bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hyperheuristic Approach for Location-Routing Problem of Cold Chain Logistics considering Fuel Consumption
Authors: Wang Zheng , Leng Longlong , Wang Shun , Li Gongfa , Zhao Yanwei
Published: January 2020

In response to violent market competition and demand for low-carbon economy, cold chain logistics companies have to pay attention to customer satisfaction and carbon emission for better development. In this paper, a biobjective mathematical model is established for cold chain logistics network in consideration of economic, social, and environmental benefits; in other words, the total cost and distribution period of cold chain logistics are optimized, while the total cost consists of cargo damage cost, refrigeration cost of refrigeration equipment, transportation cost, fuel consumption cost, penalty cost of time window, and operation cost of distribution centres. One multiobjective hyperheuristic optimization framework is proposed to address this multiobjective problem. In the framework, four selection strategies and four acceptance criteria for solution set are proposed to improve the performance of the multiobjective hyperheuristic framework. As known from a comparative study, the proposed algorithm had better overall performance than NSGA-II. Furthermore, instances of cold chain logistics are modelled and solved, and the resulting Pareto solution set offers diverse options for a decision maker to select an appropriate cold chain logistics distribution network in the interest of the logistics company.
A Complicated Entity: Acute Celiac Artery Dissection with Resultant Pancreatitis, Duodenitis, and Cholecystitis
Authors: Endler Graham T. , Curfman Karleigh R. , Hwang Jason H. , Gray John L.
Published: January 2020

Arterial dissection is a well-recognized pathology often seen in Vascular Surgery offices and Emergency Departments alike; however, visceral arterial dissection is an extremely rare, small subset of this entity. With that, an isolated celiac artery dissection as presented within this report is an exceptionally unique pathology that has scarcely been reported, and due to this, management guidelines are undefined. Given the viscera supplied by the celiac artery, many intra-abdominal structures are at risk for ischemia when damage to the celiac artery occurs, potentially witnessed by this report. Due to the exclusivity of this pathology, we are compelled to report the case of a 71-year-old male who presented with complaints of abdominal pain and was found to have an acute celiac artery dissection, which likely resulted in severe ischemic duodenitis, as well as possibly acute pancreatitis, and questionable influence on cholecystitis.
Aggressive Central Nervous System Relapse after Autologous Stem Cell Transplant in Multiple Myeloma: Case Reports and Literature Review
Authors: Bergantim Rui , Bastos Juliana , Soares Maria José , Carvalho Bruno , Soares Pedro , Marques Cristina , Costa Jennifer , Guimarães José Eduardo , Trigo Fernanda
Published: January 2020

Extramedullary disease is an aggressive presentation at diagnosis and relapse for multiple myeloma (MM) patients. Central nervous system (CNS) is a very rare manifestation of the extramedullary disease, accounting for less than 1% of MM on diagnosis and relapse. Neurological symptoms are unspecific and usually attributed to other causes. We present two patients with CNS-MM at relapse after autologous stem cell transplant highlighting the importance of clinical suspicion and interdisciplinarity at diagnostic workup as well as the need for intensive therapeutic options on such rare and aggressive cases. The presence of neurological abnormalities in anamnesis and physical examination on a patient with MM should always prompt to suspect of a CNS involvement, and active investigation must be undertaken. MRI is the standard radiological method to detect CNS-MM, with histopathological corroboration by stereotactic biopsy and CSF evaluation alongside. Treatment of CNS-MM should include two essential approaches—be able to cross the BBB and treat the systemic disease. There is no standard therapy for this extramedullary relapse, and a tailored and multiple therapy should be promptly started—intrathecal therapy, radiotherapy, and systemic therapy, including an immunomodulator.
Salivary Antioxidants and Oxidative Stress in Psoriatic Patients: Can Salivary Total Oxidant Status and Oxidative Status Index Be a Plaque Psoriasis Biomarker?
Authors: Skutnik-Radziszewska Anna , Maciejczyk Mateusz , Fejfer Katarzyna , Krahel Julita , Flisiak Iwona , Kołodziej Urszula , Zalewska Anna
Published: January 2020

The aim of our research was to evaluate redox balance parameters and biomarkers of oxidative stress (OS) in nonstimulated and stimulated saliva as well as the blood of patients with plaque psoriasis compared to healthy controls. The study involved 40 patients with plaque psoriasis and 40 generally healthy subjects matched by age and gender to the study group patients. We assayed the concentration/activity of antioxidant enzymes: salivary peroxidase (Px), catalase (CAT), and superoxide dismutase (SOD) measured in unstimulated saliva (NWS), stimulated saliva (SWS), and erythrocytes. In plasma as well as NWS and SWS, we measured the concentration/activity of reduced glutathione (GSH), total antioxidant potential (TAC), total oxidative status (TOS), oxidative stress index (OSI), and markers of oxidative modification of proteins: advanced glycation end products (AGE), advanced oxidation protein products (AOPP), and lipid oxidation products: malondialdehyde (MDA) and total lipid hydroperoxide (LOOH). In NWS and SWS, we also evaluated the rate of reactive oxygen species (ROS) production. The concentration of Px, CAT, and SOD was significantly higher in NWS of patients with plaque psoriasis vs. healthy subjects. In SWS of psoriatic patients, we observed considerably higher concentration of Px and CAT, and in erythrocytes of patients with plaque psoriasis, the concentration of GPx and CAT was significantly higher compared to that in the controls. The levels of AOPP, AGE, MDA, and LOOH were considerably higher in NWS, SWS, and plasma of the study group compared to the controls. The concentration of total protein and salivary amylase was significantly lower in NWS and SWS of psoriatic patients compared to the healthy control. In the course of plaque psoriasis, we observed redox imbalances with prevalence of oxidation reactions. Mechanisms involved in the synthesis/secretion of proteins and activity of amylase were depressed in both glands of psoriatic patients; however, they were more inhibited in the parotid gland compared to the submandibular gland. TOS concentration and OSI value in NWS and SWS may serve as diagnostic biomarkers of plaque psoriasis.
Increased Mast Cell Counts and Degranulation in Microscopic Colitis
Authors: Chi Zhikai , Xu Jing , Saxena Romil
Published: January 2020

