bluuebunny/crossref_metadata_2025 huggingface dataset:
Social isolation in chronic kidney disease and the role of mobility limitation
Authors: Moorthi Ranjani N , Latham-Mintus Kenzie
Published: December 2018

Background

Chronic kidney disease (CKD) is associated with multiple comorbidities, hospitalizations and mortality. In older adults, social isolation and poor mobility contribute to these outcomes. We tested the hypothesis that a glomerular filtration rate (GFR) <45 mL/min/1.73 m2 (CKD Stages 3b–5) is associated with social isolation and that mobility limitation is a key driver of social isolation in patients with CKD.

Methods

Data from 9119 participants, ages 57–107 years, from the 2016 wave of the Health and Retirement Study’s Venous Blood Study were used for this cross-sectional analysis. Kidney function measured by estimated GFR (eGFR) was the predictor and patients were classified as CKD Stages 3b–5 or non-CKD Stages 3b–5 (eGFR ≤45 or >45 mL/min/1.73 m2). The outcomes tested were mobility limitation assessed by self-report and social contact and participation measures assessed by the Psychosocial Life Questionnaire. The associations among kidney function, mobility and social isolation were examined with logistic and ordinary least squares regression, adjusted for covariates and testing for interaction with gender.

Results

Participants with CKD Stages 3b–5 (N = 999) compared with non-CKD Stages 3b–5 were older (74.9 versus 68.2 years, P < 0.001) and fewer were female (15% versus 58%, P < 0.001). CKD Stages 3b–5 were associated with higher odds of difficulty walking several blocks [odds ratio 1.44 (95% confidence interval 1.16–1.78)]. Participants with CKD Stages 3b–5 had reduced social contact and social participation (B = −0.23, P < 0.05; B = −0.62, P < 0.05, respectively). Women with CKD Stages 3b–5 were 2.7 times more likely to report difficulty walking several blocks than men with CKD Stages 3b–5, but social isolation in CKD Stages 3b–5 did not vary by gender. In CKD Stages 3b–5 patients, mobility limitation was a risk factor for reduced social contact and participation but did not explain the poor social contact and participation.

Conclusion

CKD Stages 3b–5 was associated with both mobility limitation and social isolation in a population-based study of older adults. In contrast to older adults without CKD Stages 3b–5, mobility limitation did not explain the lack of social contact and poor social participation, suggesting other factors are more important.
A gender-based analysis of the obesity paradox in cardiac surgery: height for women, weight for men?
Authors: Ranucci Marco , de Vincentiis Carlo , Menicanti Lorenzo , La Rovere Maria Teresa , Pistuddi Valeria
Published: December 2018

OBJECTIVES

In cardiac surgery, obesity is associated with a lower mortality risk. This study aims to investigate the association between body mass index (BMI) and operative mortality separately in female patients and male patients undergoing cardiac surgery and to separate the effects of weight and height in each gender-based cohort of patients.

METHODS

A retrospective cohort study including 7939 consecutive patients who underwent cardiac surgery was conducted. The outcome measure was the operative mortality.

RESULTS

In men, there was a U-shaped relationship between the BMI and the operative mortality, with the lower mortality rate at a BMI of 35 kg/m2. In women, the relationship is J-shaped, with the lower mortality at a BMI of 22 kg/m2. Female patients with obesity class II–III had a relative risk for operative mortality of 2.6 [95% confidence interval (CI) 1.37–4.81, P = 0.002]. The relationship between weight and mortality rate is a U-shaped bot in men and women, with the lower mortality rate at 100 kg for men and 70 kg for women. Height was linearly and inversely associated with the operative mortality in men and women. After correction for the potential confounders, height, but not weight, was independently associated with operative mortality in women (odds ratio 0.949, 95% CI 0.915–0.983; P = 0.004); conversely, in men, this association exists for weight (odds ratio 1.017, 95% CI 1.001–1.032; P = 0.034), but not height.

CONCLUSIONS

Contrary to men, in women obesity does not reduce the operative mortality in cardiac surgery, whereas the height seems to be associated with a lower mortality.
Clinical, Pathological, and Ethical Considerations for the Conduct of Clinical Trials in Dogs with Naturally Occurring Cancer: A Comparative Approach to Accelerate Translational Drug Development
Authors: Regan Daniel , Garcia Kelly , Thamm Douglas
Published: December 2018

The role of comparative oncology in translational research is receiving increasing attention from drug developers and the greater biomedical research community. Pet dogs with spontaneous cancer are important and underutilized translational models, owing to dogs’ large size and relative outbreeding, combined with their high incidence of certain tumor histotypes with significant biological, genetic, and histological similarities to their human tumor counterparts. Dogs with spontaneous tumors naturally develop therapy resistance and spontaneous metastasis, all in the context of an intact immune system. These fundamental features of cancer biology are often lacking in induced or genetically engineered preclinical tumor models and likely contribute to their poor predictive value and the associated overall high failure rate in oncology drug development. Thus, the conduct of clinical trials in pet dogs with naturally occurring cancer represents a viable surrogate and valuable intermediary step that should be increasingly incorporated into the cancer drug discovery and development pipeline. The development of molecular-targeted therapies has resulted in an expanded role of the pathologist in human oncology trials, and similarly the expertise of veterinary pathologists will be increasingly valuable to all phases of comparative oncology trial design and conduct. In this review, we provide a framework of clinical, ethical, and pathology-focused considerations for the increasing integration of translational research investigations in dogs with spontaneous cancer as a means to accelerate clinical cancer discovery and drug development.
Surgical Anatomy of the Subcallosal Artery: Implications for Transcranial and Endoscopic Endonasal Surgery in the Suprachiasmatic Region
Authors: Najera Edinson , Alves Belo Joao T , Truong Huy Q , Gardner Paul A , Fernandez-Miranda Juan C
Published: December 2018

BACKGROUND

Suprachiasmatic subcallosal lesions may have an intimate relationship with the anterior communicating artery (AcomA); injury to AcomA branches can result in basal forebrain infarction and cognitive dysfunction.

