bluuebunny/crossref_metadata_2025 huggingface dataset:
Decalcification of Breast Cancer Bone Metastases With EDTA Does Not Affect ER, PR, and HER2 Results
Authors: van Es Suzanne C. , van der Vegt Bert , Bensch Frederike , Gerritse Sophie , van Helden Erik J. , Boon Eline , Angus Lindsay , Overbosch Jelle , Menke-van der Houven van Oordt Catharina W. , Verheul Henk M. , van Herpen Carla M.L. , Jager Agnes , Oosting Sjoukje F. , de Vries Elisabeth G.E. , Schröder Carolina P.
Published: July 2019

In metastatic breast cancer (MBC), expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) guides treatment selection. In case of bone-only metastatic disease, ER, PR, and HER2 status assessment may be hampered by decalcification. We aimed to determine the optimal decalcification method, and to study discordance of receptor expression between paired primary breast tumors and optimally decalcified bone metastases. First, decalcification was simulated using acetic acid, hydrochloric/formic acid, and EDTA on 12 primary breast carcinomas. ER, PR, and HER2 immunohistochemistry (IHC) and HER2 in situ hybridization (ISH) were assessed, before and after the 3 decalcification methods. EDTA was considered the optimal method, as it did not affect IHC and as ISH failed in only 1/16 cases. Hydrochloric/formic acid altered ER and PR results, and, with acetic acid and hydrochloric/formic acid, ISH failed in, respectively, 94% and 100%. Second, ER, PR, and HER2 IHC was performed in paired primary tumors and EDTA-decalcified bone metastases obtained from patients with first presentation of MBC. Clinically relevant discordance was defined as changed receptor status with treatment implications. Paired samples of 77 patients, participating in the IMPACT-MBC trial, were evaluable. Hormonal receptor expression change was clinically relevant in 6 patients (7.9%) and HER2 expression change in 1 patient (1.3%). This study shows that EDTA decalcification minimally affects receptor expression results. The incidence of clinically relevant discordance between the primary tumor and bone metastases is low. These findings support that bone biopsies can reliably be used to assess receptor status.
Uptake of 18F-Fluciclovine in Paget Disease
Authors: Akin-Akintayo Oladunni O. , Bonta Dacian , Barron Bruce
Published: July 2019

Since its recent approval by the United States Food and Drug Administration, fluciclovine PET-CT has gained widespread use for imaging of recurrent prostate cancer patients. As an amino acid–based radiotracer transported by LAT-1 and ASCT-2 transporters, fluciclovine exploits the up-regulation of amino acid transporters in malignant cells. We present a rare case of fluciclovine uptake in Paget disease in a 58-year-old man with suspected recurrent prostate cancer and asymmetric increased left hemipelvic uptake on imaging.
A Hungry Bone Syndrome Predicted by 18F-Fluorocholine PET/CT
Authors: Paepegaey Anne-Cécile , Velayoudom Fritz-Line , Housni Selma , Gauthé Mathieu , Groussin Lionel
Published: July 2019

Predicting hungry bone syndrome (HBS) after surgical cure of primary hyperparathyroidism (PHPT) can be challenging. A 57-year-old man diagnosed with PHPT was assessed preoperatively by 18F-fluorocholine PET/CT. An intense and diffuse tracer uptake of the axial and peripheral skeleton was visualized, in addition to a pathologic uptake suggestive of hyperfunctioning parathyroid gland. After the removal of a parathyroid adenoma, a severe and prolonged HBS requiring high doses of calcium and active metabolites of vitamin D was observed. This observation suggests that intense and diffuse bone uptake on 18F-fluorocholine PET/CT could be a predictive factor for HBS in patients with PHPT.
Giant Melanotic Malignant Peripheral Nerve Sheath Tumor in the Pelvis
Authors: Liu Entao , Sun Taotao , Liu Chao , Wang Siyun , Wang Shuxia
Published: July 2019

Melanotic malignant peripheral nerve sheath tumor is an extremely rare tumor, which originates from the neural crest, and more than half the cases are associated with Carney complex (myxomas, spotty pigmentation, and endocrine abnormalities). Herein, we have presented a case of a melanotic malignant peripheral nerve sheath tumor, which is not associated with Carney complex. The patient underwent preoperative nonenhanced CT, contrast-enhanced CT, and 18F-FDG PET/CT scans, which showed a large pelvic tumor with heterogeneous enhancement and increased 18F-FDG uptake. Subsequently, the patient underwent complete resection of the tumor.
Hamartoma of Mature Cardiac Myocytes Mimicking Malignancy on 18F-FDG PET/CT Images
Authors: Jiang Yang , Ma Xiaowei , Tan Yanlin , Lu Qingqing , Wang Yunhua
Published: July 2019

Hamartoma of mature cardiac myocytes is an extremely rare type of benign cardiac tumor with a slow growth rate and generally occurs in adults. We report a case with hamartoma of mature cardiac myocytes of the right auricle demonstrating intense 18F-FDG uptake and a large amount of pericardial effusion on PET/CT mimicking malignancy in a 41-year-old man. Hamartoma of mature cardiac myocytes should be considered among the differential diagnoses when an 18F-FDG-avid primary focal cardiac mass is found in patients with malignant features on PET/CT imaging.
Evaluation of Lung Cancer and Neuroendocrine Neoplasm in a Single Scan by Targeting Both Somatostatin Receptor and Integrin αvβ3
Authors: Zheng Yumin , Wang Hanping , Tan Huangying , Cui Xiaoxia , Yao Shaobo , Zang Jie , Zhang Li , Zhu Zhaohui
Published: July 2019

Purpose

This pilot study aimed to prove the complementary value of a novel 68Gallium-labeled heterodimeric peptide, 68Ga-NOTA-3P-TATE-RGD, in detection and evaluation of tumors with somatostatin receptor subtype 2 or integrin αvβ3 overexpression, including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), neuroendocrine tumor (NET), and neuroendocrine carcinoma (NEC).