Objectives. Microscopic colitis (MC) is characterized by chronic diarrhea, normal colonoscopy findings, and mucosal inflammation in colonic biopsies and can be classified as collagenous colitis (CC) or lymphocytic colitis (LC). However, the pathogenesis of MC is largely unknown. In this study, we aimed to study mast cell counts and activation in MC.Methods. We investigated 64 biopsy samples from the surgical pathology database of Indiana University Health, which met the diagnostic criteria for CC or LC along with 20 control samples collected from 2014 to 2015. The specimens were used for the quantification of mast cells by examining the presence of intracellular and extracellular tryptase by immunohistochemistry.Results. In the lamina propria, the mast cell count was higher in both CC and LC groups than the control (mean highest count, 39/high-power field (HPF) vs. 30/HPF vs. 23/HPF;P<0.01). Extracellular tryptase was present in 10% of control subjects as compared to 41% of CC (P<0.05) and 60% of LC (P<0.001) patients. When LC patients were stratified into two groups with either <80% or >80% of fragments affected by inflammation, increased mast cell counts are only observed in the >80% involvement group compared with the control, but not the <80% involvement group.Conclusions. The increased mast cell count and degranulation are identified in MC, suggesting that mast cell activation might be involved in the pathogenesis of MC.
Exploring Current Evidence on the Past, the Present, and the Future of the Heart Team: A Narrative Review
Authors: Burlacu Alexandru , Covic Adrian , Cinteza Mircea , Lupu Paula Madalina , Deac Radu , Tinica Grigore
Published: January 2020

Introduction. Including healthcare professionals dealing with cardiovascular diseases, Heart Team is a concept/structure designed for selecting diagnostic strategies, facilitating therapeutic decisions, and improving cardiovascular outcomes in patients with complex heart pathologies, requiring input from different subspecialties and the necessity of a multidisciplinary approach. The aim of this narrative review is to search for and to summarize current evidence regarding Heart Team and to underline the future directions for the development of this concept. Methods. We searched the electronic database of PubMed, SCOPUS, and Cochrane CENTRAL for studies including Heart Team. Forty-eight studies were included, if reference was made to Heart Team structure and functionality. Results. We depicted the structure and the timeline of Heart Team, along with actual evidence-based recommendations from European Guidelines. We underlined the importance of quality of knowledge-sharing and decision-making inside the Team, analyzing bad decisions which did not reflect members’ true beliefs due to “uniformity pressure, closed mindedness, and illusion of invulnerability.” The observation that Guidelines’ indications regarding Heart Team carry a level C indication underlines the very future of this Team: randomized controlled trials proving solid benefits in an evidence-based world. Conclusions. Envisioned as a tool for optimizing the management of various complex cardiovascular pathologies, Heart Team should simplify and facilitate the activity in the cardiovascular ward. Finally, these facts should be translated into better cardiovascular outcomes and a lower psychological distress among Team participants. Despite all future changes, there must always be a constant part: the patient should remain at the very center of the Team.
Cement Grout Nonlinear Flow Behavior through the Rough-Walled Fractures: An Experimental Study
Authors: Jin Yuhao , Han Lijun , Xu Changyu , Meng Qingbin , Liu Zhenjun , Zong Yijiang
Published: January 2020

This research experimentally studied the effects of various fracture roughness (characterized by the fractal dimension D) and normal stress (normal loads FN) applied to fracture on ultrafine cement grout nonlinear flow behavior through rough-walled plexiglass fractured sample. A high-precision and effective sealing self-made apparatus was developed to perform the stress-dependent grout flow tests on the plexiglass sample containing rough-walled fracture (fracture apertures of arbitrary variation were created by high-strength springs and normal loads according to design requirements). The real-time data acquisition equipment and high-precision self-made electronic balance were developed to collect the real-time grouting pressure P and volumetric flow rate Q, respectively. At each D, the grouting pressure P ranged from 0 to 0.9 MPa, and the normal loads FN varied from 1124.3 to 1467.8 N. The experimental results show that (i) the Forchheimer equation was fitted very well to the results of grout nonlinear flow through rough-walled fractures. Besides, both nonlinear coefficient (a) and linear coefficient (b) in Forchheimer’s equation increased with increase of D and FN, and the larger the FN was, the larger the amplitude was. (ii) For normalized transmissivity, with the increase of Re, the decline of the T/T0−β curves mainly went through three stages: viscous regime, weak inertia regime, and finally strong inertia regime. For a certain D, as the normal load FN increased, the T/T0−β curves generally shifted downward, which shows good agreement with the single-phase flow test results conducted by Zimmerman. Moreover, with the increase of D, the Forchheimer coefficient β decreased. However, within smaller FN, β decreased gradually with increasing D and eventually approached constant values. (iii) At a given FN, Jc increased with increasing D.
Ankylosing Spondyloarthritis Resulting Severe Aortic Insufficiency and Aortitis: Exacerbation of Ankylosing Spondyloarthritis and Stenosis of the Main Left Coronary Artery after Mechanical Aortic Valve Implantation with Cardiopulmonary Bypass
Authors: Balčiūnaitė Agnė , Budrikis Algimantas , Rumbinaitė Eglė , Sabaliauskienė Jurgita , Patamsytė Vaiva , Lesauskaitė Vaiva
Published: January 2020

