Citations

Background The use of procurement biopsies for assessing kidney quality has been implicated as a driver of the nearly 20% kidney discard rate in the United States. Yet in some contexts, biopsies may boost clinical confidence, enabling acceptance of kidneys that would otherwise be discarded. We leveraged a novel organ offer simulation platform to conduct a controlled experiment isolating biopsy effects on offer acceptance decisions. Methods Between November 26 and December 14, 2018, 41 kidney transplant surgeons and 27 transplant nephrologists each received the same 20 hypothetical kidney offers using a crossover design with weekend “washout” periods. Mini-study 1 included four, low serum creatinine (<1.5 mg/dl) donor offers with arguably “poor” biopsy findings that were based on real offers that were accepted with successful 3-year recipient outcome. For each of the four offers, two experimental variants—no biopsy and “good” biopsy—were also sent. Mini-study 2 included four AKI offers with no biopsy, each having an offer variant with “good” biopsy findings. Results Among low serum creatinine donor offers, we found approximately threefold higher odds of acceptance when arguably poor biopsy findings were hidden or replaced with good biopsy findings. Among AKI donor offers, we found nearly fourfold higher odds of acceptance with good biopsy findings compared with no biopsy. Biopsy information had profound but variable effects on decision making: more participants appeared to have been influenced by biopsies to rule out, versus rule in, transplantable kidneys. Conclusions The current use of biopsies in the United States appears skewed toward inducing kidney discard. Several areas for improvement, including reducing variation in offer acceptance decisions and more accurate interpretation of findings, have the potential to make better use of scarce, donated organs. Offer simulation studies are a viable research tool for understanding decision making and identifying ways to improve the transplant system.

AbstractBackground and ObjectivesThe ACS‐NSQIP surgical risk calculator is an online tool that estimates the risk of postoperative complications. Sacrectomies for chordoma are associated with a high rate of complications. This study was to determine if the ACS‐NSQIP calculator can predict postoperative complications following sacrectomy.MethodsSixty‐five (42 male, 23 female) patients who underwent sacrectomy were analyzed using the Current Procedural Terminology (CPT) codes: 49215 (excision of presacral/sacral tumor), 63001 (laminectomy of sacral vertebrae), 63728 (laminectomy for biopsy/excision of sacral neoplasm) and 63307 (sacral vertebral corpectomy for intraspinal lesion). The predicted rates of complications were compared to the observed rates.ResultsComplications were noted in 44 (68%) patients. Of the risk factors available to input to the ACS‐NSQIP calculator, tobacco use (OR, 20.4; P < .001) was predictive of complications. The predicted risk of complications based off the CPT codes were: 49215 (16%); 63011 (6%); 63278 (11%) and 63307 (15%). Based on ROC curves, the use of the ACS‐NSQIP score were poor predictors of complications (49215, AUC 0.65); (63011, AUC 0.66); (63307, AUC 0.67); (63278, AUC 0.64).ConclusionThe ACS‐NSQIP calculator was a poor predictor of complications and was marginally better than a coin flip in its ability to predict complications following sacrectomy for chordoma.

A repeat survey of the Association of the Directors of Anatomic and Surgical Pathology, done 10 years after the original was used to assess trends and variability in classifying scenarios as errors, and the preferred post signout report modification for correcting error by the membership of the Association of the Directors of Anatomic and Surgical Pathology. The results were analyzed to inform on whether interpretive amendment rates might act as surrogate measures of interpretive error in pathology. An analyses of the responses indicated that primary level misinterpretations (benign to malignant and vice versa) were universally qualified as error; secondary-level misinterpretations or misclassifications were inconsistently labeled error. There was added variability in the preferred post signout report modification used to correct report alterations. The classification of a scenario as error appeared to correlate with severity of potential harm of the missed call, the perceived subjectivity of the diagnosis, and ambiguity of reporting terminology. Substantial differences in policies for error detection and optimal reporting format were documented between departments. In conclusion, the inconsistency in labeling scenarios as error, disagreement about the optimal post signout report modification for the correction of the error, and variability in error detection policies preclude the use of the misinterpretation amendment rate as a surrogate measure for error in anatomic pathology. There is little change in uniformity of definition, attitudes and perception of interpretive error in anatomic pathology in the last 10 years.