Methods

With institute review board approval and written informed consent, 32 patients with pathologically diagnosed lung cancer (18 NSCLC, 14 SCLC) and 12 patients with neuroendocrine neoplasm (8 NET, 4 NEC) patients were recruited to undergo 68Ga-NOTA-3P-TATE-RGD PET/CT. For comparison, the NSCLC patients also underwent 68Ga-NOTA-TATE PET/CT, the SCLC patients underwent 68Ga-NOTA-RGD PET/CT, and the neuroendocrine neoplasm patients underwent 18F-FDG PET/CT within 3 days. The maximum standardized uptake value (SUV) of the primary tumor (T) and mean SUV of the blood pool (B) were measured, and the T/B ratios were calculated for comparison.

Results

In the primary tumors of NSCLC, the T/B ratios of 68Ga-NOTA-3P-TATE-RGD were significantly higher than those of 68Ga-NOTA-TATE (4.54 ± 3.00 versus 4.10 ± 2.83, P = 0.0058). In SCLC, the T/B ratios of 68Ga-NOTA-3P-TATE-RGD were significantly higher than those of 68Ga-NOTA-RGD (6.06 ± 6.09 versus 2.65 ± 1.19, P = 0.0344). In NET, the T/B ratios of 68Ga-NOTA-3P-TATE-RGD were 36.13 ± 33.84, significantly higher than those of 18F-FDG (2.91 ± 1.71, P = 0.0234). In NEC, there were no significant difference between the T/B ratios of 68Ga-NOTA-3P-TATE-RGD (4.80 ± 0.85) and those of 18F-FDG (3.56 ± 0.74, P = 0.1833).

Conclusions

This proof-of-concept study preliminarily demonstrates the efficacy of the dual targeting 68Ga-NOTA-3P-TATE-RGD PET/CT in the evaluation of lung cancer and neuroendocrine neoplasm in a single scan.
18F-DCFPyL PET/CT in a Single Large Metastasis With Prostate-Specific Antigen Level of 856 ng/mL
Authors: Wondergem Maurits , Srbljin Sandra , van der Zant Friso M. , Broos Wouter A. M. , Knol Remco J. J.
Published: July 2019

Literature shows that prostate-specific membrane antigen (PSMA) PET/CT may detect biochemical recurrence of prostate cancer at low prostate-specific antigen (PSA) levels, including detection of oligometastatic disease and hence direct metastasis-directed therapy. Although it is generally accepted that higher PSA values indicate higher disease burden, few data are available on the relation between PSA levels and number of detected metastases on PSMA PET/CT. This report demonstrates a patient with high PSA levels (856 ng/mL) at time of biochemical recurrence that showed only 1 metastasis on PSMA PET/CT. Combined androgen deprivation therapy and radiation therapy resulted in a complete biochemical response.
Isolated Small Bowel Metastasis From Gastric Cancer Detected by 18F-FDG PET/CT
Authors: Fan Qiuping , Su Minggang
Published: July 2019

Small bowel metastasis is rare. Most patients are diagnosed after presenting serious complications. The primary tumors generally arise from breast, lung, and melanoma, but rarely from the stomach. Here we present a case of a gastric cancer patient with asymptomatic small bowel metastasis diagnosed at staging using 18F-FDG PET/CT. The bowel lesion could not be found on the full-dose CT component of PET/CT. Previous staging contrast CT also made a missed diagnosis. This case reminds us that PET/CT can be used to detect unsuspected metastasis. It may be suitable for routine initial staging, especially on a patient with poor prognosis.
18F-Choline PET/CT Detected Skull Base Paraganglioma
Authors: Harbourne Alexander D. , Bradley Kevin M.
Published: July 2019

We present a case of a right skull base paraganglioma detected using 18F-choline PET/CT in a 63-year-old man. The 18F-choline PET/CT scan was performed to assess a known prostate cancer. In addition, the scan demonstrated a mildly choline-avid (SUVmax, 3.8) tumor within the carotid sheath of the right skull base, extending through the jugular foramen to the cerebellomedullary and cerebellopontine angles. 18F-choline may provide a superior alternative to FDG in imaging paragangliomas of the skull base because, unlike FDG, there is no significant 18F-choline uptake in the adjacent brain.
Incidental Detection of Adrenal Pheochromocytoma on 99mTc-DTPA Renal Dynamic Scintigraphy
Authors: Mi Yanxia , Huang Jianmin , Ren Yuan , Xie Peng
Published: July 2019

A 53-year-old man with a history of primary hypertension for over 8 years underwent 99mTc-DTPA renal dynamic scintigraphy to evaluate the renal function. The images revealed an unexpected focus of abnormally increased DTPA activity in the region superior to the upper pole of the right kidney. Subsequent MRIs confirmed an adrenal mass. The results of pathological examination and immunohistochemistry after the resection of the lesion were consistent with adrenal pheochromocytoma.
Comparison of Diagnostic Performance of B-Mode Ultrasonography and Shear Wave Elastography in Cervical Lymph Nodes
Authors: Kang Hye Jin , Seo Mirinae , Sohn Yu-Mee , Yun Seong Jong , Min Sun Young , You Myung-Won , Yeon Eung Koo
Published: July 2019