Ankylosing spondyloarthritis (AS) is a chronic inflammatory rheumatic disease, strongly related to human leukocyte antigen (HLA)-B27. Cardiac involvement in AS manifests in 2 to 10% of patients as aortic insufficiency, aortitis, mitral valve fibrosis, or disturbance in the conduction of the heart. In this article, we present a case of a 49-year-old male patient with AS, who was referred to our medical institution for elective aortic valve surgery because of severe aortic regurgitation. The histological findings revealed fibrosing endocarditis of aortic valve and nonspecific aortitis of aortic root. Late postoperatively, we observed exacerbation of AS and narrowing of the main left coronary artery (LAD). Our case highlights the importance of proper treatment of AS before and after cardiac surgery. Furthermore, in this case, we suspect association between cardiopulmonary bypass, activity of AS, and coronary artery disease.
Estudo da prevalência de anemia gestacional e fatores associados na maternidade de referência do município de Joinville – SC
Authors: Schafaschek Heloisa Da Silva , Silva Caroline Figueiredo da , Silva Gustavo Figueiredo da , Guimbala Maria Augusta Baptista , Almeida Sthéfane De , Silva Jean Carl
Published: January 2020

Objetivo: Avaliar a prevalência de anemia ferropriva em gestantes em uma maternidade de referência de Santa Catarina. Métodos: Realizou-se um estudo observacional, do tipo corte transversal, de março a maio de 2017, em uma maternidade pública do Sul do Brasil. Os dados foram obtidos através da revisão dos prontuários, carteirinhas de pré-natal, e aplicação de questionário padronizado às parturientes no período de pós-parto imediato. O desfecho analisado foi a presença de anemia gestacional e construído modelos de regressão logística multinominal para cálculo de razão de chance, e ajustada para variáveis de confusão. O nível de significância estatística adotado é de 5% (p<0,05). Resultados: Das 740 parturientes avaliadas, 263 (35,6%) tiveram valor de hemoglobina que indicasse anemia gestacional em um dos três trimestres. A população anêmica caracterizou-se por menor idade materna, escolaridade e porcentagem de puérperas casadas, maior prevalência de IMC abaixo do peso e início do pré-natal mais precoce. Conclusão: A prevalência de anemia gestacional nesse estudo foi de 36,5%.
Fontan‐Associated Liver Disease: Spectrum of Disease in Children and Adolescents
Authors: Rathgeber Steven L. , Guttman Orlee R. , Lee Anna F. , Voss Christine , Hemphill Nicole M. , Schreiber Richard A. , Harris Kevin C.
Published: January 2020

Background

Information is evolving on liver disease in pediatric patients with Fontan physiology. The purpose of this investigation is to evaluate the spectrum of liver disease in a pediatric population of patients with Fontan physiology and evaluate transient elastography (
TE
) as a noninvasive marker of liver disease.

Methods and Results

We prospectively enrolled all children with Fontan physiology. All patients underwent comprehensive liver evaluation including liver enzymes (alanine aminotransferase, aspartate aminotransferase, gamma‐glutamyl transferase, alkaline phosphatase), aspartate transaminase to platelet ratio index, albumin, bilirubin, international normalized ratio, complete blood cell count, abdominal ultrasound, and
TE
. Transjugular liver biopsies and hemodynamic measurements were performed in a subset of patients. A total of 76 children (median, 11.7; interquartile range, 8.4–14.8 [56% male]) were evaluated, with 17 having a transjugular liver biopsy (median 14.8 years; interquartile range, 14.3–17.4). All biopsies showed pathological changes. The severity of liver pathology did not correlate with
TE
. There was a positive correlation between
TE
and time since Fontan (
R
=0.42,
P
<0.01), aspartate transaminase to platelet ratio index (
R
=0.29,
P
=0.02), aspartate transaminase (
R
=−0.42,
P
<0.01), and platelets (
R
=−0.42,
P
<0.01). Splenomegaly on abdominal ultrasound was correlated with
TE
(
z
=−2.2,
P
=0.03), low platelet count (
z
=1.9,
P
=0.05), low aspartate transaminase (
z
=1.9,
P
=0.02), and low alkaline phosphatase (
z
=2.4,
P
=0.02).

Conclusions

Liver disease was ubiquitous in our cohort of pediatric patients with Fontan Physiology. Given the correlation between
TE
and time from Fontan,
TE
shows potential as a prospective marker of liver pathology. However, individual measurements with
TE
do not correlate with the severity of pathology. Given the prevalence of liver disease in this population, protective measures of liver health as well as routine liver health surveillance should be implemented with consideration for hepatology consultation and biopsy in the event of abnormal liver biochemical markers or imaging.
Dissociation of Cerebral Blood Flow and Femoral Artery Blood Pressure Pulsatility After Cardiac Arrest and Resuscitation in a Rodent Model: Implications for Neurological Recovery
Authors: Crouzet Christian , Wilson Robert H. , Lee Donald , Bazrafkan Afsheen , Tromberg Bruce J. , Akbari Yama , Choi Bernard
Published: January 2020

Background

Impaired neurological function affects 85% to 90% of cardiac arrest (
CA
) survivors. Pulsatile blood flow may play an important role in neurological recovery after
CA
. Cerebral blood flow (
CBF
) pulsatility immediately, during, and after
CA
and resuscitation has not been investigated. We characterized the effects of asphyxial
CA
on short‐term (<2 hours after
CA
)
CBF
and femoral arterial blood pressure (
ABP
) pulsatility and studied their relationship to cerebrovascular resistance (
CVR
) and short‐term neuroelectrical recovery.

