bluuebunny/crossref_metadata_2025 huggingface dataset:
Misdiagnosis of High-grade Serous Ovarian Cancer With BRCA Mutation as Endometriotic Cyst Due to Its Unique Gross Morphology: A Case Report and Literature Review
Authors: Ma Qiujie , Yuan Yuliang , Wang Ying , Shao Chao , Feng Wei
Published: January 2020

It is believed that high-grade serous ovarian cancer (HGSOC) is a solid or multilocular-solid cancer. Here, we report the case of a 40-yr-old woman with a left ovarian unilocular cyst. Ultrasonography and computed tomographic examination confirmed that the cyst was thin-walled and homogenous in thickness without mural nodules. It was considered to be an endometriotic cyst. Left ovarian cyst excision specimens proved it to be HGSOC after pathologic examination. Therefore, the patient underwent radical surgery for HGSOC. Pathologic examination of radical resection specimens confirmed that the HGSOC was still in FIGO stage IA and no fallopian tube lesion was found. Considering that the patient had a history of breast cancer in both the breasts at a young age, it was hypothesized that the breast cancer susceptibility gene (BRCA) gene may have a germline mutation. Next-generation sequencing confirmed the BRCA1 (c.3770_3771delAG) germline mutation in this patient. Previous studies have reported the special morphological characteristics and growth pattern of HGSOC with BRCA mutation in the advanced stage. Our case demonstrates that HGSOC with the BRCA mutation can also be a unilocular cyst with a thin wall and uniform thickness without a mural nodule, and in the early stage, may have unique gross morphology.
Enteric Type Bartholin Gland Adenocarcinoma: An Unusual Variant of a Rare Neoplasm
Authors: Robinson Harry , Karpe Manali , Edidi Ibrahim , Fisher Ann , Drew Yvette , Ralte Angela , O’Donnell Rachel L.
Published: January 2020

Vulval cancer is rare. With Bartholin gland carcinomas representing <5% of all vulval carcinomas they present both diagnostic and management challenges. There are a small number of cases in the literature describing Bartholin gland carcinomas with unusual histology which necessitates the need to explore the possibility of metastases from elsewhere. We present a case of a 55-yr-old woman presenting with a vulval lesion within the Bartholin gland. Morphology demonstrated enteric type adenocarcinoma and the immunohistochemistry profile was positive for CK7, CK20, CDX2, CEA, and CA19-9. There was no evidence of an alternative primary cancer and the tumor was excised with negative regional sentinel node assessment. Genotyping showed no detectable mutations in KRAS, BRAF or NRAS suggesting a possible future role for anti-EGFR therapy.
A Quality Improvement Project Focused on Improving First Dose Antibiotic Timeliness for Pediatric Intensive Care Unit Patients with Severe Sepsis
Authors: Keul Ryan , Rodriguez Jordan , Coleman Ariel , Yadav Prerna
Published: January 2020

Introduction:

Recommended time to start administration of first dose antibiotics for sepsis patients is 60 minutes from time 0. Institution-specific data revealed that only one-quarter of severe sepsis patients were meeting this goal when measured from the time of provider order entry. Reliance on a pneumatic tube system for first-dose antibiotic delivery was deemed largely responsible for this finding. This project aimed to increase the percentage of pediatric intensive care unit patients with severe sepsis receiving first dose antibiotics within 60 minutes of provider order entry to ≥50%.

Methods:

Baseline data were collected from May to June 2018 and resulted in the development of a new “antibiotic champion” process, which we piloted for 1 week in early August 2018. The primary outcome measure was the cumulative percentage of patients meeting the 60-minute goal as measured from provider order entry to start of antibiotic administration. A key secondary endpoint was the median time in minutes from provider order entry to antibiotic administration.

Results:

We included 14 patients in baseline data analysis and 16 patients in the pilot. The overall percentage of patients receiving antibiotics within 60 minutes of order entry increased from 29% to 75% (P-value: 0.026). The median time from provider order entry to antibiotic administration decreased by 36.5 minutes [baseline: 84.5 (range 58.8–117) versus pilot 48 (range 32–65), P-value: 0.0017].

Conclusion:

The antibiotic champion process significantly increased the total percentage of severe sepsis patients meeting the 60-minute goal and decreased the median time to first-dose antibiotic administration for pediatric intensive care unit patients.
An Evaluation of Safety and Patient Outcomes for Hand Surgery following Prior Breast Cancer Treatment: Establishing New Recommendations in Lymphedema
Authors: Paton Madeline , Kovar Alexandra , Iorio Matthew L.
Published: January 2020

Background:

Injuries to the upper extremity lymphatic system from cancer may require measures to prevent secondary lymphedema. Guidelines were established relating to the use of tourniquet and elective hand and upper extremity surgery. However, reports in the setting of hand surgery have indicated that prior guidelines may not be protective to the patient.

Methods:

The study systematically reviewed the current literature evaluating elective hand surgery in breast cancer patients. The authors evaluated the risk of complications, including new or worsening lymphedema and infection.

Results:

One hundred ninety-eight abstracts were identified, and a bibliographic review was performed. Nine studies pertained to our subject, and four were included for final review. All studies included patients with prior breast cancer treatment involving breast surgery and axillary lymph node dissection. Pneumatic tourniquets were used during nearly all operations. Patients without presurgery ipsilateral lymphedema had a 2.7 percent incidence of developing new lymphedema and a 0.7 percent rate of postoperative infection. Patients with presurgery lymphedema had a 11.1 percent incidence of worsening lymphedema and a 16.7 percent rate of infection. However, all cases of new or exacerbated lymphedema resolved within 3 months. Tourniquet use was not found to increase rates of lymphedema.

