bluuebunny/crossref_metadata_2025 huggingface dataset:
Light sheet microscopy-based 3-dimensional histopathology of the lymphatic vasculature in Emberger syndrome
Authors: Hägerling René
Published: August 2020

Introduction Lymphovascular diseases represent a heterogenous group of inherited and sporadic disorders and refer to a range of possible underlying pathologies and pathogenesis.

Emberger Syndrome, an inherited form of lymphedema, is characterized by bilateral lower limb lymphedema, however, upper limbs do not show any signs of swelling.

To identify disease-associated histopathological alterations in patients with Emberger Syndrome and to elucidate potential histological differences between the lymphatic vasculature of upper and lower limbs, a detailed knowledge on the 3-dimensional tissue and vessel architecture is essential. However, the current gold standard in 2-dimensional histology provides only very limited spatial information.

Material and methods To elucidate the underlying vascular pathology in Emberger Syndrome on the cellular level, we applied the 3-dimensional visualization and analysis approach VIPAR (volume information-based histopathological analysis by 3D reconstruction and data extraction) to entire wholemount immunofluorescence-stained human tissue samples. VIPAR is a light sheet microscopy-based imaging technique, which allows 3-dimensional reconstruction of entire tissue biopsies followed by automated and semi-automated analysis of vascular parameters in 3-dimensional space.

Results Using VIPAR we could show that in Emberger Syndrome the dermal lymphatic vasculature is intact and non-disrupted.

However, lower limbs showed an hypoplastic lymphatic vasculature with absence of lymphatic valves in pre-collecting and collecting vessels. In contrast to the lower limbs, the lymphatic vasculature of the upper limbs showed no morphological alterations of lymphatic vessels and lymphatic valves compared to healthy controls.

Discussion Based on the 3-dimensional histopathological analysis we were able to perform a detailed phenotyping of lymphatic vessels in the upper and lower limb in Emberger Syndrome and to identify the underlying vascular pathology. In addition, we could show vascular alteration between the upper and lower limbs indicating a vascular heterogeneity of dermal lymph vessels causing the lower limb lymphedema.
Psychologische Merkmale jugendlicher Patienten vor einer
Gewichtsreduktionsbehandlung
Authors: Breinker Julius Lars , Schmidt Ricarda , Hübner Claudia , Cämmerer Jana , Körner Antje , Sergeyev Elena , Kiess Wieland , Hilbert Anja
Published: August 2020

Übergewicht und Adipositas zeigen bei Kindern und Jugendlichen eine hohe
Prävalenz und Persistenz. Entsprechende Therapien sind kaum
individualisiert und zeigen nur moderate Erfolge. Die Psychopathologie bleibt
zumeist unberücksichtigt. Die vorliegende Studie hat die
Psychopathologie von Jugendlichen mit Übergewicht und Adipositas
(N=201, Alter 12–17 Jahre) vor einer
Gewichtsreduktionsbehandlung erhoben und Alters- sowie Geschlechtseffekte
untersucht. Mittels Fragebögen wurden selbstberichtet die allgemeine
Symptombelastung, Essstörungs- und allgemeine Psychopathologie,
gewichtsbezogene Selbststigmatisierung und die körperliche und
psychische Lebensqualität erhoben. Mädchen zeigten
hypothesenkonform ein höheres Maß an gewichtsbezogener
Selbststigmatisierung und eine stärkere
Essstörungspsychopathologie als Jungen. Ältere Jugendliche
berichteten eine geringere Lebensqualität als jüngere.
Vergleiche zu Referenzgruppen aus Bevölkerungs- und
Normierungsstichproben zeigten auffälligere Werte bei Jugendlichen mit
Übergewicht und Adipositas für alle untersuchten Parameter. Eine
auffällige Psychopathologie ist demzufolge ein wichtiges Korrelat bei
Jugendlichen mit hohem Gewichtsstatus und ein potenzieller Einflussfaktor auf
den Erfolg einer Gewichtsreduktionsbehandlung. Zukünftige Studien
sollten die Psychopathologie bei Übergewicht und Adipositas weiter
differenzieren und therapeutische Ressourcen evaluieren.
Antibiotikaresistenz von E. coli aus Rinderpopulationen in Deutschland
Authors: Tenhagen Bernd-Alois , Käsbohrer Annemarie , Grobbel Mirjam , Hammerl Jens , Kaspar Heike
Published: August 2020

Gegenstand und Ziel Ziel dieser Arbeit ist, die Resistenzsituation bei Escherichia (E.) coli aus verschiedenen Rinderpopulationen zu beschreiben.

Material und Methoden Dazu wurden die minimalen Hemmkonzentrationen (MHK) von Antibiotika gegen sowohl klinische als auch nicht klinische E. coli-Isolate von Milchkühen, Mastrindern, Mastkälbern und Kälbern ausgewertet. Diese Untersuchungen erfolgten im Rahmen des Monitoringprogramms GERM-Vet (klinische Isolate) sowie im Rahmen des Zoonosen-Monitorings (nicht klinische Isolate) mithilfe der Bouillon-Mikrodilutionsmethode. Zur einheitlichen Bewertung der ermittelten MHK dienten die vom European Centre for Antimicrobial Susceptibility Testing (EUCAST) veröffentlichten epidemiologischen Grenzwerte.