Methods and Results

Male rats underwent asphyxial
CA
followed by cardiopulmonary resuscitation. A multimodal platform combining laser speckle imaging,
ABP
, and electroencephalography to monitor
CBF
, peripheral blood pressure, and brain electrophysiology, respectively, was used.
CBF
and
ABP
pulsatility and
CVR
were assessed during baseline,
CA
, and multiple time points after resuscitation. Neuroelectrical recovery, a surrogate for neurological outcome, was assessed using quantitative electroencephalography 90 minutes after resuscitation. We found that
CBF
pulsatility differs significantly from baseline at all experimental time points with sustained deficits during the 2 hours of postresuscitation monitoring, whereas
ABP
pulsatility was relatively unaffected. Alterations in
CBF
pulsatility were inversely correlated with changes in
CVR
, but
ABP
pulsatility had no association to
CVR
. Interestingly, despite small changes in
ABP
pulsatility, higher
ABP
pulsatility was associated with worse neuroelectrical recovery, whereas
CBF
pulsatility had no association.

Conclusions

Our results reveal, for the first time, that
CBF
pulsatility and
CVR
are significantly altered in the short‐term postresuscitation period after
CA
. Nevertheless, higher
ABP
pulsatility appears to be inversely associated with neuroelectrical recovery, possibly caused by impaired cerebral autoregulation and/or more severe global cerebral ischemia.
Clinical and Biomarker Predictors of Expanded Heart Failure Outcomes in Patients With Type 2 Diabetes Mellitus After a Recent Acute Coronary Syndrome: Insights From the EXAMINE Trial
Authors: Sharma Abhinav , Vaduganathan Muthiah , Ferreira João Pedro , Liu Yuyin , Bakris George L. , Cannon Christopher P. , White William B. , Zannad Faiez
Published: January 2020

Background

Improved heart failure (
HF
) risk stratification after a recent acute coronary syndrome may identify those who can benefit from therapies that reduce
HF
risk. We aimed to identify clinical and biomarker predictors for expanded
HF
outcomes in patients with type 2 diabetes mellitus after recent acute coronary syndrome.

Methods and Results

The EXAMINE (
Ex
amination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial was a multicenter, non‐inferiority, double‐masked, placebo‐controlled study which randomized 5380 patients with type 2 diabetes mellitus after recent acute coronary syndrome to alogliptin or placebo. Baseline biomarkers were measured in 5154 patients: NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity troponin I, adiponectin, growth‐differentiation‐factor‐15, and galectin‐3. Our primary outcome was cardiovascular) death,
HF
hospitalization, elevated NT‐proBNP during follow‐up, or loop diuretics initiation. The association between clinical variables, biomarkers, and outcomes were assessed using Cox regression models. In the study population, the median age was 61.0 years, 67.7% were men, and 28.0% had baseline
HF
(median follow‐up was 18 months). In multivariable analyses, NT‐proBNP had the strongest association with the primary outcome (per log
2
, hazard ratio 1.24; Wald χ
2
67.4;
P
<0.0001) followed by a prior
HF
history (hazard ratio 1.42; Wald χ
2
20.8;
P
<0.0001). A model with clinical variables and biomarkers allowed for risk prediction for expanded
HF
outcomes (C‐statistic=0.72). Discrimination results were similar for cardiovascular death or
HF
hospitalization.

Conclusions

Among patients with type 2 diabetes mellitus after recent acute coronary syndrome, the use biomarkers such as N‐terminal pro‐B‐type natriuretic peptide and clinical variables enables risk stratification for expanded
HF
outcomes.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov/
. Unique identifier:
NCT
00968708.
Sex Differences in Cardiovascular Effectiveness of Newer Glucose‐Lowering Drugs Added to Metformin in Type 2 Diabetes Mellitus
Authors: Raparelli Valeria , Elharram Malik , Moura Cristiano S. , Abrahamowicz Michal , Bernatsky Sasha , Behlouli Hassan , Pilote Louise
Published: January 2020

Background

Randomized controlled trials showed that newer glucose‐lowering agents are cardioprotective, but most participants were men. It is unknown whether benefits are similar in women.

Methods and Results

Among adults with type 2 diabetes mellitus not controlled with metformin with no prior use of insulin, we assessed for sex differences in the cardiovascular effectiveness and safety of sodium‐glucose‐like transport‐2 inhibitors (
SGLT
‐2i), glucagon‐like peptide‐1 receptor agonists (
GLP
‐1
RA
), dipeptidyl peptidase‐4 inhibitors, initiated as second‐line agents relative to sulfonylureas (reference‐group). We studied type 2 diabetes mellitus American adults with newly dispensed sulfonylureas,
SGLT
‐2i,
GLP
‐1
RA
, or dipeptidyl peptidase‐4 inhibitors (Marketscan‐Database: 2011–2017). We used multivariable Cox proportional hazards models with time‐varying exposure to compare time to first nonfatal cardiovascular event (myocardial infarction/unstable angina, stroke, and heart failure), and safety outcomes between drugs users, and tested for sex–drug interactions. Among 167 254 type 2 diabetes mellitus metformin users (46% women, median age 59 years, at low cardiovascular risk), during a median 4.5‐year follow‐up, cardiovascular events incidence was lower in women than men (14.7 versus 16.7 per 1000‐person‐year). Compared with sulfonylureas, hazard ratios (
HR
s) for cardiovascular events were lower with
GLP
‐1
RA
(adjusted
HR
‐women: 0.57, 95%
CI
: 0.48–0.68;
aHR
‐men: 0.82, 0.71–0.95), dipeptidyl peptidase‐4 inhibitors (
aHR
‐women: 0.83, 0.77–0.89;
aHR
‐men: 0.85, 0.79–0.91) and
SGLT
‐2i (
aHR
‐women: 0.58, 0.46–0.74;
aHR
‐men: 0.69, 0.57–0.83). A sex‐by‐drug interaction was statistically significant only for
GLP
‐1
RA
(
P
=0.002), suggesting greater cardiovascular effectiveness in women. Compared with sulfonylureas, risks of adverse events were similarly lower in both sexes for
GLP
‐1
RA
(
aHR
‐women: 0.81, 0.73–0.89;
aHR
‐men: 0.80, 0.71–0.89), dipeptidyl peptidase‐4 inhibitors (
aHR
‐women: 0.82, 0.78–0.87;
aHR
‐men: 0.83, 0.78–0.87) and
SGLT
‐2i (
aHR
‐women: 0.68, 0.59–0.78;
aHR
‐men: 0.67, 0.59–0.78) (all sex–drug interactions for adverse events
P
>0.05).