OBJECTIVE

To evaluate anatomic variations of the AcomA basal perforating branches, especially the subcallosal artery (ScA), for clinical implications when approaching the suprachiasmatic subcallosal region from endonasal and transcranial routes.

METHODS

The origin, course, diameter, and branching pattern of the AcomA’s perforating branches were studied in 33 specimens from transcranial and endonasal perspectives.

RESULTS

The ScA was present in 79% of the specimens as a single dominant artery arising from the posterior/posterosuperior surface of the AcomA, along with hypothalamic arteries (55%), or as a single artery (24%). It coursed posteriorly towards the lamina terminalis region, curving superiorly to the subcallosal area. The ScA gave off many branches to provide the main blood supply to the subcallosal region. Importantly, it supplies the septal/subcallosal region bilaterally. The ScA can be found posterior, superior, or inferior to the AcomA when using a transylvian, interhemispheric, or endonasal approach, respectively. In specimens with no ScA (21%), the median callosal artery (MdCA) was the dominant artery arising from the AcomA. It followed an identical course to the ScA, providing supply to the same structures bilaterally, but its distal extension reached the body/splenium of the corpus callosum. The MdCA is a ScA variant.

CONCLUSION

The ScA is a unique vessel because it supplies the septal/subcallosal region bilaterally; preservation of this vessel during surgery is crucial for successful outcomes.
Low-dose interleukin-2 therapy for the treatment of systemic lupus erythematosus
Authors: Humrich Jens Y. , Riemekasten Gabriela
Published: December 2018

Purpose of review

To provide an overview behind the concept and recent advances of low-dose interleukin-2 (IL-2) therapy in systemic lupus erythematosus (SLE).

Recent findings

A disruption of regulatory T cell homeostasis caused by an acquired deficiency of IL-2 is a crucial event in the pathogenesis of SLE. Here, we highlight the key rationales for the clinical translation of low-dose IL-2 therapy in SLE and summarize the main findings from two independent, early phase uncontrolled clinical studies that investigated the immunological and clinical responses to low-dose IL-2 therapy in patients with active SLE. Important commonalities and differences between these studies with regard to study design and results are discussed.

Low-dose IL-2 therapy is capable to promote the selective expansion of a functionally competent regulatory T cell population in a well-tolerated way and may have the potential to influence the clinical course in patients with active SLE. Although a clearer proof for the clinical efficacy of low-dose IL-2 therapy in SLE is still outstanding, these early studies provide important rationales and the scientific basis for more comprehensive and placebo-controlled trials in the future.
The immune podocyte
Authors: Bhargava Rhea , Tsokos George C.
Published: December 2018

Purpose of review

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus and is characterized by proteinuria and renal failure. Proteinuria is a marker of poor prognosis and is attributed to podocyte loss and dysfunction. It is often debated whether these cells are innocent bystanders or active participants in the pathogenesis of glomerulonephritis.

Recent findings

Podocytes share many elements of the innate and adaptive immune system. Specifically, they produce and express complement components and receptors which when dysregulated appear to contribute to podocyte damage and LN. In parallel, podocytes express major histocompatibility complex and co-stimulatory molecules which may be involved in local immune events. Podocyte-specific cytotoxic cells and possibly other immune cells contribute to glomerular damage. Autoantibodies present in lupus sera enter podocytes to upregulate calcium/calmodulin kinase which in turn compromises their structure and function.

More recent studies point to the restoration of podocyte function using cell targeted approaches to prevent and treat LN. These strategies along with podocyte involvement in the pathogenesis of LN will be addressed in this review.
Medial Plantar Artery Perforator Flap: Experience with Soft-tissue Coverage of Heel
Authors: Khan Fahad Hanif , Beg Mirza Shehab Afzal , Obaid-ur-Rahman
Published: December 2018

Background:

Soft-tissue coverage is a challenge to the ankle and foot reconstructive surgeon due to its unique requirement of simultaneously withstanding body weight and to provide sensory feedback. We share our experience of medial plantar artery perforator (MPAP) flap, which provides a robust sensate coverage to heel defects.

Methods:

Three-year retrospective study, which included soft-tissue injury to heel. All patients underwent MPAP flap for the coverage of the defect. Patients' demographic, mode of injury, defect size, flap size and survival, time to start weight bearing, return of protective sensations, and comparative 2-point discrimination with opposite heel were studied.

Results:

We studied 16 cases with heel soft-tissue injuries. Fifteen had motor vehicle accident, and 1 had chronic diabetic wound. Mean surface area of flap was 4 × 5 cm. Except 1 flap, 15 flaps had complete survival and provided reliable wound coverage with comparable normal sensation as on other foot.

