bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donor-specific antibody management in intestine transplantation: hope for improving the long-term durability of the intestine allograft?
Authors: Hawksworth Jason S. , Matsumoto Cal S. 
Published: January 2019

Purpose of review
In this review, we appraise the current status of donor-specific antibody (DSA) monitoring and treatment in the literature and highlight the current challenges in DSA management for the intestine transplant community.

Recent findings
Sensitizing events are common in patients referred for intestinal transplant, as these patients universally are repeatedly exposed to immune activation and inflammatory events. Both preformed and de novo DSA have been shown to increase rejection and graft loss in intestine recipients. Avoidance of preformed DSA with the use of virtual crossmatch (VXM) and antibody monitoring protocols to detect and treat de novo DSA may improve intestine transplant outcomes. There is no consensus on the clinical and pathologic criteria that are required to diagnose antibody-mediated rejection (AMR) in the intestine recipient. Therefore, many clinicians treat AMR based on the coincidence of DSA and acute biopsy-proven rejection. Inclusion of the liver in the intestine allograft appears to be immunologically protective in the setting of DSA with improved outcomes and a higher rate of preformed DSA clearance. Critically, DSA has been linked to chronic rejection and poor long-term outcomes in the intestine recipient.

Summary
On the basis of increasing evidence in the intestine transplant literature, it appears that avoidance of preformed DSA and aggressive monitoring and treatment of de novo DSA is a key to long-term survival following intestine transplantation.
Menin Upregulates FOXO1 Protein Stability by Repressing Skp2-Mediated Degradation in β Cells
Authors: Jiang Zongzhe , Xing Bowen , Feng Zijie , Ma Jian , Ma Xiaosong , Hua Xianxin 
Published: January 2019

Objectives
Menin, a chromatin binding protein, interacts with various epigenetic regulators to regulate gene transcription, whereas forkhead box protein O1 (FOXO1) is a transcription factor that can be regulated by multiple signaling pathways. Both menin and FOXO1 are crucial regulators of β-cell function and metabolism; however, whether or how they interplay to regulate β cells is not clear.

Methods
To examine whether menin affects expression of FOXO1, we ectopically expressed menin complementary DNA and small hairpin RNA targeting menin via a retroviral vector in INS-1 cells. Western blotting was used to analyze protein levels.

Results
Our current work shows that menin increases the expression of FOXO1. Menin stabilizes FOXO1 protein level in INS-1 cells, as shown by increased half-life of FOXO1 by menin expression. Moreover, menin represses ubiquitination of FOXO1 protein and AKT phosphorylation, We found that menin stabilizes FOXO1 by repressing FOXO1 degradation mediated by S-phase kinase-associated protein 2 (Skp2), an E3 ubiquitin ligase, promoting caspase 3 activation and apoptosis.

Conclusions
Because FOXO1 upregulates the menin gene transcription, our findings unravel a crucial menin and FOXO1 interplay, with menin and FOXO1 upregulating their expression reciprocally, forming a positive feedback loop to sustain menin and FOXO1 expression.
Early Hemoconcentration Is Associated With Increased Opioid Use in Hospitalized Patients With Acute Pancreatitis
Authors: Parsa Nasim , Faghih Mahya , Garcia Gonzalez Francisco , Moran Robert A. , Kamal Ayesha , Jalaly Niloofar Y. , Al-Grain Haitham , Akshintala Venkata S. , Makary Martin A. , Khashab Mouen A. , Kalloo Anthony N. , Singh Vikesh K. 
Published: January 2019

