bluuebunny/crossref_metadata_2025 huggingface dataset:
Success of immune checkpoint blockade therapies – mechanisms and implications for hepatology
Authors: Bengsch Bertram , Thimme Robert
Published: January 2019

The success of immune modulation by checkpoint blockade approaches is currently transforming oncology, with high and long-lasting tumor responses in patients with advanced disease across many cancer entities. Rooted in the reinvigoration of adaptive antitumor immune responses through disinhibition of negative feedback pathways, these approaches are particularly effective in patients with significant preexisting T cell responses in tumors with high neoantigen load. While promising data is starting to emerge from clinical trials in liver cancer patients, the underlying immunobiology remains poorly understood. In this review, we discuss the immunological mechanisms underlying the success of current checkpoint blockade therapies and the implications for hepatology including management of immune-related hepatitis. Checkpoint blockade therapy provides novel therapeutic options for difficult-to-treat liver cancers but also novel clinical challenges for hepatologists facing immune-related adverse events.
Stellenwert der Psychoonkologie in der Urologie
Authors: Herschbach Peter
Published: January 2019

Nationale und internationale Behandlungsleitlinien und Zertifizierungskriterien für Krebszentren schließen psychoonkologische Mitbetreuung von belasteten Patienten heute zwingend ein; das gilt selbstverständlich auch für die Uro-Onkologie. Die systematische Feststellung der individuellen Unterstützungsbedürftigkeit in der Praxis soll durch „distress screenings“ bewerkstelligt werden. Während im Allgemeinen von ca. 30 % belasteter Krebspatienten ausgegangen wird (Anteil Patienten mit hohem distress oder psychischer Komorbidität), liegt die Rate bei der größten urologischen Entität, den Prostatakrebspatienten, niedriger (bei ca. 20 %). Der Zugang zu den indizierten Psychotherapien ist für viele Patienten aus persönlichen Gründen schwierig und führt zu relativ hohen Ablehnungsquoten − trotz hoher Belastung. Dies gilt insbesondere für die Uro-Onkologie. Ein entscheidender Faktor ist die Tatsache, dass hier überwiegend ältere Männer betroffen sind, ein Personenkreis, der sich generell schwer tut, eigene Emotionen wahrzunehmen, zu kommunizieren und psychologische Unterstützung in Anspruch zu nehmen. In diesem Zusammenhang werden hohe Anforderungen an die kommunikative Kompetenz des Urologen gestellt.
Endoscopic treatment of Zenker’s diverticulum with Ligasure: simple, safe and effective
Authors: Diez Redondo Pilar , Núñez Rodríguez Henar , de Benito Sanz Marina , Torres Yuste Raúl , Pérez-Miranda Manuel
Published: January 2019

Background and study aims Zenker's diverticulum may cause disabling symptoms, especially in the elderly. Treatment has changed in recent decades from open surgery to management with flexible endoscopy, resulting in lower morbidity and mortality. The goal of this study was to present the largest series, with the longest follow-up, of patients with Zenker's diverticulum receiving outpatient treatment with flexible endoscopy using a diverticuloscope and Ligasure (Covidien, Minneapolis, Minnesota, United States), a device that allows tissue sealing and coagulation of vessels before cutting the septum between the diverticulum and esophagus.

Patients and methods We performed 79 diverticulotomies in 69 patients (65.2 % male, mean age 73.4 years). The mean diverticulum size was 2.8 cm. In three cases with a diverticulum ≤ 1.5 cm, the diverticuloscope could not be placed.

Results The technical success was 95.83 % and the clinical success 96.7 %: 84 % of the 56 patients followed for a mean of 34.6 months (24 – 64 months) had no dysphagia. The recurrence rate was 10.4 %, with a good response to a second diverticulotomy at 12 months (IQR: 11.5 – 17) in most cases. The most severe complications were two microperforations, resolved with conservative treatment, and one case of delayed bleeding endoscopically-controlled with a clip.

Conclusions Diverticulotomy of the esophageal-diverticular septum with Ligasure is an outpatient endoscopic technique that is simple, effective in the long term and very safe for the treatment of patients with Zenker's diverticulum. In symptomatic recurrences, a second procedure was equally safe and effective in most patients.
Efficacy of a novel hemostatic adhesive powder in patients with refractory upper gastrointestinal bleeding: a pilot study
Authors: Park Jin-Seok , Bang Byung Wook , Hong Su Jin , Lee Eunhye , Kwon Kye Sook , Kim Hyung Kil , Shin Yong Woon , Lee Don Haeng
Published: January 2019

Background A new hemostatic adhesive powder (UI-EWD) has been developed to reduce the high re-bleeding rates associated with the currently available hemostatic powders. The current study aimed to assess the efficacy of UI-EWD as a salvage therapy for the treatment of refractory upper gastrointestinal bleeding (UGIB).

Methods A total of 17 consecutive patients who had failed to achieve hemostasis with conventional endoscopic procedures and had undergone treatment with UI-EWD for endoscopic hemostasis in refractory UGIB were prospectively enrolled in the study. We evaluated the success rate of initial hemostasis and rate of re-bleeding within 30 days.

Results All patients underwent successful UI-EWD application at the bleeding site. Initial hemostasis occurred in 16/17 patients (94 %). Re-bleeding within 30 days occurred in 3/16 patients (19 %) who had achieved initial hemostasis. In the second-look endoscopy after 24 hours, hydrogel from UI-EWD was found attached at the bleeding site in 11/16 patients (69 %).

