Publications by authors named "Michael Koch"

461 Publications

[Salvage laryngectomy after primary radio- and radiochemotherapy : A retrospective study. German version].

HNO 2021 Apr 9. Epub 2021 Apr 9.

Hals-Nasen-Ohrenklinik, Kopf- und Hals-Chirurgie, Universitätskliniken Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Waldstraße 1, 91054, Erlangen, Deutschland.

Background: Recurrent and residual laryngeal cancer after organ-preserving radio- or radiochemotherapy is associated with a poor prognosis. Salvage surgery is the most important therapeutic option in these cases.

Objective: The study assessed rates of recurrence and residual tumor as well as survival and complication rates after salvage laryngectomy at the authors' academic cancer center.

Materials And Methods: A retrospective examination of all patients receiving laryngectomy between 2001 and 2019 due to tumor residuals or recurrence after primary radio- and radiochemotherapy was conducted.

Results: A total of 33 salvage procedures were performed. Defect reconstruction was performed by free flap surgery in 30.3% (n = 10) and regional flap surgery in 15.2% (n = 5) . One patient received regional flap surgery and free flap surgery simultaneously. Overall survival after 1, 2, and 5 years was 68.7, 47.9, and 24.2%, and disease-free survival was 81.6, 47.8, and 24.2%, respectively, with 48.5% (n = 16) postoperative tumor recurrences overall. Disease-free survival was significantly shorter for tumor extension into or onto the hypopharynx (p = 0.041). Postoperatively, 72.7% of patients developed a pharyngocutaneous fistula, of which 24.2% required surgical treatment. The hospital stay was 28.0 ± 16.1 days.

Conclusion: Salvage laryngectomy is associated with a high rate of treatable complications and high morbidity. Nevertheless, considering the advanced tumor stages treated, it allows for respectable oncological results.
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http://dx.doi.org/10.1007/s00106-021-01029-wDOI Listing
April 2021

Histopathological comparison of pleomorphic adenomas of the parotid and submandibular gland.

Oral Dis 2021 Mar 26. Epub 2021 Mar 26.

Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

Objective: The aim of this study was to investigate and compare the histopathological findings in pleomorphic adenomas (PA) of the parotid and submandibular gland with emphasis on the histological subtype and capsular characteristics.

Materials And Methods: The histopathological specimens of all patients with PAs of the parotid and submandibular gland between 2000 and 2020 were re-examined by an experienced head and neck pathologist. Patients without representative slides allowing evaluation of the whole periphery of the PA were excluded from our study sample.

Results: Nine hundred and thirty-four patients formed our study sample (327 men, 607 women, male-to-female ratio: 0.53:1). Eight hundred and forty-four cases had a PA in the parotid gland and the remaining 90 in the submandibular gland. Our comparative analysis showed that submandibular PAs are characterized by the consistent presence of an intact anatomical capsule, infrequent occurrence of pseudopodia and satellite nodules, and a low proportion of the high-risk myxoid subtype.

Conclusion: Our study highlights significant differences between PAs of the parotid and submandibular glands in their histopathological characteristics. Their differences likely underlie the favorable surgical outcome observed in PAs of the submandibular glands and may explain the propensity of PAs of the parotid glands for local recurrences.
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http://dx.doi.org/10.1111/odi.13858DOI Listing
March 2021

Long-term live imaging and multiscale analysis identify heterogeneity and core principles of epithelial organoid morphogenesis.

BMC Biol 2021 Feb 24;19(1):37. Epub 2021 Feb 24.

Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany.

Background: Organoids are morphologically heterogeneous three-dimensional cell culture systems and serve as an ideal model for understanding the principles of collective cell behaviour in mammalian organs during development, homeostasis, regeneration, and pathogenesis. To investigate the underlying cell organisation principles of organoids, we imaged hundreds of pancreas and cholangiocarcinoma organoids in parallel using light sheet and bright-field microscopy for up to 7 days.