ObjectivesOpioids are commonly required for abdominal pain in hospitalized patients with acute pancreatitis (AP). The factors associated with increased opioid requirements are unknown.MethodsThe medical records of adult inpatients with AP from 2006 to 2016 were reviewed. Patients with chronic pancreatitis, psychiatric comorbidities, intubation, chronic opioid, and illicit drug use were excluded. The total quantity of opioids required during the first 7 days of hospitalization was converted to oral morphine equivalents (OME), divided by the number of days opioids were required to obtain the mean OME per day(s) of treatment (MOME). Multiple regression analysis was performed to identify factors associated with MOME.ResultsA total of 267 patients were included. The mean (standard deviation) age was 46.9 (13.9) years and 56% were males. The most common etiology was alcohol (55.4%). The mean (standard deviation) MOME was 59.1 (54.5) mg. Although age (P= 0.008), black race (P= 0.004), and first episode of AP (P= 0.049) were associated with a lower MOME, early hemoconcentration (hematocrit ≥44%) (P< 0.001) was associated with an increased MOME.ConclusionsEarly hemoconcentration is associated with an increased opioid requirement in hospitalized patients with AP. The impact of fluid therapy in these patients merits prospective study.
Mechanism of Action and Novel IMiD-Based Compounds and Combinations in Multiple Myeloma
Authors: Nooka Ajay K. , Lonial Sagar 
Published: January 2019

Abstract
Over the last 2 decades, thalidomide analogs have induced significant antimyeloma effects via immune-modulation, antiangiogenesis and antiproliferative effects. While the exact molecular mechanism of the targets or the mediators of thalidomide activity were not known, a seminal discovery of cereblon as a thalidomide-binding protein led to explaining the mechanistic basis of antimyeloma activity for this class of agents. Identification of the mechanisms of resistance for immunomodulatory agents (IMiDs), which will have significant clinical implications, remains poorly understood. Newer cereblon modulators with differential effects and improved increased efficacy in cell lines resistant to the current IMiDs are in development with encouraging preclinical data. In this review, we have summarized the mechanisms of action of IMiDs, clinical development, and potential mechanisms of resistance. We also describe novel IMiD-based combinations and the newer cereblon modulators as well.
Collagenase Clostridium Histolyticum for Dupuytren’s Contracture: Comparing Single and Concurrent Injections
Authors: Cook Jonathan , Waughtel Jessica , Andreoni Anthony R. , Sakharpe Aniket , Friedman David W. 
Published: January 2019

Background:
The U.S. Food and Drug Administration approved collagenase clostridium histolyticum for treatment of Dupuytren’s contracture in 2010, and for the concurrent treatment of up to two cords in 2014. Although outcomes and adverse events have been well described for single injections, comparative data on concurrent injections are lacking.

Methods:
The authors reviewed 121 concurrent collagenase clostridium histolyticum injections and compared these with 177 single injections over 8 years. All injections were performed by a single surgeon, our senior author (D.F.). A retrospective cohort model was used to compare clinical outcomes and adverse events (i.e., skin tears, spontaneous cord rupture, tendon rupture, lymphadenopathy, blood blisters, and ecchymosis) between groups.

Results:
There were no statistical differences between groups in clinical success rate or change in contracture per joint. The rate of skin tears per joint in concurrent injections (22.3 percent) was not statistically different from that of single injections (18.6 percent; p = 0.46), and was consistent with previously reported rates. The rate of skin tears did not change significantly over time in either group. Concurrent injection did not influence the incidence of skin tears in a dose-dependent manner (relative risk, 1.20). Patients receiving concurrent injections experienced a higher rate of lymphadenopathy compared with those receiving single injections (p = 0.001).

Conclusions:
Concurrent collagenase clostridium histolyticum injections for Dupuytren’s contracture have a similar safety profile and treatment efficacy when compared to single injections. The authors did not find a dose-dependent relationship between skin tears and collagenase clostridium histolyticum injected.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Experimentally Induced Arterial Embolism by Hyaluronic Acid Injection: Clinicopathologic Observations and Treatment
Authors: Chen Yin , Zhang You-liang , Luo Sheng-Kang 
Published: January 2019

Background:
Although major complications of hyaluronic acid injection rarely occur, with the rapidly growing number of procedures performed and their expanding applications, such complications warrant greater attention. Our study was designed to explore optimal treatment methods for hyaluronic acid–related vascular occlusion.

Methods:
In the first part of the study, 60 rats were given intraarterial hyaluronic acid injected into the bilateral inferior epigastric arteries to establish an animal model, and were euthanized at different postinjection time points. The inferior epigastric artery was retrieved for pathologic examination. In the second part of the study, bilateral abdominal flaps supplied by the inferior epigastric artery were elevated in six groups of rats, and hyaluronic acid was injected into the right side, with each group receiving a different intervention. The flap survival rate was calculated and analyzed.

