bluuebunny/crossref_metadata_2025 huggingface dataset:
Undifferenziertes Karzinom des distalen Gallengangs vom Spindel- und Riesenzelltyp: Ein Fallbericht
Authors: Albrecht Thomas , Mehrabi Arianeb , Strobel Oliver , Vogel Monika , Stenzinger Albrecht , Bergmann Frank , Schirmacher Peter , Goeppert Benjamin
Published: January 2019

Undifferenzierte Karzinome der Gallenwege sind eine Rarität und manifestieren sich häufiger in der Gallenblase als in den extrahepatischen Gallenwegen. Wir berichten hier von einem äußerst seltenen undifferenzierten Karzinom des distalen Gallengangs vom Spindel- und Riesenzelltyp. Der Tumor ging in Form atypischer Drüsen und Einzelzellkomplexe aus dem biliären Epithel hervor und graduell in eine vorwiegend spindelzellige Architektur über, die mehr als 98 % des Tumorvolumens ausmachte. Fokal gelangten osteoklastäre, multinukleäre Riesenzellen zur Darstellung. Die immunhistochemischen Untersuchungen zeigten in den besser differenzierten, drüsigen Tumoranteilen eine kräftige Expression epithelialer Marker, die in den spindelzelligen Arealen bei Hinzutreten einer Positivität für Vimentin nur noch einzelzellig erhalten blieb. Der Tumor wies eine hohe Ki-67-Proliferationsaktivität auf und zeigte Mutationen in den Genen Cyclin D3 (CCND3), Fibroblast Growth Factor Receptor 4 (FGFR4), Neurofibromin 1 (NF1) und NOTCH3. Der hier vorgestellte Fall unterstreicht die Relevanz dieser Tumorentität jenseits von Pankreas und Gallenblase und verdeutlicht die zur Diagnosefindung unverzichtbare Kombination aus Morphologie und Immunhistochemie.
Ist Gesundheit messbar?
Authors: Heinen Arno
Published: January 2019

Von den Handgelenken fitnessbegeisterter Health-Seeker oder den Anwendungsportfolios gängiger Smartphones sind sie nicht mehr wegzudenken: Gesundheitsanwendungen wie Fitness- Tracker oder Schlaf-Apps. Doch was und wie genau messen sie und wohin führen uns die ausgewerteten Daten – zu mehr Gesundheit oder auf Irrwege? Markus Opalka interviewt Dr. med. Arno Heinen.
Simple HPLC Method for Quantitative Determination of Carbinoxamine in Human Plasma: Application in Pharmacokinetic Studies and Therapeutic Drug Monitoring
Authors: El-Masry Soha M. , El-Morsi Rasha M.
Published: January 2019

A sensitive, specific and cost-effective HPLC method was developed for quantitative determination of carbinoxamine in human plasma using liquid chromatography with ultraviolet detection. A simple liquid–liquid extraction by ethyl acetate was used to extract carbinoxamine from human plasma. Satisfactory separation was achieved by a mobile phase consisting of 20 mM ammonium dihydrogen orthophosphate containing 0.01% triethyl amine (pH adjusted to 3 by using phosphoric acid) and acetonitrile in ratio of (75:25, v/v) at a flow rate of 0.9 mL/min on Hypersil® BDS C18 column (250×4.6 mm, 5 μm) column. The UV detector was set at 260 nm. The developed method was validated in human plasma with a lower limit of quantitation of 5 ng/mL for carbinoxamine. Linearity was demonstrated over the concentration range 5–200 ng/mL. The observed within- and between-day assay precision ranged from 1.902 to 14.90%; accuracy varied between 98.87 and 108.0%. This method can be used suitably for pharmacokinetic studies and in therapeutic drug monitoring in patients treated with carbinoxamine.
Meilensteine der motorischen Entwicklung – Zwischenergebnisse
Authors: Krombholz Heinz
Published: January 2019

Die motorische Entwicklung im Babyalter wird derzeit im Rahmen einer Längsschnittstudie des Staatsinstituts für Frühpädagogik München erforscht. Unter anderem geht es um die Frage, inwieweit vorhandene Normwerte und Faktoren den Zeitpunkt beeinflussen, zu dem Kinder bestimmte Meilensteine der motorischen Entwicklung erreichen. Die Ergebnisse sind interessant für Hebammen bei der Betreuung in den ersten Lebensmonaten des Kindes und stärken Eltern in ihrem wertschätzenden Blick auf die Kompetenzen ihrer Kinder.
Use of smartphone applications to improve quality of bowel preparation for colonoscopy: a systematic review and meta-analysis
Authors: Desai Madhav , Nutalapati Venkat , Bansal Ajay , Buckles Daniel , Bonino John , Olyaee Mojtaba , Rastogi Amit
Published: January 2019

Introduction Smartphone-based applications (apps) have been used to improve the quality of bowel preparation (prep) but the success rates have been variable. We have performed a systematic review and meta-analysis to evaluate the impact of smartphone apps on bowel preparation.

Methods Electronic databases (MEDLINE, Embase, CINAHL and Cochrane) were reviewed for eligible studies of smartphone apps versus standard education before colonoscopy. The following outcomes were analyzed: pooled rate of adequacy of bowel prep among both arms and Boston bowel preparation score (BBPS) when reported. Pooled analysis was reported as odds ratio (OR) or mean difference in random effect model with Review Manager 5.3 (P ≤ 0.05 for statistical significance).

