods. PRF also acts to reduce the area of the lesion. In this article, we characterize the currently available evidence supporting the use and efficacy of RF treatments in sympathetically mediated pain (SMP) conditions. STUDY DESIGN: A comprehensive literature review. METHODS: A PubMed and Cochrane Library database search was performed for human studies applying RF treatment at sympathetic sites (sphenopalatine ganglion, stellate ganglion, cervical, thoracic, or lumbar sympathetic ganglia, celiac plexus, splanchnic nerves, superior hypogastric plexus, and ganglion impar) between January 1970 to May 2020. Data were extracted, summarized into tables, and qualitatively analyzed. RESULTS: PRF and CRF both show promise in relieving SMP conditions, such as complex regional pain syndrome (CRPS), pain in the perineal region, headache and facial pain, and oncologic and non-oncologic abdominal pain, in addition to other types of pain, with minimal complications. Furthermore, in most comparative studies, outcomes using RF treatments exceeded other interventional techniques, such as anesthetic block and chemical neurolysis. CONCLUSIONS: RF treatments can be effective in carefully selected patients who are refractory to conservative management. However, further randomized controlled studies are needed prior to implementing it into common practice.

Use of Cryotherapy for Managing Chronic Pain: An Evidence-Based Narrative.

BACKGROUND: Cryotherapy has been used to reduce chronic pain for many years due in part to its ease of use, affordability, and simplicity. It can be applied either locally (e.g., ice packs) or non-locally (e.g., partial and whole-body cryotherapy) depending on the location of the pain. OBJECTIVES: To determine the overall effectiveness of cryotherapy at reducing chronic pain by characterizing the currently available evidence supporting the use and effects of cryotherapy on chronic pain associated with chronic diseases. STUDY DESIGN: A narrative review of original research studies assessing the efficacy of cryotherapy in alleviating chronic pain. METHODS: A PubMed database search was performed to find human studies between the years 2000 and 2020 that included the application of cryotherapy in patients with chronic pain associated with chronic diseases. A review of the relevant references was also performed to gather more articles. Data was extracted, summarized into tables, and qualitatively analyzed. RESULTS: Twenty-five studies (22 randomized controlled trials, one prospective analysis, 1 one-group pretest/posttest study, and one case-control study) were included after the literature search. Both local and non-local cryotherapy applications show promise in reducing chronic pain associated with various chronic diseases including those of rheumatic and degenerative origin. Cryotherapy appears to be a safe therapy in carefully selected patients, with only minimal adverse effects reported in the literature. LIMITATIONS: Meta-analysis was not possible given the many differences between studies. Cross-study data homogenization and comparison between studies proved fairly difficult due to the lack of standardized studies, various uses and practice types of cryotherapy, and lack of control groups in some studies. CONCLUSIONS: Local and non-local cryotherapy can be low-risk and easy treatment options to add in the management of chronic pain in carefully selected patients. However, long-term effects, a standardized approach, and careful study of other chronic pain syndromes should be considered in future research to further support the use of cryotherapy in the management of chronic pain.

Inhibition of the CXCL12/CXCR4 axis prevents periurethral collagen accumulation and lower urinary tract dysfunction in vivo.

