bluuebunny/crossref_metadata_2025 huggingface dataset:
An observational study of international normalized ratio control according to NICE criteria in patients with non-valvular atrial fibrillation: the SAIL Warfarin Out of Range Descriptors Study (SWORDS)
Authors: Harris Daniel E , Thayer Daniel , Wang Ting , Brooks Caroline , Murley Geoff , Gravenor Mike , Hill Nathan R , Lister Steven , Halcox Julian
Published: November 2019

Aims 

In patients with non-valvular atrial fibrillation prescribed warfarin, the UK National Institute of Health and Care Excellence (NICE) defines poor anticoagulation as a time in therapeutic range (TTR) of <65%, any two international normalized ratios (INRs) within a 6-month period of ≤1.5 (‘low’), two INRs ≥5 within 6 months, or any INR ≥8 (‘high’). Our objectives were to (i) quantify the number of patients with poor INR control and (ii) describe the demographic and clinical characteristics associated with poor INR control.

Method and results

Linked anonymized health record data for Wales, UK (2006–2017) was used to evaluate patients prescribed warfarin who had at least 6 months of INR data. 32 380 patients were included. In total, 13 913 (43.0%) patients had at least one of the NICE markers of poor INR control. Importantly, in the 24 123 (74.6%) of the cohort with an acceptable TTR (≥65%), 5676 (23.5%) had either low or high INR readings at some point in their history. In a multivariable regression female gender, age (≥75 years), excess alcohol, diabetes heart failure, ischaemic heart disease, and respiratory disease were independently associated with all markers of poor INR control.

Conclusion 

Acceptable INR control according to NICE standards is poor. Of those with an acceptable TTR (>65%), one-quarter still had unacceptably low or high INR levels according to NICE criteria. Thus, only using TTR to assess effectiveness with warfarin has the potential to miss a large number of patients with non-therapeutic INRs who are likely to be at increased risk.
Candida albicans infection disturbs the redox homeostasis system and induces reactive oxygen species accumulation for epithelial cell death
Authors: Ren Tongtong , Zhu Hangqi , Tian Lei , Yu Qilin , Li Mingchun
Published: November 2019

Candida albicans is a common pathogenic fungus with high mortality in immunocompromised patients. However, the mechanism by which C. albicans invades host epithelial cells and causes serious tissue damage remains to be further investigated. In this study, we established the C. albicans–293T renal epithelial cell interaction model to investigate the mechanism of epithelial infection by this pathogen. It was found that C. albicans infection causes severe cell death and reactive oxygen species (ROS) accumulation in epithelial cells. Further investigations revealed that C. albicans infection might up-regulate expression of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (NOX), inhibit the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and suppress the p38–Nrf2–heme oxygenase-1 (HO-1) pathway which plays an important role in the elimination of intracellular ROS. Furthermore, epithelial cell death caused by the fungal infection could be strikingly alleviated by addition of the antioxidant agent glutathione, indicating the critical role of ROS accumulation in cell death caused by the fungus. This study revealed that disturbance of the redox homeostasis system and ROS accumulation in epithelial cells is involved in cell death caused by C. albicans infection, which sheds light on the application of antioxidants in the suppression of tissue damage caused by fungal infection.
Evolutionary Dynamics of Structural Variation at a Key Locus for Color Pattern Diversification in Cichlid Fishes
Authors: Kratochwil Claudius F , Liang Yipeng , Urban Sabine , Torres-Dowdall Julián , Meyer Axel
Published: November 2019

Color patterns in African cichlid fishes vary spectacularly. Although phylogenetic analysis showed already 30 years ago that many color patterns evolved repeatedly in these adaptive radiations, only recently have we begun to understand the genomic basis of color variation. Horizontal stripe patterns evolved and were lost several times independently across the adaptive radiations of Lake Victoria, Malawi, and Tanganyika and regulatory evolution of agouti-related peptide 2 (agrp2/asip2b) has been linked to this phenotypically labile trait. Here, we asked whether the agrp2 locus exhibits particular characteristics that facilitate divergence in color patterns. Based on comparative genomic analyses, we discovered several recent duplications, insertions, and deletions. Interestingly, one of these events resulted in a tandem duplication of the last exon of agrp2. The duplication likely precedes the East African radiations that started 8–12 Ma, is not fixed within any of the radiations, and is found to vary even within some species. Moreover, we also observed variation in copy number (two to five copies) and secondary loss of the duplication, illustrating a surprising dynamic at this locus that possibly promoted functional divergence of agrp2. Our work suggests that such instances of exon duplications are a neglected mechanism potentially involved in the repeated evolution and diversification that deserves more attention.
Plant–frugivore interactions in an urban nature reserve and its nearby gardens
Authors: Zietsman Mariki Y , Montaldo Norberto H , Devoto Mariano
Published: November 2019

In the current global context of growing urbanization, urban nature reserves play a crucial role as habitats that serve educational, recreational and conservation purposes. Biodiversity conservation within urban reserves is a challenging task, particularly since connectivity between a reserve and its surrounding artificial green spaces (e.g. gardens and parks) may affect the ecological processes within the reserve in complex ways. In this context, we studied the feeding interactions between plants and birds to provide evidence that an urban nature reserve is connected to its surrounding artificial habitats by mobile organisms. We focused on fleshy-fruited plants and frugivorous birds, and we used a network approach to describe the feeding interactions between these two guilds. The most important connecting bird was Turdus rufiventris, an abundant and obligate frugivore, whose abundance was positively linked to fruit availability in most of the study sites. The apparent increase in the abundance of T. rufiventris in one habitat when it decreases in the other suggests that the two habitats may be complementary for this species. The nature reserve, with many native plants, however, seems to be the preferred site when both habitats offer an abundant fruit supply. Our results suggest changes in either habitat can have consequences in the other one, which has broad implications for the design of management plans of urban nature reserves.
Grief and Composition as Identity
Authors: Garland C E
Published: November 2019