Results Six studies were eligible with smartphone app (810 patients) vs. standard education (855 patients, control group) for bowel prep. The smartphone app group had a higher proportion of adequate bowel prep compared to the control group: 87.5 % vs 77.5 % (five studies), pooled OR 2.67; 95 %CI 1.00 – 7.13 with P = 0.05. There was substantial heterogeneity in studies with I
2 = 78 %. When analysis was limited to randomized controlled trials (RCTs), smartphone app users had a numerically higher rate of bowel cleansing: 87.1 % vs 76.9 %; however, pooled OR was not statistically significant (OR 2.66, 95 %CI 0.92 – 7.69, P = 0.07). When studies using BBPS were evaluated (n = 3), smartphone app users had higher mean scores (better bowel prep) with a mean difference of 0.9 (95 %CI 0.5 – 1.3), which was statistically significant (P < 0.01).

Conclusion The smartphone app is a novel educational tool that can assist in achieving adequate and better bowel cleansing before colonoscopy.
Erfahrungen aus dem Modellprojekt „Allgemeine Ambulante PalliativVersorgung“ – eine qualitative Studie
Authors: Vogel Clara , Jäger Johannes , Gisch Désirée
Published: January 2019

Hintergrund In den Jahren 2015 bis 2017 führte die Kassenärztliche Vereinigung Saarland (KVS) das Modellprojekt „Allgemeine Ambulante PalliativVersorgung (AAPV)“ im Landkreis St. Wendel durch. Die begleitende Evaluation sollte förderliche und hinderliche Faktoren der neuen Versorgungsstruktur anhand der Befragung von teilnehmenden Pflegefachkräften, Hausärzten und Mitarbeitern der ambulanten Hospizhilfe aufdecken. Wie schätzen die Professionellen das Projekt aus ihrer Sicht ein?

Methodik Im Juni 2016 wurden zwei Gruppendiskussionen mit insgesamt 19 Teilnehmenden parallel durchgeführt und mittels der dokumentarischen Methode analysiert.

Ergebnisse Das AAPV-Modellprojekt führte zu einer vernetzten interprofessionellen Zusammenarbeit in der Primärversorgung. Hausärzte, Pflegefachkräfte ambulanter Pflegedienste und Mitarbeiter der ambulanten Hospizhilfe arbeiteten gemeinsam an einem Ziel: Sterben in der Häuslichkeit zu ermöglichen. Hindernisse in der Umsetzung von AAPV sahen die Diskutanten in der Bürokratie und der unzureichend empfundenen Finanzierung. Die AAPV-Implementierung wurde durch Teilnehmende als zeit- und arbeitsaufwendig wahrgenommen. Dennoch erwarten Hausärzte prospektiv eine Entlastung in ihrer Arbeit.

Schlussfolgerung Die Laufzeit des saarländischen Modellprojekts ist beendet. Momentan gelingt die Weiterführung der AAPV durch einen hausärztlichen Obmann, unterstützt durch die KVS. Nur wenn sich alle beteiligten Akteure interprofessionell verzahnen und AAPV in ihrem Leitbild verankern, können Patienten, Angehörige und Professionelle von der neuartigen Versorgungsstruktur profitieren.
Behandlungserfahrungen und soziale Unterstützung bei Personen mit Geschlechtsinkongruenz/Geschlechtsdysphorie: Eine ENIGI 5-Jahres-Follow-Up-Studie in drei europäischen Ländern
Authors: Köhler Andreas , Becker Inga , Richter-Appelt Hertha , Cerwenka Susanne , Kreukels Baudewijntje , van de Grift Tim , Elaut Els , Heylens Gunter , Nieder Timo Ole
Published: January 2019

Einleitung Geschlechtsdysphorie (GD) bezeichnet einen Leidensdruck, der sich aus der Inkongruenz zwischen körperlichen Geschlechtsmerkmalen und dem Erleben des eigenen Geschlechts ergeben kann (Geschlechtsinkongruenz, GI). Die vorliegende Arbeit beschäftigt sich mit dem Zusammenspiel von medizinischer Behandlung und sozialer Unterstützung, das bisher nur unzureichend im Langzeitverlauf untersucht wurde.

Material & Methoden Die vorgestellte Studie untersuchte n=117 Personen mit einem männlichen und n=52 mit einem weiblichen Zuweisungsgeschlecht, die sich wegen GI/GD in dem Zeitraum zwischen 2007 bis 2009 im Rahmen des European Network for the Investigation of Gender Incongruence (ENIGI) an drei Spezialambulanzen in Belgien, der Niederlande und Deutschland gewandt hatten, und 4–6 Jahre nach der Erstvorstellung mittels eines Online-Fragebogens nachbefragt wurden. Mit Hilfe zweier hierarchischer Regressionsanalysen wurden der Einfluss des Geschlechts, des Behandlungsfortschrittes und der sozialen Unterstützung zum einen auf die psychische Belastung und zum anderen auf die Lebenszufriedenheit der Teilnehmenden untersucht.

Ergebnisse Im ersten Modell waren ein weibliches Zuweisungsgeschlecht und eine bessere soziale Unterstützung signifikante Prädiktoren für eine verringerte psychische Belastung. Außerdem waren im zweiten Modell der individuelle Behandlungsfortschritt und eine ausgeprägtere soziale Unterstützung statistisch signifikant für die Vorhersage einer erhöhten Lebenszufriedenheit.

Diskussion Die Ergebnisse zeigen, dass über die körpermedizinische Behandlung hinaus die soziale Unterstützung eine wesentliche Rolle im Rahmen des geschlechtsangleichenden Prozesses spielt.
Registration bias in a clinical quality register
Authors: Hoff Geir , de Lange Thomas , Bretthauer Michael , Dahler Stein , Halvorsen Fred-Arne , Huppertz-Hauss Gert , Høie Ole , Kjellevold Øystein , Mortiz Volker , Sandvei Per , Seip Birgitte , Holme Øyvind
Published: January 2019

Background and aims The quality of medical quality registers is poorly defined and lack of trust in data due to low completeness may be a major barrier against their use in quality improvement interventions. The aim of the current observational study was to explore how selective reporting may influence adverse events registered in the Norwegian quality register for colonoscopy (Gastronet).