Conclusion UI-EWD has a high success rate for initial hemostasis in refractory UGIB and shows promising results in the prevention of re-bleeding.
Reproducibility of Inert Gas Rebreathing Method to Estimate Cardiac Output at Rest and During Cardiopulmonary Exercise Stress Testing
Authors: Okwose Nduka , Zhang Jie , Chowdhury Shakir , Houghton David , Ninkovic Srdjan , Jakovljević Saša , Jevtic Branislav , Ropret Robert , Eggett Christopher , Bates Matthew , MacGowan Guy , Jakovljevic Djordje
Published: January 2019

The present study evaluated reproducibility of the inert gas rebreathing method to estimate cardiac output at rest and during cardiopulmonary exercise testing. Thirteen healthy subjects (10 males, 3 females, ages 23–32 years) performed maximal graded cardiopulmonary exercise stress test using a cycle ergometer on 2 occasions (Test 1 and Test 2). Participants cycled at 30-watts/3-min increments until peak exercise. Hemodynamic variables were assessed at rest and during different exercise intensities (i. e., 60, 120, 150, 180 watts) using an inert gas rebreathing technique. Cardiac output and stroke volume were not significantly different between the 2 tests at rest 7.4 (1.6) vs. 7.1 (1.2) liters min−1, p=0.54; 114 (28) vs. 108 (15) ml beat−1, p=0.63) and all stages of exercise. There was a significant positive relationship between Test 1 and Test 2 cardiac outputs when data obtained at rest and during exercise were combined (r=0.95, p<0.01 with coefficient of variation of 6.0%), at rest (r=0.90, p<0.01 with coefficient of variation of 5.1%), and during exercise (r=0.89, p<0.01 with coefficient of variation 3.3%). The mean difference and upper and lower limits of agreement between repeated measures of cardiac output at rest and peak exercise were 0.4 (−1.1 to 1.8) liter min−1 and 0.5 (−2.3 to 3.3) liter min−1, respectively. The inert gas rebreathing method demonstrates an acceptable level of test-retest reproducibility for estimating cardiac output at rest and during cardiopulmonary exercise testing at higher metabolic demands.
Muskelsonografie
Authors: Krämer Heidrun , Bulinski Catherine , Habig Kathrin
Published: January 2019

Neben dem Ultraschall peripherer Nerven gewinnt auch die sonografische Beurteilung der Muskulatur bei neuromuskulären Erkrankungen zunehmend an Bedeutung. Muskelultraschall kann gut zum ‚Screening‘ bei neuromuskulären Erkrankungen angewendet werden. Die Darstellung von Faszikulationen mittels Ultraschall im Rahmen der ALS Diagnostik gewinnt immer mehr an klinischer Relevanz. Der strukturelle Muskelultraschall mit der morphologischen Beurteilung der Muskulatur kann als Screeningmethode bei Myopathien und Myositis angewendet werden, Hier ist insbesondere das Verteilungsmuster der pathologischen Muskeln beachtenswert.
Wartezeiten auf die Aufnahme in eine Psychosomatische Klinik – Ergebnisse einer prospektiven Studie in Südwürttemberg
Authors: Wietersheim Jörn von , Knoblauch Jamie Dwayne , Valdes-Stauber Juan , Albani Cornelia , Wachter Martin von , Hartmann Joachim , Rottler Edit , Jarczok Marc , Hölzer Michael , Gündel Harald
Published: January 2019

Hintergrund Wartezeiten auf die Aufnahme in eine psychosomatische Klinik verhindern die akut notwendige Behandlung und können zu verlängerter Arbeitsunfähigkeit und weiterer Chronifizierung führen. Von den meisten psychosomatischen Kliniken werden Wartezeiten berichtet, es existieren bisher jedoch keine Studien und verlässlichen Daten hierzu. Daher war es das Ziel dieser Studie, in einer definierten Region prospektiv zu untersuchen, wie lange es bis zu einem ambulanten Vorgespräch und bis zur Klinikaufnahme dauert. Weiter sollte geprüft werden, ob es externe Faktoren gibt, die diese Dauern beeinflussen.

Methode 7 Kliniken aus der Region Süd-Württemberg nahmen an dieser Untersuchung teil, 2 davon betreiben größere Tagesklinken. Die Daten wurden 2015 über 9 Monate prospektiv erhoben, insgesamt wurden 916 Aufnahmen erfasst. Erfasst wurde die Wartezeit bis zu einem Vorgespräch, in dem die Indikation geprüft wurde, und die Zeit bis zur tatsächlichen Aufnahme in die Klinik.

Ergebnisse Die Wartezeit bis zum ambulanten Vorgespräch betrug im Mittel 25 Tage (SD=31), bis zur Aufnahme nach dem Vorgespräch 56 Tage (SD=47). Insgesamt dauerte es vom Erstkontakt bis zur Aufnahme im Mittel demnach mehr als 10 Wochen. Patienten, die auf einen Tagesklinikplatz warteten, mussten noch länger warten. Ein Dringlichkeitsvermerk durch den Therapeuten des Vorgesprächs sowie eine private Krankenversicherung führten zu etwas kürzeren Wartezeiten. Die Diagnosegruppe hatte keinen Einfluss auf die Wartezeit.