The purpose of this study was to compare the diagnostic performance of B-mode ultrasonography (US) and shear wave elastography (SWE) for differentiating benign from malignant cervical lymph nodes (LNs). This study evaluated 130 cervical LNs in 127 patients. On conventional B-mode US, short-axis and long-axis diameters, long-to-short-axis ratio, cortical morphology, border, and presence of necrosis or calcification were evaluated. Maximum elasticity value (Emax) was collected for SWE. The area under the receiver operator characteristic curve (AUC), sensitivity, and specificity of B-mode US features and SWE were compared. Final histopathologic results showed 89 benign and 41 metastatic LNs. Among the B-mode US features, cortical morphology had the highest AUC (0.884). When 54 kPa of Emax was applied as a cutoff value, the SWE showed significantly lower AUC than cortical morphology (0.734, P = 0.02). Both sensitivity and specificity for cortical morphology on B-mode US were higher than for Emax (80.5% vs 65.9%, P = 0.212 and 89.9% vs 76.4%, P = 0.026, respectively). Conventional B-mode US resulted in higher diagnostic yield than SWE in evaluating cervical LNs in our study. However, further studies on potential factors that may affect the SWE velocity are needed to validate the diagnostic value of SWE.
Osteoplastic Anterior Transoral Approach for Tumors of the Middle Cranial Fossa
Authors: Nicolás Solano , Ejusmar Rivera , Lozano Alfonso , Lobo Cesar
Published: July 2019

Surgical access to tumors involving the midline skull base remains a considerable challenge for surgeons. Various surgical approaches for treating these tumors like transnasal, transantral, and endoscopic approaches sometimes have anatomical limitations. This paper describes a transoral approach with a Lefort I osteotomy that allows a great visualization, not only to the center of the skull base but also the infratemporal fossa. This technique may be used for the surgical resection of extracranial and intracranial benign tumors, and non-neoplastic intradural pathology, which does not require dural resection. The authors will review proper patient selection, surgical exposure, operative procedure, and complications.
Surgical Feasibility of Curtler-Beard Reconstruction for Large Upper Eyelid Defect
Authors: Shin Hye-Young , Chu Miyoung , Kim Ji Hyun , Paik Ji-Sun , Yang Suk-Woo
Published: July 2019

Purpose:

To report long-term surgical outcomes of Cutler-Beard reconstructive surgery in patients with large full-thickness upper eyelid defects following malignant tumor excision.

Methods:

The medical records of 5 consecutive patients with full-thickness upper eyelid defects following tumor resection who underwent Cutler-Beard surgery were reviewed retrospectively between April 2005 and November 2018. Surgical procedure comprises 2 stages: first, complete tumor resection followed by bridged full-thickness lower eyelid advancement flap; second, separation of the closed eyelid with eyelid margin repair 7 to 9 weeks later. Postoperative anatomical, functional and cosmetic outcomes, and complications were evaluated during follow-up at 22 to 77 months.

Results:

Patients were in the age group of 49 to 75 years, including 3 (60%) females and 2 (40%) males. Three of the 5 patients (60%) exhibited sebaceous cell carcinoma and 2 (40%) showed squamous cell carcinoma. Three patients (60%) underwent Cutler-Beard surgery after recurrence of primary carcinoma following previous operation. Three patients underwent revision surgery with entropion, 2 underwent correction for wound dehiscence and 1 was treated with symblepharon lysis. No serious or permanent ocular complications were observed during the operation or follow-up with the patients. The procedure resulted in good aesthetic quality and acceptable sequelae at the donor site.

Conclusions:

Cutler-Beard procedure for the reconstruction of large and full-thickness upper eyelid defects is an effective procedure with satisfactory long-term results, although a few patients may require minor revision surgery.
An Anatomical Feasibility Study Using a Great Auricular Nerve Graft for Ipsilateral Inferior Alveolar Nerve Repair
Authors: Iwanaga Joe , Altafulla Juan J. , Kikuta Shogo , Tubbs R. Shane
Published: July 2019

The great auricular nerve (GAN) has been used for trigeminal and facial nerve repair and the inferior alveolar nerve (IAN) are often sacrificed during segmental mandibulectomy. To our knowledge, only 1 case report has discussed IAN repair using GAN after segmental mandibulectomy. The goal of this study is to clarify the feasibility of using GAN for IAN repair. Eleven sides from 6 fresh frozen Caucasian cadavers were used for this study. The mean age at the time of death was 82.3 years. A submandibular skin incision was made 2 finger breadths below and parallel to the inferior border of the mandible. The GAN was identified and then the mental foramen was found via extraoral dissection. The buccal cortical bone was removed 5 mm posterior to the mental foramen to the wisdom tooth area. Next, the anteroposterior length of the window was measured. The diameter of the IAN at the first molar tooth area was measured. Finally, the GAN was cut with maximum available length to compare to the length of the window in the mandible. The anteroposterior length of the window and diameter of the IAN ranged from 23.1 to 31.2 mm and 1.2 to 2.1 mm, respectively. The length of the available GAN was longer than the ipsilateral bony window of the mandible on all sides. This study might encourage surgeons to consider a new way to treat patients who undergo segmental resection of the mandible with surgical neck dissection with injury to their IAN.
Targeting the Hedgehog Pathway Using Itraconazole to Prevent Progression of Barrett's Esophagus to Invasive Esophageal Adenocarcinoma
Authors: Kelly Ronan J. , Ansari Amir M. , Miyashita Tomoharu , Zahurak Marianna , Lay Frank , Ahmed A. Karim , Born Louis J. , Pezhouh Maryam K. , Salimian Kevan J. , Ng Christopher , Matsangos Aerielle E. , Stricker-Krongrad Anne-Heloise , Mukaisho Ken-ichi , Marti Guy P. , Chung Christine H. , Canto Marcia I. , Rudek Michelle A. , Meltzer Stephen J. , Harmon John W.
Published: July 2019

Objective:

The aim of the study was to investigate whether inhibition of Sonic Hedgehog (SHH) pathway would prevent progression of Barrett's Esophagus (BE) to esophageal adenocarcinoma.