‘It feels like I have lost a part of myself’ is frequently uttered by those grieving the death of a loved one. Despite the ubiquity of such utterances, and the palpable sense that they express something true, few philosophers have considered what, if anything, accounts for their truth. Here, I develop a suggestion from Donald Baxter according to which Composition as Identity provides us a means to understand the grief utterances literally. In doing so, I identify and develop a version of Leibniz's Law required for Composition as Identity to account for the truth of the grief utterances. In turn, this principle helps shed light on Composition as Identity's central claim: that the parts are identical to the whole. By considering objections to the resulting view, I construct a list of desiderata for other philosophers interested in accounting for the grief utterances.
Infrared renormalon in $SU(N)$ QCD(adj.) on $\mathbb{R}^3\times S^1$
Authors: Ashie Masahiro , Morikawa Okuto , Suzuki Hiroshi , Takaura Hiromasa , Takeuchi Kengo
Published: November 2019

We study the infrared renormalon in the gluon condensate in the $SU(N)$ gauge theory with $n_W$-flavor adjoint Weyl fermions (QCD(adj.)) on $\mathbb{R}^3\times S^1$ with the $\mathbb{Z}_N$ twisted boundary conditions. We rely on the so-called large-$\beta_0$ approximation as a conventional tool to analyze the renormalon, in which only Feynman diagrams that dominate in the large-$n_W$ limit are considered, while the coefficient of the vacuum polarization is set by hand to the one-loop beta function $\beta_0=11/3-2n_W/3$. In the large $N$ limit within the large-$\beta_0$ approximation, the W-boson, which acquires the twisted Kaluza–Klein momentum, produces the renormalon ambiguity corresponding to the Borel singularity at $u=2$. This provides an example that the system in the compactified space $\mathbb{R}^3\times S^1$ possesses the renormalon ambiguity identical to that in the uncompactified space $\mathbb{R}^4$. We also discuss the subtle issue that the location of the Borel singularity can change depending on the order of two necessary operations.
The difference between hypertension determined by self-report versus examination in the adult population of the USA: Continuous NHANES 1999–2016
Authors: Delhey Leanna , Shoults Catherine , Johnson Kemmian , Orloff Mohammed , Faramawi Mohammed F , Delongchamp Robert
Published: November 2019

Background

Studies have considered the validity of self-reported hypertension relative to hypertension detected by examination; no study has explored trends in the difference between these two measures. Our objective was to calculate these differences overtime within subpopulations of the USA.

Methods

We included non-Hispanic white, non-Hispanic black and Hispanic adults who participated in the National Health and Nutrition Examination Surveys from 1999 to 2016, in the analysis (N = 44 333). We subtracted self-reported hypertension from hypertension detected by examination to calculate blood pressure difference (BPD). We fit weighted linear regression models that included important covariates along with all combination of two- and three-way interactions to predict the BPD. We used the fitted lines of the models to depict the patterns of differences in the different subpopulations.

Results

Age ≥ 45 years, lack of annual clinical visit, body mass index (BMI) < 25 and time were important factors associated with increased BPD.

Conclusions

People who are ≥ 45 years, have normal BMI, or do not have annual medical visits are more likely to have a bigger BPD. We can use the calculated BPD, to adjust estimates of the prevalence of self-reported hypertension.
CRISPR‐Cas9–induced IGF1 gene activation as a tool for enhancing muscle differentiation via multiple isoform expression
Authors: Roberston Matthew J. , Raghunathan Suchi , Potaman Vladimir N. , Zhang Fan , Stewart M. David , McConnell Bradley K. , Schwartz Robert J.
Published: November 2019

Muscle wasting, or muscle atrophy, can occur with age, injury, and disease; it affects the quality of life and complicates treatment. Insulin‐like growth factor 1 (IGF1) is a key positive regulator of muscle mass. The IGF1/Igf1 gene encodes multiple protein isoforms that differ in tissue expression, potency, and function, particularly in cellular proliferation and differentiation, as well as in systemic versus localized signaling. Genome engineering is a novel strategy for increasing gene expression and has the potential to recapitulate the diverse biology seen in IGF1 signaling through the overexpression of multiple IGF1 isoforms. Using a CRISPR‐Cas9 gene activation approach, we showed that the expression of multiple IGF1 or Igf1 mRNA variants can be increased in human and mouse skeletal muscle myoblast cell lines using a single‐guide RNA (sgRNA). We found increased IGF1 protein levels in the cell culture media and increased cellular phosphorylation of AKT1, the main effector of IGF1 signaling. We also showed that the expression of Class 1 or Class 2 mRNA variants can be selectively increased by changing the sgRNA target location. The expression of multiple IGF1 or Igf1 mRNA transcript variants in human and mouse skeletal muscle myoblasts promoted myotube differentiation and prevented dexamethasone‐induced atrophy in myotubes in vitro. Our findings suggest that this novel approach for enhancing IGF1 signaling has potential therapeutic applications for treating skeletal muscle atrophy.
Neuraxial Block for Delivery Among Women With Low Platelet Counts: A Retrospective Analysis
Authors: Levy N. , Goren O. , Cattan A. , Weiniger C.F. , Matota I.
Published: November 2019