Results:
In the first part of the study, pathologic examination revealed that the composition of the emboli caused by arterial hyaluronic acid–induced occlusion changed from pure hyaluronic acid to a hyaluronic acid–thrombus mixture. In the second part of the study, flap survival rates (mean percentages) were as follows: group A, 43.29 ± 9.28 percent; group B, 54.17 ± 10.86 percent; group C, 59.27 ± 13.40 percent; group D, 64.37 ± 8.61 percent; group E, 71.92 ± 19.06 percent; and group F, 57.47 ± 13.64 percent. Group A differed significantly from groups B, C, D, and E (p < 0.001). No significant difference was observed between groups A and F (p > 0.05).

Conclusions:
The combined use of intravenous or subcutaneous hyaluronidase and urokinase was most effective in treating hyaluronic acid injection-related arterial embolism after 45 minutes and 24 hours. This treatment may be ineffective after 48 hours.
Skin Hydration Level as a Predictor for Diabetic Wound Healing: A Retrospective Study
Authors: Lee Tae-Yul , Kim Ki-Bum , Han Seung-Kyu , Jeong Seong-Ho , Dhong Eun-Sang 
Published: January 2019

Background:
In the diabetic foot, the skin may crack and develop fissures, potentially increasing vulnerability to ulceration and infection. Therefore, maintaining adequate skin hydration may be crucial for diabetic wound healing. However, no clinical study has addressed this issue. This study aimed to determine and compare the effect of the skin hydration level on diabetic wound healing with that of the tissue oxygenation level, which is recognized as the most reliable parameter in predicting diabetic wound healing.

Methods:
This retrospective study included 263 diabetic patients with forefoot ulcers. Skin hydration and transcutaneous oxygen pressure data collected before and after percutaneous transluminal angioplasty were analyzed. Skin hydration and tissue oxygenation were graded as poor, moderate, or acceptable. Wound healing outcomes were graded as healed without amputation, minor amputation, or major amputation. Wound healing outcomes were compared using four parameters: skin hydration at baseline, transcutaneous oxygen pressure at baseline, post–percutaneous transluminal angioplasty skin hydration, and post–percutaneous transluminal angioplasty transcutaneous oxygen pressure.

Results:
Each of the four parameters exhibited statistically significant correlations with wound healing outcomes. In the concurrent analysis of both skin hydration and transcutaneous oxygen pressure, skin hydration was a dominant parameter (p = 0.0018) at baseline, whereas transcutaneous oxygen pressure was a dominant parameter (p < 0.0001) following percutaneous transluminal angioplasty.

Conclusions:
Skin hydration level might be a useful predictor for diabetic wound healing. In particular, the skin hydration level before recanalization was found to be superior to transcutaneous oxygen pressure in predicting wound healing.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
Reconstruction of Diabetic Foot Defects With the Proximal Lateral Leg Perforator Flap
Authors: Lee Jiunn-Tat , Cheng Li-Fu , Hsu Honda , Wu Meng-Si , Chien Sou-Hsin 
Published: January 2019

Background
In patients with diabetic foot ulcers requiring flap reconstruction, the choice of local flaps is limited by the lack of adequate tissue available. Free flaps are often bulky, presenting footwear difficulty due to poor contouring. Here, we present our experience of using the proximal lateral leg perforator flap in the reconstruction of thin diabetic foot ulcers.

Methods
This is a retrospective study of 17 patients with diabetic foot ulcers reconstructed with the proximal lateral leg perforator flap during January 2013 and December 2015.

Results
Nine patients had varying degrees of peripheral arterial disease. The perforator was located 7 to 14 cm (mean, 9.7 cm) from the fibula head. The pedicle length ranged from 5 to 9 cm (mean, 6.9 cm). The arterial diameter of the pedicle measured 0.8 to 1.9 mm (mean, 1.4 mm). There was 1 total flap failure. One other flap complicated by venous thrombosis was successfully salvaged. All donor sites were closed primarily without morbidities. All the wounds were stable without recurrent ulceration during a mean follow-up time of 12 months.