Ergebnisse In die Untersuchung wurden insgesamt 5127 Isolate einbezogen. Die höchsten Resistenzraten (RR) gegenüber den meisten Substanzen ergaben sich bei Isolaten von erkrankten Kälbern, gefolgt von solchen von Mastkälbern und Jungrindern unter 1 Jahr am Schlachthof. Die niedrigsten RR wiesen E. coli-Isolate aus Tankmilchproben von Milchviehbetrieben und von Mastrindern im Bestand auf. Die Resistenzraten bei Mastitisisolaten waren deutlich höher als bei den nicht klinischen Isolaten aus Tankmilch, aber niedriger als bei den Isolaten von Kälbern und Jungrindern.

Schlussfolgerungen und klinische Relevanz Vor allem die RR gegenüber den besonders wichtigen Substanzklassen Cephalosporine der 3. Generation und Fluorchinolone lagen bei Kälbern mit Enteritis, aber auch bei Isolaten aus Mastitisproben höher als in anderen Tierpopulationen. Ein Zusammenhang mit dem relativ hohen Einsatz dieser Substanzen bei Milchkühen ist naheliegend, da die Kälber über die Vertränkung nicht vermarktungsfähiger Milch sowohl gegenüber Arzneimittelrückständen als auch gegenüber resistenten Bakterien exponiert sind. Der Einsatz dieser Substanzklassen in der Rinderhaltung muss auf ein Minimum reduziert werden, um die weitere Ausbreitung dieser Resistenzen gegen diese Substanzen in der Rinderhaltung einzudämmen.
Phänotypische Antibiotikaresistenzen von Bakterienisolaten aus Zier-, Zoo- und falknerisch gehaltenen Greifvögeln
Authors: Steger Leonie , Rinder Monika , Korbel Rüdiger
Published: August 2020

Gegenstand und Ziel Die Prävalenz von antibiotikaresistenten Bakterien bei Zier-, Zoo- und falknerisch gehaltenen Greifvögeln ist noch weitgehend unbekannt. Daher sollten retrospektiv Antibiogramme schnellwachsender aerober Bakterienarten ausgewertet werden.

Material und Methoden Im Auswertungszeitraum von 2007 bis 2016 standen 1036 Antibiogramme zur Verfügung. Die Bakterienisolate stammten vorzugsweise aus Süddeutschland und von 811 Vögeln aus 20 zoologischen Ordnungen (am häufigsten Papageienvögel [61,8 %] und Sperlingsvögel [14,5 %]) sowie aus Proben von klinischen Patienten und Sektionsmaterial. Die phänotypische In-vitro-Empfindlichkeit wurde mittels Plattendiffusionstest ermittelt.

Ergebnisse Die meisten Antibiogramme lagen für E. coli (n = 386 Isolate) vor, gefolgt von Staphylococcus (S.). aureus (n = 150), Enterobacter cloacae (n = 122), Klebsiella pneumoniae (n = 86) und Pseudomonas aeruginosa (n = 64). Resistenzen gegen mindestens einen antibiotischen Wirkstoff zeigten 53,1 % der E. coli-Isolate, dabei am häufigsten gegen Doxycyclin (50,3 %) und Ampicillin (46,1 %). Bei 78,0 % der S. aureus-Isolate und bei 95,9 % der Enterococcus faecalis-Isolate wurden Resistenzen gegenüber mindestens einem Wirkstoff nachgewiesen. Multiresistenzen (Resistenz gegenüber ≥ 3 Antibiotikagruppen) traten bei 37,3 % der Isolate von S. aureus auf. Bei Isolaten von Zier- und Greifvögeln wurden höhere Resistenzraten festgestellt als bei Isolaten von Zoovögeln und bei Papageienvögeln höhere Resistenzraten als bei Sperlingsvögeln. Im Untersuchungszeitraum zeigte sich bei E. coli ein tendenzieller Anstieg der Resistenzrate für Fluorchinolone (Minimum von 0 % im Jahr 2013 und Maximum von 27,3 % im Jahr 2015) und bei S. aureus eine tendenzielle Abnahme der Resistenzraten für Tetrazykline (Maximum von 39,4 % im Jahr 2007 und Minimum von 0 % in den Jahren 2014 und 2015).

Schlussfolgerung und klinische Relevanz Die Resistenzsituation von Bakterien aus Zier-, Zoo- und falknerisch gehaltenen Greifvögeln ist als problematisch zu bewerten und verdeutlicht die Wichtigkeit der Empfindlichkeitsprüfung für eine gewissenhafte Therapie. Im Fall einer Infektion mit S. aureus bei Zier-, Zoo- oder falknerisch gehaltenen Greifvögeln kann es zu einem Therapienotstand kommen.
Pleuroperitoneal true diaphragmatic hernia of the liver in a cat
Authors: Pilli Mehmet , Özgencil Fatma E. , Seyrek-Intas Deniz , Gültekin Cagri , Turgut Kürsad
Published: August 2020

A 2-year old female domestic shorthair cat was referred with intermittent vomiting. Laboratory analyses revealed only an elevated alanine aminotransferase activity. Plain thoracic radiographs showed a right-sided transdiaphragm protrusion of a liver lobe into the thoracic cavity. On abdominal ultrasound the diaphragm and liver parenchyma also presented a bulge towards the thoracic cavity. By cranial median laparotomy herniation of the quadrate liver lobe through the right aspect of the diaphragm into the thoracic cavity was confirmed. The protruding quadrate liver lobe was covered by intact parietal peritoneum. Following relocation of the liver lobe the defect was closed. Postoperatively the intermittent vomiting stopped. The purpose of this case report was to present plain radiography and abdominal ultrasonography as effective tools in the diagnosis of this rare and usually asymptomatic true herniation case along with its operative treatment.
Die Bandverletzung des oberen Sprunggelenks – eine unterschätzte Verletzung?
Authors: Fehske Kai , Lukas Christoph
Published: August 2020