Conclusion:

We suggest that MPAP flap, when available, is a good local tissue for heel wounds coverage.
Versatility of the Extensor Digitorum Brevis Muscle Flap in Lower Limb Reconstruction
Authors: Abdelrahman Islam , Elmasry Moustafa , Steinvall Ingrid , Olofsson Pia , Nettelblad Hans , Zdolsek Johann
Published: December 2018

Background:

Reconstruction of complex defects in the lower leg is a challenge. Although microvascular free tissue transfer is a popular technique, experience and available resources limit its use. Furthermore, free tissue transfer is not always required in the reconstruction of small lower leg defects, as many of them can be reconstructed with local alternatives such as an extensor digitorum brevis flap (EDB). Our aim was to describe our experience of the last 20 years with the EDB as a local muscle flap to cover small complex lower leg defects to establish its clinical feasibility and to document its associated complications.

Methods:

All adult patients who were operated with EDB flap reconstruction of the lower limb during 1997–2017 at the Department of Hand and Plastic Surgery, Linköping University Hospital, were included in this retrospective study.

Results:

Of 64 patients operated, only 7 had total flap failure, and the rate of complete success was 73% (47/64). Most of the skin defects were associated with fractures or complications thereof and were located in the ankle region, the dorsum of the foot, and the distal third of tibia or even the proximal tibia. Defects in the malleolar region and coexisting cardiovascular condition were factors associated with flap loss (either partial or total).

Conclusion:

The pedicled EDB-flap has, in our hands, proved to be a versatile and safe reconstructive option in the reconstruction of small defects in the lower leg and foot. Long-time follow-up is, however, recommended.
Malignant and Benign Phenotypes of Multimorbidity in Heart Failure
Authors: Chen Lei , Chan Yih-Kai , Busija Lucy , Norekval Tone M. , Riegel Barbara , Stewart Simon
Published: December 2018

Background:

The impact of different patterns of multimorbidity in heart failure (HF) on health outcomes is unknown.

Objectives:

The aim of this study was to test the hypothesis that, independent of the extent of comorbidity, there are distinctive phenotypes of multimorbidity that convey an increased risk for premature mortality in patients hospitalized with HF.

Methods:

We analyzed the clinical profile and health outcomes of 787 patients hospitalized with HF participating in a multidisciplinary HF management program with a minimum 12-month follow-up. A Classification and Regression Tree model was applied to explore the distinctive combinations of 10 most prevalent concurrent conditions (other than coronary artery disease and hypertension) associated with 12-month all-cause mortality.

Results:

Mean (SD) age was 74 (12) years (59% men), and 65% had left ventricular systolic dysfunction. Most patients (88%) had 3 or more comorbid conditions, with a mean of 4.3 concurrent conditions in addition to HF. A total of 248 patients (32%) died (median, 663 [IQR, 492–910] days), including 142 deaths (18%) within 12 months. Patients with concurrent dysrhythmia, anemia, and respiratory disease experienced significantly higher 12-month all-cause mortality than those without these conditions (36.1% vs 3.6%, respectively; hazard ratio, 6.1 [95% confidence interval, 2.0–19.1]). Overall, this “malignant” phenotype of multimorbidity was associated with not only a markedly increased risk of all-cause mortality but also more unplanned readmissions, longer inpatient stays, and highest costs in the short (30-day) and longer terms when compared with more “benign” phenotypes of multimorbidity.

Conclusions:

We found a differential pattern of health outcomes according to pattern of comorbidity present in older patients hospitalized with HF and exposed to postdischarge, multidisciplinary management.
Risk factors for incidentally detected and symptomatic angiodysplasias: a case–control study with the general population as reference
Authors: Grooteman Katherina V. , Dalloyaux Shelley , van den Bemt Marjon C.P. , de Graaf Jacqueline , Verbeek André L.M. , Jackson Christian S. , van Geenen Erwin J.M. , Drenth Joost P.H.
Published: December 2018

Background

There is no literature on risk factors for incidentally found angiodysplasias. In clinical practice, endoscopists may defer treatment owing to uncertainty about a causal role of any found angiodysplasia and overt or occult bleeding. The objective is to identify risk factors that distinguish incidental angiodysplasias from angiodysplasias that are the cause of symptomatic bleeding.

Participants and methods

A case–control study was conducted to compare angiodysplasia groups and a random sample from the general population. Patients with angiodysplasia were diagnosed between 2010 and 2015. Controls were from a 2005 population survey. Determinants were demographics, past medical history, lifestyle, medication and angiodysplasia characteristics. Multivariable logistic regression analyses were performed to identify independent risk factors.

Results

A total of 270 (59% men, mean age 65 years) patients with angiodysplasia and 5594 (46% men, mean age 58 years) controls were included in this study. Independent risk factors for incidental angiodysplasias are male sex [odds ratio (OR): 1.6; 95% confidence interval (CI): 1.02–2.6], thyroid dysfunction (OR: 4.1; 95% CI: 2.0–8.4), autoimmune disease (OR: 2.3; 95% CI: 1.2–4.1), chronic obstructive pulmonary disease (OR: 1.8; 95% CI: 1.0–3.2), and blood thinners (OR: 2.8; 95% CI: 1.6–4.8). Besides angiodysplasia characteristics, factors independently associated with symptomatic angiodysplasias are increased age (OR: 1.7/10 years age band; 95% CI: 1.3–2.5), valvular heart disease (OR: 10.4; 95% CI: 1.6–69.2), diabetes mellitus (OR: 2.6; 95% CI: 1.03–6.7) and hyperlipidemia (OR: 3.7; 95% CI: 1.1–12.1).