Background:

The hedgehog signaling pathway is a leading candidate as a molecular mediator of BE and esophageal adenocarcinoma (EAC). Repurposed use of existing off-patent, safe and tolerable drugs that can inhibit hedgehog, such as itraconazole, could prevent progression of BE to EAC.

Methods:

The efficacy of itraconazole was investigated using a surgical rat reflux model of Barrett's Metaplasia (BM). Weekly intraperitoneal injections of saline (control group) or itraconazole (treatment group; 200 mg/kg) were started at 24 weeks postsurgery. Esophageal tissue was harvested at 40 weeks. The role of the Hh pathway was also evaluated clinically. Esophageal tissue was harvested after 40 weeks for pathological examination and evaluation of the SHH pathway by immunohistochemistry.

Results:

BM was present in control animals 29 of 31 (93%) versus itraconazole 22 of 24 (91%). EAC was significantly lower in itraconazole 2 of 24 (8%) versus control 10 of 31 (32%), respectively (P = 0.033). Esophageal SHH levels were lower in itraconazole vs control (P = 0.12). In esophageal tissue from humans with recurrent or persistent dysplastic BE within 24 months of ablative treatment, strong SHH and Indian Hedgehog expression occurred in distal BE versus proximal squamous epithelium, odds ratio = 6.1 (95% confidence interval: 1.6, 23.4) and odds ratio = 6.4 (95% confidence interval: 1.2, 32.8), respectively.

Conclusion:

Itraconazole significantly decreases EAC development and SHH expression in a preclinical animal model of BM. In humans, BE tissue expresses higher SHH, Indian Hedgehog, and bone morphogenic protein levels than normal squamous esophageal epithelium.
Simulation-based training is associated with lower risk-adjusted mortality in ACS pediatric TQIP centers
Authors: Jensen Aaron R. , McLaughlin Cory , Subacius Haris , McAuliff Katie , Nathens Avery B. , Wong Carolyn , Meeker Daniella , Burd Randall S. , Ford Henri R. , Upperman Jeffrey S.
Published: July 2019

BACKGROUND

Although use of simulation-based team training for pediatric trauma resuscitation has increased, its impact on patient outcomes has not yet been shown. The purpose of this study was to determine the association between simulation use and patient outcomes.

METHODS

Trauma centers that participate in the American College of Surgeons (ACS) Pediatric Trauma Quality Improvement Program (TQIP) were surveyed to determine frequency of simulation use in 2014 and 2015. Center-specific clinical data for 2016 and 2017 were abstracted from the ACS TQIP registry (n = 57,916 patients) and linked to survey responses. Center-specific risk-adjusted mortality was estimated using multivariable hierarchical logistic regression and compared across four levels of simulation-based training use: no training, low-volume training, high-volume training, and survey nonresponders (unknown training use).

RESULTS

Survey response rate was 75% (94/125 centers) with 78% of the responding centers (73/94) reporting simulation use. The average risk-adjusted odds of mortality was lower in centers with a high volume of training compared with centers not using simulation (odds ratio, 0.58; 95% confidence interval, 0.37–0.92). The times required for resuscitation processes, evaluations, and critical procedures (endotracheal intubation, head computed tomography, craniotomy, and surgery for hemorrhage control) were not different between centers based on levels of simulation use.

CONCLUSION

Risk-adjusted mortality is lower in TQIP-Pediatric centers using simulation-based training, but this improvement in mortality may not be mediated by a reduction in time to critical procedures. Further investigation into alternative mediators of improved mortality associated with simulation use is warranted, including assessment of resuscitation quality, improved communication, enhanced teamwork skills, and decreased errors.

LEVEL OF EVIDENCE

Therapeutic/care management, Level III
Existing and Evolving Bioethical Dilemmas, Challenges, and Controversies in Vascularized Composite Allotransplantation: An International Perspective From the Brocher Bioethics Working Group
Authors: Magill Gerard , Benedict James , Plock Jan A. , Krones Tanja , Gorantla Vijay S.
Published: July 2019

Early results of hand and face transplants and other grafts such as those of uterus, penis, trachea, larynx, or abdominal wall have confirmed the potential for vascularized composite allotransplantation (VCA) to restore appearance, anatomy, function, independence, and social integration in patients suffering from devastating tissue deficits untreatable by conventional treatment options. Despite such promise, these novel and complex procedures face challenges and controversies that remain open to discussion and debate. Indeed, many barriers to clinical advancement and negative stakeholder perceptions still exist. The bioethical challenges surrounding VCA include but are not limited to justice and vulnerability of subjects, and their experiences with risks, benefits and outcomes, provider economy of fame, public awareness and attitudes toward transplantation, and policy and regulatory issues shaping progress of the field. The First International Workshop on Bioethical Challenges in Reconstructive Transplantation was organized by the Brocher Foundation in Hermance, Switzerland. VCA professionals representing teams from across the world examined bioethical issues in VCA related to standards for safety, efficacy, feasibility, privacy, confidentiality, and equitability. Key discussion topics from the workshop were included in a survey questionnaire implemented across VCA professionals attending the 13th Congress of International Society of VCA held in Salzburg, Austria. The insights from the Brocher workshop and International Society of VCA survey as presented here could help inform the future development of clinical practice and policy strategies in VCA to ensure value, accessibility, and acceptance of these procedures by potential donors, potential or actual recipients and their families, and providers and payers.
Protein Profiles of Pretransplant Grafts Predict Early Allograft Dysfunction After Liver Transplantation From Donation After Circulatory Death
Authors: Xie Haiyang , Zhang Liang , Guo Danjing , Yang Zhentao , Zhu Hai , Zhou Ke , Feng Xiaowen , Wei Qiang , Xu Xiao , Song Penghong , Wen Xue , Li Jianhui , Liu Jialin , Zheng Shusen
Published: July 2019

Background.