(Int J Obstet Anesth. 2018;35:4–9)

Pregnant women with low platelet counts may be denied neuraxial block due to concerns about causing a spinal-epidural hematoma (SEH). As a result of this denial, they may not receive adequate labor analgesia. In the event of a cesarean delivery, there will be a need for general anesthesia, which has increased risk in parturients. The lowest safe platelet count to perform neuraxial block is unknown.
Perinatal Depression: Recommendations for Prevention and the Challenges of Implementation
Authors: Freeman M.P.
Published: November 2019

(JAMA. 2019;321(6):550–552)

The US Preventive Services Task Force (USPSTF) issued a recommendation of referring women at risk for perinatal depression to counseling. Perinatal depression affects 11.5% of mothers in the United States annually and is associated with short and long term risks to both mother and infant. Although the USPSTF had previously recommended screening for depression in all adults, including pregnant and postpartum women, the new recommendation focused on prevention instead of screening. To enact this advised change in approach, more research is needed to determine how to identify at-risk women, connect the identified women to effective treatments, and gage the outcomes of this new approach.
Anesthetic Management of Parturients With Arnold Chiari Malformation-I: A Multicenter Retrospective Study
Authors: Gruffi T.R. , Peralta F.M. , Thakkar M.S. , Arif A. , Anderson R.F. , Orlando B. , Coffman J.C. , Nathan N. , McCarthy R.J. , Toledo P. , Habib A.S.
Published: November 2019

(Int J Obstet Anesth. 2019;37:52–56)

In patients with Arnold Chiari malformations (ACM) the cerebellum herniates through the foramen magnum and displaces the lower pons and medulla. In addition, the flow of cerebrospinal fluid from the fourth ventricle is impaired, and dynamic or static herniation of brain tissue can occur. In ∼25% of patients with ACM, the pressure gradient generated by this condition can lead to the development of a syringomyelia, which is an abnormal cavitation within the spinal cord. Type 1 Arnold Chiari malformations (ACM-1) is the most common of 4 categories of ACM, and women with ACM-I are usually not diagnosed until adulthood. Some of these patients are asymptomatic while others may manifest symptoms such as headache, ataxia, and sensorimotor impairments of the extremities.
Uterotonics in Elective Caesarean Delivery: A Randomised Noninferiority Study Comparing Carbetocin 20 and 100 µg
Authors: Tabl S. , Balki M. , Downey K. , Tomlinson G. , Farine D. , Seaward G. , Carvalho J.C.A.
Published: November 2019

(Anaesthesia. 2019;74:190–196)

Postpartum hemorrhage (PPH) is the most common cause of maternal mortality worldwide and accounts for 35% of maternal deaths. Active management of the third stage of labor is recommended in all parturients, with prophylactic uterotonic drug administration after delivery of the infant being the primary component of this active management. This strategy alone has been shown to decrease the incidence of PPH by up to 40%. The 2009 guidelines from the Society of Obstetricians and Gynaecologists of Canada (SOGC) recommended a single 100 µg intravenous bolus dose of carbetocin as the uterotonic agent of choice, rather than an oxytocin infusion, to prevent PPH after elective cesarean delivery. The rationale for recommending this dose was based on the manufacturer’s recommendation and some clinical trials. Some more recent studies, however, have suggested that doses as low as 15 µg may be effective at preventing PPH after elective cesarean delivery. The current investigators believed a larger trial comparing this smaller dose with the standard 100 µg dose was warranted to confirm these findings. This study was undertaken to compare the uterine tone intensity achieved with 20 carbetocin versus 100 µg carbetocin in women at low risk of PPH undergoing elective cesarean delivery under spinal anesthesia.
Admission Cardiotocography Versus Intermittent Auscultation of the Fetal Heart in Low-risk Pregnancy During Evaluation for Possible Labour Admission—A Multicentre Randomised Trial: The ADCAR Trial
Authors: Smith V. , Begley C. , Newell J. , Higgins S. , Murphy D.J. , White M.J. , Morrison J.J. , Canny S. , O'Donovan D. , Devane D.
Published: November 2019

(BJOG. 2019;126:114–121)

To identify which deliveries might be at greater risk of intrapartum fetal compromise and therefore may benefit from continuous cardiotocography (cCTG) during labor, either intermittent auscultation (IA) or admission cardiotocography (ACTG) is performed on women upon admission with possible labor onset. Current guidelines are based on studies evaluating the effects of ACTG on women in diagnosed labor, rather than those with signs and symptoms of possible labor onset. This study aimed to compare ACTG with IA in terms of cesarean section, obstetric intervention, and neonatal morbidity in a low-risk population of healthy pregnant women presenting for possible labor onset, before confirmation of labor.
Norepinephrine Infusion for Preventing Postspinal Anesthesia Hypotension During Cesarean Delivery
Authors: Hasanin A.M. , Amin S.M. , Agiza N.A. , Elsayed M.K. , Refaat S. , Hussein H.A. , Rouk T.I. , Alrahmany M. , Elsayad M.E. , Elshafaei K.A. , Refaie A.
Published: November 2019

(Anesthesiology. 2019;130:55–62)

Vasopressors, such as phenylephrine and ephedrine, are important tools for preventing postspinal hypotension in women undergoing cesarean delivery. Norepinephrine, a vasopressor with minimal cardiac depressant effect, has recently been introduced into obstetric anesthesia. Previous studies have supported the use of norepinephrine in the prevention of postspinal hypotension; however, there is a lack of evidence regarding optimum dosing. This study aimed to investigate optimal dosing of norepinephrine for prophylaxis against postspinal hypotension during cesarean delivery by comparing 3 infusion rates following an initial 5 μg bolus.
Nursing Skill Mix Inversely Associated with Critical Patient Outcomes
Authors: Rosenberg Karen
Published: November 2019

According to this study:

A higher nursing skill mix (that is, one that includes more RNs) is associated with improvements in 12 patient outcomes.

