Citations

Background Dynamic and functional abdominal wall reconstruction (FAWR) remains a complex challenge. The ideal flap should have a minimal donor-site morbidity and cover a large surface area with motor and sensory capabilities. The goal was to investigate the feasibility of using a free chimeric flap with anterolateral thigh (ALT) and rectus femoris (RF) components pedicled only on the motor nerve branch. Methods Ten fresh cadavers were dissected with a designed chimeric thigh flap including ALT and RF flaps. Anterolateral thigh was designed and raised with the lateral femoral cutaneous nerve integrated, and the descending branch of the lateral circumflex femoral artery was preserved. Rectus femoris was elevated and the common pedicle was dissected up to the femoral origin. Accompanying motor nerve branches were carefully dissected to their femoral origin. Results Twenty RF flaps were dissected and 9 were harvested as a true chimeric flap with ALT. The mean number of neurovascular bundles associated with RF flap was 2.11 ± 0.47, and the mean primary motor nerve average length was 9.40 ± 2.42 cm. The common vascular bundle in all 9 chimeric flaps was ligated, and the flap was rotated toward the abdomen pedicled only by primary motor nerve of the RF muscle. Nerve length was adequate for reach up to xiphoid area in all 20 flaps. Conclusions This study demonstrates the feasibility of the chimeric ALT/RF muscle free flap pedicled only by the motor nerve branch, with adequate flap rotation. Even with the limitations in a live patient, this flap would be an excellent option for FAWR in the right patient.

Abstract Context Reduced bone material strength index (BMSi) and increased cortical porosity (CtPo) have emerged as potentially contributing to fracture risk in type 2 diabetes mellitus (T2DM) patients. Objective To determine whether BMSi or CtPo are related to other diabetic complications. Design Cross-sectional observational study. Setting Subjects recruited from a random sample of southeast Minnesota residents. Participants A total of 171 T2DM patients (mean age, 68.8 years) and 108 age-matched nondiabetic controls (mean age, 67.3 years). Main Measures Bone material strength index was measured using microindentation, skin advanced glycation end-products (AGEs) measured using autofluorescence, high-resolution peripheral quantitative computed tomography at the distal radius and tibia, assessment of diabetic microvascular complications including urine microalbuminuria, retinopathy, neuropathy, and vascular disease (ankle brachial index and transcutaneous oxygen tension [TcPO2]). All analyses were adjusted for age, sex, and body mass index. Results Skin AGEs were negatively correlated with the BMSi in both T2DM (r = -0.30, P < 0.001) and control (r = -0.23, P = 0.020) subjects. In relating diabetic complications to CtPo, we found that T2DM patients with clinically significant peripheral vascular disease (TcPO2 ≤ 40 mm Hg) had higher (+21.0%, P = 0.031) CtPo at the distal tibia as compared to controls; in these subjects, CtPo was negatively correlated with TcPO2 at both the distal tibia (r = -0.39, P = 0.041) and radius (r = -0.41, P = 0.029). Conclusions Our findings demonstrate that bone material properties are related to AGE accumulation regardless of diabetes status, while CtPo in T2DM patients is linked to TcPO2, a measure of microvascular blood flow.

TPS5101 Background: There is no standard adjuvant systemic therapy that increases overall survival (OS) over surgery alone for non-metastatic RCC. Anti-PD-1 nivolumab (nivo) improves OS in metastatic RCC and is well tolerated. In mouse models, priming the immune system prior to surgery with anti-PD-1 results in superior OS compared to adjuvant dosing. Remarkable pathologic responses have been seen with neoadjuvant PD-1 in multiple ph 2 studies in bladder, lung and breast cancers. Phase 2 neoadjuvant RCC trials of nivo show preliminary feasibility and safety with no surgical delays. PROSPER RCC seeks to improve clinical outcomes by priming the immune system with neoadjuvant nivo prior to nephrectomy followed by continued immune system engagement with adjuvant blockade in patients (pts) with high risk RCC compared to standard of care surgery alone. Methods: This global, unblinded, phase 3 National Clinical Trials Network study is accruing pts with clinical stage ≥T2 or TanyN+ RCC of any histology planned for radical or partial nephrectomy. Select oligometastatic disease is permitted if the pt can be rendered ‘no evidence of disease’ within 12 weeks of nephrectomy (≤3 metastases; no brain, bone or liver). In the investigational arm, nivo is administered 480mg IV q4 weeks with 1 dose prior to surgery followed by 9 adjuvant doses. The control arm is nephrectomy followed by standard of care surveillance. There is no placebo. Baseline tumor biopsy is required only in the nivo arm but encouraged in both. Randomized pts are stratified by clinical T stage, node positivity, and M stage. 805 pts provide 84.2% power to detect a 14.4% absolute benefit in recurrence-free survival at 5 years assuming the ASSURE historical control of ~56% to 70% (HR = 0.70). The study is powered to evaluate a significant increase in OS (HR 0.67). Critical perioperative therapy considerations such as safety, feasibility, and quality of life metrics are integrated. PROSPER RCC embeds a wealth of translational studies to examine the contribution of the baseline immune milieu and neoadjuvant priming with anti-PD-1 on clinical outcomes. As of February 2020, 396 patients have been enrolled. Clinical trial information: NCT03055013 .