Materials and methods Gastronet’s database includes data provided by endoscopists, nurses and patients. All outpatient colonoscopies reported to Gastronet in 2015 were included and compared to the total number of colonoscopies performed in Norway as retrieved from the National Patient Registry. Hospitals were categorized into four groups according to reporting completeness < 50 %, 50 % to 69 %, 70 % to 89 % and ≥ 90 %. The number of recorded adverse events (AEs) and procedure time were analyzed. Multivariate logistic regression models were fitted to explore independent factors for selection bias.

Results A total of 22,364 colonoscopies were reported to the National Patient Register of which 15,855 (71 %) were registered in Gastronet. Feedback was received from 11,079 patients (50 %). The frequency of AEs increased from 0.6 % in completeness group < 50 % to 1.6 % in completeness group ≥ 90 % (P < 0.001). Long colonoscopy procedure time was associated with low reporting completeness. Patient feedback was associated with older age, cecal intubation success and sedation-free colonoscopy.

Conclusion Incomplete registration in a colonoscopy quality register is associated with underreporting of AEs. Longer procedure time, a surrogate marker for time constraint, is associated with low completeness.
A rare non-oncological pancreatic mass: eosinophilic pancreatitis diagnosis through EUS-FNA
Authors: De Moura Diogo , Rocha Rodrigo , Jukemura José , Brunaldi Vitor , Guedes Hugo , Torrez Franz , Ribeiro Igor , Gelrud Andres , De Moura Eduardo
Published: January 2019

Background and study aims Eosinophilic pancreatitis (EP) is a rare etiology of chronic pancreatitis, and few cases have been reported. It is characterized by eosinophilic infiltration of the pancreas and elevated IgE levels. EP is difficult to distinguish from pancreatic cancer based on clinical symptoms and auxiliary exams. We present a case of EP and debate the routine performance of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for resectable pancreatic mass.
Relationships Between Biochemical Markers of Hyperandrogenism and Metabolic Parameters in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
Authors: Amiri Mina , Tehrani Fahimeh , Bidhendi-Yarandi Razieh , Behboudi-Gandevani Samira , Azizi Fereidoun , Carmina Enrico
Published: January 2019

While several studies have documented an increased risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS), associations between androgenic and metabolic parameters in these patients are unclear. We aimed to investigate the relationships between biochemical markers of hyperandrogenism (HA) and metabolic parameters in women with PCOS. In this systematic review and meta-analysis, a literature search was performed in the PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science from 2000 to 2018 for assessing androgenic and metabolic parameters in PCOS patients. To assess the relationships between androgenic and metabolic parameters, meta-regression analysis was used. A total number of 33 studies involving 9905 patients with PCOS were included in this analysis. The associations of total testosterone (tT) with metabolic parameters were not significant; after adjustment for age and BMI, we detected associations of this androgen with low-density lipoproteins cholesterol (LDL-C) (β=0.006; 95% CI: 0.002, 0.01), high-density lipoproteins cholesterol (HDL-C) (β=–0.009; 95% CI: –0.02, –0.001), and systolic blood pressure (SBP) (β=–0.01; 95% CI: –0.03, –0.00). We observed a positive significant association between free testosterone (fT) and fasting insulin (β=0.49; 95% CI: 0.05, 0.91); this association remained significant after adjustment for confounders. We also detected a reverse association between fT and HDL-C (β=–0.41; 95% CI: –0.70, –0.12). There was a positive significant association between A4 and TG (β=0.02; 95% CI: 0.00, 0.04) after adjustment for PCOS diagnosis criteria. We also found significant negative associations between A4, TC, and LDL-C. Dehydroepiandrosterone sulfate (DHEAS) had a positive association with LDL-C (β=0.02; 95% CI: 0.001, 0.03) and a reverse significant association with HDL-C (β=–0.03; 95% CI: –0.06, –0.001). This meta-analysis confirmed the associations of some androgenic and metabolic parameters, indicating that measurement of these parameters may be useful for predicting metabolic risk in PCOS patients.
Management of Anterior Chamber Dislocation of a Dexamethasone Implant
Authors: Nguyen Thi , Wolfensberger Thomas
Published: January 2019

Purpose To characterise the surgical removal technique of a dislocated dexamethasone implant in the anterior chamber and to gauge its success by analysing corneal transparency and subsequent visual acuity recovery in the postoperative phase.

Methods Description of a patient who presented with an anterior chamber dexamethasone implant migration through an inferior iridotomy performed previously for a silicone oil fill in aphakia. Visual acuity had dropped to counting fingers due to marked corneal oedema.

Results The implant was removed using a 23-g needle aligned with the axis of the implant through a paracentesis. After the clinical follow-up at 2 months, best-corrected visual acuity had returned to 0.2, which remained stable at the last follow-up at 14 months with an intraocular pressure of 10 mmHg. The corneal oedema resolved completely.