BACKGROUND. Cutaneous erythema and histopathology features in patients post allogeneic hematopoietic cell transplantation (HCT) are nonspecific, making it difficult to distinguish acute graft-versus-host disease (aGVHD) from engraftment syndrome, drug reactions, viral infections, and other etiologies. Biopsies from different locations on the same patient frequently differ in aGVHD grade, and serial biopsies of a single lesion are not possible. Proper biopsy site selection, timing, and serial noninvasive microscopic monitoring may improve our understanding and management of aGVHD. In this study, we tested the feasibility of noninvasive reflectance confocal microscopy (RCM) to detect key histopathology features of cutaneous aGVHD. STUDY POPULATION. We enrolled 11 patients with high clinical suspicion of cutaneous aGVHD, as determined by a transplant physician. In total, 16 lesions of cutaneous aGVHD-affected site were imaged by RCM (6x6 mm2en face images at four different depths) and subsequently biopsied (4x4 mm punch biopsy). 9 out of 11 patients had only skin involvement, and 2 patients had skin and gut aGVHD. 5 patients had >50% body surface area (BSA) affected, 1 had 18-50% BSA, and 5 had <18% BSA. 8 out of 11 patients required systemic corticosteroids and 3 patients received topical corticosteroids. All patients were imaged before starting treatment. METHODS. We used a clinical confocal microscope (Vivascope 1500, Caliber I.D.), which enables real-time evaluation of epidermal and superficial dermal tissue at sub-cellular resolution. Four reflectance confocal microscopists blinded to histopathology independently evaluated the presence or absence of 18 RCM features1. Concurrently, four dermatopathologists blinded to clinical and confocal information determined the presence or absence of 19 histopathology features, as well as the Lerner aGVHD grade. A histologic feature was determined as "present" in a lesion when marked by most experts (expert vote) or resolved by a fifth expert in case of a disagreement among four experts. The reflectance confocal microscopist vote was then correlated to the dermatopathologist expert vote for 17 overlapping features. We also evaluated the interrater variability among microscopists and among dermatopathologists. RESULTS. The main aGVHD features by Lerner grade had > 88% correlation between RCM and histopathology: (1) basal vacuolar change, (2) presence of dyskeratotic keratinocytes, and (3) dermal inflammation. By contrast, dyskeratotic cells and inflammation at the adnexal structures had <50% correlation. This may be attributed to the fact that more adnexal structures are typically visible in the 6x6 mm2 RCM horizontal tissue view compared to vertical section histopathology. We found a similar interrater variability among RCM experts (70%) and dermatopathologists (68%). CONCLUSIONS. In this pilot study, we show that noninvasive label-free RCM of skin enables detection of the main Lerner grade features of cutaneous aGVHD. We found a similar interrater variability among reflectance confocal microscopists and among dermatopathologists who each independently evaluated the presence or absence of a list of aGVHD features. Future studies can build on this work to evaluate the feasibility of RCM to determine cutaneous aGVHD grade, as well as distinguish between rash due to aGVHD and drug reactions. ACKNOWLEDGEMENT. This work was supported in part by Career Development Award Number IK2 CX001785 from the United Sates Department of Veterans Affairs Clinical Science R&D (CSRD) Service. Saknite I, Gill M, Alessi-Fox C, Byrne M, Jagasia M, Gonzalez S, Ardigo M, Tkaczyk ER. Features of cutaneous acute graft-versus-host disease by reflectance confocal microscopy. Br J Dermatol (2019). Disclosures Christi: Caliber I.D.: Employment, Equity Ownership. Byrne:Karyopharm: Research Funding. Jagasia:Kadmon: Consultancy; Incyte: Consultancy; Janssen: Research Funding. Tkaczyk:Incyte: Consultancy.

Conventional therapies to multiple myeloma (MM) are not aimed at specific molecular targets leading ultimately to treatment resistance. Recent reports have shown that iron is instrumental in cancer development and progression and that high intracellular iron levels are associated with poor prognosis. We have demonstrated that MM cells exhibit dysregulated iron homeostasis and that limitation of cytosolic iron inhibits MM cell growth both in vitro and in vivo. The potential therapeutic role of iron should be further investigated to better understand how targeting high-iron MM cells could prevent or delay MM development and recurrence. Our study will provide crucial insights into the iron biology of MM pathogenesis and may lead to novel MM therapy. In this study, two mouse models, young Vk*MYC and old KaLwRij mice, were injected with iron dextran (1.25 mg/kg, IP, once a week). Tumor burden was monitored by serial Serum Protein Electrophoresis (SPEP) tests, flow cytometry, and immunohistochemistry. In vitro co-culturing of ARP1 MM cells with macrophages was employed to determine iron transfer. To determine iron's roles in MM evolution, we injected iron dextran into Vk*MYC mice at 8-week age. Vk*MYC mice develop MGUS around 40-50 weeks with plasma cell (PC) bone marrow infiltration and kidney damage etc. Iron-dextran was used because it is primarily taken up by macrophages. After 14-16 weeks of iron injection, M spike was detected in the injected Vk*MYC mice. The percentage of bone marrow plasma cells (CD138+) were significantly increased to 9% in the Vk*MYC mice injected with iron compared to control mice injected with vehicle by flow cytometry and immunohistochemistry. The acceleration of disease progression via iron injection was also tested in KaLwRij mice, which also spontaneously develops MGUS in old age. M protein was detected in 12 of 15 mice (80%) injected with iron dextran for 10 weeks and 1 of 5 KaLwRij (20%) control mice at 18-months of age. CD138+ B220- plasma cells were determined by flow cytometry. A significant increase of CD138+B220- plasma cells in iron treated mice (4% versus 2%) was observed compared to vehicle control mice. Deparaffined sections of bone marrow from the above mice were stained with Prussian blue and confirmed positive staining of macrophages from iron administrated mice. These results indicate that iron accelerates MGUS development in vivo. We next evaluated whether MM cells accumulate iron from the microenvironment. ARP1 MM cells were co-cultured with primary macrophages derived from mouse bone marrow to mimic disease environment in vitro. Under these conditions, MM cells induced macrophage polarization from M0 to M1 and M2. Furthermore, increased macrophage polarization was confirmed in vivo from the KaLwRij mice injected with 5TGM1 MM cells. To confirm that MM cells uptake iron from macrophages, increased intracellular ferritin levels were observed by western blot in ARP1 MM cells following co-culture with iron-loaded macrophages. We observed that this increase in intracellular ferritin was mediated via the transferrin receptor. This iron mobilization was prevented by iron chelation. Additionally, we confirmed that ferritin levels were higher in CD138+ primary human MM cells compared to CD138- non-MM cells by western blot. Our data indicate that MM cells promote macrophage polarization resulting in the transferring of iron into MM cells. The blockade of iron trafficking between MM cells and macrophages might hold a promise for the prevention and therapy in MM. Disclosures Bergsagel: Celgene: Consultancy; Ionis Pharmaceuticals: Consultancy; Janssen Pharmaceuticals: Consultancy. Zhan:BIPHARM LLC: Consultancy, Other: % Allocation of Profit.