BACKGROUND: Several studies show that prostatic fibrosis is associated with male lower urinary tract dysfunction (LUTD). Development of fibrosis is typically attributed to signaling through the transforming growth factor ß (TGF-ß) pathway, but our laboratory has demonstrated that in vitro treatment of human prostatic fibroblasts with the C-X-C motif chemokine ligand 12 (CXCL12) chemokine stimulates myofibroblast phenoconversion and that CXCL12 has the capacity to activate profibrotic pathways in these cells in a TGF-ß-independent manner. We have previously reported that feeding mice high-fat diet (HFD) results in obesity, type II diabetes, increased prostatic fibrosis, and urinary voiding dysfunction. The purpose of this study was to test the hypothesis that in vivo blockade of the CXCL12/CXCR4 axis would inhibit the development of fibrosis-mediated LUTD in HFD-fed mice. METHODS: Two-month-old male senescence-accelerated mouse prone-6 mice were fed either a HFD or low-fat diet (LFD) for 8 months. Half of each dietary group were given constant access to normal water or water that contained the C-X-C chemokine receptor type 4 (CXCR4; CXCL12 receptor) antagonist CXCR4AIII. At the conclusion of the study, mice were weighed, subjected to oral glucose tolerance testing and cystometry, and lower urinary tract tissues collected and assessed for collagen content. RESULTS: HFD-fed mice became significantly obese, insulin resistant, and hyperglycemic, consistent with acquisition of metabolic syndrome, compared with LFD-fed mice. Anesthetized cystometry demonstrated that HFD-fed mice experienced significantly longer intercontractile intervals and greater functional bladder capacity than LFD-fed mice. Immunohistochemistry demonstrated high levels of CXCR4 and CXCR7 staining in mouse prostate epithelial and stromal cells. Picrosirius red staining indicated significantly greater periurethral collagen deposition in the prostates of HFD than LFD-fed mice. Treatment with the CXCR4 antagonist CXCR4AIII did not affect acquisition of metabolic syndrome but did reduce both urinary voiding dysfunction and periurethral prostate collagen accumulation. CONCLUSIONS: This is the first study to report that obesity-induced lower urinary tract fibrosis and voiding dysfunction can be repressed by antagonizing the activity of the CXCR4 chemokine receptor in vivo. These data suggest that targeting the CXCL12/CXCR4 signaling pathway may be a clinical option for the prevention or treatment of human male LUTD.

Controlled Self-assembly of Stem Cell Aggregates Instructs Pluripotency and Lineage Bias.

Stem cell-derived organoids and other 3D microtissues offer enormous potential as models for drug screening, disease modeling, and regenerative medicine. Formation of stem/progenitor cell aggregates is common in biomanufacturing processes and critical to many organoid approaches. However, reproducibility of current protocols is limited by reliance on poorly controlled processes (e.g., spontaneous aggregation). Little is known about the effects of aggregation parameters on cell behavior, which may have implications for the production of cell aggregates and organoids. Here we introduce a bioengineered platform of labile substrate arrays that enable simple, scalable generation of cell aggregates via a controllable 2D-to-3D "self-assembly". As a proof-of-concept, we show that labile substrates generate size- and shape-controlled embryoid bodies (EBs) and can be easily modified to control EB self-assembly kinetics. We show that aggregation method instructs EB lineage bias, with faster aggregation promoting pluripotency loss and ectoderm, and slower aggregation favoring mesoderm and endoderm. We also find that aggregation kinetics of EBs markedly influence EB structure, with slower kinetics resulting in increased EB porosity and growth factor signaling. Our findings suggest that controlling internal structure of cell aggregates by modifying aggregation kinetics is a potential strategy for improving 3D microtissue models for research and translational applications.

Maternal morbidity in patients with morbidly adherent placenta treated with and without a standardized multidisciplinary approach.

OBJECTIVE: The purpose of this study was to test the hypothesis that a standardized multidisciplinary treatment approach in patients with morbidly adherent placenta, which includes accreta, increta, and percreta, is associated with less maternal morbidity than when such an approach is not used (nonmultidisciplinary approach). STUDY DESIGN: A retrospective cohort study was conducted with patients from 3 tertiary care hospitals from July 2000 to September 2013. Patients with histologically confirmed placenta accreta, increta, and percreta were included in this study. A formal program that used a standardized multidisciplinary management approach was introduced in 2011. Before 2011, patients were treated on a case-by-case basis by individual physicians without a specific protocol (nonmultidisciplinary group). Estimated blood loss, transfusion of packed red blood cells, intraoperative complications (eg, vascular, bladder, ureteral, and bowel injury), neonatal outcome, and maternal postoperative length of hospital stay were compared between the 2 groups. RESULTS: Of 90 patients with placenta accreta, 57 women (63%) were in the multidisciplinary group, and 33 women (37%) were in the nonmultidisciplinary group. The multidisciplinary group had more cases with percreta (P = .008) but experienced less estimated blood loss (P = .025), with a trend to fewer blood transfusions (P = .06), and were less likely to be delivered emergently (P = .001) compared with the nonmultidisciplinary group. Despite an approach of indicated preterm delivery at 34-35 weeks of gestation, neonatal outcomes were similar between the 2 groups. CONCLUSION: The institution of a standardized approach for patients with morbidly adherent placentation by a specific multidisciplinary team was associated with improved maternal outcomes, particularly in cases with more aggressive placental invasion (increta or percreta), compared with a historic nonmultidisciplinary approach. Our standardized approach was associated with fewer emergency deliveries.