Results: We quantified organoid behaviour at single-cell (microscale), individual-organoid (mesoscale), and entire-culture (macroscale) levels. At single-cell resolution, we monitored formation, monolayer polarisation, and degeneration and identified diverse behaviours, including lumen expansion and decline (size oscillation), migration, rotation, and multi-organoid fusion. Detailed individual organoid quantifications lead to a mechanical 3D agent-based model. A derived scaling law and simulations support the hypotheses that size oscillations depend on organoid properties and cell division dynamics, which is confirmed by bright-field microscopy analysis of entire cultures.

Conclusion: Our multiscale analysis provides a systematic picture of the diversity of cell organisation in organoids by identifying and quantifying the core regulatory principles of organoid morphogenesis.
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http://dx.doi.org/10.1186/s12915-021-00958-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903752PMC
February 2021

Angiotensin II-induced drinking behavior as a method to verify cannula placement into the cerebral ventricles of mice: An evaluation of its accuracy.

Physiol Behav 2021 Apr 26;232:113339. Epub 2021 Jan 26.

Institute for Pharmacology and Toxicology, Otto von Guericke University Magdeburg, Leipziger Straße 44, D-39120 Magdeburg, Germany; Center for Behavioral Brain Sciences, Otto von Guericke University Magdeburg, Leipziger Straße 44, D-39120 Magdeburg, Germany.

Background: Intracerebroventricular (icv) injections are frequently used in neuroscience research. In addition to histological verification of the injection sites, administration of angiotensin II (ANG II) is often used to verify the injection placements. ANG II is a peptide hormone exerting dipsogenic effects, i.e., it increases drinking, when administered into the cerebral ventricles. This study investigated the accuracy of ANG II-induced drinking as a method to verify icv cannula placements.

Methods: Male C57BL/6J mice were implanted with cannulas in the lateral ventricle. Then, icv injections of ANG II were performed and drinking behavior of the mice was recorded. After the behavioral experiment, we histologically verified the cannula placements using dye injections. Based on this, mice were grouped in "icv" and "misplaced". The effects of icv and misplaced ANG II injections on drinking behavior were used to evaluate the accuracy of ANG II-induced drinking as a method to verify icv cannula placements.

Results: In general, ANG II injections in mice with histologically verified icv cannula placements induced robust drinking responses, while misplaced injections did not. However, there were exceptions in both groups. In about one third of the mice, icv ANG II did not induce drinking or misplaced ANG II injections induced drinking, respectively.

Conclusion: These data demonstrated that ANG II-induced drinking is not a perfectly accurate method to verify icv cannula placements in mice. Therefore, we recommend to not base the decision of in- or excluding experimental subjects solely on this method, but also to histologically verify cannula placements.
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http://dx.doi.org/10.1016/j.physbeh.2021.113339DOI Listing
April 2021

Longitudinal Health Related Quality of Life After Open Radical Cystectomy: Comparison of Ileal Conduit, Indiana Pouch, and Orthotopic Neobladder.

Urology 2021 Jan 19. Epub 2021 Jan 19.

Department of Urology, Indiana University School of Medicine, Indianapolis, IN.

Objective: To characterize the health-related quality of life reported by patients who received an ileal conduit (IC), Indiana pouch, or neobladder urinary diversion after radical cystectomy.

Materials And Methods: The Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index survey was administered to patients with bladder cancer undergoing radical cystectomy and urinary diversion from 2015-2018. Surveys were completed prior to radical cystectomy and then longitudinally throughout the postoperative course.

Results: A total of 146 patients completed questionnaires over a median of 12.3 months, 83 (56.8%) received an IC, 31 (21.2%) an Indiana pouch, and 32 (21.9%) an orthotopic neobladder. There were no significant differences in health related quality of life among urinary diversion groups considering the Trial Outcome Index scores, general overall FACT-G assessment, or total Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index instruments. Patients who received IC were older and had higher Charlson Comorbidity Index scores (p <.005) yet still experienced similar improvements in health related quality of life commensurate with the other diversion cohorts. There was a significant difference in physical well-being favoring neobladder over IC or Indiana Pouch urinary diversions (p <.05).

Conclusions: To our knowledge this is the first and largest quality of life analysis comparing all three methods of urinary diversion in a longitudinal fashion utilizing a standardized, validated, treatment-specific health survey. Proper preoperative counseling is critical to ensure understanding of the benefits of available urinary diversion.
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http://dx.doi.org/10.1016/j.urology.2020.12.036DOI Listing
January 2021

Refinement of the surgical indication and increasing expertise are associated with a better quality of pathology specimen in pleomorphic adenomas.