Schlussfolgerungen Die Wartezeiten sind beträchtlich und belasten den Patienten, aber auch das Gesundheitssystem. Es wäre wünschenswert, wenn solche Wartezeiten systematisch erhoben und veröffentlicht würden. Die Politik, aber auch die Handelnden im Gesundheitswesen sollten in einem Gesprächsprozess klären, ob und wie dieser Missstand verändert werden kann.
Künstliche Intelligenz zur diagnostischen Unterstützung ausgewählter seltener lysosomaler Speichererkrankungen: Ergebnisse einer Pilotstudie
Authors: Sieg Anna-Lena , Martin Das Anibh , Maria Muschol Nicole , Köhn Anja , Lampe Christina , Kortum Xiauwei , Mehmecke Sandra , Blöß Susanne , Lechner Werner , Klawonn Frank , Grigull Lorenz
Published: January 2019

Hintergrund Die Diagnosestellung einer seltenen Stoffwechselerkrankung stellt eine Herausforderung für Familien und betreuende Ärzte dar. Um den Weg zur Diagnose zu unterstützen, wurde ein diagnostisches Werkzeug entwickelt, welches die Erfahrungen Betroffener nutzt.

Methoden 17 Interviews mit Eltern oder Betroffenen einer ausgewählten, seltenen Stoffwechselerkrankung (Mukopolysaccharidose (MPS), M. Fabry und M. Gaucher) wurden durchgeführt. Die Ergebnisse wurden in diagnostischen Fragebogen abgebildet. Die Fragebogen wurden verteilt und von Eltern oder Betroffenen mit einer gesicherten Diagnose einer MPS, eines M. Fabry oder eines M. Gaucher beantwortet. Vier kombinierte Data Mining Klassifikatoren wurden trainiert, um in den beantworteten Fragebogen Antwortmuster zu finden.

Ergebnisse Das binäre Data Mining System wurde mit 56 Fragebogen trainiert und erzielte eine Anzahl von 91% richtigen Diagnosen für die Diagnose ‚MPS’. Weitere 20 Fragebogen, die nicht Teil des Trainingsdatensatzes waren, konnten als ein erster prospektiver Test ausgewertet werden. Das System erkannte bei diesen 20 Fragebogen 18 bzw. 90% korrekte Diagnosen.

Diskussion und Schlussfolgerung Fragebogen zur Diagnoseunterstützung basierend auf Interviews mit Eltern und Betroffenen wurden entwickelt und Antwortmuster durch Data Mining Verfahren ausgewertet. Diese vorläufigen Ergebnisse illustrieren, dass Data Mining Systeme Muster in Fragebogen erkennen können. Dieser Ansatz könnte zukünftig hilfreich bei der Erkennung ausgewählter Stoffwechselerkrankungen sein.
Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MR-HIFU): Overview of Emerging Applications (Part 2)
Authors: Siedek Florian , Yeo Sin Yuin , Heijman Edwin , Grinstein Olga , Bratke Grischa , Heneweer Carola , Puesken Michael , Persigehl Thorsten , Maintz David , Grüll Holger
Published: January 2019

Background High-intensity focused ultrasound (HIFU) allows noninvasive heating of deep-seated tissues. Guidance under magnetic resonance imaging (MR-HIFU) offers spatial targeting based on anatomical MR images as well as MR-based near-real-time temperature maps. Temperature feedback allows delivery of a well-defined thermal dose enabling new applications such as the ablation of malignant tissue.

Methods Peer-reviewed publications on MR-HIFU were studied and are summarized in this review. Literature was restricted to applications in oncology.

Results Several MR-HIFU-based applications for the treatment of malignant diseases are currently part of clinical trials or translational research. Recent trials regarding the treatment of prostate cancer with MR-HIFU have already shown this to be a safe and patient-friendly method. For the treatment of breast cancer and malignancies within abdominal organs, MR-HIFU has been applied so far only in proof of concept studies.

Conclusion MR-HIFU is currently being investigated for the ablative treatment of malignant tissue in a variety of oncological applications. For example, the transrectal as well as transurethral ablation of prostate cancer using MR-HIFU was shown to be a patient-friendly, safe alternative to other local treatment options with low side effects.

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Citation Format
Association of ACE I/D Polymorphism with Risk of Diabetes in Cardiovascular Disease Patients
Authors: Hussain Misbah , Abbas Shahid , Bilal Ahmed , Aslam Muhammad Naeem , Awan Fazli Rabbi
Published: January 2019

Angiotensin converting enzyme (ACE), as part of renin angiotensin aldosterone system, is involved in blood pressure regulation and control several physiological functions. Insertion/Deletion (I/D) polymorphism of ACE has pronounced effects on development of metabolic diseases like diabetes, cardiovascular diseases (CVDs) and hypertension. However, association of I/D polymorphism with risk of diabetes in CVD patients is not known. The aim of present study was to check the association of ACE I/D polymorphism with risk of diabetes in subjects with CVD. For this, 531 subjects were sampled and divided into 3 groups; G1-H (healthy controls, n=117), G2-CN (cardiac patients without diabetes, n=271) and G3-CD (cardiac patients with diabetes, n=143). Genotyping of ACE I/D polymorphism was done by polymerase chain reaction. Allelic and genotypic frequencies were in Hardy Weinberg Equilibrium (χ2=0.11, p>0.05) and revealed high prevalence of I allele (55%) among all groups. However, II genotype was more common (37%) in G3-CD group. Level of glucose was also higher in subjects with II genotype than DD genotype (12.6±6.3 mmol/L vs. 9.7±5.1 mmol/L). Logistic regression analysis revealed that ACE II genotype increase the risk of diabetes in CVD patients by ~2 times [OR=1.94, CI: 1.24–3.01, p=0.03]; however, this association did not reach the significance level when adjusted for age and gender. In conclusion, ACE I/D polymorphism influence the risk of diabetes in CVD patients and ACE II increases this risk by ~2 fold.
EFSUMB Position Paper: Recommendations for Gastrointestinal Ultrasound (GIUS) in Acute Appendicitis and Diverticulitis
Authors: Dirks Klaus , Calabrese Emma , Dietrich Christoph , Gilja Odd , Hausken Trygve , Higginson Antony , Hollerweger Alois , Maconi Giovanni , Maaser Christian , Nuernberg Dieter , Nylund Kim , Pallotta Nadia , Ripolles Tomas , Romanini Laura , Saftoiu Adrian , Serra Carla , Wüstner Matthias , Sporea Ioan
Published: January 2019

An interdisciplinary task force of European experts summarizes the value of gastrointestinal ultrasound (GIUS) in the management of acute appendicitis and diverticulitis. Based on an extensive literature review, clinical recommendations for these highly common diseases in visceral medicine are presented.