These 12 outcomes are length of stay; ulcer, gastritis, and upper gastrointestinal bleeds; acute myocardial infarction; restraint use; failure to rescue; pneumonia; sepsis; urinary tract infection; mortality/30-day mortality; pressure injury; infections (other than urinary tract infection); and shock, cardiac arrest, or heart failure.
Pain management for patients with chronic kidney disease in the primary care setting
Authors: Lowe Kevin M. , Robinson Danny R.
Published: November 2019

Pain is routinely reported in patients with chronic kidney disease. Pain is often multifaceted, making the treatment of this complex patient population even more challenging. Understanding pain types as well as treatment options for this patient population is an important skillset for the primary care provider.
Postpositivism in Health Professions Education Scholarship
Authors: Young Meredith E. , Ryan Anna
Published: November 2019

An understanding of the diversity of perspectives within the research paradigms of health professions education (HPE) is essential for rigorous research design and more purposeful engagement with the contributions of others. In this article, the authors explicitly discuss the underlying assumptions, notions of good scholarship, and shortcomings of the postpositivism research paradigm. While postpositivism is likely one of the more familiar paradigms within HPE research, it is rarely formally or explicitly described. Drawing on key literature and contemporary examples, the authors describe the ontology, epistemology, methodologies, axiology, signs of rigor, and common critiques of postpositivism. A case study provides the focus for a practical illustration of how a postpositivist approach to education research could be applied. Suggestions for further reading are provided for those who are keen to delve deeper into the history and key tenants of the postpositivist stance.
Postoperative neurocognitive disorders
Authors: Olotu Cynthia
Published: November 2019

Purpose of review

Alterations in cognitive functions are common in the perioperative course. Although often unnoticed by physicians, these alterations might have distinct long-term consequences for the patient with regard to everyday functioning, self-dependency, and quality of life. In recent years, however, perioperative cognition has gained increased interest, both by clinicians and scientists, and knowledge of the preventive measures of postoperative cognitive decline has become mandatory for anesthetists and surgeons.

Recent findings

This review offers a brief overview of the current state of knowledge concerning perioperative changes in cognition, including its pathophysiology and prevention strategies.

Postoperative neurocognitive disorders are frequent complications, especially in elderly patients, with postoperative delirium being its most pronounced and acute postoperative form, predisposing the patient for long-term cognitive impairment. The incidence of postoperative cognitive decline can be reduced by implementing preventive measures during perioperative patient care as recommended by national and international guidelines.
Human Umbilical Cord Mesenchymal Stromal Cells Attenuate Systemic Sepsis in Part by Enhancing Peritoneal Macrophage Bacterial Killing via Heme Oxygenase-1 Induction in Rats
Authors: Jerkic Mirjana , Gagnon Stéphane , Rabani Razieh , Ward-Able Taylor , Masterson Claire , Otulakowski Gail , Curley Gerard F. , Marshall John , Kavanagh Brian P. , Laffey John G.
Published: November 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Mesenchymal stromal cells have therapeutic potential in sepsis, but the mechanism of action is unclear. We tested the effects, dose-response, and mechanisms of action of cryopreserved, xenogeneic-free human umbilical cord mesenchymal stromal cells in a rat model of fecal peritonitis, and examined the role of heme oxygenase-1 in protection.

Methods

Separate in vivo experiments evaluated mesenchymal stromal cells in fecal sepsis, established dose response (2, 5, and 10 million cells/kg), and the role of heme oxygenase-1 in mediating human umbilical cord–derived mesenchymal stromal/stem cell effects. Ex vivo studies utilized pharmacologic blockers and small inhibitory RNAs to evaluate mechanisms of mesenchymal stromal cell enhanced function in (rodent, healthy and septic human) macrophages.

Results

Human umbilical cord mesenchymal stromal cells reduced injury and increased survival (from 48%, 12 of 25 to 88%, 14 of 16, P = 0.0033) in fecal sepsis, with dose response studies demonstrating that 10 million cells/kg was the most effective dose. Mesenchymal stromal cells reduced bacterial load and peritoneal leukocyte infiltration (from 9.9 ± 3.1 × 106/ml to 6.2 ± 1.8 × 106/ml, N = 8 to 10 per group, P < 0.0001), and increased heme oxygenase-1 expression in peritoneal macrophages, liver, and spleen. Heme oxygenase-1 blockade abolished the effects of mesenchymal stromal cells (N = 7 or 8 per group). Mesenchymal stromal cells also increased heme oxygenase-1 expression in macrophages from healthy donors and septic patients. Direct ex vivo upregulation of macrophage heme oxygenase-1 enhanced macrophage function (phagocytosis, reactive oxygen species production, bacterial killing). Blockade of lipoxin A4 production in mesenchymal stromal cells, and of prostaglandin E2 synthesis in mesenchymal stromal cell/macrophage cocultures, prevented upregulation of heme oxygenase-1 in macrophages (from 9.6 ± 5.5-fold to 2.3 ± 1.3 and 2.4 ± 2.3 respectively, P = 0.004). Knockdown of heme oxygenase-1 production in macrophages ablated mesenchymal stromal cell enhancement of macrophage phagocytosis.

