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.     

Best practices to optimize utilization of the National Living Donor Assistance Center for the financial assistance of living organ donors

Living organ donors face direct costs when donating an organ, including transportation, lodging, meals, and lost wages. For those most in need, the National Living Donor Assistance Center (NLDAC) provides reimbursement to defray travel and subsistence costs associated with living donor evaluation, surgery, and follow‐up. While this program currently supports 9% of all US living donors, there is tremendous variability in its utilization across US transplant centers, which may limit patient access to living donor transplantation. Based on feedback from the transplant community, NLDAC convened a Best Practices Workshop on August 2, 2018, in Arlington, VA, to identify strategies to optimize transplant program utilization of this valuable resource. Attendees included team members from transplant centers that are high NLDAC users; the NLDAC program team; and Advisory Group members. After a robust review of NLDAC data and engagement in group discussions, the workgroup identified concrete best practices for administrative and transplant center leadership involvement; for individuals filing NLDAC applications at transplant centers; and to improve patient education about potential financial barriers to living organ donation. Multiple opportunities were identified for intervention to increase transplant programs’ NLDAC utilization and reduce financial burdens inhibiting expansion of living donor transplantation in the United States.     

Loss-of-Function Mutations in the ALPL Gene Presenting with Adult Onset Osteoporosis and Low Serum Concentrations of Total Alkaline Phosphatase

Hypophosphatasia (HPP) is a rare inherited disorder characterized by rickets and low circulating concentrations of total alkaline phosphatase (ALP) caused by mutations in ALPL. Severe HPP presents in childhood but milder forms can present in adulthood. The prevalence and clinical features of adult HPP are poorly defined. The aim of this study was to evaluate the prevalence and clinical significance of low serum total alkaline phosphatase (ALP) levels in a clinic-based population of adult osteoporotic patients. We searched for patients with low ALP in a cohort of 3285 patients referred to an osteoporosis clinic over a 10-year period and performed mutation screening of ALPL in those with low ALP (≤40 U/L) on two or more occasions. These individuals were matched with four clinic controls with a normal ALP. We also evaluated the prevalence of low ALP and ALPL mutations in 639 individuals from the general population from the same region. We identified 16/3285 (0.49%) clinic patients with low ALP and 14 (87.5%) had potentially pathogenic variants in ALPL. Eight of these individuals were heterozygous for mutations previously described in HPP and 2 were heterozygous for novel mutations (p.Arg301Trp and p.Tyr101X). These mutations were not found in clinic controls or in the general population. Eight patients with low ALP, including 4 with ALPL mutations, were treated with bisphosphonates for an average of 6.5 years. In these individuals, the rate of fractures during treatment was comparable to that in normal ALP clinic controls who were treated with bisphosphonates. We conclude that heterozygous loss-of-function mutations in ALPL are common in osteoporosis patients with low ALP. Further studies are required to determine how best these individuals should be treated. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

A systematic review of hospitalization resulting from medicine-related problems in adult patients

Aims

Medicine-related problems (MRPs) represent a major issue leading to hospitalization, especially in adult and elderly patients. The aims of this review are to investigate the prevalence, causes and major risk factors for MRPs leading to hospitalization in adult patients and to identify the main medicine classes involved.

Methods

Studies were identified through electronic searches of Medline, Embase, Scopus and International Pharmaceutical Abstracts between January 2000 and May 2013. A systematic review was conducted of both retrospective and prospective studies. Studies included were those involving hospitalization resulting from MRPs in adults (≥18 years old), whereas studies excluded were those investigating drug misuse and abuse and studies investigating MRPs in hospitalized patients. Data analysis was performed using SPSS version 20.

Results

Forty-five studies were identified, including 21 that investigated hospitalization resulting from adverse drug reactions, six studies that investigated hospitalization due to adverse drug events and 18 studies that investigated hospitalization due to MRPs. The median prevalence rates of hospitalization resulting from adverse drug reactions, adverse drug events and MRPs were 7% (interquartile range, 2.4–14.9%), 4.6% (interquartile range, 2.85–16.6%) and 12.1% (interquartile range, 6.43–22.2%), respectively. The major causes contributing to MRPs were adverse drug reactions and noncompliance. In addition, the major risk factors associated with MRPs were old age, polypharmacy and comorbidities. Moreover, the main classes of medicines implicated were medicines used to treat cardiovascular diseases and diabetes.

Conclusions

Hospitalization due to MRPs had a high prevalence, in the range of 4.6–12.1%. Most MRPs encountered were prevalent among adult patients taking medicines for cardiovascular diseases and diabetes.     

A Critical Role for Thioredoxin-Interacting Protein in Diabetes-Related Impairment of Angiogenesis

Impaired angiogenesis in ischemic tissue is a hallmark of diabetes. Thioredoxin-interacting protein (TXNIP) is an exquisitely glucose-sensitive gene that is overexpressed in diabetes. As TXNIP modulates the activity of the key angiogenic cytokine vascular endothelial growth factor (VEGF), we hypothesized that hyperglycemia-induced dysregulation of TXNIP may play a role in the pathogenesis of impaired angiogenesis in diabetes. In the current study, we report that high glucose–mediated overexpression of TXNIP induces a widespread impairment in endothelial cell (EC) function and survival by reducing VEGF production and sensitivity to VEGF action, findings that are rescued by silencing TXNIP with small interfering RNA. High glucose–induced EC dysfunction was recapitulated in normal glucose conditions by overexpressing either TXNIP or a TXNIP C247S mutant unable to bind thioredoxin, suggesting that TXNIP effects are largely independent of thioredoxin activity. In streptozotocin-induced diabetic mice, TXNIP knockdown to nondiabetic levels rescued diabetes-related impairment of angiogenesis, arteriogenesis, blood flow, and functional recovery in an ischemic hindlimb. These findings were associated with in vivo restoration of VEGF production to nondiabetic levels. These data implicate a critical role for TXNIP in diabetes-related impairment of ischemia-mediated angiogenesis and identify TXNIP as a potential therapeutic target for the vascular complications of diabetes.     

Addressing medication errors in an adult oncology department in Saudi Arabia: A qualitative study

ObjectiveThere is a wide range of strategies that could help in minimizing medication errors during healthcare delivery. We undertook a qualitative study to identify recommended solutions to minimize medication errors in an adult oncology department in Saudi Arabia from the perspectives of healthcare professionals.MethodsThis was a qualitative study conducted in an adult oncology department in Saudi Arabia. After obtaining the required ethical approvals and written consents from the participants, seven focus group discussions were carried out for data collection. A stratified purposive sampling strategy was used to recruit medical doctors, pharmacists, and nurses. NVivo Pro version 11 was used for data analyses. Inductive content analysis was adopted in the coding of collected data.ResultOur study showed that improving organizational support, staff education, and communication could help in minimizing medication errors in the adult oncology department.ConclusionThe adoption of multiple strategies is required to improve the safety of the medication process in the adult oncology department. We argue that the availability of supportive leadership should be prioritized as it plays a crucial role in determining the effectiveness and efficiency of both staff education and communication.