Conclusion This novel surgical management of a dexamethasone implant dislocation into the anterior chamber was successful and resulted in no long-term corneal damage when the implant was removed without delay. A repeated Ozurdex injection in patients with previous inferior iridotomy may require prior suturing of the iridotomy.
Evaluation of Visual Comfort and Mental Effort Under Different Light Conditions for Ultraviolet-Absorbing and Additional Blue-Filtering Intraocular Lenses for Cataract Surgery
Authors: Steinemann Alexandra , Bromundt Vivien , Chellappa Sarah , Frey Sylvia , Schmidt Christina , Schlote Torsten , Goldblum David , Cajochen Christian
Published: January 2019

Patients and Methods Patients with an ultraviolet blocking lens (UV) (n = 5) or blue filter lens (BB) (n = 8) after intraocular lens (IOL) replacement for cataract and age-adjusted controls (AACs) (n = 16) underwent a balanced crossover within-subject design. After 1.5 h of dark adaptation, they were exposed to polychromatic light at 6500 K (blue-enriched) and 2500 K and 3000 K (non-blue-enriched) for 2 hours in the evening. Visual comfort and mental effort were repeatedly assessed by the Visual Analogue Scale (0 – 100) and the Visual Comfort and Mental Effort Rating Scale (0 – 100) for each light condition. The results were compared using mixed model analysis.

Results The mean (± SD) age for AAC and patients with UV or BB was 69.8 ± 6.2 y, 70.8 ± 4 y, and 63.6 ± 5.6 y, respectively. Irrespective of the light condition, patients with UV and BB felt mentally more tired during the experiments compared to AACs (F = 6.15, p = 0.003). However, patients with BB were mentally more motivated to perform the exercises compared to patients with UV and AACs (F = 8.1, p < 0.001). Patients with BB perceived ambient light as less glary (F = 4.71, p = 0.01) than patients with UV. Blue ambient light was felt less intensely in patients with BB (F = 2.51, p = 0.042) compared to those with UV and the AACs.

Conclusion Lens replacement in older cataract patients may increase visual comfort and minimize mental effort. While subtle, the magnitude of these effects may depend on the type of intraocular lens. BB intraocular lenses may have potential benefits, as ambient light is perceived as having less glare and less visual tension.
Selenoprotein P in Patients with Nonalcoholic Fatty Liver Disease
Authors: Polyzos Stergios A. , Kountouras Jannis , Mavrouli Maria , Katsinelos Panagiotis , Doulberis Michael , Gavana Elpida , Duntas Leonidas
Published: January 2019

Objective Main aim of this study was to evaluate circulating selenoprotein P (SEPP) levels in patients with simple steatosis (SS) and nonalcoholic steatohepatitis (NASH) compared with healthy controls.

Methods Thirty-one patients with biopsy-proven NAFLD (15 with SS, 10 with borderline NASH, 6 with definite NASH) and 27 matched controls without NAFLD were enrolled. Serum SEPP levels and liver function tests plus biochemical parameters were measured with ELISA and standard methods, respectively. Homeostatic model of assessment - insulin resistance (HOMA-IR) was calculated.

Results SEPP levels were statistically different between groups (p-value for trend=0.043). In pairwise comparisons, SEPP was lower in definite NASH compared with controls (p=0.029), but not SS (p=0.18) or borderline NASH (p=0.35). SEPP was not different between controls, SS and borderline NASH. The unadjusted trend between the controls, SS and NASH patients remained essentially unchanged after adjustment for age, sex, log(ALT) and waist circumference, but it marginally lost significance when log(HOMA-IR) entered into the model. SEPP levels were not different between groups of different severity of steatosis, fibrosis, hepatocellular ballooning, lobular and portal inflammation.

Conclusions Lower SEPP levels were observed in patients with definite NASH compared with controls, a finding warranting larger studies.
Ultrasonographic Evaluation of Glycemic Control Effect on Placental Vascularization in Pregnancy with Type 1 Diabetes Mellitus
Authors: Kozinszky Zoltan , Altorjay AbelT. , Molnar Andras , Nyári Tibor , Vari Sandor G. , Nemeth Gabor , Suranyi Andrea
Published: January 2019

Aims The aim of our study was to assess the effect of glycemic control on placental vascularization in pregnancies complicated by type 1 diabetes mellitus (T1DM) and to compare dataset of optimal/suboptimal glycemic control to normal placental 3-dimensional power Doppler (3-DPD) indices in 2nd and 3rd trimester.

Methods Placental vascularization of pregnant women was prospectively evaluated by 3-DPD ((vascularization-index (VI); flow-index (FI); vascularization-flow-index (VFI)) ultrasound technique. The normal pregnancies (n=214) were compared to those complicated by T1DM (n=53) with optimal (HbA1C≤6%;≤ 42 mmol/mol) and suboptimal (HbA1C>6%;>42 mmol/mol) glycemic control.

Results Pregnancies complicated by T1DM expressed lower placental vascularization indices as compared with normal pregnancies (adjusted odds ratio (AOR) for VI:0.86; FI:0.94; VFI:0.76). Placental 3-DPD indices have a significant correlation with HbA1C and optimal glycemic control is associated with lower placental perfusion (AOR for VI:1.64; FI:1.13; VFI:2.34). Short-term adverse neonatal outcome was predicted by lower 3-DPD indices (AORVI:0.83, AORFI:0.93, AORVFI:0.66, p<0.05 for each index). Besides the glycemic control, the pregestational body mass index (BMI), had significant influences on placental perfusion.