Conclusion

The risk factor profile for incidental angiodysplasias differs from symptomatic angiodysplasias and is more profound for the latter. This knowledge could help endoscopists in the decision-making process to treat an endoscopically detected angiodysplasia.
Breastfeeding Rates and Programs in Europe
Authors: Theurich Melissa A. , Davanzo Riccardo , Busck‐Rasmussen Marianne , Díaz‐Gómez N. Marta , Brennan Christine , Kylberg Elisabeth , Bærug Anne , McHugh Laura , Weikert Cornelia , Abraham Klaus , Koletzko Berthold
Published: December 2018

Introduction:

Among the world's regions, the WHO European Region has the lowest rates of exclusive breastfeeding at the age of 6 months with approximately 25%. Low rates and early cessation of breastfeeding have important adverse health consequences for women, infants, and young children. Protecting, promoting, and supporting breastfeeding are a public health priority.

Objectives:

National breastfeeding data and monitoring systems among selected European countries and the WHO European Region are compared. Mechanisms for the support, protection, and promotion of breastfeeding are reviewed and successes and challenges in implementation of national programs are presented.

Methods:

National representatives of national breastfeeding committees and initiatives in 11 European countries, including Belgium, Croatia, Denmark, Germany, Ireland, Italy, The Netherlands, Norway, Spain, Sweden, and Switzerland, participated in a standardized survey. Results are evaluated and compared in a narrative review.

Results:

Variation exists in Europe on breastfeeding rates; methodology for data collection; and mechanisms for support, protection, and promotion of breastfeeding. Directly after birth, between 56% and 98% of infants in all countries were reported to receive any human milk, and at 6 months 38% to 71% and 13% to 39% of infants to be breastfed or exclusively breastfed, respectively. National plans addressing breastfeeding promotion, protection, and support exist in 6 of the 11 countries.

Conclusions:

National governments should commit to evidence‐based breastfeeding monitoring and promotion activities, including financial and political support, to improve breastfeeding rates in the Europe. Renewed efforts for collaboration between countries in Europe, including a sustainable platform for information exchange, are needed.
Futile Recanalization With Poor Clinical Outcome Is Associated With Increased Edema Volume After Ischemic Stroke
Authors: Nawabi Jawed , Flottmann Fabian , Hanning Uta , Bechstein Matthias , Schön Gerhard , Kemmling Andre , Fiehler Jens , Broocks Gabriel
Published: December 2018

Purpose

Futile recanalization with poor clinical outcome after endovascular treatment of acute ischemic stroke is poorly understood. Recently, vessel recanalization has been associated with reduced ischemic brain edema in patients with good clinical outcome. As edema volume (EV) may be quantified in computed tomography (CT), we hypothesized that higher EV after revascularization predicts futile recanalization with poor outcome.

Methods

In this observational study, 67 ischemic stroke patients with M1 middle cerebral artery occlusion fulfilled all inclusion criteria and were analyzed. All patients received successful endovascular recanalization (thrombolysis in cerebral infarction scale 2b/3) and subsequent follow-up CT 24 hours later. Edema volume within the infarct lesion was calculated in follow-up CT applying lesion water uptake quantification and was used to predict clinical outcome (Modified Rankin Scale [mRS] after 90 days) compared with infarct volume.

Results

The median EV after thrombectomy was 1.6 mL (interquartile range, 0.2–4.2 mL) in patients with mRS 0 to 4 and 8.6 mL (interquartile range, 2.0–49.8 mL) in patients with mRS 5 to 6 (P = 0.0008). In regression analysis, an EV increase of 1 mL was associated with an 8.0% increased likelihood of poor outcome (95% confidence interval, 2.8%–15.4%; P = 0.008). Based on univariate receiver operating characteristic curve analysis, absolute EV over 4.2 mL predicted poor outcome (mRS 5–6) with good discriminative power (area under curve, 0.74; 95% confidence interval, 0.62–0.84; specificity, 77%; sensitivity, 68%). In comparison, the area under curve for infarct volume was 0.68.

Conclusions

Elevated EV after endovascular thrombectomy was associated with poor clinical outcome and may indicate futile recanalization.
Focal Myositis of the Leg Presenting as Fever of Unknown Origin Detected by FDG PET/CT
Authors: Dong Aisheng , Bai Yushu , Wang Yang
Published: December 2018

Focal myositis is an uncommon inflammatory pseudotumor of the skeletal muscle that may mimic neoplastic and inflammatory diseases. We present one case of focal myositis involving the left proximal vastus lateralis and vastus intermedius, and left soleus showing intense FDG uptake on FDG PET/CT. This case indicates that focal myositis should be considered as a differential diagnosis in patients with focal hypermetabolic muscular lesions, including benign and malignant tumors, necrotizing autoimmune myopathy, nodular fasciitis, myositis ossificans, and muscular sarcoidosis.
Optimal Result of One-Stage Secondary Debulking Procedure After Flap Reconstruction of the Ankle
Authors: Jaramillo del Río Andrés Esteban , Hsieh Mu-han , Kuo Pao-Jen , Lin Tsan-Shiun
Published: December 2018

Background

Skin and soft tissue defect of the ankle usually mandates flap reconstruction; however, bulky flap and difficulty ambulance have been the major disadvantages after flap reconstruction of this area. We used the concept of full-thickness skin graft as a 1-stage method of secondary debulking procedure to achieve both aesthetic and functional results.

Methods

Since January of 2004 to June of 2016, 22 one-stage secondary debulking procedures were performed on 22 patients who had received reconstruction with flaps for ankle defects. Nineteen cases were free myocutaneous flaps, 2 cases were free fasciocutaneous flaps, and 1 case was a distally based sural artery flap. In the operative technique, the full-thickness skin was harvested from the flap and regrafted on the defatted fascia with tie-over dressing. The functional and cosmetic outcomes as well as complications were reviewed.