Die Bandverletzung des oberen Sprunggelenks ist eine der häufigsten Verletzungen im Sport. Landung auf dem gegnerischen Fuß oder direkter Kontakt gehören zu den häufigsten Verletzungsmechanismen. Initial zählt vor allem die klinische Diagnostik, je nach Bedarf um Röntgen, Sonografie oder MRT ergänzt. Meist wird konservativ therapiert; zunächst müssen Schmerz und Schwellung reduziert, dann die Funktion wiederhergestellt werden, bevor nach Return-to-Play-Testung in den Sport zurückgekehrt werden kann. Teilweise liegen komplexere Verletzungsmuster mit Begleitschäden vor und trotz aller Erfolge der konservativen Behandlung bleiben bestimmte Fälle dem operativen Vorgehen vorbehalten. Nicht nur die reelle Ausfallzeit der Athleten, sondern die Ausprägung von Folgeschäden und chronischen Funktionseinschränkungen und auch die damit verbundenen Behandlungskosten legen die Empfehlung nahe, eine Sprunggelenkverletzung nicht zu unterschätzen und die Therapie adäquat auszuwählen.
Nutzung der Haptoglobinkonzentration im Blutserum als Indikator im Tiergesundheitsmonitoring bei Milchkühen
Authors: Hajek Franziska , Reus Anne , Gruber Simone , Plattner Stefan , Kammer Martin , Baumgartner Christian , Smink Moniek , Döpfer Dörte , Hachenberg Sabrina , Mansfeld Rolf
Published: August 2020

Ziel Untersuchung von Zusammenhängen zwischen der Haptoglobinkonzentration im Blut und dem Auftreten einer Ketose, ausgewählten klinischen Parametern und Lahmheit bei Milchkühen.

Material und Methoden Die Datenerhebung fand in 39 bayerischen Milchviehbetrieben über 8 Monate statt. Bei den einbezogenen 712 Fleckvieh- und Braunviehkühen, deren Kalbung 10–30 Tage zurücklag, wurde eine klinische Untersuchung durchgeführt sowie eine Milch- und eine Blutprobe entnommen. Im Blut wurden die Konzentrationen von freien Fettsäuren (non-esterified fatty acids, NEFA), β-Hydroxybutyrat (BHB) und Haptoglobin (Hp) bestimmt, in der Milch die Milchinhaltsstoffe (Fett, Eiweiß, Harnstoff, Laktose, Azeton), BHB, NEFA und die somatische Zellzahl (SCC).

Ergebnisse Signifikante Korrelationen ergaben sich zwischen erhöhten Hp-Konzentrationen einerseits und erhöhten NEFA-Konzentrationen in Blut und Milch (p < 0,001), erhöhter SCC (p < 0,001), Lahmheit (p < 0,001), vermindertem Laktosegehalt (p < 0,001) sowie vermindertem Proteingehalt der Milch (p = 0,001) andererseits. In den wärmeren Sommermonaten beprobte Tiere hatten signifikant höhere Hp-Konzentrationen (p < 0,001). Erstkalbinnen wiesen signifikant höhere Hp-Werte auf als multipare Tiere (p < 0,001). Durch die Einteilung der Tiere in 4 Cluster ließ sich ein Hp-Grenzwert bestimmen, der 0,18 mg/ml betrug. Kombiniert mit einem SCC-Grenzwert von 40 500 Zellen/ml Milch konnte der Großteil der subklinisch und klinisch auffälligen Tiere ermittelt werden.

Schlussfolgerung und klinische Relevanz Die Messung der Hp-Konzentration im Blut stellt einen praktikablen Ansatz zur Unterstützung des Tiergesundheitsmonitorings im postpartalen Zeitraum dar. Zusammen mit der Auswertung der Milchmenge und der Milchinhaltsstoffe können Abweichungen von physiologischen Zuständen erkannt und betroffene Tiere zeitnah behandelt werden. Haptoglobin kann für die Bewertung des Gesundheitsstatus des Einzeltieres wie auch als Indikator für die Herdengesundheit genutzt werden.
Serial Mud Packs Induce Anti-inflammatory Effects in Knee
Osteoarthritis – A Randomized, Prospective Clinical
Study
Authors: Klemm Philipp , Dischereit Gabriel , Lange Uwe , Fetaj Shaban , Ehnert Markus
Published: August 2020

Background Mud bath and pack have been used to treat musculoskeletal
disorders since ancient times. However, the actual mechanisms of action of mud
therapy on the inflammatory processes are complex and still not clarified.

Methods Therefore, the clinical effects of serial mud packs in patients
with knee osteoarthritis were investigated on the molecular level. A total of 52
patients were recruited from an in-patient rheumatology clinic. The participants
were randomized in 2 groups: the intervention group (IG, n=26) underwent
9 mud packs in 21 days and a standardized multimodal physical therapy in an
in-patient setting, whereas the control group (CG, n=26) only received
the multimodal physical therapy. Primary outcome parameters were changes in the
serum levels of interleukin(IL)-1ß and IL-10. Secondary outcome
parameters were changes of the C-reactive protein (CRP), erythrocyte
sedimentation rate (ESR), Western Ontario and Mc Master Universities Arthritis
(WOMAC) index and pain (visual analog scale - VAS).

Results The IG presented after the serial mud packs significantly
decreased pro-inflammatory IL-1ß levels and significantly increased
anti-inflammatory IL-10 levels, whereas the CG showed no changes of the 2
cytokines. CRP and ESR remained within in the normal range in both groups
without significant changes. Furthermore, the IG presented a significant
decrease of the WOMAC index and pain (VAS).