Acta Otolaryngol 2021 Apr 20;141(4):414-418. Epub 2021 Jan 20.

Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, Germany.

Background: Traditional surgical philosophy condemns extracapsular dissection for pleomorphic adenoma as a euphemism for the enucleation of this lesion.

Objectives: The aims of the study were to trace the development of surgical treatment by pleomorphic adenomas of the parotid gland over the last 15 years and explore its effects on the histopathology specimen.

Materials And Methods: The medical records of all cases with pleomorphic adenomas of the parotid gland between 2006 and 2020 were examined for information on age, gender, and type of surgery. An experienced head and neck pathologist re-evaluated the histology slides from all the cases.

Results: The study included 844 patients. Our analysis showed an increase in the performance of extracapsular dissection from 52.8% (2006) to 63.3% (2020), and an increase in histopathology specimens with tumours completely covered by healthy tissue from 27.7% (2006) to 50% (2020).

Conclusions: Our decision-making process reached its peak in the last study years, in terms of reduced surgical invasiveness and quality of the pathology specimen.

Significance: Extracapsular dissection has gained a firm hold as an indispensable tool for the experienced parotid surgeon. Proper indication is based on careful selection of cases and the correct interpretation of preoperative features on palpation and imaging.
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http://dx.doi.org/10.1080/00016489.2021.1871947DOI Listing
April 2021

Feasibility of intraoperative assessment of safe surgical margins during laryngectomy with confocal laser endomicroscopy: A pilot study.

Auris Nasus Larynx 2021 Jan 16. Epub 2021 Jan 16.

Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstraße 1, 91054 Erlangen, Germany. Electronic address:

Objective: This pilot study aimed to assess the feasibility of intraoperative assessment of safe margins with Confocal Laser Endomicroscopy (CLE) during planned partial or total laryngectomy.

Methods: Eight patients with confirmed larynx squamous cell carcinoma (SCC) and planned partial or total laryngectomy were included in this study in March 2020. Two head and neck surgeons and one pathologist were asked to classify carcinoma or healthy epithelium in a sample of 94 representative sequences (5.640 images), blinded to the histological results (H&E staining).

Results: Healthy mucosa areas showed epithelium with cells of uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE optical biopsy of SCC demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 80.1%, 72.3%, 87.9%, 85.7%, and 76.1%, respectively. A distinct transition between healthy appearing tissue and suspicious lesions could also be detected.

Conclusion: CLE can be easily integrated into the intraoperative setting, generate real-time, in-vivo microscopic images of the larynx for evaluation and demarcation of cancer. If validated in further studies, CLE could eventually contribute to a less radical approach by enabling a more precise evaluation of the cancer margin.
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http://dx.doi.org/10.1016/j.anl.2021.01.005DOI Listing
January 2021

Human extrahepatic and intrahepatic cholangiocyte organoids show region-specific differentiation potential and model cystic fibrosis-related bile duct disease.

Sci Rep 2020 12 14;10(1):21900. Epub 2020 Dec 14.

Department of Surgery, Erasmus MC-University Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.

The development, homeostasis, and repair of intrahepatic and extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation and maturation of cholangiocyte and progenitor cells. This study aimed to characterize human extrahepatic cholangiocyte organoids (ECO) using canonical Wnt-stimulated culture medium previously developed for intrahepatic cholangiocyte organoids (ICO). Paired ECO and ICO were derived from common bile duct and liver tissue, respectively. Characterization showed both organoid types were highly similar, though some differences in size and gene expression were observed. Both ECO and ICO have cholangiocyte fate differentiation capacity. However, unlike ICO, ECO lack the potential for differentiation towards a hepatocyte-like fate. Importantly, ECO derived from a cystic fibrosis patient showed no CFTR channel activity but normal chloride channel and MDR1 transporter activity. In conclusion, this study shows that ECO and ICO have distinct lineage fate and that ECO provide a competent model to study extrahepatic bile duct diseases like cystic fibrosis.
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http://dx.doi.org/10.1038/s41598-020-79082-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736890PMC
December 2020

Investigation of Sonographic Criteria for Reliable Identification of T1-T2 Low-Grade Malignant Tumors of the Parotid Gland.