Results

The overall mean follow-up time was 12 months. After the debulking procedure, all of the grafted skins took well. The patients were able to wear their own shoes without difficulty and regained ease of ambulation. The reconstructed area was found to decrease to an average of 28.92% as compared with predebulking area. The reconstructed ankles achieve good symmetry with regard to the contralateral side (P < 0.05). All of the patients were satisfied with the results of the reconstructed ankles.

Conclusions

The 1-stage secondary debulking procedure is a safe and reproducible technique that achieves good functional and aesthetic outcomes after flap reconstruction of the ankle.
The Medial Pillar Island Flap for Oncoplastic Breast Reconstruction of Upper Pole Defects
Authors: Akyurek Mustafa , Tomczyk Eleanor , Albert Mark , Quinlan Robert
Published: December 2018

Background

Breast deformity is common following lumpectomy. Use of ptotic lower pole tissue for restoration of volume in the upper pole is quite appealing since it allows for a concomitant lift. This study presents the medial pillar island flap technique of oncoplastic breast reconstruction of upper pole defects.

Methods

Vascular anatomy of the lower pole of the breast was investigated with cadaver study. The medial pillar island flap was designed utilizing the territory of the inferior pole of the breast as an island flap pedicled medially by the internal mammary artery perforators surrounded by the soft tissue of the medial pillar. It was transposed to the upper pole lumpectomy defect as an independent flap from superomedial pedicle which was utilized for nipple transposition.

Results

The dominant internal mammary artery perforator supplying the medial pillar island flap was consistently found in the fourth interspace at a mean distance of 8.5 cm (range, 8 to 10) from the sternal midline. Thirty patients underwent the procedure, with a mean age of 61 years and mean body mass index of 28.9. The average size of the defect was 170 cm3 (range, 48 to 295 cm3). The majority of the patients (n = 28) underwent opposite breast symmetry surgery as well. The average follow up was 12 months. Complication rate was 23.3%. Reoperation rate was 16.7%. There was no evidence of flap compromise or nipple areola complex necrosis. Patient satisfaction was high, with a mean score of 4.1 (range, 2 to 5) out of 5.

Conclusions

The medial pillar island flap has reliable vascularity based on the internal mammary artery system. The flap carries lower pole breast tissue as confined by the medial and lateral pillars of a vertical mastopexy design, offering unrestricted arc of rotation for effective reconstruction of upper pole lumpectomy defects as it is completely dissected from the chest wall and the inframammary fold. The two flap design, along with superomedial pedicle, accomplishes versatility for flap inset. The technique was proven to result in safe outcomes without major complications.
Abnormal Presentation of Aggressive Fibromatosis After Radiotherapy for Keloids
Authors: Chen Yuan , Chen Yue , Liu Yong
Published: December 2018

Rationale

Keloids, dermal fibroproliferative lesions, often occur secondary to skin injury and extend beyond the margins of the original lesion. Aggressive fibromatosis (AF) is a rare condition arising from fibroblasts and is characterized clinically as a nonmetastasizing but locally invasive tumor. In this work, we present the case of a patient who developed AF in the chest 3 years after surgery and postoperative radiotherapy for keloids.

Patient Concerns

A 15-year-old female patient who underwent surgery and postoperative radiotherapy for keloids presented with AF in the chest 3 years after intervention.

Diagnoses and Outcomes

Physical examination revealed a fan-shaped scar on the manubrium sterni with a radius of 7 cm, as well as a 9 (L) × 2-cm (W) longitudinal reddish and irregularly surfaced scar arising from previous incisions. By comparing this case with similar cases reported previously, we infer that a history of exposure to radiation is the main factor that contributes to the development of AF in patients suffering from keloid scars. We also discussed the clinical characteristics of AF and treatment options and suggest factors that should be considered when using radiotherapy in patients with keloids.

Lessons

To our knowledge, this is the first reported case of AF developing in a patient after radiotherapy for keloids. Radiotherapy may be a causal factor of AF.
Donor Site Morbidities of Iliac Crest Bone Graft in Craniofacial Surgery
Authors: Boehm Kaitlin S. , Al-Taha Mona , Morzycki Alexander , Samargandi Osama A. , Al-Youha Sarah , LeBlanc Martin R.
Published: December 2018

Background

The iliac crest bone graft (ICBG) is criticized for high donor site morbidity. Recent research suggests this morbidity is related to the patient population for which the ICBG is harvested. This systematic review is the first to delineate the type and incidence of ICBG donor site complications in craniofacial surgery.

Methods

Two independent reviewers conducted a systematic review of multiple databases (MEDLINE, EMBASE, CINAHL, PEDRO, and Cochrane Central Register of Controlled Trials) from 1917 to 2017. All studies utilizing the ICBG for craniofacial indications were included. Donor site morbidities, including immediate and chronic pain, hematoma, seroma, infection, hypertrophic/painful scarring, nerve injury, muscle herniation, iliac crest fracture, and gait disturbance, were recorded. A weighted incidence for each morbidity, excluding immediate pain, was calculated. An average visual analog scale score was calculated for immediate pain.