In patients with acute appendicitis, preoperative sonography has been established as a routine procedure in most European countries for medical and legal reasons. Routine sonography in these patients may reduce the rate of unnecessary surgery by half. The sensitivity, specificity, and accuracy of ultrasound reach values above 90 % and are equivalent to CT and MRI. However, the high operator dependence may be a problem, for example in point-of-care ultrasound in emergency departments. Structured training programs, quality controls and standardized ultrasound reporting should be increasingly implemented.

In the case of suspected acute diverticulitis, “ultrasound first” should also be a basic element in the approach to all patients. Sonography can confirm the diagnosis and allows early risk stratification. As treatment strategies have become less aggressive and more tailored to the stage of diverticulitis, accurate staging has become increasingly important. GIUS and CT have proven to have similar sensitivity and specificity. Especially in cases of uncomplicated diverticulitis, GIUS will be the one and only imaging procedure. CT may work as a backup and has particular advantages for diverticulitis located in the distal sigmoid, inflammation deep in the small pelvis and insufficient ultrasound scanning conditions. This step-up approach (ultrasound first and CT only in case of a negative or inconclusive ultrasound result) has proven to yield the best accuracy.
Effect of Artemisia Aucheri.L and Bupivacaine Encapsulated Nanoparticles on Nociceptive Pain
Authors: Moradkhani Mahmoud Reza , Karimi Arash
Published: January 2019

Aim The purpose of this study was to evaluate the antinociceptive interaction between bupivacaine and Artemisia aucheri. L encapsulated nanoparticles.

Methods and materials The effect of bupivacaine and Artemisia aucheri.L alone, and their encapsulated co-administration was assessed using the 3% formalin test in rat. Increasing doses of bupivacaine (31.6, 100, 178, and 316 mg/kg) or Artemisia aucheri.L (5.6, 10, 17.8, and 31.6 mg/kg) were given i.p. 10 min before 3% formalin administration.

Results The possible mechanism(s) of action were analyzed for the encapsulated co-administration, naloxone (1 mg/kg) and N (G)-nitro-L-arginine methyl ester (L-NAME) (3 mg/kg) were used. Interaction index and isobolographic analysis and the demonstrated a synergistic effect. The experimental ED30 was lower as compared with theoretical ED30. Naloxone was shown to reduce the antinociceptive effect of the encapsulated co-administration.

Discussion These data suggest that the bupivacaine and Artemisia aucheri.L encapsulated nanoparticles gave a synergistic effect.
Analysis of Terpenes in Cannabis sativa L. Using GC/MS: Method Development, Validation, and Application
Authors: Ibrahim Elsayed , Wang Mei , Radwan Mohamed , Wanas Amira , Majumdar Chandrani , Avula Baharthi , Wang Yan-Hong , Khan Ikhlas , Chandra Suman , Lata Hemant , Hadad Ghada , Abdel Salam Randa , Ibrahim Amany , Ahmed Safwat , ElSohly Mahmoud
Published: January 2019

Terpenes are the major components of the essential oils present in various Cannabis sativa L. varieties. These compounds are responsible for the distinctive aromas and flavors. Besides the quantification of the cannabinoids, determination of the terpenes in C. sativa strains could be of importance for the plant selection process. At the University of Mississippi, a GC-MS method has been developed and validated for the quantification of terpenes in cannabis plant material, viz., α-pinene, β-pinene, β-myrcene, limonene, terpinolene, linalool, α-terpineol, β-caryophyllene, α-humulene, and caryophyllene oxide. The method was optimized and fully validated according to AOAC (Association of Official Analytical Chemists) guidelines against reference standards of selected terpenes. Samples were prepared by extraction of the plant material with ethyl acetate containing n-tridecane solution (100 µg/mL) as the internal standard. The concentration-response relationship for all analyzed terpenes using the developed method was linear with r2
values > 0.99. The average recoveries for all terpenes in spiked indoor cultivated samples were between 95.0 – 105.7%, with the exception of terpinolene (67 – 70%). The measured repeatability and intermediate precisions (% relative standard deviation) in all varieties ranged from 0.32 to 8.47%. The limit of detection and limit of quantitation for all targeted terpenes were determined to be 0.25 and 0.75 µg/mL, respectively. The proposed method is highly selective, reliable, and accurate and has been applied to the simultaneous determination of these major terpenes in the C. sativa biomass produced by our facility at the University of Mississippi as well as in confiscated marijuana samples.
Epitympanic Diaphragm: Endoscopic Functional Tympanoplasty
Authors: Boddepalli Sreerama , Boddepalli Rajesh
Published: January 2019

Background Simple closure of tympanic membrane perforation is not a successful myringoplasty. It has to obey a lot of functional aspects of the middle ear cleft. Certain factors play a role in failure cases. The endoscopic functional myringoplasty or tympanoplasty is a clear visualization of all the parts of the middle ear; examination and removal of the disease from the hidden parts of the middle ear, examination of inter-attico-tympanic diaphragm; and removal of blocks, if any, in isthmus, to reestablish the gas exchange pathways and finally preserve the middle ear mucosa at maximum to further restore the ventilation.