Conclusions VI displayed the best screening ability for suboptimal glycemic control with a sensitivity of 90.9%. The suboptimal glycemic control has a direct deteriorating effect on placental vasculature. Therefore the ultrasound examination could be an adjunct diagnostic modality for pregnant women with T1DM.
One-Pot Reductive Acetylation of Aldehydes using 1-Hydrosilatrane in Acetic Acid
Authors: James Reuben , Herlugson Sharon , Varjosaari Sami , Skrypai Vladislav , Shakeel Zainab , Gilbert Thomas , Adler Marc
Published: January 2019

A one-pot, direct reductive acetylation of aldehydes was achieved under mild conditions using 1-hydrosilatrane as a safe and easily accessible catalyst. Described herein is a facile synthesis that produces acylated primary alcohols that can serve as valuable building blocks for organic synthesis. The method has good functional group tolerance and works for a range of aryl aldehydes, with the notable exception of electron-rich arenes. A library of esters was isolated by flash chromatography in yields as high as 92%.
New Strategies for Activation of Phosphonates/Phosphates to Forge Functional Phosphorus Compounds
Authors: Kang Jun , Huang Hai
Published: January 2019

Organophosphonate analogues are important structural motifs that are present in bioactive natural products, pharmaceuticals, and agrochemicals. Because they are useful in a broad range of applications, much effort has focused on developing efficient synthetic methods that enable access to organophosphonates and their derivatives. However, currently available synthetic procedures rely on harsh reaction conditions and are limited to a narrow substrate scope. Our lab has recently made important advances in leveraging inert phosphonates/phosphates into functional phosphorus compounds such as mixed phosphonates, phosphates, and mixed aryl phosphate derivatives. Presented herein is an overview of recent achievements in the synthesis of phosphonate/phosphate derivatives and a summary of our recent accomplishments in Tf2O-promoted activating strategy of phosphonate analogues.

1 Introduction

2 Direct Activating Strategy of Phosphonate Analogues

3 Late-stage Phosphonylation of Natural Compounds

4 Potential Applications

5 Summary
Desymmetrization of σ-Symmetric Biphenyl-2,6-diyl Diacetate Derivatives by Lipase-Catalyzed Hydrolysis: Unexpected Effect of C(3′)-Substituent on the Enantiotopic Group Selectivity
Authors: Matsumoto Takashi , Ochiai Mio , Akisawa Yuki , Kajiyama Daichi
Published: January 2019

Highly enantioselective desymmetrization of σ-symmetric 3′-substituted 2′,6′-dimethoxybiphenyl-2,6-diyl diacetate derivatives to the corresponding monoacetates was effected by using Rhizopus oryzae lipase (ROL) and porcine pancreatic lipase (PPL), despite the remoteness of the C(3′) substituent from the acetate groups. ROL promoted hydrolysis of the pro-S acetates, irrespective of the type of C(3′) substituent, whereas PPL promoted hydrolysis of the pro-R acetates, and selectivity was only attainable when the C(3′) substituent was a polar group.
Selective ortho-Metalation of a Fluoroarene with Knochel–Hauser Base and Reactions with Various Electrophiles
Authors: Baenziger Markus , Eswaran Sumesh , Jiang Yifan , Kasinathan Gopu
Published: January 2019

Selective ortho-metalation of 1-bromo-2-(1,1-difluoroethyl)-4-fluorobenzene was achieved with the Knochel–Hauser base (TMPMgCl·LiCl) in position 5 of the aromatic ring. The magnesiated intermediate was reacted with a variety of electrophiles to obtain the products in good yields. The work was successfully extended to a Negishi coupling, after transmetalation with ZnCl2 and Pd-catalyzed reaction with 4-iodotoluene.
Synthesis of 8-HEPE and 10-HDoHE in both (R)- and (S)-Forms via Wittig Reactions with COOH-Ylides
Authors: Suganuma Yuta , Saito Shun , Kobayashi Yuichi
Published: January 2019

Wittig reactions using carboxy (CO2H) ylides derived from a carboxylic phosphonium salt and NaN(TMS)2 (NaHMDS) in a 1:1 ratio were applied to the synthesis of 8-HEPE and 10-HDoHE, which are metabolites of eicosapentaenoic acid and docosahexaenoic acid, respectively. The attempted Wittig reaction of 3-(TBS-oxy)pentadeca-4E,6Z,9Z,12Z-tetraenal with the carboxy ylide (2 equiv) derived from Br– Ph3P+(CH2)4CO2H and NaHMDS (1:1) competed with the elimination of the TBS-oxy group at C3 to give a mixture of the Wittig product and the elimination product in 45–50% and 30–40% yields, respectively. The elimination was suppressed completely by using three equiv of the carboxy ylides in THF/HMPA (7–8:1), and the subsequent desilylation gave 8-HEPE in (R)- and (S)-forms. Similarly, both enantiomers of 10-HDoHE were synthesized.
Bilateral Tuberculous Otitis Media: A Rare Presentation
Authors: Vijayendra Honnurappa , Mahajan Nilesh , Vijayendra Vinay
Published: January 2019

Introduction Tuberculosis is one of the most common infectious diseases in India. Tuberculosis of the middle ear is rare, usually seen in association with pulmonary tuberculosis or in patients with history of pulmonary tuberculosis. It is an uncommon and frequently misdiagnosed form of tuberculosis. In our experience, we have seen 50% of cases of tuberculous otitis media without pulmonary tuberculosis. These cases presented with rapid deterioration of hearing with more sensorineural component in hearing loss.

Case Report This is a case report of 34-year-old woman presented to us with worsening of hearing over short duration of 3 months. She developed right profound hearing loss and left moderately severe mixed hearing loss, which deteriorated within duration of 2 weeks. Very few cases have been reported in literature affecting both the ears. In our experience, we have seen seven such cases with bilateral ear involvement.

Conclusion Tuberculosis of the middle ear is a rare condition. For complete cure, medical therapy should be given at least for 9 months including 2 months 4 tablets (AKT4) and 7 months 3 tablets (AKT3) regimes, according to the INDEX-TB guidelines provided by government of India for extrapulmonary tuberculosis. Surgical treatment should be always added as emergency to prevent progression of sensorineural hearing loss and in cases of complications such as facial palsy.
Correlation between Carotid–Cochlear and Sensorineural Hearing Loss: A Cross-Sectional Study
Authors: Sekar Raghul , Alexander Arun , Krishnan Nagarajan
Published: January 2019

Background Sensorineural hearing loss is a condition with several etiologies and varies with the age of the individual. Carotid–cochlear interval is the minimum distance between basal turn of cochlea and the genu of petrous part of internal carotid artery. It is believed that constant pulsations from carotid can cause fluid pressure changes within the cochlea leading to damage to hair cells causing hearing loss.