Conclusions

Newer glucose‐lowering drugs were associated with lower risk of cardiovascular events than sulfonylureas, with greater effectiveness of
GLP
‐1
RA
in women than men. Overall, they appeared safe, with a better safety profile for
SGLT
‐2i than for
GLP
‐1
RA
regardless of sex.
Gender Differences in Risk Factors Associated With Pulmonary Artery Systolic Pressure, Heart Failure, and Mortality in Blacks: Jackson Heart Study
Authors: Lakshmanan Suvasini , Jankowich Matthew , Wu Wen‐Chih , Blackshear Chad , Abbasi Siddique , Choudhary Gaurav
Published: January 2020

Background

Pulmonary hypertension is prevalent in black individuals, especially women. Elevated pulmonary artery systolic pressure (
PASP
) is associated with significant morbidity and mortality.

Methods and Results

We developed linear and proportional hazards models to examine potential gender‐related differences in risk factors for elevated
PASP
(estimated by transthoracic echocardiography) and
PASP
‐associated clinical outcomes (incident heart failure admissions and mortality) in
JHS
(Jackson Heart Study) participants.
JHS
is a prospective observational cohort study of heart disease in blacks from the Jackson, Mississippi, metropolitan area. The study cohort included participants with measurable transtricuspid gradients (n=3286) at the time of first/baseline examination, 2000–2004. The median age (interquartile range) of patients at baseline was 57.8 years (18.6 years) with 67.5% being women. The median
PASP
at baseline was higher in women (men: 26 mm Hg [interquartile range 8], women: 27 mm Hg [interquartile range 9]. In multivariate linear regression analyses with
PASP
, significant gender interactions were noted for age, chronic lung disease, pulse pressure, and obstructive spirometry. In exploratory analyses stratified by gender, body mass index, and obstructive and restrictive spirometry patterns were associated with
PASP
in women, and chronic lung disease was associated with
PASP
in men. Age and pulse pressure had stronger associations with
PASP
in women compared with men. There was a significant interaction between gender and
PASP
for heart failure admissions but not mortality.

Conclusions

Specific cardiopulmonary risk factors are associated with elevated
PASP
in women and men. Women with elevated
PASP
have a higher risk of incident heart failure admissions. Future research is needed to understand associated gender‐specific mechanisms that can help identify targeted prevention and management strategies for patients with elevated
PASP
.
Human CardioChimeras: Creation of a Novel “Next‐Generation” Cardiac Cell
Authors: Firouzi Fareheh , Sinha Choudhury Sarmistha , Broughton Kathleen , Salazar Adriana , Bailey Barbara , Sussman Mark A.
Published: January 2020

Background

CardioChimeras produced by fusion of murine c‐kit
+
cardiac interstitial cells with mesenchymal stem cells promote superior structural and functional recovery in a mouse model of myocardial infarction compared with either precursor cell alone or in combination. Creation of human CardioChimeras (
hCCs
) represents the next step in translational development of this novel cell type, but new challenges arise when working with c‐kit
+
cardiac interstitial cells isolated and expanded from human heart tissue samples. The objective of the study was to establish a reliable cell fusion protocol for consistent optimized creation of
hCC
s and characterize fundamental
hCC
properties.

Methods and Results

Cell fusion was induced by incubating human c‐kit
+
cardiac interstitial cells and mesenchymal stem cells at a 2:1 ratio with inactivated Sendai virus. Hybrid cells were sorted into 96‐well microplates for clonal expansion to derive unique cloned
hCC
s, which were then characterized for various cellular and molecular properties.
hCC
s exhibited enhanced survival relative to the parent cells and promoted cardiomyocyte survival in response to serum deprivation in vitro.

Conclusions

The generation of
hCC
is demonstrated and validated in this study, representing the next step toward implementation of a novel cell product for therapeutic development. Feasibility of creating human hybrid cells prompts consideration of multiple possibilities to create novel chimeric cells derived from cells with desirable traits to promote healing in pathologically damaged myocardium.
Renal Hydrogen Peroxide Production Prevents Salt‐Sensitive Hypertension
Authors: Cuevas Santiago , Asico Laureano D. , Jose Pedro A. , Konkalmatt Prasad
Published: January 2020

Background

The regulation of sodium excretion is important in the pathogenesis of hypertension and salt sensitivity is predictive of cardiovascular events and mortality. C57Bl/6 and
BALB
/c mice have different blood pressure sensitivities to salt intake. High salt intake increases blood pressure in some C57Bl/6J mouse strains but not in any
BALB
/c mouse strain.