Predicting the development of early allograft dysfunction (EAD) following liver transplantation (LT) remains challenging for transplant clinicians. The objectives of this study are to investigate the potential relationship between the protein profiles of pretransplant grafts and the onset of EAD, and then combine with clinical parameters to construct a mathematically predictive model.

Methods.

Clinical data of 121 LT procedures from donation after circulatory death at the authors’ center were analyzed. The expression levels of 7 studied proteins were determined by immunohistochemistry. Another independent cohort of 37 subjects was designed for further validation of the predictive model.

Results.

With an incidence of 43.0% (52/121), EAD was linked to significantly increased risk of acute kidney injury and renal replacement therapy, as well as reduced 6-month patient and liver graft survival. Allograft weight and high intrahepatic vascular endothelial growth factor (VEGF) expression were identified as independent risk factors of EAD and survival outcomes. Liver grafts with high VEGF expression exhibited delayed functional recovery within the first postoperative week. The combination of VEGF overexpression and EAD yielded the highest frequency of renal dysfunction and the worst survival. Based on allograft weight and intrahepatic VEGF expression, an EAD risk assessment model was developed. The incidence of EAD differed significantly between grafts with risk scores ≥−1.72 and <−1.72. The model functioned well in the validation cohort.

Conclusions.

Pretransplant intrahepatic protein profiling contributes to the estimation of early graft performance and recipient outcomes following LT. The predictive model could allow for an accurate prediction of EAD.
Factors That Complicated the Implementation of a Program of Donation After Unexpected Circulatory Death of Lungs and Kidneys. Lessons Learned From a Regional Trial in the Netherlands
Authors: Venema Leonie H. , Brat Aukje , Nijkamp Danielle M. , Krikke Christina , Leuvenink Henri G.D. , de Jongh Wim C. , Tromp Tjarda N. , Van der Vliet J. Adam , Bens Bas W.J. , Erasmus Michiel E.
Published: July 2019

Background.

Organ shortage remains a problem in transplantation. An expansion of the donor pool could be the introduction of unexpected donation after circulatory death (uDCD) donors. The goal of this study was to increase the number of transplantable kidneys and lungs by implementing a uDCD protocol.

Methods.

A comprehensive protocol for uDCD donation was developed and implemented in the emergency departments (EDs) of 3 transplant centers. All out-of-hospital cardiac arrest (OHCA) patients were screened for uDCD donation. Inclusion criteria were declaration of death in the ED, age (<50 y for kidneys, <65 y for lungs), witnessed arrest, and basic and advanced life support started within 10 and 20 min, respectively.

Results.

A total of 553 OHCA patients were reported during the project, of which 248 patients survived (44.8%). A total of 87 potential lung and 42 potential kidneys donors were identified. A broad spectrum of reasons resulted in termination of all uDCD procedures. Inclusion and organ-specific exclusion criteria were the most common reason for not proceeding followed by consent. None of the potential donors could be converted into an actual donor.

Conclusion.

Although uDCD potential was shown by successful recognition of potential donors in the ED, we were not able to transplant any organs during the study period. The Dutch Emergency medical service guidelines to stop futile OHCA in the prehospital setting and the strict use of inclusion and exclusion criteria like age and witnessed arrest hampered the utilization. A prehospital uDCD protocol to bring all OHCA patients who are potential uDCD candidates to an ED would be helpful in creating a successful uDCD program.
Comparison of Tacrolimus and Cyclosporine Combined With Methotrexate for Graft Versus Host Disease Prophylaxis After Allogeneic Hematopoietic Cell Transplantation
Authors: Huang Bingsong , Lin Xiaohong , Zhang Zhicheng , Zhang Yixi , Zheng Zhouying , Zhong Chunlong , He Xiaoshun , Chen Maogen
Published: July 2019

Background.

After patients receive hematopoietic stem cell transplantation (HSCT), both cyclosporine (CsA) and tacrolimus (TAC) in combination with methotrexate (MTX) are recommended as the standard prophylaxis strategy for graft versus host disease (GVHD) by the European Group of Blood and Marrow Transplantation. However, the advantage of TAC combined with MTX lacks conclusive evidence.

Methods.

We searched online databases for studies comparing CsA + MTX and TAC + MTX in patients who received HSCT. The odds ratio (OR) and 95% confidence interval (CI) were applied to compare the pooled data.

Results.

We found a significant reduction in the grade II to IV acute GVHD (aGVHD) rate (OR, 0.42; CI, 0.28-0.61; P < 0.00001), grade III to IV aGVHD rate (OR, 0.59; CI, 0.38-0.92; P = 0.02), chronic GVHD rate (OR, 0.79; CI, 0.62-1.00; P = 0.05), and nonrelapse mortality rate (OR, 0.62; CI, 0.40-0.95; P = 0.03) and an increase in the overall survival (OS) rate (only in those received from unrelated donor) (OR, 1.30; CI, 1.15-1.48; P < 0.0001) in the TAC + MTX group. Similar outcomes occurred for the relapse rate and disease-free survival rate in both groups.

Conclusions.

TAC + MTX has a superior effect in the prevention of aGVHD in patients who received HSCT and further prolongs the OS in patients who received from unrelated donor transplants. CsA + MTX prolongs the OS in patients who received HSCT from HLA-identical sibling donors. The leukemic relapse and disease-free survival rate were not different between the 2 regimens. Thus, we conclude that TAC + MTX was superior to CsA + MTX, especially for HSCT patients with nonmalignant disorders. Further studies are still required to evaluate the effect of TAC or CsA combined with other suppressors in the treatment regimen following HSCT.
Glycocalyx Damage Within Human Liver Grafts Correlates With Graft Injury and Postoperative Graft Function After Orthotopic Liver Transplantation
Authors: Schiefer Judith , Faybik Peter , Koch Stefan , Tudor Bianca , Kollmann Dagmar , Kuessel Lorenz , Krenn Claus G. , Berlakovich Gabriela , Baron David M. , Baron-Stefaniak Joanna
Published: July 2019

Background.