Conclusions

Human umbilical cord mesenchymal stromal cells attenuate systemic sepsis by enhancing peritoneal macrophage bacterial killing, mediated partly via upregulation of peritoneal macrophage heme oxygenase-1. Lipoxin A4 and prostaglandin E2 play key roles in the mesenchymal stromal cell and macrophage interaction.
A Randomized Trial of Continuous Versus Intermittent Skin-to-Skin Contact After Premature Birth and the Effects on Mother–Infant Interaction
Authors: Sahlén Helmer Charlotte , Birberg Thornberg Ulrika , Frostell Anneli , Örtenstrand Annica , Mörelius Evalotte
Published: November 2019

Background:

Premature birth affects opportunities for interaction between infants and mothers. Skin-to-skin contact (SSC) is standard care in neonatal care but has not been sufficiently studied regarding the effects on interaction between preterm infant and mothers.

Purpose:

The purpose of this study was to compare interaction between preterm infants and their mothers after continuous versus intermittent SSC from birth to discharge. A secondary aim was to study a potential dose–response effect between time in SSC and quality of interaction.

Methods:

Families were randomly assigned to either continuous (n = 17) or intermittent (n = 14) SSC before delivery. Interaction was measured from videotapes of a Still-Face Paradigm collected at 4 months' corrected age. Face-to-face interaction was coded according to Ainsworth's Maternal Sensitivity Scales and the Maternal Sensitivity and Responsivity Scales-R. Dose–response correlations were calculated between mean time spent in SSC and each of the interaction scales.

Results:

There were no statistically significant differences between groups in maternal interactive behavior toward their infants regarding sensitivity, interference, availability, acceptance, withdrawal, or intrusivity. There was no correlation between mean time in SSC and quality of interaction.

Implications for Practice:

Continuous SSC from birth to discharge was not superior to intermittent SSC concerning mother–infant interaction between preterm infants and their mothers at 4 months' corrected age. However, compared with other studies, mean time in SSC was also high in the intermittent group.

Implications for Research:

Further studies are needed to find out how interaction between parents and preterm infants can be improved, supported, and facilitated in the neonatal intensive care unit (NICU) and whether there is an optimal dose for SSC.
Demographics, risk factors, and complication or readmission rates after multiligament knee reconstruction: A retrospective cohort study
Authors: Sivasundaram Lakshmanan , Paliobeis Andrew , Labelle Mark W. , Kim Chang-Yeon , Trivedi Nikunj N. , Karns Michael J. , Salata Michael J. , Voos James E.
Published: November 2019

Background:

Multi-ligament knee injuries are complex and relatively rare injuries. As a result outcome data available to guide treatment are limited, and management strategies often are debated.

Methods:

Patients who underwent multiligament knee reconstructions between 2005 and 2015 were identified in the National Surgical Quality Improvement Program (NSQIP) database using validated CPT codes. Thirty-day complication and readmission rates after multiligament knee repair or reconstruction were identified. A multivariable logistic regression model was then used to identify statistically significant associations between patient factors and outcomes.

Results:

We identified 481 patients with an average age of 30.1±14.9 yr, and 67.2% male predominance. Using the American Society of Anesthesiologists (ASA) classification system, 222 patients (46.2%) were “Healthy” (ASA 1), 218 patients (45.3%) had “Mild Systemic Disease” (ASA 2), and 38 (7.9%) patients had “Severe Systemic Disease” (ASA 3). Of the sample 96.3% underwent multiligament knee reconstruction on an outpatient basis with 75.9% (365 patients) of the procedures performed in an outpatient surgery center. At 30-days postoperatively, the sample had a 6.2% overall complication rate; 4.8% of patients had a minor complication, and 1.5% of patients had a major complication. The most common minor and major complications were superficial surgical site infection and pulmonary embolus, respectively.

Conclusions:

Multiligament knee injuries commonly occur in young, relatively healthy individuals. This study indicates that reconstructive procedures are quite safe and supports the premise that multiligament knee reconstructions can be safely performed even as an outpatient.

Level of Evidence:

Level III.
The Collapsing Foot: It’s All About the Ligaments!
Authors: Hummel Amelia , de Cesar Netto Cesar , Garfinkel Jonathan , Deland Jonathan
Published: November 2019

There are many surgical techniques described for the deltoid ligament and spring ligament reconstruction in the treatment of a collapsing flatfoot. In some cases, addressing these ligaments may offer a way to treat a collapsing flatfoot that preserves the talonavicular and subtalar joints. Preservation of these joints may lead to better outcomes for patients, as their functionality is not limited by hindfoot fusions. Preliminary evidence suggests that patients, when properly selected for, show good long-term outcomes after undergoing surgical reconstruction of those ligaments. The technique for spring ligament and deltoid ligament reconstruction in cases of collapsing flatfoot deformity is described in this article.

