bluuebunny/crossref_metadata_2025_split huggingface dataset:
Familial Aggregation of Plastic Surgical Procedures
Authors: Timberlake Andrew T. , Steinbacher Derek M. 
Published: August 2018

Summary:
A growing number of patients seeking plastic surgical procedures in the authors’ practice are first-degree relatives of previous surgical patients. Three possibilities for procedural coalescence within a family unit include (1) similar morphologic and anatomical patterns within relatives; (2) a captive “audience” (family members) appreciates firsthand the surgical result and positive difference, be it functional or aesthetic; or (3) the rapport established between surgeon and patient leads that patient to recommend his or her surgeon to others. The purpose of this study was to identify the authors’ recent cohort of family members undergoing similar or related procedures performed by the same surgeon (D.M.S.), and understand the diagnoses, factors, and rationale for “passing the torch” to other family members to undergo surgery. Survey responses from 17 members of 10 families who sought elective procedures after an index family member indicated that both the result of the first operation and rapport with the surgeon were important factors in their decision to undergo surgery (mean Likert response ± SD, 4.94 ± 0.24). Ninety-four percent of family members (16 of 17) indicated that the result of the original procedure was the most important factor in their decision to undergo subsequent procedures performed by the same surgeon. Eighty-eight percent of family members (15 of 17) seeking subsequent procedures were not considering undergoing surgery before observing the result of the first index procedure. The data demonstrate the importance of achieving an excellent surgical result in earning the trust of patients and establishing strong family referral patterns.
Manipulating the Microcirculation in Sepsis – the Impact of Vasoactive Medications on Microcirculatory Blood Flow: A Systematic Review
Authors: Potter Elizabeth K. , Hodgson Luke , Creagh-Brown Ben , Forni Lui G. 
Published: August 2018

ABSTRACT

Background:
Sepsis is life-threatening organ dysfunction because of a dysregulated host response to infection. Disturbed microvascular blood flow is associated with excess mortality and is a potential future target for interventions. This review addresses the evidence for pharmacological manipulation of the microcirculation in sepsis assessed by techniques that evaluate the sublingual microvasculature.

Methods:
Systematic review using a published protocol. Eligibility criteria were studies of septic patients published from January 2000 to February 2018. Interventions were drugs aimed at improving perfusion. Outcome was improvement in microvascular flow using orthogonal polarization spectral, sidestream dark field, or incident dark field imaging (Grades of Recommendation, Assessment, Development, and Evaluation criteria used).

Results:
Two thousand six hundred and six articles were screened and 22 included. (6 randomized controlled trials, 12 interventional, 3 observational, and 1 pilot, n = 572 participants). Multiple measurement techniques were described, including: automated analyses, subjective, and composite scoring systems. Norepinephrine was not found to improve microvascular flow (low-grade evidence, n = 6 studies); except in chronic hypertension (low, n = 1 study). Addition of arginine vasopressin or terlipressin to norepinephrine maintained flow while decreasing norepinephrine requirements (high, n = 2 studies). Neither dobutamine nor glyceryl trinitrate consistently improved flow (low, n = 6 studies). A single study (n = 40 participants) demonstrated improved flow with levosimendan (high). In a risk of bias assessment 16/16 interventional, pilot and observational studies were found to be high risk.

Conclusions:
There is no robust evidence to date that any one agent can reproducibly lead to improved microvascular flow. Furthermore, no study demonstrated outcome benefit of one therapeutic agent over another. Updated consensus guidelines could improve comparable reporting of measurements and reduce bias, to enable meaningful comparisons around the effects of individual pharmacological agents.
Myocardial Redox Hormesis Protects the Heart of Female Mice in Sepsis
Authors: Luptak Ivan , Croteau Dominique , Valentine Catherine , Qin Fuzhong , Siwik Deborah A. , Remick Daniel G. , Colucci Wilson S. , Hobai Ion A. 
Published: August 2018