Destruction of the endothelial glycocalyx has been observed within lung and kidney grafts during ischemic organ preservation. We aimed to quantify glycocalyx damage within human liver grafts after organ preservation and correlate the results with graft injury and postoperative graft function in patients undergoing orthotopic liver transplantation (OLT).

Methods.

Syndecan-1 (Sdc-1) was measured as indicator of glycocalyx degradation in effluents of 38 liver grafts and serum of patients undergoing OLT. Effluent Sdc-1 concentrations were correlated with hepatic injury markers from the effluent. Furthermore, we assessed the association of Sdc-1 with early allograft dysfunction (EAD), 1-year graft survival, and 1-year patient survival.

Results.

Effluent Sdc-1 concentrations correlated with effluent concentrations of hepatocellular injury markers, including alkaline phosphatase (R = 0.543, P = 0.003), aspartate aminotransferase (R = 0.420, P = 0.029), and lactate (R = 0.574, P = 0.002). Sdc-1 effluent concentrations were greater in patients who developed EAD compared with those without EAD (4720 [4374–5133] vs 3838 [3202–4240] ng/mL, P = 0.015). Furthermore, receiver operating characteristics analyses revealed that effluent Sdc-1 concentrations (AUC = 0.82, P = 0.017) and serum Sdc-1 concentrations (AUC = 0.84, P = 0.006) were associated with the development of EAD. These results were confirmed by regression analyses. No association was found between Sdc-1 and 1-year graft survival or 1-year patient survival.

Conclusions.

Our data suggest that the glycocalyx is damaged within human liver grafts during preservation and the extent of glycocalyx damage correlates with the severity of hepatocellular injury. Recipients of livers grafts with greater glycocalyx damage might be at higher risk for development of EAD after OLT.
An Unusual Case of Median Neuropathy: Application of Short Segmental Sensory Nerve Stimulation
Authors: Luetmer Marianne T. , Laughlin Ruple S.
Published: July 2019

A 55-year-old woman presented with an 18-month history of intermittent left-hand paresthesias affecting her first, second, and third digits. A small, immobile, nontender midline mass on the volar aspect of the left wrist was also present. Evaluation included normal routine nerve conduction studies and needle electromyography. An ultrasound was performed in the electromyography laboratory, verifying median nerve involvement of the mass within the proximal carpal tunnel. This finding guided the electromyographer to perform the unconventional technique of sensory nerve short segmental stimulation across the carpal tunnel, which confirmed focal slowing across the lesion, achieving electrodiagnostic confirmation of median nerve impairment. This case of atypical carpal tunnel syndrome due to a median nerve schwannoma demonstrates both the utility and specificity of short segmental sensory stimulation in some cases of median neuropathy at the wrist and the value of sonography in the electromyography laboratory.
Catastrophic Abdominal Wall After Repair of Enterocutaneous Fistula
Authors: Jerez González José Antonio , Quiñones Sánchez Cristina , Márquez Rodríguez Francisca
Published: July 2019

BACKGROUND:

Repair of an enterocutaneous fistula (ECF) is challenging, particularly when complications occur. This case describes the use of negative pressure wound therapy (NPWT) and microadhesive dressings with polyabsorbent fibers and an acrylic core, with and without lipidocolloid and nano-oligosaccharide factors, in the management of a patient with a large abdominal wound and ECF.

CASE:

An 84-year-old woman underwent abdominoperineal resection with colostomy, hysterectomy, and subsequent chemotherapy and radiotherapy for colorectal cancer. She experienced complications, ultimately resulting in ECF of the jejunum. Initial management with NPWT was used to promote abdominal wound healing, while protecting exposed bowel loops proved challenging because of leakage of stoma effluent that impeded the formation of granulation tissue. In order to promote wound healing and prevent infection, we applied a microadhesive dressing composed of polyabsorbent fibers with an acrylic core and lipidocolloid and nano-oligosaccharide factors that facilitated autolytic debridement and healing.

CONCLUSIONS:

Use of NPWT with the microadhesive dressing proved successful in the management of this complex and challenging ECF.
Bladder Self-management in the Transition to Adulthood With Spina Bifida in 3 Countries
Authors: Faleiros Fabiana , Warschausky Seth , Käppler Christoph , Schutt William , Cintra Michel M. , Rabeh Soraia A. N. , Gimenes Fernanda R. E.
Published: July 2019

PURPOSE:

The purpose of this study was to evaluate bladder self-management in transition to adult care for patients with spina bifida (SB) in 3 countries with similar clinical practice and different social, cultural, and economic milieu.

STUDY DESIGN:

Cross-sectional study.

SUBJECTS AND SETTING:

The sample comprised 90 participants: 27 reside in Brazil, 36 reside in Germany, and 27 reside in the United States. Demographic characteristics of the sample are based on country. The distribution of sex in the Brazilian sample was 18 males and 9 females, the German group had 11 males and 25 females, and the United States group had 8 males and 19 females. The age range of the cumulative sample was 13 to 29 years. The age of the German sample (mean 23.56, standard deviation [SD] 4.60 years) was significantly higher (analysis of variance,F(2, 87)= 13.62,P< .001) than the other 2 groups (Brazil mean 20.56 years, SD 5.24; US mean 19.44 years, SD 4.70).

METHODS:

Demographic, clinical, and social variable data were collected via an online questionnaire distributed to multiple regions of Germany and a multidisciplinary myelomeningocele clinic at the University of Michigan in the Midwestern United States. In Brazil, participants completed a printed version of the survey. In Germany and the United States, an electronic version of the survey was made available online. German and English versions of the survey, originally developed in Portuguese for persons residing in Brazil, were translated and validated.