Methods Endoscopic tympanoplasty was performed in 100 patients with large tympanic membrane perforations and patent eustachian tube, using 4-mm “0” and “45” degree endoscopes by proper visualization of the tympanic diaphragm and isthmus in every patient and clearing its blockage if present.

Results Among the 100 patients, 78 had epitympanic diaphragm blockage at the level of isthmus, 5 patients were found with closed tensor tympani folds, both vertical and horizontal without any ventilatory routes in them. Although in all the patients the eustachian tube was patent, we found majority of them had a dysventilation at the level of the epitympanic diaphragm. Thus, by performing endoscopic ventilatory pathway clearance and tympanoplasty, we achieved 94% positive results.

Conclusion Epitympanic diaphragm is a functional barrier between upper and lower compartments of the middle ear cleft, which play important role in the ventilation and partial pressure regulation, blockage of its isthmus may lead to tympanic membrane retractions and perforations. With the aid of endoscopes of various degrees, removing any pathological blocks, recreating proper ventilation, reestablishing gas exchange mechanism, and maximum preservation of normal mucosa for the gas exchange are the aims of an endoscopic functional tympanoplasty procedure.
Bromine-Radical-Mediated Site-Selective Allylation of C(sp3)–H Bonds
Authors: Ueda Mitsuhiro , Maeda Ayami , Hamaoka Kanako , Sasano Mika , Fukuyama Takahide , Ryu Ilhyong
Published: January 2019

The C(sp3)–H allylation of alkanes is investigated by using allyl bromides under radical reaction conditions. In many cases, methine C–H allylation preceded methylene and methyl C–H allylation with complete or a high degree of site selectivity. The C–H allylation of allylic compounds, such as allylbenzene, gives 1,5-dienes with the SH2′ reactions of the allyl radicals occurring at the less hindered carbon.
Metal Enolates – Enamines – Enol Ethers: How Do Enolate Equivalents Differ in Nucleophilic Reactivity?
Authors: Leonov Artem , Timofeeva Daria , Ofial Armin , Mayr Herbert
Published: January 2019

The kinetics of the reactions of trimethylsilyl enol ethers and enamines (derived from deoxybenzoin, indane-1-one, and α-tetralone) with reference electrophiles (p-quinone methides, benzhydrylium and indolylbenzylium ions) were measured by conventional and stopped-flow photometry in acetonitrile at 20 °C. The resulting second-order rate constants were subjected to a least-squares minimization based on the correlation equation lg k = s
N(N + E) for determining the reactivity descriptors N and s
N of the silyl enol ethers and enamines. The relative reactivities of structurally analogous silyl enol ethers, enamines, and enolate anions towards carbon-centered electrophiles are determined as 1, 107, and 1014, respectively. A survey of synthetic applications of enolate ions and their synthetic equivalents shows that their behavior can be properly described by their nucleophilicity parameters, which therefore can be used for designing novel synthetic transformations.
Synthesis and Evaluation of Cyclic Acetals of Serine Hydroxylamine for Amide-Forming KAHA Ligations
Authors: Baldauf Simon , Bode Jeffrey
Published: January 2019

The α-ketoacid–hydroxylamine (KAHA) ligation allows the coupling of unprotected peptide segments. The most widely used variant employs a 5-membered cyclic hydroxylamine that forms a homoserine ester as the primary ligation product. While very effective, monomers that give canonical amino acid residues are in high demand. In order to preserve the stability and reactivity of cyclic hydroxylamines, but form a canonical amino acid residue upon ligation, we sought to prepare cyclic derivatives of serine hydroxylamine. An evaluation of several cyclization strategies led to cyclobutanone ketals as the leading structures. The preparation, stability, and amide-forming ligation of these serine-derived ketals are described.
Kinetically Controlled Fischer Glycosidation under Flow Conditions: A New Method for Preparing Furanosides
Authors: Masui Seiji , Manabe Yoshiyuki , Hirao Kohtaro , Shimoyama Atsushi , Fukuyama Takahide , Ryu Ilhyong , Fukase Koichi
Published: January 2019

Kinetically controlled Fischer glycosidation was achieved under flow conditions. β-Hydroxy-substituted sulfonic acid functionalized silica (HO-SAS) was used as an acid catalyst. This reaction directly converted aldohexoses into kinetically favored furanosides to enable the practical synthesis of furanosides. After optimization of the reaction temperature and residence time, glucofuranosides, galactofuranosides, and mannofuranosides were synthesized in good yields.
Asymmetric Synthesis of Chiral 1,3-Dimethyl Units Through a Double Michael Reaction of Nitromethane and Crotonaldehyde Catalyzed by Diphenylprolinol Silyl Ether
Authors: Hayashi Yujiro , Toda Shunsuke
Published: January 2019

An efficient synthetic route to install chiral 1,3-dimethyl units through a double Michael reaction of crotonaldehyde and nitromethane catalyzed by diphenylprolinol silyl ether is developed. Either 1,3-syn- or 1,3-anti-dimethyl units are obtained selectively depending on the enantiomer of the diphenylprolinol silyl ether catalyst used. The side chain of pneumocandin B0 is synthesized enantioselectively by using the present method as a key step.
Complementary Reactivity of 1,6-Enynes with All-Metal Aromatic Trinuclear Complexes and Carboxylic Acids
Authors: Cecchini Chiara , Lanzi Matteo , Cera Gianpiero , Malacria Max , Maestri Giovanni
Published: January 2019