ABSTRACT
Mice challenged with lipopolysaccharide develop cardiomyopathy in a sex and redox-dependent fashion. Here we extended these studies to the cecal ligation and puncture (CLP) model.
We compared male and female FVB mice (wild type, WT) and transgenic littermates overexpressing myocardial catalase (CAT). CLP induced 100% mortality within 4 days, with similar mortality rates in male and female WT and CAT mice. 24 h after CLP, isolated (Langendorff) perfused hearts showed depressed contractility in WT male mice, but not in male CAT or female WT and CAT mice. In WT male mice, CLP induced a depression of cardiomyocyte sarcomere shortening (ΔSS) and calcium transients (ΔCai), and the inhibition of the sarcoplasmic reticulum Ca2+ ATPase (SERCA). These deficits were associated with overexpression of NADPH-dependent oxidase (NOX)-1, NOX-2, and cyclooxygenase 2 (COX-2), and were partially prevented in male CAT mice. Female WT mice showed unchanged ΔSS, ΔCai, and SERCA function after CLP. At baseline, female WT mice showed partially depressed ΔSS, ΔCai, and SERCA function, as compared with male WT mice, which were associated with NOX-1 overexpression and were prevented in CAT female mice.
In conclusion, in male WT mice, septic shock induces myocardial NOX-1, NOX-2, and COX-2, and redox-dependent dysregulation of myocardial Ca2+ transporters. Female WT mice are resistant to CLP-induced cardiomyopathy, despite increased NOX-1 and COX-2 expression, suggesting increased antioxidant capacity. Female resistance occurred in association with NOX-1 overexpression and signs of increased oxidative signaling at baseline, indicating the presence of a protective myocardial redox hormesis mechanism.
High Operator and Hospital Volume Are Associated With a Decreased Risk of Death and Stroke After Carotid Revascularization
Authors: Poorthuis Michiel H. F. , Brand Eelco C. , Halliday Alison , Bulbulia Richard , Bots Michiel L. , de Borst Gert J. 
Published: August 2018

Objective:
To examine the association between operator or hospital volume and procedural outcomes of carotid revascularization.

Background:
Operator and hospital volume have been proposed as determinants of outcome after carotid endarterectomy (CEA) or carotid artery stenting (CAS). The magnitude and clinical relevance of this relationship are debated.

Methods:
We systematically searched PubMed and EMBASE until August 21, 2017. The primary outcome was procedural (30 days, in-hospital, or perioperative) death or stroke. Obtained or estimated risk estimates were pooled with a generic inverse variance random-effects model.

Results:
We included 87 studies. A decreased risk of death or stroke following CEA was found for high compared to low operator volume with a pooled adjusted odds ratio (OR) of 0.50 (95% confidence interval [CI] 0.28–0.87; 3 cohorts), and a pooled unadjusted relative risk (RR) of 0.59 (95% CI 0.42–0.83; 9 cohorts); for high compared to low hospital volume with a pooled adjusted OR of 0.62 (95% CI 0.42–0.90; 5 cohorts), and a pooled unadjusted RR of 0.68 (95% CI 0.51–0.92; 9 cohorts). A decreased risk of death or stroke after CAS was found for high compared to low operator volume with an adjusted OR of 0.43 (95% CI 0.20–0.95; 1 cohort), and an unadjusted RR of 0.50 (95% CI 0.32–0.79; 1 cohort); for high compared to low hospital volume with an adjusted OR of 0.46 (95% CI 0.26–0.80; 1 cohort), and no significant decreased risk in a pooled unadjusted RR of 0.72 (95% CI 0.49–1.06; 2 cohorts).

Conclusions:
We found a decreased risk of procedural death and stroke after CEA and CAS for high operator and high hospital volume, indicating that aiming for a high volume may help to reduce procedural complications.

Registration:
This systematic review has been registered in the international prospective registry of systematic reviews (PROSPERO): CRD42017051491.
Stem Cell Mobilization Is Lifesaving in a Large Animal Preclinical Model of Acute Liver Failure
Authors: Ahmadi Ali R. , Chicco Maria , Wesson Russell N. , Anders Robert A. , Dor Frank J. M. F. , IJzermans Jan N. M. , Creamer Tyler J. , Williams George M. , Sun Zhaoli , Cameron Andrew M. 
Published: August 2018

Introduction:
Acute liver failure (ALF) affects 2000 Americans each year with no treatment options other than liver transplantation. We showed previously that mobilization of endogenous stem cells is protective against ALF in rodents. The objective of this study was to assess whether stem cell mobilizing drugs are lifesaving in a large animal preclinical model of ALF, to assess readiness for a clinical trial.

Methods:
Male Yorkshire pigs (14–18 kg) were divided into 2 groups, control (n = 6) and treatment (n = 6). All pigs received an intravenous bolus of the hepatotoxin D-galactosamine (0.5 g/kg) via central line and were followed up until death or day 28. Treated animals received simultaneous intramuscular injection of plerixafor (1 mg/kg) and G-CSF (2 μg/kg) at baseline, 24 and 48 hours after toxin infusion to mobilize endogenous stem cells, as previously described. Control animals received saline.

