The risks of radiation therapy and lymphedema in shoulder surgery

BackgroundRadiation therapy has proven efficacy for cancer treatment but is not without short- and long-term side effects, including radiation-induced lymphedema. There has been limited evidence on the secondary effects of prior radiation therapy on shoulder surgery. The purpose of this study is to evaluate the short-term outcomes of shoulder arthroplasty and rotator cuff repair (RCR) in patients who have undergone ipsilateral radiation therapy and/or have preoperative upper extremity lymphedema.MethodsDuke Enterprise Data Unified Content Explorer was used to query for patients who underwent RCR at our institution. Patients with radiation therapy for breast or lung cancer prior to ipsilateral RCR or shoulder arthroplasty were included. Patients with less than 2 years of follow-up were excluded. Data variables included primary tumor type, dates of cancer diagnoses, radiation treatment, axillary lymph node dissection (aLND), presence of lymphedema, index shoulder operations, most recent follow-up, and surgical and medical complications within the 90-day postoperative period. Additional oncologic variables included total Gray (Gy) delivered.ResultsTwenty-one patients underwent radiation therapy and subsequent shoulder arthroplasty or RCR (13 RCR, 3 total shoulder arthroplasty, 5 reverse shoulder arthroplasty). There were 20 females and 1 male with an average age of 65.6 years (47-82) and average clinical follow-up of 4.4 years (2.0-7.4). Oncologic diagnoses included lung (4.8%) and breast (95.2%) cancer. Average radiation dose delivered was 53.3 Gy (38.5-64) in the cohort. The average time from last external beam radiation therapy to shoulder surgery was 4.3 years (0.3-18.0). One of 13 (7.7%) 90-day postoperative complications was reported in the RCR cohort: a superficial vein thrombosis. One of 8 (12.5%) 90-day complications was reported in the arthroplasty cohort: a clinically suspected but radiographically absent acromial stress fracture in a reverse shoulder arthroplasty that did not require operative intervention. Overall, there were no revisions, reoperations, or shoulder-related unplanned inpatient 90-day readmissions. Among 10 patients with prior aLND, 3 (30%) (2 RCR, 1 arthroplasty) experienced new or worsening upper extremity lymphedema within the immediate postoperative period.ConclusionA minority of patients having undergone prior radiation therapy and aLND who subsequently underwent ipsilateral shoulder surgery experienced worsening subjective upper extremity lymphedema. Although 10% of these radiation therapy patients experienced minor complications within 90 days of their shoulder surgery, none were severe enough to merit inpatient admission or revision surgery.     

von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively

Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.     

Predictors of hospital transfer and associated risks of mortality in acute pancreatitis

BackgroundThere is limited research in prognosticators of hospital transfer in acute pancreatitis (AP). Hence, we sought to determine the predictors of hospital transfer from small/medium-sized hospitals and outcomes following transfer to large acute-care hospitals.MethodsUsing the 2010–2013 Nationwide Inpatient Sample (NIS), patients ≥18 years of age with a primary diagnosis of AP were identified. Hospital size was classified using standard NIS Definitions. Multivariable analyses were performed for predictors of “transfer-out” from small/medium-sized hospitals and mortality in large acute-care hospitals.ResultsAmong 381,818 patients admitted with AP to small/medium-sized hospitals, 13,947 (4%) were transferred out to another acute-care hospital. Multivariable analysis revealed that older patients (OR = 1.04; 95%CI 1.03–1.06), men (OR = 1.15; 95%CI 1.06–1.24), lower income quartiles (OR = 1.54; 95%CI 1.35–1.76), admission to a non-teaching hospital (OR = 3.38; 95%CI 3.00–3.80), gallstone pancreatitis (OR = 3.32; 95%CI 2.90–3.79), pancreatic surgery (OR = 3.14; 95%CI 1.76–5.58), and severe AP (OR = 3.07; 95%CI 2.78–3.38) were predictors of “transfer-out”. ERCP (OR = 0.53; 95%CI 0.43–0.66) and cholecystectomy (OR = 0.14; 95%CI 0.12–0.18) were associated with decreased odds of “transfer-out”.Among 507,619 patients admitted with AP to large hospitals, 31,058 (6.1%) were “transferred-in” from other hospitals. The mortality rate for patients “transferred-in” was higher than those directly admitted (2.54% vs. 0.91%, p < 0.001). Multivariable analysis revealed that being “transferred-in” from other hospitals was an independent predictor of mortality (OR = 1.47; 95% CI 1.22–1.77).ConclusionsPatients with AP transferred into large acute-care hospitals had a higher mortality than those directly admitted likely secondary to more severe disease. Early implementation of published clinical guidelines, triage, and prompt transfer of high-risk patients may potentially offset these negative outcomes.     

Detection of circulating crosslinked fibrin derivatives by a heat extraction-SDS gradient gel electrophoretic technique

A technique has been developed to identify and quantitate unique plasmic degradation products of crosslinked fibrin in plasma. In this method, fibrin derivatives are extracted by heat precipitation and dissolved with disulfide bond reduction, after which the crosslinked gamma-gamma chain remnants are identified by SDS-polyacrylamide gradient gel electrophoresis and quantitated by densitometric analysis. A heterogenous group of gamma-gamma chains with molecular weights between 100,000 and 76,000 daltons was identified in lysates of crosslinked fibrin during plasmic degradation in vitro. Three stages of crosslinked fibrin degradation have been arbitrarily defined based primarily on the extent of degradation of these gamma-gamma polypeptide chains. As little as 20 microgram of crosslinked fibrin digests added to 1 ml of normal plasma could be detected by the heat-extraction--gel- electrophoresis technique, identifying the gamma-gamma derivatives with molecular weights of 96,000, 86,000, 82,000, and 76,000 daltons. Plasmic derivatives of gamma-gamma chains were not found in normal plasma, but they were identified in the plasma of patients with disseminated intravascular coagulation and deep-vein thrombosis, both before and in increased quantity during successful thrombolytic therapy.     