Abstract Context Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment. Objective Multicenter survey on current clinical approaches in managing AI during pregnancy. Design Retrospective anonymized data collection from 19 international centers from 2013 to 2019. Setting and Patients 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%). Results Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes. Conclusions This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.

ABSTRACT Osteoporosis is a chronic condition that reflects reduced bone strength and an associated increased risk for fracture. As a chronic condition, osteoporosis generally requires sustained medical intervention(s) to limit the risks for additional bone loss, compromise of skeletal integrity, and fracture occurrence. Further complicating this issue is the fact that the abrupt cessation of some therapies can be associated with an increased risk for harm. It is in this context that the COVID-19 pandemic has brought unprecedented disruption to the provision of health care globally, including near universal requirements for social distancing. In this Perspective, we provide evidence, where available, regarding the general care of patients with osteoporosis in the COVID-19 era and provide clinical recommendations based primarily on expert opinion when data are absent. Particular emphasis is placed on the transition from parenteral osteoporosis therapies. It is hoped that these recommendations can be used to safely guide care for patients with osteoporosis until a return to routine clinical care standards is available. © 2020 American Society for Bone and Mineral Research.

Abstract Patients with Type 2 Diabetes (T2D) are at higher fracture risk despite having relatively normal or even increased BMD by DXA. Increased cortical porosity has emerged as a potential factor contributing to fragility fractures in T2D. However, there is conflicting evidence whether T2D patients have increased cortical porosity. We hypothesized that microvascular complications have an important role in cortical porosity. Thus, we performed high-resolution peripheral quantitative computed tomography imaging at the distal radius and tibia to evaluate bone microarchitecture in men with T2DM age ≥ 50 yrs or postmenopausal women with T2DM and nondiabetic controls. Comprehensive diabetic complications were assessed in all patients including urine microalbuminuria, retinopathy, neuropathy (touch, temperature, and vibration sensation), ankle brachial index (ABI) and transcutaneous oxygen tension (TcPO2). Percent differences between groups were obtained from linear regression models adjusting for age, BMI, and sex. Relationships between variables were assessed using adjusted Spearman correlations. A total of 164 T2D patients (mean age 68.9 ±7.8 yrs.; 56.7% men; HbA1C=7.7 ±0.9%; mean diabetes duration 15.2 yrs.) and 107 nondiabetic controls (mean age 67.3±8.8 yrs.; 42.1% men; HbA1C =5.4 ±0.3%) were recruited to the study. Overall, there was a trend for increased cortical porosity at the distal tibia in the T2D group (+12.2%; p=0.063) compared with nondiabetic controls. Of note, TcPO2 was negatively correlated with cortical porosity at the distal radius (r= -0.17; p= 0.039) and distal tibia (r= -0.15; p= 0.073). In particular, the Low TcPO2 (≤40 mmHg) group (n=29) had greater cortical porosity at the distal tibia (+19.6 %; p=0.037) compared with the High TcPO2 (>40 mmHg) group (n=133). In addition, the low TcPO2 group had a significant increase in cortical porosity in the distal tibia (+24.8% p=0.020) compared with nondiabetic controls. In conclusion, this is the first evidence in humans indicating that TcPO2, a measure of microvascular blood flow, is linked to cortical porosity in the distal radius and tibia in T2D patients. Our findings may explain the conflicting findings regarding cortical porosity in T2D because only T2D patients with impaired microvascular blood flow have increased cortical porosity. Collectively, our data indicate that cortical porosity is a microvascular complication of longstanding T2D.