Methods and Results

We determined the cause of the difference in salt sensitivity between C57Bl/6 and
BALB
/c mice. Basal levels of superoxide and H
2
O
2
were higher in renal proximal tubule cells (
RPTC
s) from
BALB
/c than C57Bl/6J mice. High salt diet increased H
2
O
2
production in kidneys from
BALB
/c but C57Bl/6J mice. High sodium concentration (170 mmol/L) in the incubation medium increased H
2
O
2
levels in
BALB
/c‐
RPTC
s but not in C57Bl/6J‐
RPTC
s. H
2
O
2
(10 μmol/L) treatment decreased sodium transport in
RPTC
s from
BALB
/c but not C57Bl/6J mice. Overexpression of catalase in the mouse kidney predisposed
BALB
/c mice to salt‐sensitive hypertension.

Conclusions

Our data show that the level of salt‐induced H
2
O
2
production negatively regulates
RPTC
sodium transport and determines the state of salt sensitivity in 2 strains of mice. High concentrations of antioxidants could prevent H
2
O
2
production in renal proximal tubules, which would result in sodium retention and increased blood pressure.
Normal Systolic Blood Pressure at Presentation With Acute Ischemic Stroke Predicts Cardioembolic Etiology
Authors: Moores Margaret , Yogendrakumar Vignan , Bereznyakova Olena , Alesefir Walid , Pettem Hailey , Stotts Grant , Dowlatshahi Dar , Shamy Michel
Published: January 2020

Background

Early insight into the possible etiology of ischemic stroke allows for early initiation of mechanism‐specific secondary stroke prevention. Initial systolic blood pressure during acute ischemic stroke may relate to stroke etiology. We sought to determine whether normotension at presentation with acute ischemic stroke predicts cardioembolic etiology.

Methods and Results

All patients presenting with acute ischemic stroke within 12 hours of symptom onset at a comprehensive stroke center from January 2015 to December 2017 were assessed. Normotension was defined as systolic blood pressure ≤130 mm Hg. The primary exposure was blood pressure on arrival at the hospital, and the primary outcome was cardioembolic etiology. Multivariable regression with stepwise selection was used to adjust for relevant covariates. We included 683 patients in our analysis, 303 (44%) of whom were diagnosed with cardioembolic etiology at 6 months. The probability of cardioembolic etiology was inversely associated with
systolic blood pressure
, and initial
systolic blood pressure
was significantly associated with cardioembolic etiology (
odds ratio:
1.15; 95%
CI,
1.05 to 1.26). Normotension was associated with 2.62‐fold increased odds of cardioembolic etiology (95%
CI,
1.46 to 4.72).

Conclusions

Normotension at presentation with acute ischemic stroke strongly predicts cardioembolic etiology. These patients may especially benefit from early and prolonged cardiac investigations.
Progression of Arterial Stiffness is Associated With Midlife Diastolic Blood Pressure and Transition to Late‐Life Hypertensive Phenotypes
Authors: Webb Alastair John Stewart
Published: January 2020

Background

Hypertension‐associated cardiovascular events are particularly associated with elevated systolic blood pressure (
SBP
) in late life, yet long‐term interactions between
SBP
, diastolic
BP
(
DBP
) and arterial stiffness in development of late‐life hypertensive phenotypes remain unclear.

Methods and Results

In the
UK
Biobank, we determined associations between arterial stiffness index (
ASI
),
SBP
,
DBP
, and their progression, and transition from normotension (<140/90 mm Hg) to hypertension or elevated
ASI
(>10 m/s). Associations were determined by general linear and logistic regression, adjusted for cardiovascular risk factors and variability of measurements across follow‐ups. Mean values of baseline
SBP
,
DBP
, and
ASI
were determined stratified by deciles of age, blood pressure, and
ASI
, with CIs determined by bootstrapping. In 169 742 participants at baseline,
ASI
was more strongly associated with
DBP
than
SBP
, before and after adjustment for risk factors (β:
SBP
, −0.01 [
P
<0.001];
DBP
, 0.06 [
P
<0.001]), while
DBP
was more strongly associated with progression of
ASI
(n=13 761; β: SBP, 0.013 [
P
=0.01];
DBP
, 0.038 [
P
<0.001]). Baseline
ASI
was associated with increasing
SBP
during follow‐up (β=0.02,
P
<0.001) but not
DBP
(β=0.0004,
P
=0.39), but was associated with a younger age of transition from rising to falling
DBP
(highest versus lowest quartile: 51.2; 95% CI, 49.9–52.3 versus 60.4; 95% CI, 59.6–61.3 [
P
<0.001]).
ASI
predicted the development of isolated systolic hypertension (odds ratio, 1.30; 95% CI, 1.22–1.39), particularly after adjustment for measurement variability (odds ratio, 2.29).

Conclusions

Midlife
DBP
was the strongest predictor of progression of arterial stiffness, while arterial stiffness was associated with earlier transition to a falling
DBP
. Prevention of long‐term harms associated with arterial stiffness may require more intensive control of midlife
DBP
.
Audiovisual Multisensory Processing in Young Adults With Attention-Deficit/Hyperactivity Disorder
Authors: McCracken Heather S. , Murphy Bernadette A. , Burkitt James J. , Glazebrook Cheryl M. , Yielder Paul C.
Published: January 2020

Multisensory integration is a fundamental form of sensory processing that is involved in many everyday tasks. Those with Attention-Deficit/Hyperactivity Disorder (ADHD) have characteristic alterations to various brain regions that may influence multisensory processing. The overall aim of this work was to assess how adults with ADHD process audiovisual multisensory stimuli during a complex response time task. The paradigm used was a two-alternative forced-choice discrimination task paired with continuous 64-electrode electroencephalography, allowing for the measurement of response time and accuracy to auditory, visual, and audiovisual multisensory conditions. Analysis revealed that those with ADHD () respond faster than neurotypical controls () when presented with auditory, visual, and audiovisual multisensory conditions, while also having race model violation in early response latency quantiles. Adults with ADHD also had more prominent multisensory processing over parietal-occipital brain regions at early post-stimulus latencies, indicating that altered brain structure may have important outcomes for audiovisual multisensory processing. The present study is the first to assess how those with ADHD respond to multisensory conditions during a complex response time task, and demonstrates that adults with ADHD have unique multisensory processing when assessing both behavioral response time measures and neurological measures.
The Emergence and Early Fate of the Three Rs Concept
Authors: Balls Michael , Parascandola John
Published: January 2020

