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.

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.

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.

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.