Level of Evidence: Diagnostic Level V—Expert Opinion. See Instructions for Authors for a complete description of levels of evidence.
The successful use of pembrolizumab in a renal transplant recipient with metastatic melanoma
Authors: Hanna Daire L. , Law Steven J. , Merrick Sophie A. , Heptinstall Lauren , Bass Paul , Dupont Peter , Sheri Amna
Published: November 2019

We report a case in which a renal transplant recipient with metastatic melanoma had an excellent response to treatment with second line programmed cell death protein 1 (PD-1) inhibitor therapy, pembrolizumab. Acute cellular allograft rejection on initiation of PD-1 inhibitor was successfully reversed with methylprednisolone. By converting the patient to sirolimus and giving predose prednisolone, pembrolizumab was continued with stable renal function and an excellent oncological response. This case supports the efficacy of PD-1 inhibitors in patients who are chronically immunosuppressed, and suggests an approach to maintain transplant function.
Differential Efficacy of Anti-VEGF Antibodies Based on Sex and Race in a Diverse Cohort of Advanced Nonsquamous Non–Small Cell Lung Cancer
Authors: Sukrithan Vineeth , Barbaro Alexander , Chergui Adel , Ko Brian , Lin Juan , Cheng Haiying , Goel Sanjay
Published: November 2019

Objectives:

Bevacizumab with chemotherapy improved overall survival (OS) in the E4599 trial in metastatic nonsquamous non–small cell lung cancer (NS-NSCLC). A meta-analysis demonstrated an OS benefit with bevacizumab only in a subset of nonwhite patients. We explored the efficacy of antivascular endothelial growth factor antibodies (AVA) in a diverse cohort.

Materials and Methods:

Patients with advanced (stage IIIB/IV, American Joint Committee Cancer 7th edition) recurrent or metastatic NS-NSCLC diagnosed January 2006 to December 2017 at a single medical center were included. Survival analysis was performed with log-rank testing of the Kaplan-Meier estimator. Univariate models were constructed, and significant variables, age, sex, race were incorporated into a multivariate Cox proportional hazard model. Data analysis was performed on SAS.

Results:

A total of 171 patients, 80 were treated with AVA and 91 were untreated. Median age: 63 years, 55% females, 19% non-Hispanic whites, 44% blacks and 32% Hispanic whites; median 40 pack-years of smoking; 11.7% had sensitizing epidermal growth factor receptor mutations. Patients who received AVA had a survival benefit (26.6 vs. 19 mo, P=0.025). Adjusting for age, sex, race/ethnicity, epidermal growth factor receptor mutations, Eastern Cooperative Oncology Group performance status and number of metastases; AVA therapy was associated with improved OS (adjusted hazard ratio=0.62; P=0.049). In a subgroup analysis, females had survival benefit with AVA (median survival: 29.1 vs. 14.2 mo, log-rank P=0.02) which was significant in the adjusted model (adjusted hazard ratio=0.52; P=0.049).

Conclusions:

In a diverse cohort of patients with advanced NS-NSCLC, a survival benefit was confirmed with AVA. The greatest magnitude of benefit was in blacks and non-Hispanic whites. A significant survival benefit was limited to female patients.
Aspirin for the Primary Prevention of Cardiovascular Disease
Authors: Cicci Jonathan D. , Iyer Prashanth , Clarke Megan M. , Mazzella Anthony J.
Published: November 2019

Cardiovascular disease is the leading cause of death globally, and deaths due to coronary heart disease or stroke account for over half of all cardiovascular deaths in the United States. While many important advances have been made in the treatment and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), morbidity and mortality remain high. Aspirin has been commonly used for the primary and secondary prevention of ASCVD for decades and is an easily accessible therapeutic option. While it is a cornerstone of secondary prevention, its role in primary prevention is less clear and professional guidelines have differed in their recommendations. As literature has substantially evolved over the past 40 years, so too has our understanding of aspirin’s role in the primary prevention of ASCVD. This article reviews landmark clinical trials of aspirin in primary prevention and highlights key changes in dosing strategies and demographics.
Cutaneous Metastases From a Cribriform Adenocarcinoma of the Minor Salivary Glands
Authors: Boyd Alan S.
Published: November 2019

Cutaneous metastases from solid tumor malignancies often emanate from breast, gastrointestinal, and lung tumors. Adenocarcinomas from minor salivary gland cancers may involve the skin contiguously but rarely as metastatic deposits. Furthermore, these metastases are usually locoregional and not distal. Recently, an uncommon neoplasm termed cribriform adenocarcinoma of the minor salivary glands has been described, and although it often spreads to cervical lymph nodes, metastatic involvement of the skin has not been reported.
Mohs Micrographic Surgery for Advanced Centrofacial Tumors
Authors: Norris Ivy I. , Weinberger Christine H. , Holmes Todd E. , Goldman Glenn D.
Published: November 2019

BACKGROUND

Mohs surgery was developed for the treatment of advanced skin cancers. Advanced centrofacial tumors are among the most challenging lesions.

OBJECTIVE

The objective of the study was to review the most complex midface cases from our practice and to delineate how to plan the approach to these lesions, how to remove them in a step-by-step fashion, and how the patients were managed in a multidisciplinary manner when indicated.

METHODS

We reviewed 15 years of the most complex tumors to present to our practice for which Mohs micrographic surgery was performed. Follow-up for patients ranged from 3 to 13 years and is ongoing.

RESULTS

Twenty cases were identified in which tumors of the central face extended to bone and created extensive operative wounds. Eleven lesions were recurrent at presentation, and 9 had perineural disease. These cases are reviewed sequentially and demonstrate the challenges, successes, and pitfalls of Mohs micrographic surgery in the treatment of the most difficult tumors. Two patients died from disease.