RESULTS:

The majority of participants (94.4%) performed intermittent catheterization (IC), 76.5% performed IC independently, whereas 23.5% required assistance with IC or catheterized with aids (handles, leg spreaders, and penis or labia holder). There were no statistically significant group differences in independent self-catheterization by gender. There were significant national group differences in level of lesion (P= .016), use of shunt (P= .012), and medication for bladder management (P< .001). Among participants 18 years and older, there were significantly higher levels of education in the German and the US samples than in the Brazilian sample (P< .001).

CONCLUSIONS:

Although there were national group differences in medical characteristics and management of SB, differences in independent self-catheterization were not significant. Findings suggest that support from family/caregivers and health care providers appears to facilitate transition to independent self-care, regardless of national context.
Time of Onset to Changes in Skin Condition During Exposure to Synthetic Urine
Authors: Phipps LeeAnn , Gray Mikel , Call Evan
Published: July 2019

PURPOSE:

The purpose of this study was to evaluate the impact of incontinence on epithelial-moisture barrier function and the subsequent risk for incontinence-associated dermatitis by exposing healthy volunteers to a premium incontinence pad wet with synthetic urine.

DESIGN:

Prospective, single-group study.

PARTICIPANTS AND SETTING:

Thirty women 65 years or older participated in the study. Participants had healthy skin of the buttocks, perineal, and perigenital areas and were not incontinent of urine or stool. The study was conducted at a contracted clinical research facility in Southeastern United States.

METHODS:

Four hundred milliliters of synthetic urine was distributed across the width of a premium incontinence pad with wicking technology containing a superabsorbent polymer core. Participants laid supine for a total of 4 hours, with the wet pad under the buttocks. Skin assessments were conducted at baseline prior to contact with the wet pad, at 15 minutes, 30 minutes, and 1, 2, and 4 hours after exposure to the synthetic urine. Outcome measures were skin moisture content, cutaneous pH, transepidermal water loss (TEWL), mean coefficient of friction values (static and dynamic), and tolerability evaluations (expert clinical grader–assessed erythema and participant-assessed discomfort).

RESULTS:

Mean moisture content of the skin increased from 46.19 ± 22.1 to 1845.28 ± 542.7 micro-Siemens (μS) after just 15 minutes of exposure and was significantly increased at all time points compared to baseline (P < .001). Cutaneous pH increased from 5.67 ± 0.5 to 6.25 ± 0.1 after 15 minutes; pH was higher at all time points compared to baseline (P < .001). Passive transfer of water through the stratum corneum (TEWL) showed an increase from 9.02 ± 2.2 g/m2/h at baseline to 16.83 ± 5.2 g/m2/h at 4 hours (P < .001). There was a significant increase from baseline to 4 hours in mean coefficient of static friction (0.32 ± 0.01 vs 0.47 ± 0.03; P < .00001) as well as mean coefficient of dynamic friction (0.29 ± 0.01 vs 0.42 ± 0.02; P < .00001). There was a significant increase in erythema and an increase in participant-assessed discomfort at all time points (P < .005).

CONCLUSIONS:

Our findings suggest that impairment of the skin's epithelial-moisture barrier function associated with inflammation and development of incontinence-associated dermatitis begins rapidly after an incontinence event, even with the use of a premium pad with wicking technology. Study findings also suggest that prompt attention to incontinence events is needed to prevent moisture-associated skin damage (incontinence-associated dermatitis) even when absorbent pads are used.
Gastric leishmaniasis in the setting of HIV/AIDS infection at Community Hospital in Southeastern United States
Authors: Douse Dontre' M. , Goldstein Randi S. , Montgomery David J. , Sinnott Michael
Published: July 2019

Introduction. Visceral leishmaniasis, caused by the Leishmania donovani complex, is responsible for over 20 000 deaths per year. This disease often affects the immunocompromised with an increased prevalence in those with human immunodeficiency virus (HIV). The immunocompromised are not only more susceptible to infection, but disseminated disease including gastric leishmaniasis. This is a case of gastric leishmaniasis occurring in a non-endemic region in a patient with comorbid HIV.

Case Presentation. The patient is a 39 year old originally from Central America currently living in Southeast Georgia. His history is significant for HIV, alcohol abuse, tobacco dependency and bone marrow biopsy-proven leishmaniasis. He denied any recent travel. At initial presentation, he had abdominal pain, nausea/vomiting, chills and dysphagia along with leukopenia and thrombocytopenia. Treatment with amphotericin B was initiated for his leishmaniasis as well as highly active antiretroviral therapy (HAART). The patient was discharged home on a 3 month course of amphotericin B with continued HAART therapy. Following resolution of his acute symptoms, six months later, the patient developed acute abdominal pain with nausea prompting presentation to the emergency department. Leishmaniasis was found again following bone marrow biopsy and the patient restarted amphotericin B and HAART. Several years later the patient presented again with similar symptoms, this time with accompanying rectal bleeding. The patient received an esophagogastroduodenoscopy and on gastric mucosal biopsy was found to have gastric leishmaniasis.