Results:
All control animals (6/6) succumbed to liver failure within 91 hours, confirmed by clinical, biochemical, and histopathological evidence of ALF. In the treatment group (5/6) animals survived indefinitely despite comparable biochemical changes during the first 48 hours (P = 0.003). White blood cell count increased by a mean of 4× in the treated group at the peak of mobilization (P = 0.0004).

Conclusions:
Stem cell mobilizing drugs were lifesaving in a preclinical large animal model of ALF. Since no therapeutic options other than liver transplantation are currently available for critically ill patients with ALF, a multicenter clinical trial is warranted.
Pure Laparoscopic Donor Hepatectomies
Authors: Samstein Benjamin , Griesemer Adam , Halazun Karim , Kato Tomoaki , Guarrera James V. , Cherqui Daniel , Emond Jean C. 
Published: August 2018

Objective:
In order to minimize the impact of donation, fully laparoscopic donor hepatectomy (LDH) is being investigated at a few centers throughout the world. We report here our experience with 51 living donor pure laparoscopic hepatectomies.

Background:
Adoption of minimal access techniques to living donor liver transplantation (LDLT) has been slowed by concerns about donor safety and the quality of the grafts.

Methods:
Of 344 donor hepatectomies (DHs) for living donor liver transplantation (LDLT) since 1998, 51 pure LDH have been performed since 2009. We report here our experience with 51 living donor pure laparoscopic hepatectomy (LH), based on prospectively collected data. There were 31 left lateral sectionectomy and 20 full lobectomies LH. We matched full lobe LH to open DH prior to introduction of LH.

Results:
LH increased from 21% of all DH in first 5 years of performing LH to 45% of DH in the most recent 3 years. Laparoscopic donors were more likely female, had lower body mass index, smaller total livers, and smaller allografts but longer operating room times. In the total LD experience, total 5 donors were converted to open surgery (10%), 2 donors required transfusion (4%), and there was 2 donor bile leaks (4%). Recipient patient and graft 1-year survival was 98% and 94%.

Conclusions:
Our experience indicates that LDH for LDLT can be safely used with appropriate attention to learning curve and progression from left lateral sectionectomy to right hepatectomy.
Propensity Score–Matched Analysis Comparing Minimally Invasive Ivor Lewis Versus Minimally Invasive Mckeown Esophagectomy
Authors: van Workum Frans , Slaman Annelijn E. , van Berge Henegouwen Mark I. , Gisbertz Suzanne S. , Kouwenhoven Ewout A. , van Det Marc J. , van den Wildenberg Frits J. H. , Polat Fatih , Luyer Misha D. P. , Nieuwenhuijzen Grard A. P. , Rosman Camiel 
Published: August 2018

Introduction:
Totally minimally invasive esophagectomy (TMIE) is increasingly used in treatment of patients with esophageal carcinoma. However, it is currently unknown if McKeown TMIE or Ivor Lewis TMIE should be preferred for patients in whom both procedures are oncologically feasible.

Methods:
The study was performed in 4 high-volume Dutch esophageal cancer centers between November 2009 and April 2017. Prospectively collected data from consecutive patients with esophageal cancer localized in the distal esophagus or gastroesophageal junction undergoing McKeown TMIE or Ivor Lewis TMIE were included. Patients were propensity score matched for age, body mass index, sex, American Society of Anesthesiologists classification, Charlson Comorbidity Index, tumor type, tumor location, clinical stage, neoadjuvant treatment, and the hospital of surgery. The primary outcome parameter was anastomotic leakage requiring reintervention or reoperation. Secondary outcome parameters were operation characteristics, pathology results, complications, reinterventions, reoperations, length of stay, and mortality.

Results:
Of all 787 included patients, 420 remained after matching. The incidence of anastomotic leakage requiring reintervention or reoperation was 23.3% after McKeown TMIE versus 12.4% after Ivor Lewis TMIE (P = 0.003). Ivor Lewis TMIE was significantly associated with a lower incidence of pulmonary complications (46.7% vs 31.9%), recurrent laryngeal nerve palsy (9.5% vs 0.5%), reoperations (18.6% vs 11.0%), 90-day mortality (7.1% vs 2.9%), shorter median intensive care unit length of stay (2 days vs 1 day) and shorter median hospital length of stay (12 vs 11 days) (all P < 0.05). R0 resection rate was similar between the groups. The median number of examined lymph nodes was 21 after McKeown TMIE and 25 after Ivor Lewis TMIE (P < 0.001).

