Timing of parathyroidectomy for tertiary hyperparathyroidism with end-stage renal disease: A cost-effectiveness analysis

BackgroundTertiary hyperparathyroidism associated with end-stage renal disease is characterized by progression from secondary hyperparathyroidism to an autonomous overproduction of parathyroid hormone that leads to adverse health outcomes. Rates of parathyroidectomy (PTX) have decreased with the use of calcimimetics. Optimal timing of PTX in relation to kidney transplant remains controversial. We aimed to identify the most cost-effective strategy for patients with tertiary hyperparathyroidism undergoing kidney transplant.MethodsWe constructed a patient level state transition microsimulation to compare 3 management schemes: cinacalcet with kidney transplant, cinacalcet with PTX before kidney transplant, or cinacalcet with PTX after kidney transplant. Our base case was a 55-year-old on dialysis with tertiary hyperparathyroidism awaiting kidney transplant. Outcomes, including quality-adjusted life years, surgical complications, and mortality, were extracted from the literature, and costs were estimated using Medicare reimbursement data.ResultsOur base case analysis demonstrated that cinacalcet with PTX before kidney transplant was dominant, with a lesser cost of $399,287 and greater quality-adjusted life years of 10.3 vs $497,813 for cinacalcet with PTX after kidney transplant (quality-adjusted life years 9.4) and $643,929 for cinacalcet with kidney transplant (quality-adjusted life years 7.4).ConclusionCinacalcet alone with kidney transplant is the least cost-effective strategy. Patients with end-stage renal disease-related tertiary hyperparathyroidism should be referred for PTX, and it is most cost-effective if performed prior to kidney transplant.     

Optimizing the fellowship interview process: Perspectives from applicants and program directors of the comprehensive endocrine surgery fellowship program

BackgroundApproximately 80% of general surgery residents undertake some form of fellowship training. Our objective was to characterize goals and burdens of the interview process among applicants to Comprehensive Endocrine Surgery Fellowship programs.MethodsParticipants included trainees from 2013 to 2019. Results for ranking questions are presented as a mean rank reported out of the total number of selections.ResultsResponse rate was 54% (n = 75). The most important goal for interviews was meeting the faculty (mean rank 2.4/9), followed by “behind the scenes information” and “make a good impression” (mean rank 3.6 and 3.7, respectively). The most substantial burden for the applicant was expense (mean rank 2.1/7), followed by time away from residency (mean rank 3.1/7). The economic burden of 51% of the applicants was $2,500 to $7,500. Geographic location and expense were the top 2 reasons applicants declined offers of interviews. Despite the process, 76% of respondents indicated that no improvements to the interview process are necessary. Alternative strategies such as videoconferencing or centralized interviews received little support (<10%).ConclusionDespite identifying several burdens, survey respondents believed that in-person interviews are an integral component of the fellowship application process. Indeed, 70% of applicants do not have a first-choice program before interviews, and meeting the faculty is ranked as the greatest priority goal. Our data illustrate the importance of individual specialties evaluating and optimizing their own processes for fellowship interviews.     

Re-evaluating Blood Markers as Predictors of Outcome in Multivisceral and Intestinal Transplantation

BackgroundMultivisceral transplant (MVTx) and isolated intestinal transplant (ITx) are complex surgical procedures. The subsequent proinflammatory state in the immediate postoperative period makes interpretation of blood markers difficult.MethodWe aimed to establish the course of various blood markers after MVTx/ITx, and to evaluate their use as diagnostic markers of complications. This was a single center prospective cohort. We analyzed blood markers collected preoperatively, on alternate days for the first postoperative week, and then weekly for 4 weeks. This study was in compliance with The Declaration of Helsinki.ResultsOver a 16-month period (July 2017-October 2018), 20 subjects aged 2 to 67 years with a median age of 24.5 years received MVTx/ITx. Twelve recipients (60%) had an infection. Neutrophil lymphocyte count ratio (NLCR) was higher than established upper limits of normal, regardless of infection status. NLCR and white blood cell count were useful to identify infected MVTx/ITx recipients, with P values <.05 for 2 and 1 of 7 time points post transplant, respectively. Higher preoperative eosinophil% predicted future acute cellular rejection (P value .023).ConclusionsThis is the first study to extensively track the course of blood markers post MVTx/ITx and identified NLCR and white blood cell count as potential diagnostic blood markers of infection.     

Predictive Value of DXA Appendicular Lean Mass for Incident Fractures,Falls, and Mortality,Independent of Prior Falls,FRAX, and BMD: Findings from the Women's Health Initiative (WHI)

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX^®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height²) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height² (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height² was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height² and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height², depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height² and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Early Effects of Abaloparatide on Bone Formation and Resorption Indices in Postmenopausal Women With Osteoporosis