Conclusions The results suggest an additive anti-inflammatory effect of
serial mud packs within a multimodal physical therapy concept in patients with
knee osteoarthritis and could explain the beneficial clinical effects.
Reference Values for Pulmonary Single-Breath Diffusing Capacity – Results of the “Study of Health in Pomerania”
Authors: Schäper C. , Stubbe B. , Bollmann T. , Ittermann T. , Gläser S. , Völzke H. , Doerr M. , Habedank D. , Obst A. , Ewert R.
Published: August 2020

Objectives The assessment of pulmonary single-breath diffusing capacity is a frequently performed diagnostic procedure and considered as an important tool in medical surveillance examinations of pulmonary diseases.

The aim of this study was to establish reference equations for pulmonary single-breath diffusing capacity parameters in a representative adult-population across a wide age range and to compare the normative values from this sample with previous ones.

Methods Diffusing capacity measurement was carried out in 3566 participants (1811 males) of a cross-sectional, population-based survey (“Study of Health in Pomerania – SHIP”).

Results Individuals with cardiopulmonary disorders and current smoking habits were excluded, resulting in 1786 healthy individuals (923 males), aged 20 – 84 years. Prediction equations for both sexes were established by quantile regression analyses, taking into consideration the influence of age, height, weight and former smoking.

Conclusion The study provides a novel set of prediction equations for pulmonary single-breath diffusing capacity in an adult Caucasian population. The results are comparable to previously reported equations, underline their importance and draw attention to the need for up-to-date reference equations that adequately take into account both the subjects’ origin, age, anthropometric characteristics and the equipment used.
Ontologies, Knowledge Representation, and Machine Learning for Translational Research: Recent Contributions
Authors: Robinson Peter N. , Haendel Melissa A.
Published: August 2020

Objectives: To select, present, and summarize the most relevant papers published in 2018 and 2019 in the field of Ontologies and Knowledge Representation, with a particular focus on the intersection between Ontologies and Machine Learning.

Methods: A comprehensive review of the medical informatics literature was performed to select the most interesting papers published in 2018 and 2019 and that document the utility of ontologies for computational analysis, including machine learning.

Results: Fifteen articles were selected for inclusion in this survey paper. The chosen articles belong to three major themes: (i) the identification of phenotypic abnormalities in electronic health record (EHR) data using the Human Phenotype Ontology ; (ii) word and node embedding algorithms to supplement natural language processing (NLP) of EHRs and other medical texts; and (iii) hybrid ontology and NLP-based approaches to extracting structured and unstructured components of EHRs.

Conclusion: Unprecedented amounts of clinically relevant data are now available for clinical and research use. Machine learning is increasingly being applied to these data sources for predictive analytics, precision medicine, and differential diagnosis. Ontologies have become an essential component of software pipelines designed to extract, code, and analyze clinical information by machine learning algorithms. The intersection of machine learning and semantics is proving to be an innovative space in clinical research.
Medical Information Extraction in the Age of Deep Learning
Authors: Hahn Udo , Oleynik Michel
Published: August 2020

Objectives: We survey recent developments in medical Information Extraction (IE) as reported in the literature from the past three years. Our focus is on the fundamental methodological paradigm shift from standard Machine Learning (ML) techniques to Deep Neural Networks (DNNs). We describe applications of this new paradigm concentrating on two basic IE tasks, named entity recognition and relation extraction, for two selected semantic classes—diseases and drugs (or medications)—and relations between them.

Methods: For the time period from 2017 to early 2020, we searched for relevant publications from three major scientific communities: medicine and medical informatics, natural language processing, as well as neural networks and artificial intelligence.

Results: In the past decade, the field of Natural Language Processing (NLP) has undergone a profound methodological shift from symbolic to distributed representations based on the paradigm of Deep Learning (DL). Meanwhile, this trend is, although with some delay, also reflected in the medical NLP community. In the reporting period, overwhelming experimental evidence has been gathered, as illustrated in this survey for medical IE, that DL-based approaches outperform non-DL ones by often large margins. Still, small-sized and access-limited corpora create intrinsic problems for data-greedy DL as do special linguistic phenomena of medical sublanguages that have to be overcome by adaptive learning strategies.

Conclusions: The paradigm shift from (feature-engineered) ML to DNNs changes the fundamental methodological rules of the game for medical NLP. This change is by no means restricted to medical IE but should also deeply influence other areas of medical informatics, either NLP- or non-NLP-based.
Design and Use of Semantic Resources: Findings from the Section on Knowledge Representation and Management of the 2020 International Medical Informatics Association Yearbook
Authors: Dhombres Ferdinand , Charlet Jean ,   Section Editors for the IMIA Yearbook Section on Knowledge Representation and Management
Published: August 2020

Objective: To select, present, and summarize the best papers in the field of Knowledge Representation and Management (KRM) published in 2019.

Methods: A comprehensive and standardized review of the biomedical informatics literature was performed to select the most interesting papers of KRM published in 2019, based on PubMed and ISI Web Of Knowledge queries.

Results: Four best papers were selected among 1,189 publications retrieved, following the usual International Medical Informatics Association Yearbook reviewing process. In 2019, research areas covered by pre-selected papers were represented by the design of semantic resources (methods, visualization, curation) and the application of semantic representations for the integration/enrichment of biomedical data. Besides new ontologies and sound methodological guidance to rethink knowledge bases design, we observed large scale applications, promising results for phenotypes characterization, semantic-aware machine learning solutions for biomedical data analysis, and semantic provenance information representations for scientific reproducibility evaluation.