In the 60th year since the publication of The Principles of Humane Experimental Technique by W.M.S. Russell and R.L. Burch, we visited the W.M.S. and Claire Russell Archive at the University of Nottingham to discover, or confirm, answers to certain questions: the origins of the UFAW project which led to its writing; the relationship between Russell and Burch; the project plan; the origin of the Three Rs ( Replacement, Reduction, Refinement) concept; the drafting, publication and response to the appearance of the book; and the future careers of its authors. We report on our findings, though many other questions have yet to be answered.
The Overt and Hidden Use of Animal-Derived Products in Alternative Methods for Skin Sensitisation: A Systematic Review
Authors: Marigliani Bianca , Sehn Felipe Perraro , Silva Josemar Vinicius Maiworm Abreu , Balottin Luciene Bottentuit López , Augusto Elisabeth de Fatima Pires , Buehler Anna Maria
Published: January 2020

In vitro methods that can replace animal testing in the identification of skin sensitisers are now a reality. However, as cell culture and related techniques usually rely on animal-derived products, these methods may be failing to address the complete replacement of animals in safety assessment. The objective of this study was to identify the animal-derived products that are used as part of in vitro methods for skin sensitisation testing. Thus, a systematic review of 156 articles featuring 83 different in vitro methods was carried out and, from this review, the use of several animal-derived products from different species was identified, with the use of fetal bovine serum being cited in most of the methods (78%). The use of sera from other animals, monoclonal antibodies and animal proteins were also variously mentioned. While non-animal alternatives are available and methods free of animal-derived products are emerging, most of the current methods reported used at least one animal-derived product, which raises ethical and technical concerns. Therefore, to deliver technically and ethically better in vitro methods for the safety assessment of chemicals, more effort should be made to replace products of animal origin in existing methods and to avoid their use in the development of new method protocols.
Patellofemoral Cartilage Restoration: A Systematic Review and Meta-analysis of Clinical Outcomes
Authors: Hinckel Betina B. , Pratte Eli L. , Baumann Charles A. , Gowd Anirudh K. , Farr Jack , Liu Joseph N. , Yanke Adam B. , Chahla Jorge , Sherman Seth L.
Published: January 2020

Background:

Many surgical options for treating patellofemoral (PF) cartilage lesions are available but with limited evidence comparing their results.

Purpose:

To determine and compare outcomes of PF cartilage restoration techniques.

Study Design:

Systematic review and meta-analysis.

Methods:

PRISMA (Preferred Reporting Items for Systematic Meta-Analyses) guidelines were followed by utilizing the PubMed, EMBASE, and Cochrane Library databases. Inclusion criteria were clinical studies in the English language, patient-reported outcomes after PF cartilage restoration surgery, and >12 months’ follow-up. Quality assessment was performed with the Coleman Methodology Score. Techniques were grouped as osteochondral allograft transplantation (OCA), osteochondral autograft transfer (OAT), chondrocyte cell–based therapy, bone marrow–based therapy, and scaffolds.

Results:

A total of 59 articles were included. The mean Coleman Methodology Score was 71.8. There were 1937 lesions (1077 patellar, 390 trochlear, and 172 bipolar; 298 unspecified). The frequency of the procedures was as follows, in descending order: chondrocyte cell–based therapy (65.7%), bone marrow–based therapy (17.2%), OAT (8%), OCA (6.6%), and scaffolds (2.2%). When compared with the overall pooled lesion size (3.9 cm2; 95% CI, 3.5-4.3 cm2), scaffold (2.2 cm2; 95% CI, 1.8-2.5 cm2) and OAT (1.5 cm2; 95% CI, 1.1-1.9 cm2) lesions were smaller ( P < .001), while chondrocyte cell–based therapy lesions were larger (4.7 cm2; 95% CI, 4.1-5.3 cm2; P = .039). Overall, the instability pool was 11.9%, and the anatomic risk factors pool was 32.1%. Statistically significant improvement was observed on at least 1 patient-reported outcome in chondrocyte cell–based therapy (83%), OAT (78%), OCA (71%), bone marrow–based therapy (64%), and scaffolds (50%). There were no significant differences between any group and the overall pooled change in International Knee Documentation Committee score (30.2; 95% CI, 27.4-32.9) and Lysholm score (25.2; 95% CI, 16.9-33.5). There were no significant differences between any group and the overall pooled rate in minor complication rate (7.6%; 95% CI, 4.7%-11.9%) and major complication rate (8.3%; 95% CI, 5.7%-12.0%); however, OCA had a significantly greater failure rate (22.7%; 95% CI, 14.6%-33.4%) as compared with the overall rate (6.8%; 95% CI, 4.7%-9.5%).

Conclusion:

PF cartilage restoration leads to improved clinical outcomes, with low rates of minor and major complications. There was no difference among techniques; however, failures were higher with OCA.
Morphologic Variants of Posterolateral Tibial Plateau Impaction Fractures in the Setting of Primary Anterior Cruciate Ligament Tear
Authors: Bernholt David L. , DePhillipo Nicholas N. , Grantham W. Jeffrey , Crawford Matthew D. , Aman Zachary S. , Kennedy Mitchell Iung , LaPrade Robert F.
Published: January 2020

Background:

Impaction fractures of the posterolateral tibial plateau commonly occur in the setting of anterior cruciate ligament (ACL) tears, with considerable variability found in fracture size and morphologic features.