Conclusion
The thin, pliable proximal lateral leg perforator flap is an option for the reconstruction of small to moderate diabetic foot defects especially when it is located over the dorsal foot or the ankle. The flap is simple and quick to harvest without sacrificing a major artery. Although it is limited by the short length and the small diameter of the pedicle, for experienced microsurgeons, the success rate is high.
The Power of Patient Norms
Authors: Rochlin Danielle H. , Leon Daniel Sotelo , Yu Caroline , Long Chao , Nazerali Rahim , Lee Gordon K. 
Published: January 2019

Introduction
Enhanced recovery after surgery pathways designed to optimize postoperative care have become increasingly popular across multiple surgical specialties with proven benefits. In this retrospective cohort study, we present a comparative evaluation of the impact of protocol-based postoperative care on free autologous breast reconstruction patients.

Methods
With institutional review board approval, we performed a chart review of patients who underwent breast reconstruction with free autologous tissue transfer by a single surgeon from 2006 to 2017. Patients were managed according to a postoperative protocol since 2006 that initially called for discharge home on postoperative day (POD) 4 for unilateral cases and POD 5 for bilateral cases. In May 2015, the protocol was revised to discharge home on POD 3 for all cases. Patients who underwent reconstruction before (2006 to April 2015) and after (May 2015 to 2017) the change in postoperative protocol were compared.

Results
A total of 432 patients (647 breasts) underwent free autologous breast reconstruction during the study period. Flaps were predominantly muscle-sparing transverse rectus abdominis myocutaneous (56.3%) or deep inferior epigastric perforator (30.3%) flaps. Average patient age was 51.6 years (range, 29.7–80.3 years). Unilateral reconstructions were performed for 167 patients before and 50 patients after the protocol change; average hospital length of stay (LOS) was 4.5 and 3.4 days, respectively (P < 0.001). Bilateral reconstructions were performed for 153 patients before and 62 patients after the protocol change; average hospital LOS was 5.1 and 3.5 days, respectively (P < 0.001). There was no significant increase in patients with major or minor complications.

Conclusions
Revising our postoperative protocol to reduce expected LOS was associated with an overall faster time to discharge without negative consequences in patients who underwent unilateral and bilateral free autologous breast reconstruction. Use of protocols to guide behavior not only can improve the patient experience by promoting a quicker return home, but may also have the added benefit of decreasing healthcare expenditures through reduced inpatient utilization.
Colorectal Surgical Site Infection Prevention Kits Prior to Elective Colectomy Improve Outcomes
Authors: Deery Sarah E. , Cavallaro Paul M. , McWalters Sean T. , Reilly Syrene R. , Bonnette Holly M. , Rattner David W. , Mort Elizabeth A. , Hooper David C. , del Carmen Marcela G. , Bordeianou Liliana G. 
Published: January 2019

Introduction:
Patient compliance with preoperative mechanical and antibiotic bowel preparation, skin washes, carbohydrate loading, and avoidance of fasting are key components of successful colorectal ERAS and surgical site infection (SSI)-reduction programs. In July 2016, we began a quality improvement project distributing a free SSI Prevention Kit (SSIPK) containing patient instructions, mechanical and oral bowel preparation, chlorhexidine washes, and carbohydrate drink to all patients scheduled for elective colectomy, with the goal of improving patient compliance and rates of SSI.

Methods:
This was a prospective data audit of our first 221 SSIPK+ patients, who were compared to historical controls (SSIPK−) of 1760 patients undergoing elective colectomy from January 2013 to March 2017. A 1:1 propensity score system accounted for nonrandom treatment assignment. Matched patients’ complications, particularly postoperative infection and ileus, were compared.

Results:
SSIPK+ (n = 219) and SSIPK− (n = 219) matched patients were statistically identical on demographics, comorbidities, BMI, surgical indication, and procedure. SSIPK+ patients had higher compliance with mechanical (95% vs 71%, P < 0.001) and oral antibiotic (94% vs 27%, P < 0.001) bowel preparation. This translated into lower overall SSI rates (5.9% vs 11.4%, P = 0.04). SSIPK+ patients also had lower rates of anastomotic leak (2.7% vs 6.8%, P = 0.04), prolonged postoperative ileus (5.9% vs 14.2%, P < 0.01), and unplanned intubation (0% vs 2.3%, P = 0.02). Furthermore, SSIPK+ patients had shorter mean hospital length of stay (3.1 vs 5.4 d, P < 0.01) and had fewer unplanned readmissions (5.9% vs 14.6%, P < 0.001). There were no differences in rates of postoperative pneumonia, urinary tract infection, Clostridium difficile colitis, sepsis, or death.