Anabolic osteoporosis drugs improve bone mineral density by increasing bone formation. The objective of this study was to evaluate the early effects of abaloparatide on indices of bone formation and to assess the effect of abaloparatide on modeling-based formation (MBF), remodeling-based formation (RBF), and overflow MBF (oMBF) in transiliac bone biopsies. In this open-label, single-arm study, 23 postmenopausal women with osteoporosis were treated with 80 μg abaloparatide daily. Subjects received double fluorochrome labels before treatment and before biopsy collection at 3 months. Change in dynamic histomorphometry indices in four bone envelopes were assessed. Median mineralizing surface per unit of bone surface (MS/BS) increased to 24.7%, 48.7%, 21.4%, and 16.3% of total surface after 3 months of abaloparatide treatment, representing 5.5-, 5.2-, 2.8-, and 12.9-fold changes, on cancellous, endocortical, intracortical, and periosteal surfaces (p < .001 versus baseline for all). Mineral apposition rate (MAR) was significantly increased only on intracortical surfaces. Bone formation rate (BFR/BS) was significantly increased on all four bone envelopes. Significant increases versus baseline were observed in MBF on cancellous, endocortical, and periosteal surfaces, for oMBF on cancellous and endocortical surfaces, and for RBF on cancellous, endocortical, and intracortical surfaces. Overall, modeling-based formation (MBF + oMBF) accounted for 37% and 23% of the increase in bone-forming surface on the endocortical and cancellous surfaces, respectively. Changes from baseline in serum biomarkers of bone turnover at either month 1 or month 3 were generally good surrogates for changes in histomorphometric endpoints. In conclusion, treatment with abaloparatide for 3 months stimulated bone formation on cancellous, endocortical, intracortical, and periosteal envelopes in transiliac bone biopsies obtained from postmenopausal women with osteoporosis. These increases reflected stimulation of both remodeling- and modeling-based bone formation, further elucidating the mechanisms by which abaloparatide improves bone mass and lowers fracture risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Burosumab for the Treatment of Tumor-Induced Osteomalacia

Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate metabolism, skeletal health, and quality of life. UX023T-CL201 is an ongoing, open-label, phase 2 study investigating the safety and efficacy of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous skeletal hypophosphatemia syndrome (CSHS). Key endpoints were changes in serum phosphorus and osteomalacia assessed by transiliac bone biopsies at week 48. This report focuses on 14 patients with TIO, excluding two diagnosed with X-linked hypophosphatemia post-enrollment and one with CSHS. Serum phosphorus increased from baseline (0.52 mmol/L) and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p < 0.0001). Most measures of osteomalacia were improved at week 48: osteoid volume/bone, osteoid thickness, and mineralization lag time decreased; osteoid surface/bone surface showed no change. Of 249 fractures/pseudofractures detected across 14 patients at baseline, 33% were fully healed and 13% were partially healed at week 144. Patients reported a reduction in pain and fatigue and an increase in physical health. Two patients discontinued: one to treat an adverse event (AE) of neoplasm progression and one failed to meet dosing criteria (receiving minimal burosumab). Sixteen serious AEs occurred in seven patients, and there was one death; all serious AEs were considered unrelated to treatment. Nine patients had 16 treatment-related AEs; all were mild to moderate in severity. In adults with TIO, burosumab exhibited an acceptable safety profile and was associated with improvements in phosphate metabolism and osteomalacia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..     

Kidney Function after Treatment for Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study

BackgroundSurvivors of childhood cancer may be at increased risk for treatment-related kidney dysfunction. Although associations with acute kidney toxicity are well described, evidence informing late kidney sequelae is less robust.MethodsTo define the prevalence of and risk factors for impaired kidney function among adult survivors of childhood cancer who had been diagnosed ≥10 years earlier, we evaluated kidney function (eGFR and proteinuria). We abstracted information from medical records about exposure to chemotherapeutic agents, surgery, and radiation treatment and evaluated the latter as the percentage of the total kidney volume treated with ≥5 Gy (V5), ≥10 Gy (V10), ≥15 Gy (V15), and ≥20 Gy (V20). We also used multivariable logistic regression models to assess demographic and clinical factors associated with impaired kidney function and Elastic Net to perform model selection for outcomes of kidney function.ResultsOf the 2753 survivors, 51.3% were men, and 82.5% were non-Hispanic White. Median age at diagnosis was 7.3 years (interquartile range [IQR], 3.3–13.2), and mean age was 31.4 years (IQR, 25.8–37.8) at evaluation. Time from diagnosis was 23.2 years (IQR, 17.6–29.7). Approximately 2.1% had stages 3–5 CKD. Older age at evaluation; grade ≥2 hypertension; increasing cumulative dose of ifosfamide, cisplatin, or carboplatin; treatment ever with a calcineurin inhibitor; and volume of kidney irradiated to ≥5 or ≥10 Gy increased the odds for stages 3–5 CKD. Nephrectomy was significantly associated with stages 3–5 CKD in models for V15 or V20.ConclusionsWe found that 2.1% of our cohort of childhood cancer survivors had stages 3–5 CKD. These data may inform screening guidelines and new protocol development.     

Evaluation of the Relationship Between Aspects of Medical Complexity and Work Relative Value Units (wRVUs) for Foot and Ankle Surgical Procedures

Work relative value units (wRVUs) have been assigned to current procedural terminology codes in an effort to help establish physician compensation. However, the ability of these to accurately and efficiently capture the time, technical, and perioperative managerial aspects required of various procedures has recently been called into question for several surgical subspecialties. Therefore, the objective of this investigation was to evaluate various measures of medical complexity against wRVUs for foot and ankle surgical procedures. The 2018 American College of Surgeons National Surgical Quality Improvement Program database was utilized to identify and extract data related to the perioperative medical complexity of 16 foot and ankle surgical current procedural terminology codes. We observed a “weak” positive relationship between wRVUs and operation time as defined by a correlation coefficient of 0.234 (p < .001). Other variables associated with medical complexity in the perioperative period were found to significantly vary between wRVUs categories, but these differences were neither consistently nor directly associated with assigned relative values. We conclude that wRVUs might not always represent an efficient means for determining compensation for foot and ankle surgical procedures.