Conclusions:

Based on the available evidence, there is no increased risk of complications for elective hand surgery in patients with prior breast cancer treatment. Breast cancer patients with preexisting ipsilateral lymphedema carry slightly increased risk of postoperative infection and worsening lymphedema. It is the authors’ opinion and recommendation that elective hand surgery with a tourniquet is not a contradiction in patients who have received previous breast cancer treatments.
Impact of Physician Payments on Microvascular Breast Reconstruction: An All-Payer Claim Database Analysis
Authors: Panchal Hina , Shamsunder Meghana G. , Sheinin Avraham , Sheckter Clifford C. , Berlin Nicholas L. , Nelson Jonas A. , Allen Robert , Rubin David , Kozlow Jeffrey H. , Matros Evan
Published: January 2020

Background:

Rates of autologous breast reconstruction are stagnant compared with prosthetic techniques. Insufficient physician payment for microsurgical autologous breast reconstruction is one possible explanation. The payment difference between governmental and commercial payers creates a natural experiment to evaluate its impact on method of reconstruction. This study assessed the influence of physician payment differences for microsurgical autologous breast reconstruction and implants by insurance type on the likelihood of undergoing microsurgical reconstruction.

Methods:

The Massachusetts All-Payer Claims Database was queried for women undergoing immediate autologous or implant breast reconstruction from 2010 to 2014. Univariate analyses compared demographic and clinical characteristics between different reconstructive approaches. Logistic regression explored the relative impact of insurance type and physician payments on breast reconstruction modality.

Results:

Of the women in this study, 82.7 percent had commercial and 17.3 percent had governmental insurance. Implants were performed in 80 percent of women, whereas 20 percent underwent microsurgical autologous reconstruction. Women with Medicaid versus commercial insurance were less likely to undergo microsurgical reconstruction (16.4 percent versus 20.3 percent; p = 0.063). Commercial insurance, older age, and obesity independently increased the odds of microsurgical reconstruction (p < 0.01). When comparing median physician payments, governmental payers reimbursed 78 percent and 63 percent less than commercial payers for microsurgical reconstruction ($1831 versus $8435) and implants ($1249 versus $3359, respectively). Stratified analysis demonstrated that as physician payment increased, the likelihood of undergoing microsurgical reconstruction increased, independent of insurance type (p < 0.001).

Conclusions:

Women with governmental insurance had lower odds of undergoing microsurgical autologous breast reconstruction compared with commercial payers. Regardless of payer, greater reimbursement for microsurgical reconstruction increased the likelihood of microsurgical reconstruction. Current microsurgical autologous breast reconstruction reimbursements may not be commensurate with physician effort when compared to prosthetic techniques.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Can You Trust What You Watch? An Assessment of the Quality of Information in Aesthetic Surgery Videos on YouTube
Authors: Gray Megan C. , Gemmiti Amanda , Ata Ashar , Jun Brandon , Johnson Philip K. , Ricci Joseph A. , Patel Ashit
Published: January 2020

Background:

Videos on YouTube can be posted without regulation or content oversight. Unfortunately, many patients use YouTube as a resource on aesthetic surgery, leading to misinformation. Currently, there are no objective assessments of the quality of information on YouTube about aesthetic surgery.

Methods:

YouTube was queried for videos about the 12 most common aesthetic surgical procedures, identified from the 2015 American Society of Plastic Surgeons procedural statistics between May and June of 2016. The top 25 results for each search term were scored using the modified Ensuring Quality Information for Patients criteria based on video structure, content, and author identification. Average Ensuring Quality Information for Patients score, view count, and video duration were compared between authorship groups.

Results:

A total of 523 videos were graded after excluding duplicates. The mean modified Ensuring Quality Information for Patients score for all videos was 13.1 (SE, 0.18) of a possible 27. The videos under the search “nose reshaping” had the lowest mean score of 10.24 (SE, 0.74), whereas “breast augmentation” had the highest score of 15.96 (SE, 0.65). Physician authorship accounted for 59 percent of included videos and had a higher mean Ensuring Quality Information for Patients score than those by patients. Only three of the 21 search terms had a mean modified Ensuring Quality Information for Patients score meeting criteria for high-quality videos.

Conclusions:

The information contained in aesthetic surgery videos on YouTube is low quality. Patients should be aware that the information has the potential to be inaccurate. Plastic surgeons should be encouraged to develop high-quality videos to educate patients.
Recent Advances in Implant-Based Breast Reconstruction
Authors: Colwell Amy S. , Taylor Erin M.
Published: January 2020

Learning Objectives:

After reading this article, the participant should be able to: 1. Understand the indications for implant-based breast reconstruction and the indications for nipple preservation compared to skin-sparing or skin-reducing patterns. 2. Understand the indications for direct-to-implant breast reconstruction versus tissue expander/implant breast reconstruction and the advantages and disadvantages of total, partial, or no muscle coverage. 3. Understand the role of acellular dermal matrix or mesh in reconstruction. 4. Learn the advantages and disadvantages of different types and styles of implants and develop a postoperative plan for care and pain management.