Conclusion:
Provision of a free-of-charge SSIPK is associated with higher patient compliance with preoperative instructions and significantly lower rates of surgical site infections, lower rates of prolonged postoperative ileus, and shorter hospital stays with fewer readmissions. Widespread utilization of such a bundle could therefore lead to significantly improved outcomes.
Automated noninvasive evaluation of blood flow and oxygenation in rats integrated with systemic physiological monitoring
Authors: Torres Filho Ivo P. , Barraza David , Williams Charnae , Hildreth Kim , Dubick Michael A. 
Published: January 2019

BACKGROUND
Many studies evaluating blood flow and oxygen partial pressure (Po
2) do not directly measure both parameters, are confined to few locations/microvessels, and depend on investigator's selection of measuring sites. Moreover, clinically/physiologically relevant systemic parameters are not simultaneously recorded. We implemented an automated system for prolonged blood flow/Po
2 acquisition in large areas while collecting relevant systemic information.

METHODS
In anesthetized animals, cardiorespiratory parameters were continuously recorded. Other data were collected at baseline and hourly after 4 hours of hemorrhagic shock. A cremaster muscle was spread over a pedestal fixed to a motorized stage. One 2-dimensional tissue scan allowed 16 noninvasive Po
2 measurements using oxygen-dependent phosphorescence quenching and fiber optics. Blood flow was estimated using laser speckle contrast imaging in the same areas used for Po
2 measurements. At each timepoint, blood was sampled for extensive biochemistry/coagulation profile.

RESULTS
The system was used successfully by different operators. A set of flow/Po
2 measurements was completed in less than 90 seconds. Muscle flow and Po
2 correlated with some but not several systemic parameters, emphasizing the importance of performing both local and systemic evaluations.

CONCLUSION
System advantages include integration between local and over 40 systemic parameters, unbiased data collection/analysis, improved performance/sampled area, easy expansion, implementation and maintenance, no customized programming, and simplified training. Combining this system with trauma/prolonged HS models will enhance our ability to investigate tissue stability and select better resuscitation strategies to improve outcomes and survival.

LEVEL OF EVIDENCE
Diagnostic test, level V.
Somatosensory Evoked Potentials as a Stand-Alone Tool During Spine Surgery: An Egyptian Preliminary Report
Authors: Abdelkader Ann Ali , Zohdi Ahmed , El Gohary Amira M. , El-Hadidy Reem Atef , AlMahdy Rania A. 
Published: January 2019

Purpose:
Monitoring of somatosensory evoked potentials (SSEPs) serves as an early warning system to detect spinal cord injury and is correlated with postoperative sensory findings. It is an indirect indicator of motor function. This study aimed to evaluate the usefulness of intraoperative SSEPs monitoring as a stand-alone tool during spinal surgeries when motor evoked potentials are not available, to prevent and predict new postoperative neurologic deficits. Motor evoked potentials were not used as the equipment needed to record them was not available at the time of this study.

Methods:
This study included 50 patients, aged 14 to 67 years, undergoing extramedullary manipulations, decompression of an epidural abscess or neoplasm, removal of intramedullary tumor, or arteriovenous malformation or spine correction procedures. Somatosensory evoked potentials were analyzed for latency and peak-to-peak amplitude. Critical SSEP changes were defined as a 50% decrease in amplitude or a 10% increase in latency.

Results:
Somatosensory evoked potentials had an overall sensitivity of 81.8%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 91.3%.

Conclusions:
Intraoperative SSEPs have proved to be highly sensitive and specific for iatrogenic injury, mechanical stress caused by cord traction/compression, dural traction, lowered systemic blood pressure, and cord hypothermia. The reversibility of intraoperative SSEP changes showed a highly significant relation to the number of cases with new postoperative deficits as well as type and site of pathologic study (P = 0.00, P = 0.01, and P = 0.00, respectively) but not with the level of pathologic study (P = 0.49).