Conclusion. This manuscript highlights the key features of this case, including recognizing leishmaniasis clinically, proving diagnosis through definitive testing and understanding the connection between leishmaniasis and HIV.
Phenome-wide association study of TTR and RBP4 genes in 361,194 individuals reveals novel insights in the genetics of hereditary and senile systemic amyloidoses
Authors: De Lillo Antonella , De Angelis Flavio , Di Girolamo Marco , Luigetti Marco , Frusconi Sabrina , Manfellotto Dario , Fuciarelli Maria , Polimanti Renato
Published: July 2019

Transthyretin (TTR) gene has a causal role in a hereditary form of amyloidosis (ATTRm) and is potentially involved in the risk of senile systemic amyloidosis (SSA). To understand the genetics of ATTRm and SSA, we conducted a phenome-wide association study of TTR gene in 361,194 participants of European descent testing coding and non-coding variants. Among the 382 clinically-relevant phenotypes tested, TTR non-coding variants were associated with 26 phenotypic traits after multiple testing correction. These included signs related to both ATTRm and SSA such as chronic ischaemic heart disease (rs140226130, p=2.00×10−6), heart failure (rs73956431, p=2.74×10−6), atrial fibrillation (rs10163755, p=4.63×10−6), dysphagia (rs2949506, p=3.95×10−6), intestine diseases (rs970866, p=7.14×10−6) and anxiety (rs554521234, p=8.85×10−6). Consistent results were observed for TTR disease-causing mutation Val122Ile (rs76992529) with respect to carpal tunnel syndrome (p=6.41×10−6) and mononeuropathies of upper limbs (p=1.22×10−5). Sex differences were also observed in line with ATTRm and SSA epidemiology. Additionally, we explored possible modifier genes related to TTR function, observing convergent associations of RBP4 variants with the clinical phenotypes associated with TTR locus. In conclusion, we provide novel insights regarding the molecular basis of ATTRm and SSA based on large-scale cohort, expanding our understanding of the phenotypic spectrum associated with TTR gene variation.
Localization of a feline autosomal dominant dwarfism locus: a novel model of chondrodysplasia
Authors: Lyons L.A. , Fox D.B. , Chesney K.L. , Britt L.G. , Buckley R.M. , Coates J.R. , Gandolfi B. , Grahn R.A. , Hamilton M.J. , Middleton J.R. , Sellers S.T. , Villani N.A. , Pfleuger S. ,   the 99 Lives Consortium
Published: July 2019

Despite the contribution of a few major genes for disproportionate dwarfism in humans, many dwarf patients are yet genetically undiagnosed. In domestic cats, disproportionate dwarfism has led to the development of a defined breed, the Munchkin or Minuet. This study examined the genetic aspects of feline dwarfism to consider cats as a new biomedical model. DNA from dwarf cats was genetically analyzed using parentage, linkage, and genome-wide association studies as well as whole genome sequencing. Each genetic approach localized the dwarfism phenotype to a region on cat chromosome B1. No coding variants suspected as causal for the feline dwarfism were identified but a critical region of ∼5.7 Mb from B1:170,278,183-175,975,857 was defined, which implicates a novel gene controlling disproportionate dwarfism. A yet unidentified but novel gene variant, likely structural or regulatory, produces disproportionate dwarfism in cats, which may define undiagnosed human patients.
Genetic analysis of the STIM1 gene in chronic pancreatitis
Authors: Masson Emmanuelle , Zou Wen-Bin , Ruffert Claudia , Holste Vanessa , Michl Patrick , Mössner Joachim , Ewers Maren , Laumen Helmut , Wu Hao , Zhou Dai-Zhan , Li Zhao-Shen , Yu Dong , Boulling Arnaud , Maréchal Cédric Le , Cooper David N. , Chen Jian-Min , Witt Heiko , Rosendahl Jonas , Liao Zhuan , Férec Claude
Published: July 2019

Chronic pancreatitis is a complex disease that involves many factors, both genetic and environmental. Over the past two decades, molecular genetic analysis of five genes that are highly expressed in human pancreatic acinar cells, namely PRSS1, PRSS2, SPINK1, CTRC and CTRB1/CTRB2, has established that a trypsin-dependent pathway plays a key role in the etiology of chronic pancreatitis. Since Ca2+ deregulation can lead to intracellular trypsin activation in experimental acute pancreatitis, we analyzed STIM1 (encoding stromal interaction molecule-1, the main regulator of Ca2+ homeostasis in pancreatic acinar cells) as a candidate modifier gene in French, German and Chinese patients with chronic pancreatitis. The French and German subjects were analyzed by Sanger sequencing whereas the Chinese subjects were analyzed by targeted next-generation sequencing confirmed by Sanger sequencing. A total of 37 rare coding variants (35 missense and 2 nonsense) were identified, which were enriched in patients as compared with controls [2.28% (47/2,057) vs. 0.99% (33/3,322); odds ratio = 2.33, P = 0.0001]. This is the first large case-control study to demonstrate a putative association of rare STIM1 coding variants with chronic pancreatitis. Functional analysis will be required to clarify whether or not the rare STIM1 variants detected predispose to pancreatitis.
Population genetics of the highly polymorphicRPP8gene family
Authors: MacQueen Alice , Tian Dacheng , Chang Wenhan , Holub Eric , Kreitman Martin , Bergelson Joy
Published: July 2019

Plant NLR resistance genes provide some of the most extreme examples of polymorphism in eukaryotic genomes, rivalling even the vertebrate major histocompatibility complex. Surprisingly, this is also true inArabidopsis thaliana, a predominantly selfing species with low heterozygosity. Here, we investigate how gene duplication and intergenic exchange contribute to this extraordinary variation.RPP8is a three-locus system that is configured chromosomally as either a direct-repeat tandem duplication or as a single copy locus, plus a locus 2 Mb distant. We sequenced 48RPP8alleles from 37 accessions ofA. thalianaand 12RPP8alleles fromA. lyratato investigate the patterns of interlocus shared variation. The tandem duplicates display fixed differences and share less variation with each other than either shares with the distant paralog. A high level of shared polymorphism among alleles at one of the tandem duplicates, the single-copy locus and the distal locus, must involve both classical crossing over and intergenic gene conversion. Despite these polymorphism-enhancing mechanisms, the observed nucleotide diversity could not be replicated under neutral forward-in-time simulations. Only by adding balancing selection to the simulations do they approach level of polymorphism observed atRPP8. In this NLR gene triad, genetic architecture, gene function and selection all combine to generate diversity.