Breast reconstruction with implants has seen a decade of advances leading to more natural breast reconstructions and lower rates of complications.
Challenging Traditional Thinking: Early Free Tissue Transfer for Active Hemifacial Atrophy in Children
Authors: Israel Jacqueline S. , Chen Jenny T. , Farmer Rebecca L. , Siebert John W.
Published: January 2020

Background:

Hemifacial atrophy (Parry-Romberg syndrome) is an enigmatic craniofacial disorder characterized by progressive facial atrophy. Early age at onset is associated with significant skeletal involvement and jaw abnormalities. Standard reconstructive dogma dictates that the disease should “burn out,” with at least 2 years of no disease progression, before pursuing reconstructive intervention. The purpose of this article is to present the senior author’s (J.W.S.) experience treating preadolescent children with free soft-tissue transfer for reconstruction of progressing hemifacial atrophy, and to review surgical techniques in this patient population.

Methods:

Pediatric free tissue transfer cases performed by the senior author were reviewed. Free tissue transfer using a circumflex scapular adipofasciocutaneous flap was performed to treat deformities arising from hemifacial atrophy.

Results:

Thirty-six patients aged 3 to 6 years underwent free tissue transfer in the presence of progressing, active disease. Follow-up ranged from 7 months to 25 years. There were no cases of flap loss. In all patients, the disease process seemed to be altered, with no symptoms recurring to date.

Conclusions:

The authors believe that early microsurgical correction of hemifacial atrophy in children as young as 3 years is reliable and effective. The authors theorize that the interposition of vascularized, healthy tissue may alter or even halt the progression of disease, and may also prevent the skeletal hypoplasia classically seen in older patients. Further study incorporating autologous fat grafting as a control procedure may provide additional insight into this challenging disease process.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Spare Roof Technique: A New Technique for Hump Removal—The Step-by-Step Guide
Authors: Gonçalves Ferreira Miguel , Santos Mariline , Rosa Francisco , Sousa Cecília A. , Santos Jorge , Dourado Nuno , Amarante José
Published: January 2020

Humpectomy is one of the most common steps in reduction rhinoplasty among Caucasian patients. The most widespread procedures to address hump removal are both the “en bloc humpectomy” (with reconstruction of the middle third with spreader grafts) and the “split hump technique” (with confection of spreader flaps). The spare roof technique, for rhinoplasty reduction, has been developed over the past 4 years. In this technique, the upper lateral cartilages are completely preserved—even the hidden part under the caudal aspect of the nasal bones. It consists of five main steps: step 1, the upper lateral cartilages are released from the dorsal aspect of the nasal septum; step 2, a 1-mm strip of the dorsal septum is taken in each movement as required; step 3, ostectomy of the caudal aspect of nasal bones, keeping the upper lateral cartilages intact and releasing the “lateral” (left and right) pyriform aperture ligament; step 4, classic medial and lateral osteotomies (closing the open bony roof); and step 5, suturing the upper lateral cartilages to the dorsal septum and thus avoiding the natural spring effect. The outcomes of the first 100 patients have been validated by a prospective, interventional, and longitudinal study performed on patients undergoing primary rhinoplasty by means of the spare roof technique. This study confirms that the spare roof technique significantly improved patient quality of life regarding nose function and appearance. It is a reliable technique that can help deliver consistently good results in Caucasian and Mediterranean patients with a dorsal hump seeking rhinoplasty.
Regional Patterns of Fluid and Fat Accumulation in Patients with Lower Extremity Lymphedema Using Magnetic Resonance Angiography
Authors: Dayan Joseph H. , Wiser Itay , Verma Richa , Shen Jody , Talati Nishi , Goldman Debra , Mehrara Babak J. , Smith Mark L. , Dayan, M.D. Erez , Coriddi, M.D. Michelle , Kagan Alexander
Published: January 2020

Background:

Fat accumulation is frequently observed in patients with lymphedema but is not accounted for in existing staging systems. In addition, the specific regional patterns of fat and fluid accumulation remain unknown and might affect outcomes following medical or surgical intervention. The purpose of this study was to evaluate fluid and fat distribution in patients with lower extremity lymphedema using magnetic resonance angiography.

Methods:

Magnetic resonance angiographic examinations of patients with lower extremity lymphedema were reviewed. Fluid-fat grade and location were assessed by three observers. Three-point scales were developed to grade fluid (0 = no fluid, 1 = reticular pattern of fluid, and 2 = continuous stripe of subcutaneous fluid) and fat (0 = normal, 1 = subcutaneous thickness less than twice that of the unaffected side, and 2 = subcutaneous thickness greater than twice that of the unaffected side) accumulation.

Results:

In total, 76 magnetic resonance angiographic examinations were evaluated. Using the proposed grading system, there was good interobserver agreement for fat and fluid accumulation location (91.5 percent; κ = 0.9), fluid accumulation grade (95.7 percent; κ = 0.95), and fat accumulation grade (87.2 percent; κ = 0.86). Patients with International Society of Lymphology stage 2 lymphedema had a wide range of fluid and fat grades (normal to severe). The most common location of fluid accumulation was the lateral lower leg, whereas the most common location of fat accumulation was the medial and lateral lower leg.