Conclusion: In the KRM selection for 2019, research on knowledge representation demonstrated significant contributions both in the design and in the application of semantic resources. Semantic representations serve a great variety of applications across many medical domains, with actionable results.
Public Health and Epidemiology Informatics: Recent Research Trends Moving toward Public Health Data Science
Authors: Cossin Sébastien , Thiébaut Rodolphe ,   Section Editors for the IMIA Yearbook Section on Public Health and Epidemiology Informatics
Published: August 2020

Objectives: To introduce and summarize current research in the field of Public Health and Epidemiology Informatics.

Methods: PubMed searches of 2019 literature concerning public health and epidemiology informatics were conducted and the returned references were reviewed by the two section editors to select 14 candidate best papers. These papers were then peer-reviewed by external reviewers to allow the Editorial Committee a curated selection of the best papers.

Results: Among the 835 references retrieved from PubMed, two were finally selected as best papers. The first best paper leverages satellite images and deep learning to identify remote rural communities in low-income countries; the second paper describes the development of a worldwide human disease surveillance system based on near real-time news data from the GDELT project. Internet data and electronic health records are still widely used to detect and monitor disease activity. Identifying and targeting specific audiences for public health interventions is a growing subject of interest.

Conclusions: The ever-increasing amount of data available offers endless opportunities to develop methods and tools that could assist public health surveillance and intervention belonging to the growing field of public health Data Science. The transition from proofs of concept to real world applications and adoption by health authorities remains a difficult leap to make.
Direct Deoxygenative Intramolecular Acylation of Biarylcarboxylic Acids
Authors: Zhu Chengjian , Xie Jin , Li Yantao , Xu Wentao
Published: August 2020

A photocatalyzed intramolecular cyclization is developed for the synthesis of fluorenones. In this photoredox reaction, triphenylphosphine is used as an inexpensive and effective deoxygenative reagent for biarylcarboxylic acids to give acyl radicals, which quickly undergo intramolecular radical cyclization. Reactions in the presence of air and continuous flow photoredox technology demonstrate the generality and practicality of this process.
A Study to Ascertain the Expression of Aquaporin 4 and Neuropeptide Y in the Jejunal Mucosa Secondary to Traumatic Brain Injury in Humans
Authors: Patil Parag Parshuram , Subramanian Arulselvi , Aggarwal Garima , Lalwani Sanjeev , Agrawal Deepak
Published: August 2020

Introduction Gastrointestinal (GI) dysfunction is a common complication in patients with traumatic brain injury (TBI). Studies in rats have shown alterations in intestinal mucosa to correlate with severity and duration of TBI. There is lack of such evidence in humans. So we intended to find correlation between histopathological changes and expression of aquaporin 4 (AQ4) and neuropeptide Y (NPY) in jejunal mucosa in post TBI patients.

Materials and Methods Autopsy specimens of jejunum were obtained from patients who had died due to TBI (n = 20), patients dying due to traumatic injury other than TBI, and patients who were brought dead (diseased controls n = 20). Abdominal trauma was the exclusion criterion for both. Jejunal specimens were grossly examined and then analyzed histopathologically and graded immunohistochemically for AQ4 and NPY. Unpaired t-test was used to compare results.

Results After exclusion, 19 cases and 17 controls were studied. No significant difference was observed in the microscopic findings between cases and controls (p-value = 0.70). The expression of AQ4 was more in cases (p-value = 0.04). NPY expression was not significantly different (p-value = 0.93).

Conclusion AQ4 can hence be used as a marker of GI injury post TBI. Histopathological examination cannot distinguish between these changes.
Sinonasal Malignancy and Orbital Exenteration Sparing Cancer Surgery
Authors: Reyes Camilo , Patel Mihir , Solares C. Arturo
Published: August 2020

This article reviews the most common locations and natural history of sinonasal carcinomas. It also reviews surgical indications and current evidence regarding adjuvant and neoadjuvant therapies. In the past, orbital clearance was generally done for ethmoid and maxillary cancers, even without a marked neoplastic infiltration; however, such indications have changed in the recent years due to advances in our understanding of the disease, as well as new chemotherapeutic and radiotherapy protocols. Surgical resection of tumors close to the orbit exhibits the challenging task of balancing treatment goals and patient's desires.
Siblings with Infantile Neuroaxonal Dystrophy
Authors: Agarwal Pulkit , Goswami Jyotindra Narayan
Published: August 2020

A 2 years 3 months male toddler with motor delay and his female sibling with history of marked global developmental regression following an intercurrent febrile illness were both noted to have phospholipase A2G6 (PLA2G6) mutation, confirming the diagnosis of infantile neuroaxonal dystrophy (INAD). This case report attempts to familiarize readers with the pleomorphic presentation of INAD and the role of early clinical identification, examination, and prompt genetic testing in establishing a diagnosis.
Clinical Outcomes of May–Thurner Syndrome in Pediatric Patients: A Single Institutional Experience
Authors: Warad Deepti M. , Rao Amulya Nageswara , Bjarnason Haraldur , Rodriguez Vilmarie
Published: August 2020

Introduction May–Thurner syndrome (MTS) is a vascular anatomic variant resulting in compression of the left common iliac vein by the right common iliac artery, affecting approximately 22% of the population. In adults, following acute deep vein thrombosis (DVT) of the iliofemoral veins, the incidence of postthrombotic syndrome (PTS) and recurrent DVT are high if treated with anticoagulation alone, warranting adjunctive treatment with thrombolysis and stent placement. However, there is paucity of literature documenting the course of treatment and associated outcomes in pediatric patients with MTS.