Objective To study the correlation between carotid–cochlear interval and degree of hearing loss at different frequencies in patients with sensorineural deafness and compare this interval with normal subjects.

Methods Seventy cases with sensorineural hearing loss between 18 and 60 years undergoing HRCT temporal bone were grouped together and 70 cases with normal hearing undergoing CT nose and paranasal sinuses were grouped together. Carotid–cochlear interval measured in both the groups was correlated with the degree and frequency of hearing loss and compared with normal subjects.

Results The mean carotid–cochlear interval in sensorineural hearing loss and in normal subjects was found to be 1.30 + 0.68 (SD) mm and 1.83 + 0.74 (SD) mm, respectively with p < 0.001. The coefficient of correlation between carotid–cochlear interval and pure tone average in patients with sensorineural deafness was r = −0.740 with p-value < 0.001.

Conclusion Carotid–cochlear interval is significantly low in patients with sensorineural hearing loss and bears a strong negative correlation with the degree of hearing loss at mid- and high-frequency ranges. Thus we hypothesize that pulsations from carotid artery cause damage to hair cells in the organ of Corti producing audiological symptoms such as hearing loss.
Surgical Care and Outcomes Assessment Program (SCOAP): A Nuanced, Flexible Platform for Colorectal Surgical Research
Authors: Simianu Vlad , Kumar Anjali
Published: January 2019

The Surgical Care and Outcomes Assessment Program (SCOAP) is a surgeon-led quality improvement (QI) initiative developed in Washington State to track and reduce variability in surgical care. It has developed into a collaboration of over two-thirds of the hospitals in the state, who share data and receive regular benchmarking reports. Data are abstracted at each site by trained abstractors. While there has some overlap with other national QI databases, the data captured by SCOAP has clinical nuances that make it pragmatic for studying surgical care. We review the unique properties of SCOAP and offer some examples of its novel applications.
Review of Colorectal Studies Using the National Cancer Database
Authors: Kelley Katherine , Tsikitis V.
Published: January 2019

The National Cancer Database (NCDB) is a large clinical oncology database developed with data collected from Commission on Cancer (CoC)-accredited facilities. The CoC is managed under the American College of Surgeons, and is a multidisciplinary team that maintains standards in cancer care delivery in health care settings. This database has been used in multiple cancer-focused studies and reports on cancer diagnosis, hospital-level, and patient-related demographics. The focus of this review is to explore and discuss the use of NCDB in colorectal surgery research. Furthermore, our aim for this review is to formulate a guide for researchers who are interested in using the NCDB to complete colorectal research.
“Locked” Scapholunate Instability Diagnosed with 4D Computed Tomography Scan
Authors: Bain Gregory I. , Krishna Sathya Vamsi , MacLean Simon , Carr Renee , Slavotinek John
Published: January 2019

Background Scapholunate instability (SLI) has a wide range of clinical and radiological presentations. The management depends on the stage of the disorder. Subluxation of scaphoid is pathognomonic feature of the SLI. We describe a patient with SLI with a dislocated proximal pole of scaphoid, out of the distal radius scaphoid fossa. The 4D (three-dimensions + time) computed tomography (CT) scan demonstrated that the scaphoid did not reduce throughout wrist motion.

Case Description A 20-year-old male presented with SLI following a fall skateboarding. The 4D CT scan revealed the dislocated scaphoid that did not reduce with wrist motion. He underwent open reduction of the proximal pole of scaphoid and SL reconstruction using flexor carpi radialis (FCR) tendon graft with the Quad tenodesis technique. At 1 year, he had improved pain, wrist functions, and maintained satisfactory radiological alignment.

Literature Review We are not aware of any previous description of the dorsal scaphoid dislocation in association with scapolunate instability.

Clinical Relevance We recommend that the SLI staging classification needs to be expanded to include dislocation (locked) stage. The 4D CT has a significant role in identifying the instability and its reducibility.

Level of Evidence This is a level V study.
Abdominal Manifestations of Neuroendocrine Tumors
Authors: Marcal Leonardo , Patnana Madhavi , Yedururi Sireesha , Chuang Hubert , Devine Catherine , Cox Veronica , Dasari Arvind , Loyer Evelyne
Published: January 2019

Despite being rare, the incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (NETs) is rising. They are a heterogeneous group of tumors with differences in clinical presentations, genetics, and imaging features. Advances in pathological classification, imaging (including recent radiotracer approval for functional imaging in the Unites States), and therapy have impacted management of these tumors. It is important in the multidisciplinary approach to patient care to be familiar with the tumor biology, imaging techniques for diagnosis and staging, and therapeutic options. This article will discuss these new developments, particularly focusing on pancreatic and small bowel NETs.
Differential Presentation of Congenital Cholesteatoma in Twins with Atypical Location
Authors: HN Udayabhanu , Lauda Lorenzo , Caruso Antonio , Sanna Mario
Published: January 2019

Objective We present an extremely rare report of congenital cholesteatoma (CC) in identical twins with atypical location.

Methods Two consecutive cases of CC in identical twins from diagnosis to treatment and a literature review are presented.

Results The twin children presented to our otology and lateral skull base clinic with different clinical picture. Both underwent thorough audiological workup and imaging and early surgical intervention. The 6-year follow-up of these two children has been uneventful with no recurrence of disease and hearing restoration.