Ultrasound Med Biol 2021 Mar 10;47(3):471-477. Epub 2020 Dec 10.

Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany. Electronic address:

The aim of this study was to investigate sonographic findings of low-grade malignant tumors of the parotid gland. The sonographic findings of all patients treated for T1-T2 low-grade carcinomas of the parotid gland between 2003 and 2018 were retrospectively examined and compared with those of patients with pleomorphic adenomas for the following parameters: definition of tumor margins, echotexture, echogenicity, shape and vascularization. Statistical analysis was performed using the χ test. A p value of <0.05 was considered statistically significant. A total of 310 patients (62 with T1-T2 low-grade malignant tumors, 248 with pleomorphic adenomas) were evaluated. Our analysis detected a statistically significant difference in the definition of margins, echotexture, echogenicity and shape. Furthermore, we could detect a specific pattern (anechoic islets in a small hypoechoic lesion with distal enhancement) appearing far more frequently in low-grade malignant lesions. It seems that there is still potential to reduce the incidence of the false working hypothesis "benign lesion" on imaging of low-grade malignant tumors.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.11.010DOI Listing
March 2021

Development of the First Potential Nonpeptidic Positron Emission Tomography Tracer for the Imaging of CCR2 Receptors.

ChemMedChem 2021 Feb 23;16(4):640-645. Epub 2020 Nov 23.

Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, 48149, Münster, Germany.

Herein we report the design and synthesis of a series of highly selective CCR2 antagonists as F-labeled PET tracers. The derivatives were evaluated extensively for their off-target profile at 48 different targets. The most potent and selective candidate was applied in vivo in a biodistribution study, demonstrating a promising profile for further preclinical development. This compound represents the first potential nonpeptidic PET tracer for the imaging of CCR2 receptors.
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http://dx.doi.org/10.1002/cmdc.202000728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983900PMC
February 2021

Responses of spinal trigeminal neurons to noxious stimulation of paranasal cavities - a rat model of rhinosinusitis headache.

Cephalalgia 2021 Apr 17;41(5):535-545. Epub 2020 Nov 17.

Institute of Physiology and Pathophysiology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.

Background: The pathophysiology of headaches associated with rhinosinusitis is poorly known. Since the generation of headaches is thought to be linked to the activation of intracranial afferents, we used an animal model to characterise spinal trigeminal neurons with nociceptive input from the dura mater and paranasal sinuses.

Methods: In isoflurane anaesthetised rats, extracellular recordings were made from neurons in the spinal trigeminal nucleus with afferent input from the exposed frontal dura mater. Dural and facial receptive fields were mapped and the paranasal cavities below the thinned nasal bone were stimulated by sequential application of synthetic interstitial fluid, 40 mM potassium chloride, 100 µM bradykinin, 1% ethanol (vehicle) and 100 µm capsaicin.

Results: Twenty-five neurons with input from the frontal dura mater and responses to chemical stimulation of the paranasal cavities were identified. Some of these neurons had additional receptive fields in the parietal dura, most of them in the face. The administration of synthetic interstitial fluid, potassium chloride and ethanol was not followed by significant changes in activity, but bradykinin provoked a cluster of action potentials in 20 and capsaicin in 23 neurons.

Conclusion: Specific spinal trigeminal neurons with afferent input from the cranial dura mater respond to stimulation of paranasal cavities with noxious agents like bradykinin and capsaicin. This pattern of activation may be due to convergent input of trigeminal afferents that innervate dura mater and nasal cavities and project to spinal trigeminal neurons, which could explain the genesis of headaches due to disorders of paranasal sinuses.
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http://dx.doi.org/10.1177/0333102420970467DOI Listing
April 2021

Orexin deficiency affects sociability and the acquisition, expression, and extinction of conditioned social fear.

Brain Res 2021 Jan 5;1751:147199. Epub 2020 Nov 5.