Methods A retrospective chart review of pediatric patients (≤ 18 years of age) with radiologic confirmation of MTS with or without DVT evaluated and/or treated at our institution from January 1, 2005 through December 31, 2015 was conducted.

Results Seventeen patients (4 male; 13 female) were identified. Median age was 15.4 years (range 8.8–17.1 years) with a median follow-up of 1.2 years (range 0.4–7.5 years). Thirteen (76.5%) patients presented with left lower extremity DVT. Management included catheter-directed thrombolysis (n = 5), systemic thrombolysis (n = 1), and mechanical thrombectomy (n = 1). Fifteen patients were treated with anticoagulation including two patients with endovascular stents without DVT. Median duration of anticoagulation was 6.3 months (range 3.2–18.7 months). Ten patients (59%) underwent stent placements.

Complete and partial thrombus resolution was noted in six patients each and no resolution in one patient. Four patients had recurrence/progression of thrombus (n = 3 with stents) at a median time of 29 days (range 12–495 days). No bleeding complications were observed. Clinically documented or self-reported PTS was noted in 8 patients (62%).

Conclusion There are no clear guidelines for MTS management in children and adolescents. In our cohort, thrombolysis, anticoagulation, or stent placements were not associated with bleeding risks, with recurrence/progression of DVT and signs and symptoms of PTS noted in 30 and 62%, respectively. Further studies are needed to determine a standardized treatment approach of the pediatric patient with MTS with or without thrombosis.
Lurking Infantile Pertussis: Experience from a Tertiary Care Center in Northern India
Authors: Bhattacharya Deepanjan , Dash Nabaneeta , Kavitha Thondi Kkandy , Sharma Megha , Gautam Vikas , Verma Sanjay
Published: August 2020

Objectives The aim is to study the clinical laboratory profile and outcome of infants with laboratory confirmed pertussis.

Methods In this retrospective study, records of 30 infants with laboratory confirmed pertussis, admitted to the pediatric department of a tertiary care hospital, were reviewed. Clinical features, laboratory parameters, and outcomes were noted.

Results Median (interquartile range age was 10 (7–24.5) weeks, with a male preponderance. Large majority (60%) of enrolled infants were less than 16 weeks of age and nine (30%) developed pertussis even before 8 weeks of age. Cough was universal (100%), followed by rapid breathing (73%), fever (70%), and apnea (10%). Bubble continuous positive airway pressure (CPAP), nasal prongs oxygen, and invasive ventilation were required in 15 (54%), 11 (39%), and 2 (7%) infants, respectively; 12 (40%) needed to be admitted to the pediatric intensive care unit. Anemia was observed in 28 (93%) and leukemoid reaction in 15 (50%). All except one were discharged successfully. None of the mothers had received tetanus, diphtheria, and pertussis or Tdap vaccination during pregnancy.

Conclusion Our study reports the continued occurrence of infantile pertussis in the community, suggesting reconsideration of our vaccination policy, including maternal immunization.
Role of Toll-Like Receptors 2 and 4 Genes Polymorphisms in Neonatal Sepsis in a Developing Country: A Pilot Study
Authors: Khaled Bedewy M. , Noha Abou Seada M. , Manal Antonios A. M. , Engy Saleh M.
Published: August 2020

Objective Toll-like receptors (TLR) are one of the key molecules that alert the immune system to the presence of microbial infections. This study attempts to elucidate the role of TLR2 and TLR4 polymorphisms in neonatal sepsis.

Methods A case–control study including 30 neonates with confirmed sepsis compared with 20 neonates in a control group. TLR2 and TLR24 gene polymorphisms were confirmed by polymerase chain reaction.

Results The majority of infections were attributed to gram-negative organisms (72.5%) namely Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Results also revealed that incidence of TLR polymorphism was significantly different between the sepsis and control groups (p = 0.016). The most common polymorphism was TLR2; Arg 753 Gln (16.7%). Presence of TLR polymorphism was also associated with a longer duration of therapy (a median of 10 days for cases with positive polymorphism compared with 6.5 days for negative cases; p = 0.001).

Conclusion This pilot study suggests that any polymorphisms in TLR2 and TLR4 might have a role that interferes with the innate immune response of newborn.
Radial Shortening Osteotomy for Symptomatic Kienböck's Disease: Complications and Long-Term Patient-Reported Outcome
Authors: van Leeuwen Wouter F. , Pong Taylor M. , Gottlieb Rachel W. , Deml Christian , Chen Neal , van der Heijden Brigitte E.P.A.
Published: August 2020

Objective To determine the rate of salvage procedures and any other unplanned reoperations in patients with symptomatic Kienböck's disease who were treated with radial shortening osteotomy. In addition, we studied patient-reported outcome in the long term using Patient-Reported Outcome Measure Information System (PROMIS) instruments.

Patients and Methods We performed a retrospective review of all patients who underwent radial shortening osteotomy for stage 2 and 3A Kienböck's disease. Patients who had concomitant revascularization were grouped separately. We collected demographic data, data regarding type of surgery and reoperations, and radiographic data. Patient-reported outcome measures were the PROMIS Upper Extremity Computer Adaptive Testing (CAT) and Pain Interference instruments, the abbreviated Disabilities of Arm, Shoulder, and Hand (QuickDASH), and the 0 to 10 numeric rating scale for pain and satisfaction.