Purpose:

The primary objective was to characterize different morphologic variants of posterolateral tibial plateau impaction fractures. The secondary objective was to investigate the association between these impaction fracture variants and concomitant meniscal and ligamentous injuries.

Study Design:

Cross-sectional study; Level of evidence 3.

Methods:

Patients treated for primary ACL tears and having magnetic resonance imaging available were included in this study, and magnetic resonance images were reviewed with denotation of displaced posterolateral tibial impaction fractures. A classification system was created based on morphologic variants of impaction fractures; associations were evaluated through use of independent chi-square testing.

Results:

There were 825 knees meeting the inclusion criteria, with displaced posterolateral tibial plateau impaction fractures present in 407 knees (49.3%). We observed 3 distinct morphologic variants of lateral tibial plateau impaction fractures: (I) posterior cortical buckle not involving the articular surface; (II) posterior impaction fracture involving the articular surface, with subtypes based on (A) tibial plateau depth bone loss <10% and (B) bone loss >10%; and (III) displaced osteochondral fragment, with subtypes for (A) shear or (B) depressed fragment. Type IIIA impaction fractures were associated with an increased incidence of lateral meniscus posterior root tears (33.3% vs 12.4%; P = .009) and an increased incidence of lateral meniscal tears (83.3% vs 56.7%; P = .024) compared with all knees without type IIIA impaction fracture. An increased incidence of medial collateral ligament (MCL) tears was noted in patients with type IIIA impaction fractures compared with those who had no fracture or had another fracture type (61.1% vs 20.1%; P < .001). Type IIIB impaction fractures were associated with an increased incidence of lateral meniscal tears (80.0% vs 56.2%; P = .005).

Conclusion:

A high prevalence of displaced posterolateral tibial plateau impaction fractures occur in the setting of ACL tears, and they can be classified into distinct morphologic subtypes. Posterolateral tibial plateau impaction fractures with displaced depressed or shear fragments were both associated with an increased incidence of lateral meniscal tears, whereas impaction fractures with a shear fragment were associated with an increased incidence of lateral meniscus posterior root tears and MCL tears.
Design and realization of a normothermic perfusion system for laboratory tests on pig liver
Authors: Mazzantini Lucrezia , Dimitri Mattia , Staderini Fabio , Cianchi Fabio , Corvi Andrea
Published: January 2020

Ex vivo testing is a fundamental step in the development of new medical devices; indeed without it, it is impossible to proceed with in vivo tests. At the University of Florence, a robotic tool for microwave thermal ablation is under development. Up to now, the thermoablation tests for the validation of the tool were carried out on non-perfused ex vivo livers, providing results that inevitably differ from those obtainable with an in vivo liver. The aim is to design, and consequently create, a compact and transportable system which allows to perfuse a swine liver with physiological solution and heparin. This device should also allow the organ to be transported from the explantation place to the laboratory, keeping it under normothermal condition. The perfusor was designed to simulate the physiological flow within the liver in the most realistic way possible. The design, construction, and optimization of the perfusor have been addressed using the physiological values of hepatic flow and pressure identified in the literature, neglecting in the first instance any load losses. Therefore, open circuit tests were conducted, validated through perfusion tests on freshly explanted pig liver; during these tests, the surface temperature of the organ was recorded using an infrared camera, and the fluid temperature was verified using an immersion probe. The perfusion test showed a good alignment with the open circuit tests, demonstrating the validity of the simplifications adopted to treat the complex vascular structure of the liver.
Intraoperative glycemic control in patients undergoing Orthotopic liver transplant: a single center prospective randomized study
Authors: Kumar Sathish S. , Pelletier Shawn J. , Shanks Amy , Thompson Aleda , Sonnenday Christopher J. , Picton Paul
Published: January 2020

Background

Perioperative hyperglycemia is associated with poor outcomes yet evidence to guide intraoperative goals and treatment modalities during non-cardiac surgery are lacking. End-stage liver disease is associated with altered glucose homeostasis; patients undergoing liver transplantation display huge fluctuations in blood glucose (BG) and represent a population of great interest. Here, we conduct a randomized trial to compare the effects of strict versus conventional glycemic control during orthotopic liver transplant (OLT).

Methods

Following approval by the Institutional Review Board of the University of Michigan Medical School and informed consent, 100 adult patients undergoing OLT were recruited. Patients were randomized to either strict (target BG 80–120 mg/dL) or conventional (target BG 180–200 mg/dL) BG control with block randomization for diabetic and nondiabetic patients. The primary outcomes measured were 1-year patient and graft survival assessed on an intention to treat basis. Graft survival is defined as death or needing re-transplant (www.unos.org). Three and 5-year patient and graft survival, infectious and biliary complications were measured as secondary outcomes. Data were examined using univariate methods and Kaplan-Meir survival analysis. A sensitivity analysis was performed to compare patients with a mean BG of ≤120 mg/dL and those > 120 mg/dL regardless of treatment group.

Results

There was no statistically significant difference in patient survival between conventional and strict control respectively;1 year, 88% vs 88% (p-0.99), 3 years, 86% vs 84% (p- 0.77), 5 years, 82% vs 78. % (p-0.36). Graft survival was not different between conventional and strict control groups at 1 year, 88% vs 84% (p-0.56), 3 years 82% vs 76% (p-0.46), 5 years 78% vs 70% (p-0.362).

Conclusion

There was no difference in patient or graft survival between intraoperative strict and conventional glycemic control during OLT.

Trial registration

Clinical trial number and registry: www.clinicaltrials.gov NCT00780026. This trial was retrospectively registered on 10/22/2008.