Conclusion Multiple theories exist to explain this rare pathology. Modified Levenson’s criteria define it as white mass behind intact tympanic membrane. Atypical location of CC with recurrent otitis media is not uncommon; hence, further study is required. To our best knowledge, this is the second reported occurrence in identical twins but first report with differential presentation and atypical location in both cases.
Development of a Customized Interbody Fusion Device for Treatment of Canine Disc-Associated Cervical Spondylomyelopathy
Authors: Parr William , Tan Christopher , Walsh William , Brunel Laurencie , Joffe Michelle
Published: January 2019

Objectives The main purpose of this study was to design, manufacture and implant a customized three-dimensional (3D) printed, intervertebral spacer to treat disc-associated cervical spondylomyelopathy (DACSM) in dogs. This study also used advanced imaging to assess implant movement, subsidence and interbody fusion.

Animals Two client-owned dogs with DACSM.

Method Customized interbody devices were designed and 3D printed in titanium alloy. The devices were implanted in dogs diagnosed with DACSM. The dogs were evaluated at time points 0, 2 and 6 months to determine clinical outcome, degree of interbody fusion, implant migration and subsidence.

Results Progressive fusion was noted across the affected intervertebral space by 6 months. Implants mildly shifted cranially in the 2-month interim. There was no subsidence of the intervertebral device through the vertebral end plates in dog 1 and minimal in dog 2 (∼0.5 mm). Clinically, the neurological status improved in both dogs.

Conclusions The customized interbody devices restored the intervertebral space and resulted in a degree of interbody fusion and resolution of clinical signs.

Clinical Significance This report illustrates preliminary outcomes of DACSM treated with a customized, end plate conforming, intervertebral device. Collaboration between clinicians and engineers with advanced manufacturing technologies can provide a cutting-edge standard of care for patients suffering from DACSM.
Thrombopoietin Receptor Agonist Use for Immune Thrombocytopaenia
Authors: Neunert Cindy E.
Published: January 2019

Management of patients with corticosteroid-refractory immune thrombocytopaenia (ITP) possesses a significant challenge to practitioners. Until recently, options included splenectomy and immunosuppression. With improved knowledge of both thrombopoiesis and the pathophysiology of ITP, novel drug development with thrombopoietin-receptor agonists (TPO-RAs) was undertaken. Two agents, romiplostim and eltrombopag, are currently approved for use in patients with chronic ITP. Both agents have been shown to increase the platelet count, improve health-related quality of life and reduce bleeding symptoms and concomitant medication use. This review will highlight the discovery of TPO-RA agents, appraise key clinical trials and explore future directions.
A Comparison of Owner-Assessed Long-Term Outcome of Arthroscopic Intervention versus Conservative Managemento f Dogs with Medial Coronoid Process Disease
Authors: Dempsey Lara , Maddox Thomas , Comerford Eithne , Pettitt Rob , Tomlinson Andrew
Published: January 2019

Objectives The purpose of this study was to compare the long-term outcome of dogs with medial coronoid process disease (MCPD) treated with arthroscopic intervention versus conservative management.

Materials and Methods Medical records of dogs with MCPD treated by arthroscopic intervention or conservative management over an 8-year period were retrospectively reviewed. Long-term outcome (>12 months) was assessed via owner questionnaire including Liverpool Osteoarthritis in Dogs (LOAD) scores and Canine Brief Pain Inventory scores.

Results Data from 67 clinically affected elbow joints (67 dogs) diagnosed with MCPD on computed tomography were included. Forty-four dogs underwent arthroscopic intervention and 23 dogs were treated with conservative management. The median LOAD and Pain Severity Score (PSS) for dogs in the arthroscopic intervention group compared with the conservatively managed group were not significantly different (p = 0.066 and p = 0.10, respectively). The median Pain Interference Score (PIS) was significantly higher in the arthroscopic intervention group versus the conservative management group (p = 0.028). There was no significant difference after controlling for age. For LOAD, PSS and PIS, older age at diagnosis was all significantly associated with higher scores (p = 0.048, p = 0.026 and p = 0.046, respectively) and older age at time of questionnaire completion showed a stronger association with the scores (p ≤0.001 for all).

Clinical Significance Arthroscopic intervention showed no long-term benefit over conservative management for dogs with MCPD.
Phenomenological Characterization of Low-Potency Homeopathic Preparations by Means of Pattern Formation in Evaporating Droplets
Authors: Kokornaczyk Maria , Würtenberger Sandra , Baumgartner Stephan
Published: January 2019

Background Evaporation-induced pattern formation in droplets has been applied to test effects of high potencies. Here we propose for the first time the droplet evaporation method (DEM) as a tool to characterize low potencies on a qualitative and quantitative basis.

Materials and Methods The present investigation consisted of: (1) screening of 18 different substances of mineral, vegetal, and animal origin in the 1x to 6x potency range; choice of four substances with characteristic pattern-forming properties; (2) replication experiments aiming at the differentiation of four homeopathic preparations at the same potency levels (2x–6x); and (3) control experiments performed on three preparations. The DEM experimental protocol consisted of the evaporation of droplets of the analyzed potency per se, placed on microscope slides and in controlled conditions. The resulting patterns were photographed and subjected to computerized image analysis.

Results The screening experiments yielded a wide variety of patterns. Homeopathic preparations of mineral origin showed the largest variety of forms, whereas potencies of vegetal origin mostly created dendritic patterns, probably due to diffusion-limited aggregation. The here-analyzed image analysis variables (gray-level distribution, entropy, and inverse difference moment) allowed a highly significant differentiation of patterns prepared from four substances (Echinacea, Baptisia, Luffa, and Spongia) at the same potency levels in the range 2x to 4x, whereas patterns obtained from potencies 5x and 6x could no longer be differentiated and resembled the pattern of pure solute (purified water). The control experiments showed reasonable experimental model stability.