Results We included 48 patients who had radial shortening osteotomy alone, and 17 patients who had a combined procedure of radial shortening and direct revascularization. The rate of unplanned reoperations was 33% (16 of 48) in those who had radial shortening osteotomy and 24% (4 of 17) in those who had a combined procedure. Six (13%) of 48 patients underwent proximal row carpectomy due to failed radial shortening osteotomy. No salvage procedures were performed after combined radial shortening/revascularization. Median PROMIS Physical Function CAT scores were 56 (interquartile range [IQR]: 44–56) and 56 (IQR: 41–56), respectively. Median PROMIS Pain Interference scores were 39 (IQR: 39–52) and 39 (IQR: 39–49), respectively. Median QuickDASH scores were 2.3 (IQR: 0–23) and 4.5 (IQR: 2.3–14), respectively.

Conclusion Radial shortening osteotomy for symptomatic Kienböck's disease yields reasonable long-term function. We observed that approximately one in eight patients underwent salvage surgery after radial shortening, and this should be taken into account when making the initial decision to treat Kienböck's disease surgically. There appeared to be no benefit of direct revascularization in addition to radial shortening in terms of patient-reported outcome in the long term.

Level of Evidence This is a Level IV, therapeutic study.
Impact of Excess Weight Gain on Risk of Postpartum Infection in Class III Obesity
Authors: Mitchell Courtney J. , Adkins LaMani , Tucker Ann , Brown Haywood , Siegel Anne , Dotter-Katz Sarah
Published: August 2020

Objective To assess the impact of gestational weight gain >20 pounds (more than Institute of Medicine [IOM] recommendations) on postpartum infectious morbidity in women with class III obesity.

Methods This is a retrospective cohort of term, nonanomalous singleton pregnancies with body mass index ≥40 at a single institution from 2013 to 2017. Pregnancies with multiple gestation, late entry to care, and missing weight gain data are excluded. Primary outcome is a composite of postpartum infection (endometritis, urinary tract, respiratory, and wound infection). Secondary outcomes include components of composite, wound complication, readmission, and blood transfusion. Bivariate statistics compared demographics, pregnancy complications, and delivery characteristics of women exceeding IOM guidelines (GT20) with those who did not (LT20). Regression models were used to estimate adjusted odds of outcomes.

Results Of 374 women, 144 (39%) gained GT20 and 230 (62%) gained LT20. Primiparous, nonsmokers more likely gained GT20 (p < 0.05). No significant difference in other demographics. Among women who gained GT20, 10.4% had postpartum infectious morbidity compared with 3.0% in LT20 (p < 0.01). Wound infection is more common in the GT20 group (7.6 vs. 2%, p = 0.02). After adjustment, women who gained GT20 had threefold higher odds of postpartum infectious morbidity (adjusted odds ratio: 3.17, 95% confidence interval: 1.17, 8.60).

Conclusion Women with class III obesity who gain more than the IOM recommends are at increased risk for postpartum infectious morbidity.
Coronavirus Disease 2019 in a Premature Infant: Vertical Transmission and Antibody Response or Lack Thereof
Authors: Rivera-Hernandez Pedro , Nair Jayasree , Islam Shamim , Davidson Lauren , Chang Arthur , Elberson Valerie
Published: August 2020

With the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, several reports highlight its effects on pregnant women. Based on scant available data, vertical transmission is considered unlikely. We present here a preterm neonate born to a critically ill mother with SARV-CoV-2 with early evidence of infection with a positive reverse transcription polymerase chain reaction on day 1. Lack of parental contact prior to testing and strict adherence to recommended airborne precautions perinatally suggest vertical transmission of infection. Critical maternal illness and medications may have contributed to the need for extensive resuscitation at birth and highlight the importance of close fetal monitoring. Infant lacked immunoglobulin G antibody response by 3 weeks, presumably secondary to mild clinical course and prematurity. Effects of SARS-CoV-2 in preterm infants, their antibody response and potential for asymptomatic carriage remain uncertain.
The Spectrum of Disease Severity in Cirrhosis and Its Implications for Hemostasis
Authors: Stotts Matthew J. , Lisman Ton , Intagliata Nicolas M.
Published: August 2020

Bleeding and thrombosis are both common complications that patients with advanced liver disease experience. While hemostatic pathways remain largely intact with cirrhosis, this balance can quickly shift in the direction of bleeding or clotting in an unpredictable manner. A growing body of literature is attempting to shed light on difficult scenarios that clinicians often face, ranging from predicting and mitigating bleeding risk in those who need invasive procedures to determining the best strategies to manage both bleeding and thrombotic complications when they occur. Studies examining hemostasis in those with advanced liver disease, however, often include heterogeneous cohorts with varied methodology. While these studies often select a cohort of all types and degrees of cirrhosis, emerging evidence suggests significant differences in underlying systemic inflammation and hemostatic abnormalities among specific phenotypes of liver disease, ranging from compensated cirrhosis to decompensated cirrhosis and acute-on-chronic liver failure. It is paramount that future studies account for these differing disease severities if we hope to address the many critical knowledge gaps in this field.
Lost in Transition: The Long and Winding Road Toward Epilepsy Surgery—An Analysis of Obstacles Prior to Surgery and Call for Orchestrated Health Care Efforts in Epilepsy
Authors: Graf Wolfgang , Kasper Burkhard S. , Sharma Sunjay , Kasper Ekkehard M.
Published: August 2020