Abstract Patients with Type 2 Diabetes (T2D) are at increased fracture risk despite having relatively normal or even increased BMD by DXA. The critical aspect of bone quality deterioration in T2D patients could explain this clinically important discrepancy. Material composition is a component of bone quality that has emerged as a potential factor contributing to fragility fractures in T2D patients. However, there is sparse evidence regarding whether T2D patients have decreased bone material properties compared with non-diabetic controls. We hypothesized that increased production of advanced glycation endproducts (AGEs) has an important role in reducing bone material strength in patients with and without diabetes. Thus, we used the OsteoProbe®, a bone microindentation device that provides an index of cortical bone material properties (Bone Material Strength index – BMSi) in men with T2D age ≥ 50 yrs or postmenopausal women with T2D and nondiabetic controls. We also utilized a non-invasive measure of skin AGEs (AGE Reader®) to evaluate AGEs accumulation through skin autofluorescence. Linear regression models were used to assess group differences with and without adjusting for age, Body Mass Index (BMI), and sex. Relationships between variables were assessed using adjusted Pearson correlations. A total of 152 T2D patients (mean age 68.5 ±7.6 yrs.; 59.2% men; HbA1C=7.7 ±1.0%; mean diabetes duration 15.5 yrs.) and 105 non-diabetic controls (mean age 67.2±8.8 yrs.; 41.0% men; HbA1C =5.4 ±0.3%) were recruited to the study. Overall, there was no difference in BMSi between T2DM and control subjects: unadjusted (p= 0.636); adjusted (p= 0.695). However, skin AGEs were negatively correlated with BMSi (r= -0.23, p <0.001). In subgroup analyses, skin AGEs were also negatively associated with BMSi in both T2DM (r= -0.23, p=0.004) and control (r= -0.21, p=0.033) subjects. In conclusion, these findings demonstrate that a higher burden of AGEs is associated with worse bone quality. Our findings may explain the conflicting findings regarding reductions in BMSi in T2D because only T2D patients with a high level of AGEs accumulation have impaired BMSi. Moreover, the association of skin AGEs with BMSi in non-diabetic subjects emphasizes the important role of AGEs in decreasing bone quality and potentially contributing to fracture risk. Collectively, our data indicate that non-invasive skin AGEs measurement could be used as a tool to evaluate bone quality in patients with T2D as well as in the non-diabetic population.

Abstract Context Several studies have reported increased risk of fragility fractures in patients with mild autonomous cortisol secretion (MACS), discordant to the degree of bone density deterioration. Objective To evaluate the effect of MACS on bone metabolism in patients with adrenal adenomas. Design Cross-sectional study with prospective enrollment, 2014-2019 Setting Referral center. Patients 213 patients with adrenal adenomas: 22 Cushing syndrome (CS), 92 MACS and 99 nonfunctioning adrenal tumors (NFAT). Main Outcome Measures Osteocalcin, procollagen I intact N-terminal (PINP), C-terminal telopeptide (CTX), sclerostin. Results Patients with CS demonstrated lower markers of bone formation compared with patients with MACS and NFAT (CS vs MACS vs NFAT: mean osteocalcin 14.8 vs 20.1 vs 21.3 ng/mL [P < 0.0001]; mean PINP 34.8 vs 48.7 vs 48.5 µg/L [P = 0.003]). Severity of cortisol excess was inversely associated with sclerostin (CS vs MACS vs NFAT: mean sclerostin 419 vs 538 vs 624 ng/L, [P < 0.0001]). In a multivariable model of age, sex, body mass index, cortisol, and bone turnover markers, sclerostin was a significant predictor of low bone mass in patients with MACS (OR 0.63 [CI 95%, 0.40–0.98] for each 100 ng/L of sclerostin increase). After adrenalectomy, osteocalcin, CTX, and sclerostin increased by a mean difference of 6.3 ng/mL, 0.12 ng/mL, and 171 pg/mL (P = 0.02 for all), respectively. Conclusions Lower sclerostin level in patients with MACS reflects a reduction in osteocyte function or number associated with exposure to chronic cortisol excess. Increase in bone turnover markers after adrenalectomy suggests restoration of favorable bone metabolism.