Conclusions DEM seems to be a promising tool for qualitative phenomenological characterization of homeopathic preparations in low potency. We propose the application of the current experimental model for investigating further research topics in this field, such as the comparison of potencies versus simple dilutions or the contribution of component remedies to the patterns formed by homeopathic combination medicines.
Disorders of Emotional Communication in Traumatic Brain Injury
Authors: Wauters Lisa , Marquardt Thomas
Published: January 2019

Traumatic brain injury (TBI) leads to a wide array of behavioral and cognitive deficits. Individuals with TBI often demonstrate difficulties with the recognition and expression of emotion communicated through multiple modalities including facial expression, vocal prosody, and linguistic content. Deficits in emotional communication contribute to a pattern of social pragmatic communication problems, leading to decreased psychosocial function. Growing evidence supports intervention targeting affective processing. This article summarizes the current evidence for evaluation and treatment of affective processing disorders in TBI.
Teaching Electroencephalography: Persistent Altered Sensorium with Ominous Appearing Electroencephalographic Activity
Authors: D'Souza Delon , Sarma Gosala R. K. , T. Elizabeth V.
Published: January 2019

A 51-year-old man presented with persistent altered sensorium following a seizure. His magnetic resonance imaging (MRI) showed features of focal encephalitis involving the left temporal, parietal, and occipital regions. His electroencephalogram (EEG) showed ongoing epileptiform discharges over the left hemisphere. This article discusses dilemmas in the diagnosis of nonconvulsive status epilepticus in such a case scenario.
Benign Central Airway Obstruction
Authors: Oberg Catherine , Holden Van , Channick Colleen
Published: January 2019

Benign central airway obstruction (CAO) is responsible for significant morbidity due to dyspnea and impaired quality of life. While iatrogenic causes, including stenosis after endotracheal intubation, tracheostomy tube placement, and surgery, account for the majority of cases of benign CAO, there are a multitude of other causes including infections, inflammatory disorders, extrinsic compression, benign endobronchial tumors, and tracheobronchomalacia. The approach to management depends on the underlying process responsible for the disorder and may include systemic therapy, endoscopic therapy, and surgery. In this review, we aim to provide a general overview of the presentation, evaluation, and management of nonmalignant CAO followed by a more in-depth review of several of the more common causes of this disorder.
Disturbed Laminar Blood Flow Causes Impaired Fibrinolysis and Endothelial Fibrin Deposition In Vivo
Authors: Glise Lars , Larsson Pia , Jern Sverker , Borén Jan , Levin Malin , Ny Tor , Fogelstrand Per , Bergh Niklas
Published: January 2019

Endothelial expression of tissue-type plasminogen activator (t-PA) is crucial for maintaining an adequate endogenous fibrinolysis. It is unknown how endothelial t-PA expression and fibrinolysis are affected by blood flow in vivo. In this study, we investigated the impact of different blood flow profiles on endothelial t-PA expression and fibrinolysis in the arterial vasculature. Induction of disturbed laminar blood flow (D-flow) in the mouse carotid artery potently reduced endothelial t-PA messenger ribonucleic acid and protein expression, and caused fibrin deposition. En face immunohistochemistry demonstrated that arterial areas naturally exposed to D-flow had markedly lower endothelial t-PA levels than areas with sustained laminar blood flow (S-flow), and displayed pronounced fibrin deposition despite an intact endothelium. In t-PA and plasminogen-deficient mice, fibrin deposition did not extend into S-flow areas, indicating that areas of D-flow and S-flow differ, not only in fibrinolytic capacity, but also in coagulation. Furthermore, plasminogen accumulation was found at D-flow areas, and infusion of recombinant t-PA activated fibrinolysis and significantly reduced the fibrin deposits. In conclusion, D-flow potently impairs the fibrinolytic capacity and causes endothelial fibrin deposition in vivo. Our data also indicate that t-PA is the limiting factor for efficient fibrinolysis at the thrombosis-prone D-flow areas in the arterial vasculature.
Transbronchial Cryobiopsies
Authors: Wallace W. , Shaikh Faisal , Lynch Joseph , Oh Scott
Published: January 2019

Transbronchial lung cryobiopsy (TBLCB) is a relatively new and promising technique for the acquisition of larger amounts of higher quality lung tissue for the diagnosis of lung diseases. There is a growing body of literature describing a diagnostic yield comparable to surgical lung biopsy with a favorable safety profile. Due to its advantages TBLCB has garnered significant interest with more institutions beginning to adopt this technique. However, several questions remain including its role in the diagnostic algorithm, indications, and technique. Herein we provide a review of the available literature describing diagnostic yield, complications, and differing techniques as well as a perspective from pathology.
Linear Endobronchial Ultrasound: What's New?
Authors: Mehta Atul , He Tao
Published: January 2019

Since its advent more than a decade ago, real-time linear endobronchial ultrasound (EBUS) guided transbronchial needle aspiration has revolutionized the diagnosis and staging of nonsmall cell lung cancer (NSCLC), and has become the standard of care with widespread acceptance. It is also extensively used to diagnose other disease entities such as malignancy besides NSCLC, benign diseases, or infectious processes. Ancillary studies have shown its superior safety profile and cost-effectiveness. In recent years, linear EBUS has been expanding its clinical applications owing to the emerging new tools such as the 19-gauge (19G) needle and miniforceps. Meanwhile, with several ground-breaking discoveries in lung cancer treatment over the past few years, linear EBUS has found its way to fit into this scheme as a safe and effective diagnostic tool. This review summarizes the most recent evidence on evaluating the performance of linear EBUS-guided biopsy in various clinical situations.