Results

Forty-four studies, with 2801 patients, were included. Oral and maxillofacial (50%) and cleft reconstruction (40%) were the primary indications for surgery. Average immediate pain visual analog scale scores on postoperative days 1 and 14 were 6.3 and 1.3, respectively. The incidence of donor site morbidities was as follows: acute (45.7%) and chronic (1.5%) gait disturbance, acute (17.8%) and chronic nerve changes (1.4%), hypertrophic/painful scar (9.1%), chronic pain (3.1%), hematoma (2.2%), seroma (2.0%), infection (1.0%), iliac crest fracture (1.2%), and muscle herniation (0%).

Conclusions

Chronic morbidity was lower than previously documented. Rare chronic morbidity illustrates that the ICBG remains a viable surgical option. The authors hope this review will facilitate surgical planning and informed consent.
Surgical Technique for Nasal Cleft Repair
Authors: Chapchay Katya , Zaga Jonathan , Billig Allan , Adler Neta , Margulis Alexander
Published: December 2018

Background

Congenital nasal cleft is a very rare yet challenging deformity to reconstruct. Atypical craniofacial clefts that involve the nasal ala are designated as number 1 and number 2 under the Tessier classification system. These clefts typically present as notches in the medial one-third of either nasal ala and may be accompanied by a malpositioned cartilaginous framework. Nasal clefts are smaller and far less common than familiar clefts of the lip and palate, but they pose equally challenging reconstructive planning.

Methods

Our described technique relies on usage of existing nasal tissue near the cleft. Local tissue rearrangement using a laterally based rotational alar flap, a medially based triangular flap, and a nasal wall advancement flap restores normal anatomy and provides an aesthetically pleasing result.

Results

Five children with isolated nasal cleft were treated by the senior author (A.M.) between 2010 and 2017. All patients presented with clefts of the soft tissue with no underlying cartilaginous involvement. There were no postoperative complications. Excellent aesthetic outcome was achieved in all patients.

Conclusion

Isolated nasal cleft can be properly corrected with the described procedure in a single stage and with optimal result.
Activation of AMP-Activated Protein Kinase by A769662 Ameliorates Sepsis-Induced Acute Lung Injury in Adult Mice
Authors: Kitzmiller Laura , Ledford John R. , Hake Paul W. , O’Connor Michael , Piraino Giovanna , Zingarelli Basilia
Published: December 2018

A serious consequence of sepsis is acute lung injury, whose severity is particularly impacted by the age of the patient. AMP-activated protein kinase (AMPK) is a crucial regulator of cellular metabolism, which controls mitochondrial biogenesis and autophagy. Here, we investigated the effect of pharmacological activation of AMPK with A769662 on lung injury by using a model that would preferably mimic the clinical condition of adult patients. Male C57BL/6 retired breeder mice (7–9 months old) were subjected to sepsis by cecal ligation and puncture (CLP). Mice received vehicle or A769662 (10 mg/kg) intraperitoneally at 1 h after CLP. At 6 h after CLP, vehicle-treated mice exhibited severe lung injury and elevation of plasma pro-inflammatory cytokines when compared with control mice. At molecular analysis, lung injury was associated with downregulation of AMPKα1/α2 catalytic subunits and reduced phosphorylation of AMPKβ1 regulatory subunit. Treatment with A769662 ameliorated lung architecture, reduced bacterial load in lung and blood, and attenuated plasma levels of interleukin-6. This protective effect was associated with nuclear phosphorylation of AMPKα1/α2 and AMPKβ1, increased nuclear expression of peroxisome proliferator-activated receptor γ co-activator-α and increased autophagy, as evaluated by the light-chain (LC)3B-I and LC3B-II content, without changes in sirtuin-1 cellular dynamics. Treatment with A769662 alone or in combination with the antimicrobial agent imipenem (25 mg/kg) increased survival rate (29% and 51%, respectively) when compared with vehicle treatment (10%) at 7 days after CLP. These data suggest that pharmacological activation of AMPK might be a beneficial approach for the treatment of sepsis in adult population.
Redefining postinjury fibrinolysis phenotypes using two viscoelastic assays
Authors: Stettler Gregory R. , Moore Ernest E. , Moore Hunter B. , Nunns Geoffrey R. , Silliman Christopher C. , Banerjee Anirban , Sauaia Angela
Published: December 2018

INTRODUCTION

Fibrinolysis was initially defined using rapid thrombelastography (rTEG). The cutoffs for the pathologic extremes of the fibrinolytic system, hyperfibrinolysis and shutdown, were both defined based on association with mortality. We propose to redefine these phenotypes for both TEG and for rotational thrombelastometry, the other commonly used viscoelastic assay.

METHODS

Rotational thrombelastometry, rTEG, and clinical data were prospectively collected on trauma patients admitted to an urban Level I trauma center from 2010 to 2016. Hyperfibrinolysis was defined as the Youden index from EXTEM-clot lysis index 60 minutes after clotting time (CLI60) and rTEG-fibrinolysis 30 minutes after achieving MA (LY30) for predicting massive transfusion (>10 red blood cell units, or death per 6 hours after injury) as a surrogate for severe bleeding. Patients identified as having hyperfibrinolysis were then removed from the data set, and the cutoff for fibrinolysis shutdown was derived as the optimal cutoff for predicting mortality in the remaining patients.

RESULTS

Overall, 216 patients (median age, 36 years (interquartile range, 27–49 years), 82% men, 58% blunt injury) were included. Of these, 16% required massive transfusion, and 12.5% died. Rapid thrombelastography phenotypes were redefined as hyperfibrinolysis: rTEG-LY30 greater than7.7%, physiologic rTEG-LY30 0.6% to7.6%, and shutdown rTEG-LY30 less than 0.6%. EXTEM-CLI60 fibrinolysis phenotypes were hyperfibrinolysis CLI60 less than 82%, physiologic (CLI60, 82–97.9%), and shutdown (CLI60 > 98%). Weighted kappa statistics revealed moderate agreement between rotational thrombelastometry– and rTEG-defined fibrinolysis (k = 0.51; 95% confidence interval, 0.39–0.63), with disagreement mostly in the shutdown and physiologic categories.