The distinct reactivity of 1,6-enynes in the presence of a trinuclear metal complex activated by a carboxylic acid is presented. The triplatinum catalyst enables the cyclization of the substrate and subsequent incorporation of a nucleophile in the final product. In contrast, sequential cyclization/double bond shift occurs under analogous conditions in the presence of the corresponding tripalladium complex.
Electrochemical Synthesis of 2-Hydroxy-para-terphenyls by Dehydrogenative Anodic C–C Cross-Coupling Reaction
Authors: Lips Sebastian , Franke Robert , Waldvogel Siegfried R.
Published: January 2019

The anodic C–C cross-coupling reaction provides fast access to a wide range of bi- and terarylic scaffolds by electrochemically mediated arylation reactions. Herein, a metal- and reagent-free electrosynthetic protocol for the synthesis of nonsymmetrical 2-hydroxy-para-teraryl derivatives is presented for the first time. It is scalable, easy to conduct, and allows the use of a broad variety of different functional groups.
Copper-Catalyzed Decarboxylative N-Arylation of Indole-2-carboxylic Acids
Authors: Zhang Yan , Hu Zhe-Yao , Li Xin-Chang , Guo Xun-Xiang
Published: January 2019

A novel decarboxylative N-arylation of indole-2-carboxylic acids with aryl halides is developed. The reaction proceeds efficiently in the presence of Cu2O as the catalyst to give the corresponding N-aryl indoles in high yields. This synthetic method shows good functional group tolerance and offers an alternative route to construct N-aryl indoles.
2-Zincoethylzincation of 2-Alkynylamines and 1-Alkynylphosphines Catalyzed by Titanium(IV) Isopropoxide and Ethylmagnesium Bromide
Authors: Kadikova Rita , Ramazanov Ilfir , Mozgovoi Oleg , Gabdullin Azat , Dzhemilev Usein
Published: January 2019

Titanium(IV) isopropoxide and ethylmagnesium bromide catalyzed reaction of 2-alkynylamines with Et2Zn, followed by deuterolysis/hydrolysis and iodinolysis, affords substituted (Z)-pent-2-en-2,5-d
2-1-amines, (Z)-pent-2-en-1-amines (65–88%), and substituted (Z)-2,5-diiodopent-2-en-1-amines (55–63%). It is suggested that the reaction proceeds through the formation of cyclic organotitanium derivatives. The reaction between 1-alkynylphosphines and Et2Zn in the presence of catalytic amounts of Ti(O-iPr)4 and EtMgBr leads to trisubstituted 1-alkenylphosphine oxides with high regioselectivity and stereoselectivity.
Bell's Palsy: A Need for Paradigm Shift?
Authors: Jain Shraddha , Kumar Sunil
Published: January 2019

Introduction Bell's palsy (BP) is considered to be idiopathic facial palsy. Some schools of thought believe it to be a part of polyneuropathy, whereas other scientists have other plausible explanations for the condition and all these were reviewed.

Methods The literature on BP was retrieved using the Cochrane Database of Systematic Reviews, PubMed, and Google Scholar. Keywords and phrases used during the search included “Bell's palsy,” “polyneuropathy,” “anatomical factors,” and “autoimmunity.”

Results There are only few studies that have tried to find out the association of BP with peripheral nerve conduction abnormalities. In most studies conducted, positive correlation was found. There are many theories of its etiology, with the reactivation of herpes simplex virus isoform 1 and/or herpes zoster virus (HZV) from the geniculate ganglia being the most strongly suspected cause.

Conclusion In the future, large studies will be required to determine the association between peripheral neuropathy and BP and elucidate the real etiology in every case. There will also be a need to determine whether BP should still be considered idiopathic and isolated.
Effect of Silver Nitrate and Epidermal Growth Factor on Nonhealing Tympanic Membrane Perforations: A Randomized Controlled Study
Authors: Bhat Vikram , Veetil Bijiraj , Mathad Vidyashree
Published: January 2019

Introduction Most tympanic membrane perforations in chronic otitis media require surgical myringoplasty for closure. This study aimed to find out a simple nonsurgical outpatient procedure to close these perforations that could reduce the hospital stay, medical cost, and morbidity in these patients.

Materials and Methods The study was conducted in a tertiary referral hospital in a single-blind randomized controlled trial design with two groups, each with a sample size of 40 ears. Only small-size central nonhealing traumatic and chronic otitis media perforations were recruited. Pure tone audiometry and otomicroscopy were performed in all eligible patients who consented to take part in the study. Group 1 was treated with silver nitrate chemical cautery alone. Group 2 received epidermal growth factor gel application in addition to chemical cautery. Both the groups were followed up for a minimum period of 3 months. The same investigations were performed during follow-up.

Results and Observations The outcome was considered a success whether there was closure of perforation or reduction in the size of perforation. The success rate of these nonhealing perforations was found to be significantly higher in group 2 (71.42%) than in group 1 (47.36%). Hearing gain was observed in closed perforations of both the groups.

Conclusion Epidermal growth factor application enhances the healing effect of silver nitrate in small nonhealing tympanic membrane perforations. The encouraging results of epidermal growth factor have vast applications in improving outcomes of surgical myringoplasty and treatment of residual perforations remaining after the same.
Preauricular Transzygomatic Approach for Infratemporal Fossa and Surrounding Skull Base Lesion: An Institutional Experience
Authors: Jain Rajat , Keshri Amit , Manogaran Ravi , Kumar Raj , Keeranghat Pearly
Published: January 2019

Background Preauricular transzygomatic surgical approach (PTZA) can be used to approach and resect tumors of infratemporal fossa (ITF) and surrounding skull base lesion. Various modifications in this approach can be used to approach various critical areas such as cavernous sinus, sphenoid sinus.