Conclusions:
Ivor Lewis TMIE is associated with a lower incidence of anastomotic leakage, 90-day mortality and other postoperative morbidity compared to McKeown TMIE in patients in whom both procedures are oncologically feasible.
Gastric Bypass Surgery Reduces De Novo Cases of Type 2 Diabetes to Population Levels
Authors: Backman Olof , Bruze Gustaf , Näslund Ingmar , Ottosson Johan , Marsk Richard , Neovius Martin , Näslund Erik 
Published: August 2018

Objective:
The aim of this study was to determine long-term changes in pharmacological treatment of type 2 diabetes after primary Roux-en-Y gastric bypass (RYGB) surgery, in patients with and without pharmacological treatment of diabetes preoperatively.

Summary of Background Data:
Several studies have shown that gastric bypass has good effect on diabetes, at least in the short-term. This study is a nationwide cohort study using Swedish registers, with basically no patients lost to follow-up during up to 7 years after surgery.

Methods:
The effect of RYGB on type 2 diabetes drug treatment was evaluated in this nationwide matched cohort study. Participants were 22,047 adults with BMI ≥30 identified in the nationwide Scandinavian Surgical Obesity Registry, who underwent primary RYGB between 2007 and 2012. For each individual, up to 10 general population comparators were matched on birth year, sex, and place of residence. Prescription data were retrieved from the nationwide Swedish Prescribed Drug Register through September 2015. Incident use of pharmacological treatment was analyzed using Cox regression.

Results:
Sixty-seven percent of patients with pharmacological treatment of type 2 diabetes before surgery were not using diabetes drugs 2 years after surgery and 61% of patients were not pharmacologically treated up to 7 years after surgery. In patients not using diabetes drugs at baseline, there were 189 new cases of pharmacological treatment of type 2 diabetes in the surgery group and 2319 in the matched general population comparators during a median follow-up of 4.6 years (incidence: 21.4 vs 27.9 per 10,000 person-years; adjusted hazard ratio 0.77, 95% confidence interval 0.67–0.89; P < 0.001).

Conclusions:
Gastric bypass surgery not only induces remission of pharmacological treatment of type 2 diabetes but also protects from new onset of pharmacological diabetes treatment. The effect seems to persist in most, but not all, patients over 7 years of follow-up.
Genomic landscape and chronological reconstruction of driver events in multiple myeloma
Authors: Maura Francesco , Bolli Niccoló , Angelopoulos Nicos , Dawson Kevin J. , Leongamornlert Daniel , Martincorena Inigo , Mitchell Thomas J. , Fullam Anthony , Gonzalez Santiago , Szalat Raphael , Rodriguez-Martin Bernardo , Samur Mehmet Kemal , Glodzik Dominik , Roncador Marco , Fulciniti Mariateresa , Tai Yu Tzu , Minvielle Stephane , Magrangeas Florence , Moreau Philippe , Corradini Paolo , Anderson Kenneth C. , Tubio Jose M. C. , Wedge David C. , Gerstung Moritz , Avet-Loiseau Herve , Munshi Nikhil , Campbell Peter J. 
Published: August 2018

AbstractMultiple myeloma (MM) has a heterogeneous genome, evolving through both pre-clinical and post-diagnosis phases. Here, using sequences from 67 MM genomes serially collected from 30 patients together with public datasets, we establish a hierarchy of driver lesions. Point mutations, structural variants and copy number aberrations define at least 7 genomic subgroups of MM, each with distinct sets of co-operating driver mutations. Complex structural events are major drivers of MM, including chromothripsis, chromoplexy and a replication-based mechanism of templated insertions: these typically occur early. Hyperdiploidy also occurs early, with individual chromosomes often gained in more than one chronological epoch of MM evolution, showing a preferred order of acquisition. Positively selected point mutations frequently occur in later phases of disease development, as do structural variants involving MYC. Thus, initiating driver events of MM, drawn from a limited repertoire of structural and numerical chromosomal changes, shape preferred trajectories of subsequent evolution.
The Network of Cancer Genes (NCG): a comprehensive catalogue of known and candidate cancer genes from cancer sequencing screens
Authors: Repana Dimitra , Nulsen Joel , Dressler Lisa , Bortolomeazzi Michele , Venkata Santhilata Kuppili , Tourna Aikaterini , Yakovleva Anna , Palmieri Tommaso , Ciccarelli Francesca D. 
Published: August 2018