CONCLUSION

Mohs surgery is an excellent technique for the removal of extensive midfacial lesions and allows for the surgical removal of lesions that might otherwise be considered inoperable. Approach to these lesions requires careful planning, meticulous surgical technique, excellence in histology, and an experienced reconstructive surgeon. Such tumors often require a multidisciplinary approach, imaging, and adjuvant therapy. All such cases require diligent follow-up. Although many such lesions will be cured, regional recurrence and metastasis may result, even when clear margins are achieved.
Outcomes of Mohs Micrographic Surgery at the American Society for Dermatologic Surgery International Traveling Mentorship Program International Mohs Fellowship Recognition Units: A Retrospective Survey of 5889 Cases From South Africa, Romania, and the Netherlands
Authors: du Plessis Pieter J. , Leventer Mihaela , Krekels Gertruud , de Wet Jacob D. , Laeuchli Severin
Published: November 2019

BACKGROUND

The American Society for Dermatologic Surgery (ASDS) International Traveling Mentorship Program (ITMP) has initiated an International Mohs Fellowship Recognition Program, with 3 centers accredited to date.

OBJECTIVE

To describe and compare the outcomes of Mohs micrographic surgery (MMS) at the three units.

METHODS

From patient files, we extracted demographic information, as well as tumor type, location of tumor, tumor histology, stages of MMS, and outcomes.

RESULTS

At the 3 units, 3,899 patients were treated with MMS over a 5-year period in the South African unit, and 1,141 cases in the Romanian unit. Over a 3-year period, 849 cases were treated in the Netherlands unit. Basal cell carcinomas (BCCs) constituted 78.9% (South African unit), 79% (Romanian unit), and 97.2% (Netherlands unit), and squamous cell carcinomas (SCCs) 17.7% (South African unit), 19% (Romanian unit), and 0.7% (Netherlands unit) of the tumors treated. The recurrence rate following MMS was low, at 0.1% (South African Unit) and 0.17% (Romanian Unit) of cases at the end of the study period, with a median follow-up time of 2 years.

CONCLUSION

Mohs micrographic surgery is an effective treatment modality for removing BCC and SCC at ASDS ITMP–recognized International Mohs Fellowship units.
Multidisciplinary Tumor Boards in Dermatologic Surgery
Authors: Chen David L. , Cintolo-Gonzalez Jessica , Cook Deborah , Devenney Brent , Goldman Glenn D. , Greene Laura , Harlow Seth , Holmes Todd , Rehman Hibba , Sajisevi Mirabelle , Anker Chris
Published: November 2019

BACKGROUND

Recent advances in diagnostic and therapeutic modalities have made oncologic care ever more challenging, and multidisciplinary tumor boards (MTBs) are increasingly being used as a forum to discuss and coordinate care for complex oncology patients. Literature on the use of MTBs specific to cutaneous oncology and dermatologic surgery remains limited.

OBJECTIVE

To share our experiences with cutaneous oncology MTBs at the University of Vermont Medical Center (UVMMC).

METHODS

We describe the formation, timing, participation, clinical discussion, case follow-up, and coordination of care of our MTBs.

RESULTS

A log of all cases discussed at cutaneous oncology MTBs from August 2018 to August 2019 is presented as an example. Five specific cases are described in further detail to demonstrate critical components of multidisciplinary care.

CONCLUSION

The MTBs at UVMMC has created a collaborative environment for providers in multiple specialties to jointly formulate and coordinate optimal treatment plans for difficult cases, particularly when treatment guidelines do not exist or are insufficient. Furthermore, MTBs can serve as an educational forum for all participants.
Who Are the Undiagnosed? Disparities in Hypertension Diagnoses in Vulnerable Populations
Authors: Meador Margaret , Lewis Joy H. , Bay R. Curtis , Wall Hilary K. , Jackson Chanaye
Published: November 2019

This study builds upon a project that developed clinical criteria to identify undiagnosed hypertension patients “hiding in plain sight” (HIPS) by examining patient characteristics to understand whether there are disparities in hypertension diagnosis. We examined electronic health record demographic data for patients identified by the HIPS criteria and subgroups at 3 Missouri health centers. Identified patients who returned for a follow-up visit and were subsequently diagnosed with hypertension tended to be older, black/African American, uninsured, and classified as having obesity. Younger, white, healthy weight females were less likely to be diagnosed. These findings point to exploring possible biases/other nonclinical factors in hypertension diagnosis.
Embracing and Advancing the Consumerist Era in Healthcare
Authors: Taylor Kay
Published: November 2019

The advent of consumerism—especially increasing demands for data, convenience, and transparency—has emboldened and empowered individuals to expect a consumer-centric experience in every aspect of their lives. The Amazon Prime consumer model has instilled an expectation that every transaction should be friction free, with no exception made for healthcare. Indeed, amid the myriad changes in healthcare in recent years, consumerism is making a pronounced impact on every aspect of healthcare delivery.

EvergreenHealth, an integrated two-hospital healthcare system based in Kirkland, Washington, is addressing the demands of its patient-consumers. We serve nearly 1 million residents at a 318-bed medical center and four medical specialty buildings in Kirkland and a 72-bed hospital in Monroe, Washington. In addition, our 350-member physician multispecialty group encompasses 13 primary care clinics, 5 urgent care clinics, 3 emergency departments, and 26 specialty care practices. EvergreenHealth has been named one of America’s 100 Best Hospitals by Healthgrades for three consecutive years (2017–2019), and we earned Healthgrades’ Outstanding Patient Experience Award in 2018. In providing an exceptional patient experience, we are seeing that the patient’s new role as consumer is an accelerating trend that will continue to drive change and force all health systems to adopt new ways of operating.