Materials and Methods Clinical charts were reviewed to determine the association among pathological variables, surgical procedures, and outcomes.

Results Three out of seven were malignant tumors and required pterional craniotomy and postoperative radiotherapy. 4 out of 7 were benign tumors and required craniofacial osteotomies.

Conclusion PTZA is a versatile approach for tumor of ITF with or without intracranial extradural extension and cosmetically better than other approaches. This approach is better suited for lateral ITF tumors that are difficult to access through endoscopic approaches.
Surveillance, Epidemiology, and End Results (SEER) and SEER-Medicare Databases: Use in Clinical Research for Improving Colorectal Cancer Outcomes
Authors: Daly Meghan , Paquette Ian
Published: January 2019

The Surveillance, Epidemiology, and End Results (SEER) program is a clinical database, funded by the National Cancer Institute (NCI), which was created to collect cancer incidence, prevalence, and survival data from U.S. cancer registries. By capturing approximately 30% of the U.S. population, it serves as a powerful resource for researchers focused on understanding the natural history of colorectal cancer and improvement in patient care. The linked SEER-Medicare database is a robust database allowing investigators to perform studies focusing on health disparities, quality of care, and cost of treatment in oncologic disease. Since its infancy in the early 1970s, the database has been utilized for thousands of studies resulting in novel publications that have shaped our management of colorectal cancer among other malignancies.
Vocal Fold Polyps: Literature Review
Authors: Vasconcelos Daniela , Gomes Adriana , Araújo Cláudia
Published: January 2019

Introduction Vocal fold polyps are one of the most frequent benign laryngeal lesions, impacting the quality of life of those affected by them, primarily the vocal production. Despite being a well-established therapy in conjunction with surgery, speech therapy alone may also be effective in treating these lesions. As such, otolaryngologists and speech therapists need updated bibliographic knowledge on the issue.

Objective To describe the literature findings on vocal fold polyps that discuss prevalence, etiology, histology, physiopathology, vocal characteristics or treatment.

Data Synthesis The present study is a review article based on a bibliographic search using platforms, databases and search engines, with no restrictions on means of publication, methodological quality or language. All the articles on vocal fold polyps pertaining to the object of study published in the past 15 years were included. Among the characteristics investigated, the most discussed were prevalence of men, smoking as an etiological cofactor, the possibility of histological differentiation from vocal nodules, the relationship with cover minor structural alterations, and the indication and effectiveness of different treatment options.

Conclusion Despite the discrepancies found in the present literature review on vocal fold polyps, there has been a notable scientific progress in the otolaryngologic techniques and in the effectiveness of speech therapy as initial treatment, with direct and indirect techniques, corroborating the need for scientific investigation of the issue.
Evaluation of Eustachian Tube Function in Mucosal Chronic Otitis Media: A Cost-Effective Method for Developing Countries
Authors: Bhat Vikram , Marimuthu Gowri , Herur Kiran , Yadav Mona
Published: January 2019

Background In the developing nations, the sinonasal region is routinely screened in chronic otitis media, but Eustachian tube is not as it is not cost-effective. Hence, we innovated an inexpensive device named Eustachian barotubometer.

Materials and Methods A prospective case–control study was performed on ­mucosal type of chronic otitis media and traumatic tympanic perforation (100 cases each). Eustachian tube function was assessed by the Eustachian barotubometer (forced and physiological opening) and nasopharyngoscopy.

Results Eustachian tube dysfunction was found to be five times higher in cases than controls. Both forced opening function and physiological opening function were ­poorer in cases than controls. However, the difference was statistically significant only in physiological opening function (p = 0.003). Among the cases with dysfunctional tubes, 86.7% were hypofunctional, whereas 13.3% were totally blocked.

Conclusion Eustachian tube function was affected in 15% of cases of mucosal ­chronic otitis media as compared with controls in this study. This novel device could be ­conveniently used to help decide the right time to undertake middle ear surgery.
Investigation of the Origin of Voltage Generation in Potentized Homeopathic Medicine through Raman Spectroscopy
Authors: Bhattacharya Tara , Maitra Payaswini , Bera Debbethi , Das Kaushik , Bandyopadhyay Poonam , Das Sukhen , Shankar Bhar Durga , Singha Achintya , Nandy Papiya
Published: January 2019

Background For the study of homeopathic medicines in proper perspective, emerging techniques in material science are being used. Vibrational spectroscopy is one such tool for providing information on different states of hydrogen bonding as an effect of potentization. The associated change in electrical properties is also correlated with this effect.

Objective From the vibrational spectra, the changes in hydrogen bonding due to dilution followed by unidirectional vigorous shaking (together termed potentization) of 91% ethanol and two homeopathic medicines Chininum purum and Acidum benzoicum have been studied. The aim was to correlate the result with the change in the electrical properties of the system.

Methods Raman spectroscopy was used to study the vibrational spectra. A U-shaped glass tube (electrochemical cell), where one arm contained bi-distilled water and the other arm alcohol/homeopathic medicine (the arms being separated by a platinum foil), was used to measure the voltage generated across two symmetrically placed platinum electrodes.

Results For all samples, it was observed that potentization affected the intensity of OH stretching bands at the frequencies 3240 cm−1, 3420 cm−1 and 3620 cm−1, corresponding to strong hydrogen bond, weak hydrogen bond and broken hydrogen bond, respectively. With the increase in potency, in the presence and absence of the two medicines in ethanol, the number of OH groups linked by strong hydrogen bonds decreased, while the number of OH groups with weak hydrogen bonds increased. With the increase in potentization, the number of OH groups with broken hydrogen bonds showed a difference in the presence and absence of the medicine.