Conclusion:

The proposed magnetic resonance angiographic grading system may help stratify patients with International Society of Lymphology stage 2 lymphedema on the basis of tissue composition.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Diagnostic, IV.
Concomitant Imbalances of Systemic and Mucosal Immunity Increase HIV Acquisition Risk
Authors: Morrison Charles S. , Chen Pai-Lien , Yamamoto Hidemi , Gao Xiaoming , Chipato Tsungai , Anderson Sharon , Barbieri Robert , Salata Robert , Doncel Gustavo F. , Fichorova Raina N.
Published: January 2020

Background:

We previously reported association of increased cervical RANTES and decreased secretory leukocyte protease inhibitor (SLPI) with higher risk of HIV acquisition in reproductive-age women. We now examine the interaction of concomitantly altered systemic and cervical immunity on such risk.

Methods:

We measured immune biomarkers in 4390 cervical and 2390 paired serum specimens at quarterly visits in 218 HIV seroconverters and 784 seronegative women. We assessed proinflammatory (IL-1β, IL-6, IL-8, MIP-3α, and RANTES), anti-inflammatory (IL-1RA and SLPI), vascular activation (vascular endothelial growth factor and Intercellular Adhesion Molecule-1) and defensin (BD2) cervical biomarkers and systemic (peripheral blood) C reactive protein (CRP), IL-6, IL-7, and sCD14 as indicators of immune dysregulation. Biomarker levels were Box–Cox transformed and odds ratios for HIV acquisition calculated based on top quartile or higher/lower than median levels for all HIV-negative visits.

Results:

Subsequent HIV acquisition was associated with 5 of 14 individual biomarkers: low systemic CRP [odds ratio (OR) = 1.49, 1.21–1.83] and IL-6 (OR = 1.23, 1.00–1.51), high cervical BD-2 (OR = 1.33, 1.11–1.58) and RANTES (OR = 1.20, 1.01–1.43), and low cervical IL-1RA (OR = 0.65, 0.48–0.86). Low systemic CRP concomitant with altered cervical immunity, especially high BD2, conveyed highest HIV risk (1.63, 1.29–2.05). Additional markers of increased risk emerged when low systemic CRP coincided with: low systemic IL-6 and IL-7 (OR = 1.53, 1.18–1.97); high cervical IL-8 and MIP-3α (OR = 1.40, 1.07–1.83); high cervical IL-1β and IL-6 (OR = 1.43, 1.09–1.86); or low cervical SLPI (OR = 1.36, 1.08–1.71).

Conclusions:

Changes in both peripheral and mucosal immunity may precede and predispose women to HIV infection. Suppressed systemic immunity (ie, low CRP) alone or in combination with imbalanced cervical innate immunity (high proinflammatory and low anti-inflammatory mediators) indicated increased vulnerability to infection. Understanding these combined effects on HIV susceptibility is essential to preventing new infections.
HLA-DRB1*15:02 Is Associated With Iodinated Contrast Media–Related Anaphylaxis
Authors: Chung Soo Jie , Kang Dong Yoon , Lee Whal , Lee Seung Bok , Kim Sujeong , Lee Seung-Eun , Sim Da Woon , Kang Min-Gyu , Park Kyung Hee , Jung Jae-Woo , Yun James , Kang Hye-Ryun
Published: January 2020

Background

The incidence of severe reaction induced by iodinated contrast media (ICM) has increased over the years with an increasing use of imaging modalities. Although ICM anaphylaxis is rare, it can be life-threatening, but currently, there is no biomarker that can identify individuals at risk of ICM anaphylaxis.

Objective

The aim of this study is to investigate the genetic susceptibility of ICM anaphylaxis.

Methods

Patients who had ICM anaphylaxis were enrolled in the study, and their blood samples were collected for genotyping of human leukocyte antigen (HLA)-A, -B, -C, and -DR. The results were compared with those of healthy Korean general population. MRGPRX2 gene in ICM anaphylaxis group was also sequenced and compared with the Korean standard database of genetic polymorphism.

Results

The frequencies of 3 HLA alleles (B*52:01, C*12:02, and DRB1*15:02) were significantly higher in 47 patients with ICM anaphylaxis. In particular, HLA-DRB1*15:02 was 5 times more frequent in the ICM anaphylaxis group than the Korean general population (34.0% vs 6.6%; odds ratio, 7.306; 95% confidence interval, 3.622–14.740), and this difference was most pronounced in subjects with iohexol-induced anaphylaxis (odds ratio, 16.516; 95% CI, 5.241–52.047; P < 0.0001). Eight single nucleotide polymorphisms were identified in MRGPRX2 gene, but their frequencies were not different in those with ICM anaphylaxis compared with the general Korean population.

Conclusions

HLA-DRB1*15:02 is associated with ICM anaphylaxis in the Korean population.
Three-Dimensional Assessment of Pharyngeal Volume on Computed Tomography Scans: Applications to Anesthesiology and Endoscopy
Authors: Gibelli Daniele , Cellina Michaela , Gibelli Stefano , Oliva Antonio Giancarlo , Termine Giovanni , Sforza Chiarella
Published: January 2020

Pharyngeal volume is important in anesthesiology for correctly assessing intubation procedures. However, most of studies are based on patients in upright position and do not assess possible relationships between pharyngeal volume and cranial size. This study aims at measuring pharyngeal volume in CT-scans and to assess possible statistically significant differences according to sex.