CONCLUSION

We confirmed the U-shaped distribution of death related to fibrinolysis system abnormalities. Both rTEG LY30 and EXTEM CLI60 can identify the spectrum of fibrinolytic phenotypes, have moderate agreement, and can be used to guide hemostatic resuscitation.

LEVEL OF EVIDENCE

Diagnostic study, level III.
Outcomes after single-look trauma laparotomy: A large population-based study
Authors: Bowie Jason M. , Badiee Jayraan , Calvo Richard Y. , Sise Michael J. , Wessels Lyndsey E. , Butler William J. , Dunne Casey E. , Sise C. Beth , Bansal Vishal
Published: December 2018

BACKGROUND

Outcomes following damage control laparotomy for trauma have been studied in detail. However, outcomes following a single operation, or “single-look trauma laparotomy” (SLTL), have not. We evaluated the association between SLTL and both short-term and long-term outcomes in a large population-based data set.

METHODS

The California Office of Statewide Health Planning and Development patient discharge database was evaluated for calendar years 2007 through 2014. Injured patients with SLTL during their index admission were identified using International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes. Diagnosis and procedure codes were used to identify specific abdominal organ injuries, surgical interventions, and perioperative complications. Subsequent acute care admissions were examined for postoperative complications and related surgical interventions. Clinical characteristics, injuries, surgical interventions, and outcomes were analyzed by mechanism of injury.

RESULTS

There were 2113 patients with SLTL during their index admission; 712 (33.7%) had at least one readmission to an acute care facility. Median time to first readmission was 110 days. Penetrating mechanism was more common than blunt (60.6% vs. 39.4%). Compared to patients with penetrating injury, blunt-injured patients had a significantly higher median Injury Severity Score (9 vs. 18, p < 0.0001) and a significantly higher mortality rate during the index admission (4.1% vs. 27.0%, p < 0.0001). More than 30% of SLTL patients requiring readmission had a surgery-related complication. The most common primary reasons for readmission were bowel obstruction (17.7%), incisional hernia (11.8%), and infection (9.1%). There was no significant association between mechanism of injury and development of surgery-related complications requiring readmission.

CONCLUSIONS

Patients with SLTL had postinjury morbidity and mortality, and more than 30% required readmission. Complication rates for SLTL were comparable to those reported for emergency general surgery procedures. Patients should be educated on signs and symptoms of the most common complications before discharge following SLTL. Further investigation should focus on the factors associated with the development of these complications.

LEVEL OF EVIDENCE

Prognostic and epidemiologic study, level III.
A mathematical model of flow-mediated coagulation identifies factor V as a modifier of thrombin generation in hemophilia A:
Authors: Link Kathryn G , Stobb Michael T , Sorrells Matthew G. , Bortot Maria , Ruegg Katherine , Manco-Johnson Marilyn J , Di Paola Jorge A , Sindi Suzanne S. , Fogelson Aaron L , Leiderman Karin , Neeves Keith B
Published: December 2018

Hemophilia A is a bleeding disorder categorized as severe, mild, and moderate deficiencies in factor VIII (FVIII). Within these categories the variance in bleeding severity is significant and the origins unknown. The number of parameters that could modify bleeding are so numerous that experimental approaches are not feasible for considering all possible combinations. Consequently, we turn to a mathematical model of coagulation under flow to act as a screening tool to identify parameters that are most likely to enhance thrombin generation. We performed global sensitivity analysis on 110,000 simulations that varied coagulation factor levels by 50-150% of their normal values in humans while holding FVIII levels at 1%. These simulations identified low factor V (FV) levels as the strongest candidate, with additional enhancement when combined with high prothrombin levels. This prediction was confirmed in two experimental models: Partial FV inhibition boosted fibrin deposition in flow assays performed at 100 1/s on collagen-tissue factor surfaces using whole blood from individuals with mild and moderate FVIII deficiencies. Low FV (~50%) or partial FV inhibition also augmented thrombin generation in FVIII-inhibited or FVIII-deficient plasma in calibrated automated thrombography. These effects were amplified by high prothrombin levels in both experimental models. Our mathematical model suggests a mechanism in which FV and FVIII compete to bind to factor Xa to initiate thrombin generation in low FV, FVIII-deficient blood. This unexpected result was made possible by a mechanistic mathematical model, providing an example of the potential of such models in making predictions in complex biological networks.
Design of nanoparticulate group 2 influenza hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages
Authors: Corbett Kizzmekia S , Moin Syed M , Yassine Hadi M , Cagigi Alberto , Kanekiyo Masaru , Boyoglu-Barnum Seyhan , Myers Sky I , Tsybovsky Yaroslav , Wheatley Adam K , Schramm Chaim A , Gillespie Rebecca A , Shi Wei , Wang Lingshu , Zhang Yi , Andrews Sarah F , Joyce M Gordon , Crank Michelle C , Douek Daniel C , McDermott Adrian B , Mascola John R , Graham Barney S , Boyington Jeffrey C
Published: December 2018