Institute for Pharmacology and Toxicology, Otto von Guericke University Magdeburg, Leipziger Straße 44, D-39120 Magdeburg, Germany; Center for Behavioral Brain Sciences, Otto von Guericke University Magdeburg, Leipziger Straße 44, D-39120 Magdeburg, Germany.

Accumulating evidence indicates that the central orexin (hypocretin) system plays an important role in regulating emotional processes in both humans and rodents. Thus, the orexin system has been repeatedly implicated in the pathophysiology of several neuropsychiatric disorders, such as anxiety disorders. Among others, symptoms like social fear and social withdrawal are frequently observed in these disorders. Based on this, we investigated the role of orexin deficiency in social (fear) behavior. For that, female and male orexin-deficient mice were tested for (1) sociability and social novelty, and (2) acquisition, expression, and extinction of conditioned social fear. We found that female orexin-deficient mice displayed reduced sociability and decreased preference for social novelty compared to their wild-type littermates. These effects of orexin deficiency were not observed in males. Moreover, orexin deficiency facilitated the acquisition and/or expression of conditioned social fear and impaired the extinction of social fear in both sexes. Taken together, our results indicate an important, partly sex-dependent, regulatory role of the orexin system in social (fear) behavior. Our findings support the hypothesis of orexin being an integrator of motivation, affect, and emotion.
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http://dx.doi.org/10.1016/j.brainres.2020.147199DOI Listing
January 2021

Influence of p16 status on indication and outcome of salvage neck dissection in oropharyngeal cancer.

Acta Otolaryngol 2021 Feb 28;141(2):187-192. Epub 2020 Oct 28.

Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.

Background: Human papillomavirus (HPV)+ and HPV- oropharyngeal squamous cell carcinomas (OPSCC) are separate tumor entities.

Aims/objectives: The aim of this study was to examine if the p16 status influences the need and outcome of a salvage neck dissection (SND) after primary radiochemotherapy (pRCT).

Material And Methods: Retrospective study of 164 patients ( = 108 p16-,  = 56 p16+) who underwent pRCT for OPSCC between 2009 and 2016. HPV status was defined p16 immunohistochemical staining. Clinical nodal status was assessed using ultrasound and computed tomography of the neck with contrast.

Results: Of the 56 p16+ patients, 17 (30.4%) patients were given an indication for a SND after pRCT with 4 (23.5%) patients showing persistent malignant nodes. Of the 108 p16- patients, 24 (22.2%) patients underwent a SND with 8 (33.3%) patients showing persistent malignant nodes. There was no significant association of the p16 status and neither the indication for SND (p(Chi(two-sided)-Test) = 0.25, ϕ = 0.34) nor the occurrence of positive nodes (p(Chi(two-sided)-Test) = 0.74, ϕ = 0.50). The probability for persistence of the ypN + nodal status independent of HPV-status was 29.2%(12/41).

Conclusions And Significance: There was neither a significant association between the p16 status and the indication for a SND nor for persistent malignant nodal disease after pRCT.
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http://dx.doi.org/10.1080/00016489.2020.1831697DOI Listing
February 2021

Failure of pedicled flap reconstruction in the head and neck area: A case report of a bilateral subclavian artery stenosis.

Int J Surg Case Rep 2020 12;76:381-385. Epub 2020 Oct 12.

Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich Alexander University of Erlangen-Nuremberg, Waldstrasse 1, 91054 Erlangen, Germany. Electronic address:

Introduction: Pedicled flap reconstruction still plays an essential role in head and neck surgery as an alternative to free grafts. Two standard methods are the pectoralis major and the deltopectoral flap, which are generally characterized by their reliable perfusion. This case describes bilateral arteriosclerosis of the subclavian artery as a possible cause of flap failure.

Presentation Of Case: We report on a 65-year-old patient with a multilevel carcinoma of the right pharynx. Due to the unique patient history, a free flap reconstruction was not possible. After resection of the primary, we performed reconstruction with a pedicled pectoralis major flap.

Discussion: Postoperatively, we observed necrosis of the pectoralis major flap. Secondary defect reconstructions were performed with a deltopectoral flap first from the right and then, in the case of necrosis, from the left side. Stenosing arteriosclerotic plaques of the subclavian artery on both sides were the cause of flap failure.