In fact, I believe that those health systems that embrace the consumerist era of healthcare by investing and innovating in ways that meet patient-consumer needs will remain viable even as sentiments shift, technology evolves, and new threats emerge. In contrast, those that do not heed the consumer’s clarion call are in for difficult times.
Severe impaired blood pressure control caused by baroreflex failure as a late sequela of neck irradiation
Authors: Piani Federica , Landolfo Matteo , Fiorini Giulia , D’Addato Sergio , Mancia Giuseppe , Borghi Claudio
Published: November 2019

A 64-year-old man, whose medical history was significant only for locally advanced squamocellular carcinoma of the right palatine tonsil treated with extended neck radiotherapy 9 years before, was evaluated for traumatic cerebral haemorrhage secondary to syncope after a postural change. The selective angiographic study of cerebral vessels was negative. No heart arrhythmias were recorded at ECG monitoring. The 24-h ABPM revealed sudden pressor and depressor episodes during day-time and a reverse dipper pattern during night-time. Noninvasive autonomic nervous system function testing showed supine hypertension and orthostatic hypotension caused by afferent baroreflex failure. According to literature, even if only few cases are described, neck irradiation can be assumed to be the major cause of baroreflex failure. No treatment is currently approved. The patient was treated with a selective beta-blocker (bisoprolol) administered at bedtime. Repeated ABPM after 1 month of therapy showed absence of sudden pressor and depressor episodes and no dipper pattern during night-time.
RANIBIZUMAB TREATMENT IN TREATMENT-NAIVE NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Holz Frank G. , Figueroa Marta S. , Bandello Francesco , Yang Yit , Ohji Masahito , Dai Hong , Wykrota Halina , Sharma Sanjay , Dunger-Baldauf Cornelia , Lacey Sue , Macfadden Wayne , Mitchell Paul ,   on behalf of all the LUMINOUS study investigators
Published: November 2019

Purpose:

To evaluate the effectiveness, safety, and treatment patterns of ranibizumab 0.5 mg in treatment-naive patients with neovascular age-related macular degeneration enrolled in LUMINOUS study.

Methods:

This 5-year, prospective, multicenter, observational study recruited 30,138 adult patients (treatment-naive or previously treated with ranibizumab or other ocular treatments) who were treated according to the local ranibizumab label.

Results:

Six thousand two hundred and forty-one treatment-naive neovascular age-related macular degeneration patients were recruited. Baseline (BL) demographics were, mean (SD) age 75.0 (10.2) years, 54.9% females, and 66.5% Caucasian. The mean (SD) visual acuity (VA; letters) gain at 1 year was 3.1 (16.51) (n = 3,379; BLVA, 51.9 letters [Snellen: 20/92]) with a mean (SD) of 5.0 (2.7) injections and 8.8 (3.3) monitoring visits. Presented by injection frequencies <3 (n = 537), 3 to 6 (n = 1,924), and >6 (n = 918), visual acuity gains were 1.6 (14.93), 3.3 (16.57), and 3.7 (17.21) letters, respectively. Stratified by BLVA <23 (n = 382), 23 to <39 (n = 559), 39 to <60 (n = 929), 60 to <74 (n = 994), and ≥74 (n = 515), visual acuity change was 12.6 (20.63), 6.7 (17.88), 3.6 (16.41), 0.3 (13.83), and −3.0 (11.82) letters, respectively. The incidence of ocular/nonocular adverse events was 8.2%/12.8% and serious adverse events were 0.9%/7.4%, respectively.

Conclusion:

These results demonstrate the effectiveness and safety of ranibizumab in treatment-naive neovascular age-related macular degeneration patients.
Efficacy and Safety of Intense Pulsed Light in Patients With Meibomian Gland Dysfunction—A Randomized, Double-Masked, Sham-Controlled Clinical Trial
Authors: Piyacomn Yonrawee , Kasetsuwan Ngamjit , Reinprayoon Usanee , Satitpitakul Vannarut , Tesapirat Lita
Published: November 2019

Purpose:

To study the efficacy and safety of intense pulsed light (IPL) in patients with meibomian gland dysfunction (MGD).

Methods:

This prospective randomized double-masked sham-controlled trial included 114 patients with MGD. Patients were randomized into the IPL or sham group. Either the IPL or sham procedure was performed on days 0, 15, and 45. Ocular Surface Disease Index (OSDI), visual analog scale, visual acuity, tear breakup time, meibum quality and expressibility, meibography grade, ocular surface staining, tear film lipid layer thickness, tear osmolarity, Schirmer test, tear interleukin-1 receptor agonist, and interleukin-6 levels were examined on days 0, 15, and 45 and at months 3 and 6. Subgroup analysis according to stage and the patient's compliance to conventional treatment were also analyzed. Any adverse events during the study were recorded. A multilevel mixed-effect linear regression model was used. P value less than 0.05 was considered statistically significant.

Results:

At 6 months, tear breakup time, meibum quality grades, expressibility grades, and OSDI were better in the IPL group (5.23 ± 2.91 vs. 3.11 ± 0.99 seconds, P < 0.001; 8.74 ± 4.74 vs. 13.19 ± 5.01, P < 0.001; 0.50 ± 0.67 vs. 1.12 ± 0.70, P < 0.001; 24.29 ± 16.92 vs. 32.71 ± 20.07, P < 0.05). OSDI, meibum quality, and expressibility in the IPL group began to improve at day 15 (P < 0.001), whereas the results in the sham group began to improve at day 45 (P < 0001). No adverse event occurred after IPL.

Conclusions:

IPL is effective and safe for MGD treatment in all stages regardless of compliance.