Eighty healthy subjects (40 males and 40 females) aged between 21 and 86 years were retrospectively chosen from a hospital database of maxillofacial CT-scans; 3D segmentation was performed separately for naso-, oro- and laryngopharyngeal portion through ITK-SNAP software, and their volume was calculated. Three cranial measurements were obtained: distance between anterior and posterior nasal spine, upper facial height (nasion-prosthion) and biorbital breadth (ectoconchion-ectoconchion distance).

The effect of sex on volume for each pharyngeal portion was assessed through one-way ANCOVA test using each of the 3 cranial measurements as covariate (P < 0.05).

On average, the volume of nasopharynx, oropharynx and laryngopharynx was 7.2 ± 2.7 cm3, 7.5 ± 4.2 cm3, 3.5 ± 2.2 cm3 respectively in males, and 6.4 ± 2.9 cm3, 5.2 ± 2.1 cm3, 3.0 ± 1.8 cm3 in females. Statistically significant differences according to sex were found only for oropharyngeal volume, independently from cranial measurements (P < 0.05).

This study provides data concerning volume of pharyngeal air space in supine subjects: these reference standards can be useful for anaesthesiologic procedures.
Innate and Adaptive Immune Correlates of Chronic and Self-limiting EBV DNAemia in Solid-organ Transplant Recipients
Authors: Ferreira Victor H. , Batist Judah , Humar Atul , Kumar Deepali
Published: January 2020

Background.

Epstein-Barr virus (EBV) DNAemia is a major risk factor for posttransplant lymphoproliferative disorder; however, immune correlates of EBV DNAemia in the transplant setting are limited.

Methods.

Peripheral blood mononuclear cells were collected from 30 transplant recipients with self-limiting EBV DNAemia (SLD; n = 11) or chronic EBV DNAemia (CD; n = 19) at enrollment and 4–8 weeks later. Mass cytometry was used to characterize innate and T-cell immune correlates of EBV DNAemia. Furthermore, flow cytometry was used to measure the frequency of EBV-specific T-cell responses between groups following stimulation with an EBV-infected cell lysate.

Results.

Unsupervised analysis of the innate compartment (CD3–CD19– cells) identified 5 CD11c+ clusters at higher abundance in the SLD group (false discovery rate ≤ 1%). These clusters expressed CD11b, CD45RO, CD14, CD123, CD127, and CD38, among others. Unsupervised profiling of the T-cell compartment (CD3+CD19–) revealed 2 CD4+ T-cell clusters at higher frequency among those with SLD (false discovery rate ≤ 1%), which expressed CD45RA, CCR7, CD27, CD28, and CD40L—suggestive of a naive T cell (TN). Manual biaxial gating confirmed increased frequencies of conventional dendritic cells (3.1% versus 2.1%; P = 0.023) and CD4+ TN (4.4% versus 1.9%; P = 0.018) among those with SLD. Last, frequencies of interferon-γ–producing EBV-specific CD4+ T cells were significantly lower in the CD group relative to those with SLD (4243 versus 250 cells/106 cells; P = 0.015).

Conclusions.

CD is associated with a reduction of CD11c+ cells, CD4+ TN, and interferon-γ–producing EBV-specific CD4+ T cells, suggesting an interplay between innate and adaptive immune compartments may be important for regulating EBV DNAemia.
Mycophenolate Monotherapy in HLA-Matched Kidney Transplant Recipients: A Case Series of 20 Patients
Authors: Hennes Anthony J. , Holdener Kimberly E. , Burlingham William J. , Mandelbrot Didier A. , Parajuli Sandesh , Mohamed Maha A. , Garg Neetika , Aziz Fahad , Astor Brad C. , Djamali Arjang
Published: January 2020

Background.

The ideal minimizing strategy for maintenance immunosuppression in HLA-matched kidney transplant recipients (KTR) is unknown. We hypothesized that mycophenolate (MPA) monotherapy is a safe and effective approach for maintenance therapy in this group of KTR.

Methods.

Data were abstracted for 6-antigen HLA-matched KTR between 1994 and 2013. Twenty recipients receiving MPA monotherapy secondary to infection, cancer, calcineurin inhibitor (CNI) side effects, or immunosuppression minimization strategies were evaluated in this case series.

Results.

MPA monotherapy had a low incidence of death-censored graft failure (3.19/100 person-y), rejection (0/100 person-y), hospitalization (1.62/100 person-y), malignancy (3.61/100 person-y), and infection (1.75/100 person-y). Further, 12-month mean or median serum creatinine (1.29 mg/dL), estimated glomerular filtration rate (64.3 mL/min/1.73 m2), urine protein creatinine ratio (143.2 mg/g), hemoglobin (13.9 g/dL), platelets (237.8 K/uL), and white blood cell count (9.04 K/uL) were favorable. There was a successful conversion rate of 90% (18 of 20) with 2 patients converting back to CNI-based regimens secondary to recurrence of membranous nephropathy and post-transplant lymphoproliferative disorder.

Conclusions.