Difficult-to-treat epilepsy is defined as ongoing seizures despite adequate pharmacological treatment. This condition is affecting a significant percentage of epilepsy patients and is estimated to be as high as one-third of all patients. Epilepsy surgery, targeting the removal of the key parts of cerebral convolutions responsible for seizure generation and often including a structural lesion, can be a very successful approach. However, this necessitates careful patient selection by comprehensive investigations, proving the localization of the epileptogenic zone as well as measures to make such surgeries safe. With careful selection as a prerequisite, the percentage of patients achieving seizure freedom by neurosurgical intervention is high, approximating two-thirds of all epilepsy surgeries performed. In contrast, the average duration of a patient's pharmacoresistant focal epilepsy prior to surgery anywhere around the globe is around 20 years. Given that typical patients are ∼30 to 40 years of age at the time of surgery, many patients have been living with chronic seizures since childhood or adolescence. This means that most of these patients have been going through several stages of medical care for years or even decades, both as children and adults, without ever being fully investigated and/or selected for surgery which is concerning. Yet, there is no set standard for a timeline leading toward successful surgery in epilepsy. It is obvious that the average transit period from the moment of first seizure manifestation until the day of successful surgery takes much too long. This is the reason why we see these patients lost in transition.
Safety of Coupled Arterial Anastomosis in Autologous Breast Reconstruction
Authors: McLaughlin Mariel , Porter Brooke E. , Cohen-Shohet Rachel , Leyngold Mark M.
Published: August 2020

Background This study compares the outcomes of coupled versus hand-sewn arterial anastomosis in microvascular breast reconstruction.

Methods Retrospective chart review of breast reconstruction free flaps performed between 2013 and 2018 was conducted. Primary end points included flap loss, intraoperative arterial anastomosis revision, and operating room takeback. The decision to couple the arterial anastomosis was based on patient's age, surgeon's preference, history of radiation, and vessel quality. All anastomoses were performed under ×3.5 loupe magnification to internal mammary or thoracodorsal vessels.

Results Authors reviewed 104 free flaps; two were lost in hand-sewn group; no flaps were lost in coupled group. There was no significant difference in anastomotic revision rate between coupled and hand-sewn arterial anastomosis (p = 0.186) or return to operating room (OR) between coupled and hand-sewn flaps (p = 1.000). Reasons for takeback included venous congestion and hematoma.

Conclusion This study reflects that coupled arterial anastomosis in breast reconstruction may be safely performed without increased risk in anastomotic revision, takeback, or flap loss. Decision to couple should be based on surgeon skill, patient age and history, and assessment of flap and recipient site vasculature.
Choledochal Cysts Resected during Childhood Show No Mutations of KRAS and BRAF as Early Markers of Malignancy in Cholangiocytes
Authors: Uecker Marie , Lehmann Ulrich , Braubach Peter , Schukfeh Nagoud , Madadi-Sanjani Omid , Ure Benno M. , Petersen Claus , Kuebler Joachim F.
Published: August 2020

Introduction In patients with choledochal cysts (CDC), a hyperplasia-dysplasia-carcinoma sequence can lead to biliary tract malignancy. The limited data available suggest that the risk decreases considerably after excision in childhood. We analyzed samples of resected CDC from pediatric patients histologically and performed mutational analysis of the proto-oncogenes KRAS and BRAF as early markers of malignant alteration in cholangiocytes.

Materials and Methods After institutional review board approval, patients undergoing resection for CDC in our center from 2011 to 2019 were retrospectively identified. Histopathological reports were searched for inflammation and endothelial alteration. Cases with sufficient tissue specimen were tested for KRAS codon 12/13 and BRAF codon 600 mutations by pyrosequencing.

Results In total, 42 patients underwent resection for choledochal cyst in the study period. Median age at surgery was 2.4 years (range = 18 days–18 years). Histopathological analysis showed no malignancy, but various degrees of inflammation or fibrosis in approximately 50% of the patients and in all age groups. Sufficient tissue for mutation analysis was available for 22 cases, all of which tested negative for KRAS or BRAF mutation.

Conclusion In our series, chronic inflammatory changes were frequently present in CDC of infants and children. However, the lack of KRAS and BRAF mutations suggests that no malignant changes have been initiated in this group of European patients undergoing early resection.
Ethical Publication Standards in Articles Reporting on Novel Surgical Methods: Analysis of Three Pediatric Surgical Journals
Authors: Uecker Marie , Ure Benno M. , Dingemann Jens
Published: August 2020

Introduction According to the Declaration of Helsinki, medical research and new therapeutic interventions involving human subjects require prior informed consent and ethical approval. In 2010, 46% of pediatric surgical publications lacked documentation of ethical approval and 84% lacked documentation of informed parental consent with lowest rates of ethical adherence found in articles concerning novel methods. The aim of this study was to investigate whether adherence to ethical standards has improved in pediatric surgical publications.

Materials and Methods All 3,093 consecutive articles published in Journal of Pediatric Surgery, European Journal of Pediatric Surgery, and Pediatric Surgery International over the last 5 years were systematically reviewed for publications describing novel surgical methods. Novel methods were defined as surgical methods not published before or not considered common practice. The publications were reviewed as to whether ethical approval and informed consent to participate was documented.

Results In total, 105 articles describing novel surgical methods were identified (61 Journal of Pediatric Surgery, 16 European Journal of Pediatric Surgery, and 28 Pediatric Surgery International). Authors reported on new operative techniques (62%), modified techniques (31%), or use of new materials (7%). Ethical approval was documented in 52% of the articles with almost half reporting approval for retrospective data analysis only but not the application of the novel method. Informed consent was documented in 21% of publications. Complications were reported in 48% of the studies, including recurrences and reinterventions for the unsuccessful novel methods. Two authors reported mortalities due to underlying disease, one of which failed to report prior ethical approval or informed consent.

Conclusion Adherence to ethical publication principles in pediatric surgery has improved over the last years but is still lacking in many publications. When implementing new methods, prior ethical approval and informed consent and their documentation are mandatory, specifically in the light of potential hazard to patients.