ABSTRACTThe Network of Cancer Genes (NCG) is a manually curated repository of 2,372 genes whose somatic modifications have a known or predicted cancer driver role. These genes were collected from 275 publications, including two sources of known cancer genes and 273 cancer sequencing screens of 119 cancer types in 31 primary sites from 34,905 cancer donors. This represents a more than 1.5-fold increase in content as compared to the previous version. NCG also annotates properties of cancer genes, such as duplicability, evolutionary origin, RNA and protein expression, miRNA and protein interactions, protein function and essentiality. NCG is accessible athttp://ncg.kcl.ac.uk/.
Large-scale whole-genome sequencing of three diverse Asian populations in Singapore
Authors: Wu Degang , Dou Jinzhuang , Chai Xiaoran , Bellis Claire , Wilm Andreas , Shih Chih Chuan , Soon Wendy Wei Jia , Bertin Nicolas , Khor Chiea Chuen , DeGiorgio Michael , Davila Dominguez Sonia Maria , Tan Patrick , Shabbir Asim , Moh Angela , Tan Eng-King , Foo Jia Nee ,   Tan Tock Seng Hospital Healthy Control Workgroup, Foo Roger S. , Lam Carolyn S.P. , Richards A. Mark , Cheng Ching-Yu , Aung Tin , Wong Tien Yin , Liu Jianjun , Wang Chaolong ,   on behalf of the SG10K Consortium
Published: August 2018

AbstractAsian populations are currently underrepresented in human genetics research. Here we present whole-genome sequencing data of 4,810 Singaporeans from three diverse ethnic groups: 2,780 Chinese, 903 Malays, and 1,127 Indians. Despite a medium depth of 13.7×, we achieved essentially perfect (>99.8%) sensitivity and accuracy for detecting common variants and good sensitivity (>89%) for detecting extremely rare variants with <0.1% allele frequency. We found 89.2 million single-nucleotide polymorphisms (SNPs) and 9.1 million small insertions and deletions (INDELs), more than half of which have not been cataloged in dbSNP. In particular, we found 126 common deleterious mutations (MAF>0.01) that were absent in the existing public databases, highlighting the importance of local population reference for genetic diagnosis. We describe fine-scale genetic structure of Singapore populations and their relationship to worldwide populations from the 1000 Genomes Project. In addition to revealing noticeable amounts of admixture among three Singapore populations and a Malay-related novel ancestry component that has not been captured by the 1000 Genomes Project, our analysis also identified some fine-scale features of genetic structure consistent with two waves of prehistoric migration from south China to Southeast Asia. Finally, we demonstrate that our data can substantially improve genotype imputation not only for Singapore populations, but also for populations across Asia and Oceania. These results highlight the genetic diversity in Singapore and the potential impacts of our data as a resource to empower human genetics discovery in a broad geographic region.
NRF2 activates a partial Epithelial-Mesenchymal Transition and is maximally present in a hybrid Epithelial/Mesenchymal phenotype
Authors: Bocci Federico , Tripathi Satyendra C , Vilchez Mercedes Samuel A , George Jason T , Casabar Julian P , Wong Pak Kin , Hanash Samir M , Levine Herbert , Onuchic José N , Jolly Mohit Kumar 
Published: August 2018

AbstractThe Epithelial-Mesenchymal Transition (EMT) is a key process implicated in cancer metastasis and therapy resistance. Recent studies have emphasized that cells can undergo partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype - a cornerstone of tumour aggressiveness and poor prognosis. These cells can have enhanced tumour-initiation potential as compared to purely epithelial or mesenchymal ones and can integrate the properties of cell-cell adhesion and motility that facilitates collective cell migration leading to clusters of Circulating Tumour Cells (CTCs) - the prevalent mode of metastasis. Thus, identifying the molecular players that can enable cells to maintain a hybrid E/M phenotype is crucial to curb the metastatic load. Here, using an integrated computational-experimental approach, we show that the transcription factor NRF2 can prevent a complete EMT and instead stabilize a hybrid E/M phenotype. Knockdown of NRF2 in hybrid E/M non-small cell lung cancer cells H1975 and bladder cancer cells RT4 destabilised a hybrid E/M phenotype and compromised the ability to collectively migrate to close a wound in vitro. Notably, while NRF2 knockout simultaneously downregulated E-cadherin and ZEB-1, overexpression of NRF2 enriched for a hybrid E/M phenotype by simultaneously upregulating both E-cadherin and ZEB-1 in individual RT4 cells. Further, we predict that NRF2 is maximally expressed in hybrid E/M phenotype(s) and demonstrate that this biphasic dynamic arises from the interconnections among NRF2 and the EMT regulatory circuit. Finally, clinical records from multiple datasets suggest a correlation between a hybrid E/M phenotype, high levels of NRF2 and its targets and poor survival, further strengthening the emerging notion that hybrid E/M phenotype(s) may occupy the ‘metastatic sweet spot’.