Circulating interleukin-6 is associated with disease progression,but not cachexia in pancreatic cancer

Background

Cachexia is a wasting syndrome characterized by involuntary loss of >5% body weight due to depletion of adipose and skeletal muscle mass. In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown. In this study we sought to evaluate IL-6 as a biomarker of cancer cachexia while accounting for disease progression.

Achieving Health Equity in Embedded Pragmatic Trials for People Living with Dementia and Their Family Caregivers

Embedded pragmatic clinical trials (ePCTs) advance research on Alzheimer's disease/Alzheimer's disease and related dementias (AD/ADRD) in real-world contexts; however, health equity issues have not yet been fully considered, assessed, or integrated into ePCT designs. Health disparity populations may not be well represented in ePCTs without special efforts to identify and successfully recruit sites of care that serve larger numbers of these populations. The National Institute on Aging (NIA) Imbedded Pragmatic Alzheimer's disease (AD) and AD-Related Dementias (AD/ADRD) Clinical Trials (IMPACT) Collaboratory's Health Equity Team will contribute to the overall mission of the collaboratory by developing and implementing strategies to address health equity in the conduct of ePCTs and ensure the collaboratory is a national resource for all Americans with dementia. As a first step toward meeting these goals, this article reviews what is currently known about the inclusion of health disparities populations of people living with dementia (PLWD) and their caregivers in ePCTs, highlights unique challenges related to health equity in the conduct of ePCTs, and suggests priority areas in the design and implementation of ePCTs to increase the awareness and avoidance of pitfalls that may perpetuate and magnify healthcare disparities. J Am Geriatr Soc 68:S8–S13, 2020 .     

Water-dispersible magnetic carbon nanotubes as T2-weighted MRI contrast agents

An efficient MRI T₂-weighted contrast agent incorporating a potential liver targeting functionality was synthesized via the combination of superparamagnetic iron oxide (SPIO) nanoparticles with multiwalled carbon nanotubes (MWCNTs). Poly(diallyldimethylammonium chloride) (PDDA) was coated on the surface of acid treated MWCNTs via electrostatic interactions and SPIO nanoparticles modified with a potential targeting agent, lactose–glycine adduct (Lac–Gly), were subsequently immobilized on the surface of the PDDA–MWCNTs. A narrow magnetic hysteresis loop indicated that the product displayed superparamagnetism at room temperature which was further confirmed by ZFC (zero field cooling)/FC (field cooling) curves measured by SQUID. The multifunctional MWCNT-based magnetic nanocomposites showed low cytotoxicity in vitro to HEK293 and Huh7 cell lines. Enhanced T₂ relaxivities were observed for the hybrid material (186 mm⁻¹ s⁻¹) in comparison with the pure magnetic nanoparticles (92 mm⁻¹ s⁻¹) due to the capacity of the MWCNTs to “carry” more nanoparticles as clusters. More importantly, after administration of the composite material to an in vivo liver cancer model in mice, a significant increase in tumor to liver contrast ratio (277%) was observed in T₂ weighted magnetic resonance images.     

Roles of notch signalling in mandibular condylar cartilage

Importance

Notch proteins are cell surface transmembrane spanning receptors which mediate critically important cellular functions through direct cell–cell contact. Interactions between Notch receptors and their ligands regulate cell fate decisions such differentiation, proliferation and apoptosis in numerous tissues. We have previously shown using immunohistochemistry that Notch1 is localized primarily to the prechondroblastic (chondroprogenitor) layer of the mandibular condylar cartilage (MCC).

Objective

To test if Notch signalling changes patterns of proliferation and differentiation in the MCC and to investigate if Notch signalling acts downstream of Fibroblast Growth Factor 2 (FGF-2).

Methods

Condylar cartilage explants were cultured over serum-free DMEM containing either 0 or 50 nM DAPT, a Notch signal inhibitor. Explants were used for RNA extraction and immunohistochemistry.

Results

Analysis of gene array data demonstrated that the perichondrial layer of the MCC is rich in Notch receptors (Notch 3 and 4) and Notch ligands (Jagged and Delta) as well as various downstream facilitators of Notch signalling. Disruption of Notch signalling in MCC explants decreased proliferation (Cyclin B1 expression) and increased chondrocyte differentiation (Sox9 expression). Moreover, we found that the actions of FGF-2 in MCC are mediated in part by Notch signalling.

Conclusion

These data suggest that Notch signalling contributes to the regulation of proliferation and differentiation in the MCC.     

Alterations in the thyroids of rats treated for long periods with di-(2-ethylhexyl) phthalate or with hypolipidaemic agents

Treatment of rats for periods of 3 months or longer with the hypolipidaemic drugs clofibrate and fenofibrate or with the plasticiser di-(2-ethylhexyl) phthalate causes alterations in the thyroid. The colloid is shrunken and contains calcium-rich inclusions. Electron microscopy shows increases in the number and size of lysosomes, hypertrophy of the Golgi apparatus and dilation of the rough endoplasmic reticulum. These changes are consistent with persistent hyperactivity in the gland.