Our findings indicate that MPA monotherapy may be a promising immunosuppression minimization strategy for HLA-matched KTR.
Site of Origin of the Ophthalmic Artery Influences the Risk for Retinal Versus Cerebral Embolic Events
Authors: Rossin Elizabeth J. , Gilbert Aubrey L. , Koen Nicholas , Leslie-Mazwi Thabele M. , Cunnane Mary E. , Rizzo Joseph F.
Published: January 2020

Background:

Embolic events leading to retinal ischemia or cerebral ischemia share common risk factors; however, it has been well documented that the rate of concurrent cerebral infarction is higher in patients with a history of transient ischemic attack (TIA) than in those with monocular vision loss (MVL) due to retinal ischemia. Despite the fact that emboli to the ophthalmic artery (OA) and middle cerebral artery share the internal carotid artery (ICA) as a common origin or transit for emboli, the asymmetry in their final destination has not been fully explained. We hypothesize that the anatomic location of the OA takeoff from the ICA may contribute to the differential flow of small emboli to the retinal circulation vs the cerebral circulation.

Methods:

We report a retrospective, comparative, case–control study on 28 patients with retinal ischemia and 26 patients with TIA or cerebral infarction caused by embolic events. All subjects underwent either computed tomography angiography or MRA. The location of the ipsilateral OA origin off the ICA was then graded in a blinded fashion and compared between cohorts. Vascular risk factors were collected for all patients, including age, sex, hypertension, hyperlipidemia, arrhythmia, diabetes, coronary artery disease, and smoking.

Results:

We find that in patients with retinal ischemia of embolic etiology, the ipsilateral OA takeoff from the ICA is more proximal than in patients with cerebral infarcts or TIA (P = 0.0002). We found no statistically significant differences in demographic, vascular, or systemic risk factors.

Conclusions:

We find that the mean anatomical location of the OA takeoff from the ICA is significantly more proximal in patients with MVL due to retinal ischemia compared with patients with TIA or cerebral ischemia. This finding contributes significantly to our understanding of a long observed but poorly understood phenomenon that patients with MVL are less likely to have concurrent cerebral ischemia than are patients with TIA.
Unilateral Fourth Nerve Palsy due to Presumed Metastatic Melanoma
Authors: Pasol Joshua , Mellon Eric A. , Feun Lynn G. , Saigal Gaurav M. , Diwanji Tejan P. , Komotar Ricardo J.
Published: January 2020

An 81-year-old man with a history of metastatic melanoma presented with sudden onset of painless, binocular vertical diplopia. The clinical examination was consistent with a right fourth nerve palsy. An MRI of the head revealed a mass dorsal to the right tectum at the level of the inferior colliculus. An MRI just 4 months prior did not show a lesion in that location. An MRA of the head did not show an aneurysm. This is a rare case of an isolated fourth nerve palsy believed to be due to metastatic melanoma compressing the nerve along the dorsal midbrain.
Climate change, ecosystems and abrupt change: science priorities
Authors: Turner Monica G. , Calder W. John , Cumming Graeme S. , Hughes Terry P. , Jentsch Anke , LaDeau Shannon L. , Lenton Timothy M. , Shuman Bryan N. , Turetsky Merritt R. , Ratajczak Zak , Williams John W. , Williams A. Park , Carpenter Stephen R.
Published: January 2020

Ecologists have long studied patterns, directions and tempos of change, but there is a pressing need to extend current understanding to empirical observations of abrupt changes as climate warming accelerates. Abrupt changes in ecological systems (ACES)—changes that are fast in time or fast relative to their drivers—are ubiquitous and increasing in frequency. Powerful theoretical frameworks exist, yet applications in real-world landscapes to detect, explain and anticipate ACES have lagged. We highlight five insights emerging from empirical studies of ACES across diverse ecosystems: (i) ecological systems show ACES in some dimensions but not others; (ii) climate extremes may be more important than mean climate in generating ACES; (iii) interactions among multiple drivers often produce ACES; (iv) contingencies, such as ecological memory, frequency and sequence of disturbances, and spatial context are important; and (v) tipping points are often (but not always) associated with ACES. We suggest research priorities to advance understanding of ACES in the face of climate change. Progress in understanding ACES requires strong integration of scientific approaches (theory, observations, experiments and process-based models) and high-quality empirical data drawn from a diverse array of ecosystems.

This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions’
The development of Anthropocene biotas
Authors: Thomas Chris D.
Published: January 2020

Biodiversity has always responded dynamically to environmental perturbations in the geological past, through changes to the abundances and distributions of genes and species, to the composition of biological communities, and to the cover and locations of different ecosystem types. This is how the ‘nature’ that exists today has survived. The same is true in the Anthropocene. The entire planet surface has been altered by humans, ranging from direct vegetation transformation and removal of most of the world's megafauna, through to atmospheric changes in greenhouse gasses and consequent climatic changes and ocean acidification. These anthropogenic perturbations have led to the establishment of genes and species in new locations, thus generating novel communities and ecosystems. In this historical context, recent biological changes should be seen as responses to multiple drivers of change, rather than being a problem
per se
. These changes are the means by which the biosphere is adjusting to and will ultimately survive the Anthropocene. Thus, management and conservation of the biological world, and our place in it, requires a transition from trying to minimize biological change to one in which we facilitate dynamism that accelerates the rates at which species and ecosystems adjust to human-associated drivers of change.