The voltage measurements for ethanol show that, with succussion, the magnitude of voltage increased with the two medicines at lower potencies, but not at higher potency where the voltage is lower. Acidum benzoicum, which is acidic in nature, had higher voltage values (113mV, 130 mV and 118 mV at 6C, 30C and 200C, respectively), compared with Chininum purum, which is basic in nature (20 mV, 85 mV and 65 mV at 6C, 30C and 200C, respectively).

Conclusion The experimental results indicate a correlation between the vibrational and electrical properties of the homeopathic medicines Acidum benzoicum and Chininum purum at different potencies.
Complications and Long-Term Outcome in 16 Canine Cementless Hybrid Hip Arthroplasties
Authors: Matiasovic Matej , Steger Helmut , Böttcher Peter , Bayer Karol
Published: January 2019

Objective The purpose of this study was to retrospectively evaluate the complications and long-term outcomes of total hip arthroplasty (THA) using a hybrid cementless system.

Materials and Methods Medical records of dogs that underwent THA using a combined implant system consisting of Innoplant Screw Cup, Kyon taper head and Zurich cementless (Z-THA) stem between March 2010 and March 2015 were reviewed. Dogs with a minimum follow-up of 2 years were included. Signalment, complications and outcome at the latest follow-up examination were recorded.

Results Sixteen hybrid THA were performed in 12 dogs. Mean follow-up was 42.5 months. Overall complications occurred in three arthroplasties (19%) including luxation (n = 1), aseptic cup loosening (n = 1) and implant failure with screw breakage followed by stem subsidence (n = 1). Two arthroplasties including prosthesis luxation and aseptic cup loosening were successfully revised using the here described hybrid system and achieved full functional outcome at the last follow-up examination. One arthroplasty with screw breakage and secondary stem subsidence was treated conservatively and achieved an acceptable outcome.

Conclusion Hybridization of the Innoplant Screw Cup, Kyon taper head and Zurich cementless for initial THA surgery is feasible. In comparison with the reported complications and outcomes for single implant THA systems, the hybrid THA did not prove to have greater clinical benefits for use in primary THA surgery.
Technique and Outcome of a Modified Tibial Plateau Levelling Osteotomy for Treatment of Concurrent Medial Patellar Luxation and Cranial Cruciate Ligament Rupture in 76 Stifles
Authors: Beale Brian , Hudson Caleb , Flesher Kathryn
Published: January 2019

Objectives The main aim of this article is to describe the technique and outcome of a modified tibial plateau levelling osteotomy (TPLO) that simultaneously levels the tibial plateau and realigns the quadriceps mechanism through medial translation of the proximal tibial segment in dogs less than 15 kg.

Materials and Methods A retrospective medical records search identified dogs with concurrent cranial cruciate ligament rupture (CCLR) and medial patellar luxation (MPL). A study group (76 stifles) treated with a modified TPLO was compared with a non-tibial translation group (45 stifles) corrected with traditional surgical technique. Signalment, arthroscopic findings, adjunctive surgical procedures, osteotomy healing time and complications were recorded. Tibial plateau angle, proximal tibial segment medialization, width of the tibial osteotomy, mechanical medial proximal tibial angle and mechanical medial distal tibial angle were measured and recorded on preoperative and postoperative radiographs.

Results Overall complication rate was 18.4% in the treatment group and 28.9% in the non-tibial translation group. Reluxation occurred in 6.6% of cases in the study group and in 8.8% of cases in the non-tibial translation group. There was no statistical difference in healing time between groups.

Clinical Significance A modified TPLO can be used to treat patients with concurrent MPL and CCLR with good clinical outcome. Complication rates are comparable to traditional repairs for MPL. No major differences were appreciated between study and a non-tibial translation groups for variables compared.
Diagnosis and Management of Borderline Hip Dysplasia and Acetabular Retroversion
Authors: Holland Tai , Thomas-Aitken Holly , Goetz Jessica , Willey Michael
Published: January 2019

Borderline hip dysplasia and acetabular retroversion are common radiographic findings in young individuals with and without hip pain. Orthopaedic surgeons should be knowledgeable about the radiographic findings, diagnosis, and appropriate nonsurgical and surgical treatment of these conditions. Borderline hip dysplasia is generally defined by a lateral center edge angle of Wiberg from 20 to 25° (some define as 18–25°) and is a cause of joint microinstability. The degree of soft tissue laxity can have significant implications for joint stability in patients with borderline hip dysplasia. The most common presenting symptoms are groin pain and lateral hip pain. Acetabular retroversion is defined by radiographic findings of crossover sign, ischial spine sign, and posterior wall sign. Individuals with symptomatic retroversion have a clinical presentation consistent with impingement, groin pain with flexion activities, and less commonly lateral hip pain. Physical therapy has been shown to improve symptoms in a subset of individuals with these conditions. There are multiple recent publications about arthroscopic treatment of patients with borderline hip dysplasia. These reports generally find that good short-term outcomes can be expected when using arthroscopic techniques that include labral preservation/repair and capsular plication. There are limited reports of periacetabular osteotomy as a treatment for borderline hip dysplasia. Publications focusing specifically on surgical treatment of acetabular retroversion are also infrequent. Periacetabular osteotomy has been shown to have superior long-term clinical outcomes to surgical hip dislocation with anterior rim trimming in patients with all three radiographic findings of retroversion. Arthroscopic treatment has been shown to have good short-term outcomes. Future work in the areas of borderline hip dysplasia and acetabular retroversion should focus on reporting long-term clinical follow-up of these surgical treatments and using computation techniques as a tool to determine appropriate surgical and nonsurgical treatment for each individual patient.