Influenza vaccines targeting the highly-conserved stem of the hemagglutinin (HA) surface glycoprotein have the potential to protect against pandemic and drifted seasonal influenza viruses not covered by current vaccines. While HA stem-based immunogens derived from group 1 influenza A have been shown to induce intra-group heterosubtypic protection, HA stem-specific antibody lineages originating from group 2 may be more likely to possess broad cross-group reactivity. We report the structure-guided development of mammalian cell-expressed candidate vaccine immunogens based on influenza A group 2 H3 and H7 HA stem trimers displayed on self-assembling ferritin nanoparticles using an iterative, multipronged approach involving helix stabilization, loop optimization, disulfide bond addition, and side chain repacking. These immunogens were thermostable, formed uniform and symmetric nanoparticles, were recognized by cross-group-reactive broadly neutralizing antibodies (bNAbs) with nanomolar affinity, and elicited protective, homosubtypic antibodies in mice. Importantly, several immunogens were able to activate B cells expressing inferred unmutated common ancestor (UCA) versions of cross-group-reactive human bNAbs from two multi-donor classes, suggesting they could initiate elicitation of these bNAbs in humans.
Highly reproducible 16S sequencing facilitates measurement of host genetic influences on the stickleback gut microbiome
Authors: Small Clayton M. , Currey Mark , Beck Emily A. , Bassham Susan , Cresko William A.
Published: December 2018

Multicellular organisms interact with resident microbes in important ways, and a better understanding of host-microbe interactions is aided by tools such as high-throughput 16S sequencing. However, rigorous evaluation of the veracity of these tools in a different context from which they were developed has often lagged behind. Our goal was to perform one such critical test by examining how variation in tissue preparation and DNA isolation could affect inferences about gut microbiome variation between two genetically divergent lines of threespine stickleback fish maintained in the same lab environment. Using careful experimental design and intensive sampling of individuals, we addressed technical and biological sources of variation in 16S-based estimates of microbial diversity. After employing a two-tiered bead beating approach consisting of tissue homogenization followed by microbial lysis in subsamples, we found an extremely minor effect of DNA isolation protocol relative to among-host microbial diversity differences. Individual abundance estimates for rare OTUs, however, showed much lower reproducibility. We found that the stickleback gut microbiome was highly variable, even among siblings housed together, but that an effect of host genotype (stickleback lineage) was detectable for some microbial taxa. Our findings demonstrate the importance of appropriately quantifying biological and technical variance components when attempting to understand major influences on high-throughput microbiome data.
Biased visibility in HiC datasets marks dynamically regulated condensed and decondensed chromatin states genome-wide
Authors: Chandradoss Keerthivasan Raanin , Guthikonda Prashanth Kumar , Kethavath Srinivas , Dass Monika , Singh Harpreet , Nayak Rakhee , Kurukuti Sreenivasulu , Sandhu Kuljeet Singh
Published: December 2018

Proximity ligation based techniques, like HiC, involve restriction digestion followed by ligation of formaldehyde cross-linked chromatin. We showed that the HiC datasets have significant bias due to differential accessibility of chromatin domains to restriction endonucleases. Through analysis of lamina-associated domains (LADs), inactive X-chromosome in mammals and polytene bands in fly, we established that the DNA in condensed chromatin had lesser accessibility to nucleases used in HiC as compared to that in decondensed chromatin. The observed bias was independent of known systematic biases attributed to length and GC content of the restriction fragments and was not appropriately corrected by computational methods. We identified novel condensed domains outside LADs, which were bordered by insulators and were dynamically associated with the developmentally regulated epigenetic and transcriptional states. Our observations suggested that the corrected read counts of existing HiC datasets can be reliably repurposed to study the dynamics of chromatin condensation and decondensation and that the existing HiC datasets should be interpreted with cautions.
Real-time detection of circulating tumor cells in living animals using functionalized large gold nanorods
Authors: Dutta Rebecca , Liba Orly , SoRelle Elliott D , Winetraub Yonatan , Ramani Vishnu , Jeffrey Stefanie S. , Sledge George W. , de la Zerda Adam
Published: December 2018

Optical coherence tomography (OCT) with significant speckle reduction can be used with highly-scattering contrast agents for noninvasive, contrast-enhanced imaging of living tissue at the cellular scale. The advantages of reduced speckle noise and improved targeted contrast can be harnessed to track objects as small as 2 μm in vivo, with the potential for cell tracking and counting in living subjects. Here we demonstrate the use of Large Gold Nanorods (LGNRs) as contrast agents for detecting individual micron-sized polystyrene beads and single myeloma cells in blood circulation using speckle modulating-OCT (SM-OCT). This is the first time that OCT has been used to image at the individual cell scale in vivo. This technical capability presents an exciting opportunity for the dynamic detection and quantification of tumor cells circulating in living subjects.
Differential Expression Analysis of ZIKV Infected Human RNA Sequence Reveals Potential Biomarkers
Authors: Jabeen Almas , Ahmad Nadeem , Raza Khalid
Published: December 2018

Zika virus (ZIKV) is considered to be an emerging viral outbreak due to its link to diseases like microcephaly, Guillain-Barre Syndrome in human. In this paper, we identify differentially expressed genes (DEGs) using RNA-seq data. In this study, we adopted the RNA-seq analysis pipeline to quantify RNA-seq data into read counts. Our analysis uncovers the significant DEGs which may be involved in the altered biological process somehow. Here, we report the list of significant DEGs, out of which three genes are found to be highly differentially expressed. In addition, our analysis also predicts other moderate DEGs, low DEGs whose differential expression was induced due to ZIKV infections.