This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions’.
Planning for climate change through additions to a national protected area network: implications for cost and configuration
Authors: Lawler Joshua J. , Rinnan D. Scott , Michalak Julia L. , Withey John C. , Randels Christopher R. , Possingham Hugh P.
Published: January 2020

Expanding the network of protected areas is a core strategy for conserving biodiversity in the face of climate change. Here, we explore the impacts on reserve network cost and configuration associated with planning for climate change in the USA using networks that prioritize areas projected to be climatically suitable for 1460 species both today and into the future, climatic refugia and areas likely to facilitate climate-driven species movements. For 14% of the species, networks of sites selected solely to protect areas currently climatically suitable failed to provide climatically suitable habitat in the future. Protecting sites climatically suitable for species today and in the future significantly changed the distribution of priority sites across the USA—increasing relative protection in the northeast, northwest and central USA. Protecting areas projected to retain their climatic suitability for species cost 59% more than solely protecting currently suitable areas. Including all climatic refugia and 20% of areas that facilitate climate-driven movements increased the cost by another 18%. Our results indicate that protecting some types of climatic refugia may be a relatively inexpensive adaptation strategy. Moreover, although addressing climate change in conservation plans will have significant implications for the configuration of networks, the increased cost of doing so may be relatively modest.

This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions’.
Co-producing ecosystem services for adapting to climate change
Authors: Lavorel Sandra , Locatelli Bruno , Colloff Matthew J. , Bruley Enora
Published: January 2020

Ecosystems can sustain social adaptation to environmental change by protecting people from climate change effects and providing options for sustaining material and non-material benefits as ecological structure and functions transform. Along adaptation pathways, people navigate the trade-offs between different ecosystem contributions to adaptation, or adaptation services (AS), and can enhance their synergies and co-benefits as environmental change unfolds. Understanding trade-offs and co-benefits of AS is therefore essential to support social adaptation and requires analysing how people co-produce AS. We analysed co-production along the three steps of the ecosystem cascade: (i) ecosystem management; (ii) mobilization; and (iii) appropriation, social access and appreciation. Using five exemplary case studies across socio-ecosystems and continents, we show how five broad mechanisms already active for current ecosystem services can enhance co-benefits and minimize trade-offs between AS: (1) traditional and multi-functional land/sea management targeting ecological resilience; (2) pro-active management for ecosystem transformation; (3) co-production of novel services in landscapes without compromising other services; (4) collective governance of all co-production steps; and (5) feedbacks from appropriation, appreciation of and social access to main AS. We conclude that knowledge and recognition of co-production mechanisms will enable pro-active management and governance for collective adaptation to ecosystem transformation.

This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions’.
Understanding the value and limits of nature-based solutions to climate change and other global challenges
Authors: Seddon Nathalie , Chausson Alexandre , Berry Pam , Girardin Cécile A. J. , Smith Alison , Turner Beth
Published: January 2020

There is growing awareness that ‘nature-based solutions' (NbS) can help to protect us from climate change impacts while slowing further warming, supporting biodiversity and securing ecosystem services. However, the potential of NbS to provide the intended benefits has not been rigorously assessed. There are concerns over their reliability and cost-effectiveness compared to engineered alternatives, and their resilience to climate change. Trade-offs can arise if climate mitigation policy encourages NbS with low biodiversity value, such as afforestation with non-native monocultures. This can result in maladaptation, especially in a rapidly changing world where biodiversity-based resilience and multi-functional landscapes are key. Here, we highlight the rise of NbS in climate policy—focusing on their potential for climate change adaptation as well as mitigation—and discuss barriers to their evidence-based implementation. We outline the major financial and governance challenges to implementing NbS at scale, highlighting avenues for further research. As climate policy turns increasingly towards greenhouse gas removal approaches such as afforestation, we stress the urgent need for natural and social scientists to engage with policy makers. They must ensure that NbS can achieve their potential to tackle both the climate and biodiversity crisis while also contributing to sustainable development. This will require systemic change in the way we conduct research and run our institutions.

This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions’.
Climate change mitigation and nature conservation both require higher protected area targets
Authors: Roberts Callum M. , O'Leary Bethan C. , Hawkins Julie P.
Published: January 2020

Nations of the world have, to date, pursued nature protection and climate change mitigation and adaptation policies separately. Both efforts have failed to achieve the scale of action needed to halt biodiversity loss or mitigate climate change. We argue that success can be achieved by aligning targets for biodiversity protection with the habitat protection and restoration necessary to bring down greenhouse gas concentrations and promote natural and societal adaptation to climate change. Success, however, will need much higher targets for environmental protection than the present 10% of sea and 17% of land. A new target of 30% of the sea given high levels of protection from exploitation and harm by 2030 is under consideration and similar targets are being discussed for terrestrial habitats. We make the case here that these higher targets, if achieved, would make the transition to a warmer world slower and less damaging for nature and people.

This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions’.
Tipping positive change
Authors: Lenton Timothy M.
Published: January 2020

Tipping points exist in social, ecological and climate systems and those systems are increasingly causally intertwined in the Anthropocene. Climate change and biosphere degradation have advanced to the point where we are already triggering damaging environmental tipping points, and to avoid worse ones ahead will require finding and triggering positive tipping points towards sustainability in coupled social, ecological and technological systems. To help with that I outline how tipping points can occur in continuous dynamical systems and in networks, the causal interactions that can occur between tipping events across different types and scales of system—including the conditions required to trigger tipping cascades, the potential for early warning signals of tipping points, and how they could inform deliberate tipping of positive change. In particular, the same methods that can provide early warning of damaging environmental tipping points can be used to detect when a socio-technical or socio-ecological system is most sensitive to being deliberately tipped in a desirable direction. I provide some example targets for such deliberate tipping of positive change.

This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions'.
Halioglobus maricola sp. nov., isolated from coastal seawater
Authors: Li Shan-Hui , Song Jaeho , Lim Yeonjung , Joung Yochan , Kang Ilnam , Cho Jang-Cheon
Published: January 2020

A Gram-stain-negative, rod-shaped, aerobic, non-flagellated, chemoheterotrophic bacterium, designated IMCC14385T, was isolated from surface seawater of the East Sea, Republic of Korea. The 16S rRNA gene sequence analysis indicated that IMCC14385T represented a member of the genus

Halioglobus

sharing 94.6–97.8 % similarities with species of the genus. Whole-genome sequencing of IMCC14385T revealed a genome size of 4.3 Mbp and DNA G+C content of 56.7 mol%. The genome of IMCC14385T shared an average nucleotide identity of 76.6 % and digital DNA–DNA hybridization value of 21.6 % with the genome of

Halioglobus japonicus

KCTC 23429T. The genome encoded the complete poly-β-hydroxybutyrate biosynthesis pathway. The strain contained summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c), summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c) and C17 : 1
ω8c as the predominant cellular fatty acids as well as ubiquinone-8 (Q-8) as the respiratory quinone. The polar lipids detected in the strain were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, five unidentified phospholipids, an unidentified aminolipid, an unidentified aminophospholipid and four unidentified lipids. On the basis of taxonomic data obtained in this study, it is suggested that IMCC14385T represents a novel species of the genus

Halioglobus

, for which the name Halioglobus maricola sp. nov. is proposed. The type strain is IMCC14385T (=KCTC 72520T=NBRC 114072T).
Large mosaic copy number variations confer autism risk
Authors: Sherman Maxwell A. , Rodin Rachel E. , Genovese Giulio , Dias Caroline , Barton Alison R. , Mukamel Ronen E. , Berger Bonnie , Park Peter J. , Walsh Christopher A. , Loh Po-Ru
Published: January 2020

Although germline de novo copy number variants are a known cause of autism spectrum disorder (ASD), the contribution of mosaic (early-developmental) copy number variants (mCNVs) has not been explored. Here, we assessed the contribution of mCNVs to ASD by ascertaining mCNVs in genotype array intensity data from 12,077 ASD probands and 5,500 unaffected siblings in the Simons Simplex Collection (SSC) and Simons Powering Autism Research for Knowledge (SPARK) cohorts. We detected 46 mCNVs in probands and 19 mCNVs in siblings ranging from 49 kb to 249 Mb and affecting 2.8-73.8% of cells. In both cohorts, probands carried a significant burden of large (>4 Mb) mCNVs (P = 0.043 and P = 6.6 × 10−3 in SSC and SPARK, respectively), which were present in a total of 25 probands but only 1 sibling (OR=11.4, 95% CI=1.5-84.2). Surprisingly, we did not observe mosaic analogues of the short de novo CNVs recurrently observed in ASD. Event size positively correlated with severity of ASD symptoms (P = 0.016), and four probands exhibited clinical symptoms consistent with syndromes previously associated with genes or regions disrupted by their respective mosaic mutations. In analyses of post-mortem brain tissue from 60 additional probands, we further detected and experimentally validated two mCNVs including a complex 10.3 Mb duplication on chromosome 2. These results indicate that mosaic CNVs contribute a previously unexplained component of ASD risk.
Pilot study demonstrating changes in DNA hydroxymethylation enable detection of multiple cancers in plasma cell-free DNA
Authors: Bergamaschi Anna , Ning Yuhong , Ku Chin-Jen , Ellison Chris , Collin Francois , Guler Gulfem , Phillips Tierney , McCarthy Erin , Wang Wendy , Antoine Michael , Scott Aaron , Lloyd Paul , Ashworth Alan , Quake Steve , Levy Samuel
Published: January 2020

Our study employed the detection of 5-hydroxymethyl cytosine (5hmC) profiles on cell free DNA (cfDNA) from the plasma of cancer patients using a novel enrichment technology coupled with sequencing and machine learning based classification method. These classification methods were develoiped to detect the presence of disease in the plasma of cancer and control subjects. Cancer and control patient cfDNA cohorts were accrued from multiple sites consisting of 48 breast, 55 lung, 32 prostate and 53 pancreatic cancer subjects. In addition, a control cohort of 180 subjects (non-cancer) was employed to match cancer patient demographics (age, sex and smoking status) in a case-control study design.

Logistic regression methods applied to each cancer case cohort individually, with a balancing non-cancer cohort, were able to classify cancer and control samples with measurably high performance. Measures of predictive performance by using 5-fold cross validation coupled with out-of-fold area under the curve (AUC) measures were established for breast, lung, pancreatic and prostate cancer to be 0.89, 0.84, 0.95 and 0.83 respectively. The genes defining each of these predictive models were enriched for pathways relevant to disease specific etiology, notably in the control of gene regulation in these same pathways. The breast cancer cohort consisted primarily of stage I and II patients, including tumors < 2 cm and these samples exhibited a high cancer probability score. This suggests that the 5hmC derived classification methodology may yield epigenomic detection of early stage disease in plasma. Same observation was made for the pancreatic dataset where >50% of cancers were stage I and II and showed the highest cancer probability score.