Conclusion: Preoperative angiography of the subclavian artery is not a standard diagnostic procedure in the surgical planning of pedicled flap reconstruction in the head and neck region. In exceptional cases, we recommend angiographic imaging of the supplying vessels to make a more precise flap selection and avoid complications.
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http://dx.doi.org/10.1016/j.ijscr.2020.10.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575643PMC
October 2020

Simultaneous Application of Ultrasound and Sialendoscopy and its Value in the Management of Sialolithiasis.

Ultraschall Med 2020 Oct 15. Epub 2020 Oct 15.

Department of Otolaryngology, Head and Neck Surgery, FA University of Erlangen-Nuremberg, Erlangen, Germany.

Objective:  Ultrasound (US) and sialendoscopy (SE) are routinely used in patients presenting with sialolithiasis in the submandibular (SMG) and parotid gland (PG). The objective was to assess the value of the simultaneous application of US and SE in the management of sialolithiasis.

Study Design:  Retrospective study.

Setting: Tertiary referral center for salivary gland diseases.

Participants: Patients in whom US and SE as single investigation tools were neither conclusive nor useful in the management of sialolithiasis were investigated using both methods simultaneously (simUS + SE).

Main Outcome Measures: Establishment of the final diagnosis and/or contribution to the planning/performing of treatment in sialolithiasis.

Results:  74 patients were examined by simUS + SE (58.1 % SMG and 41.9 % PG). In all patients (unclear) hyperechoic reflexes were assessed and/or localized by SE-controlled US navigation. 68.9 % of the patients were investigated for diagnostic or differential-diagnostic reasons including distinguishing extraductal from intraductal calcifications and/or to exclude residual stones after therapy. In 52.7 % simUS + SE was used to plan and/or perform further treatment, in 20.3 % to enable performing a combined approach (all PG) and in 29.7 % to evaluate and plan the most adequate therapy (mainly intraductal vs. extracorporeal shock wave lithotripsy, 68.2 % of these SMG). In two cases SE-controlled and US-guided stone extraction was performed.

Conclusion:  SimUS + SE is an innovative approach which proved to be very useful in managing sialolithiasis. It added valuable information regarding the establishment of a diagnosis or differential diagnosis, planning and performing the most adequate treatment, intraoperative control of therapy and postoperative follow-up.
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http://dx.doi.org/10.1055/a-1270-7174DOI Listing
October 2020

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer.

J Urol 2021 Mar 6;205(3):769-779. Epub 2020 Oct 6.

University of Chicago.

Purpose: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT).

Materials And Methods: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy.

Results: In all, 72 (63%) had grade group 2 and 77 (67%) had NCCN® intermediate risk disease. Median treatment delivery time was 51 minutes with 98% (IQR 95-99) thermal coverage of target volume and spatial ablation precision of ±1.4 mm on magnetic resonance imaging thermometry. Grade 3 adverse events occurred in 9 (8%) men. The primary endpoint (U.S. Food and Drug Administration mandated) of prostate specific antigen reduction ≥75% was achieved in 110 of 115 (96%) with median prostate specific antigen reduction of 95% and nadir of 0.34 ng/ml. Median prostate volume decreased from 37 to 3 cc. Among 68 men with pretreatment grade group 2 disease, 52 (79%) were free of grade group 2 disease on 12-month biopsy. Of 111 men with 12-month biopsy data, 72 (65%) had no evidence of cancer. Erections (International Index of Erectile Function question 2 score 2 or greater) were maintained/regained in 69 of 92 (75%). Multivariate predictors of persistent grade group 2 at 12 months included intraprostatic calcifications at screening, suboptimal magnetic resonance imaging thermal coverage of target volume and a PI-RADS™ 3 or greater lesion at 12-month magnetic resonance imaging (p <0.05).

Conclusions: The TACT study of magnetic resonance imaging-guided transurethral ultrasound whole gland ablation in men with localized prostate cancer demonstrated effective tissue ablation and prostate specific antigen reduction with low rates of toxicity and residual disease.
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http://dx.doi.org/10.1097/JU.0000000000001362DOI Listing
March 2021

Ultrasound in the diagnosis of parotid duct obstruction not caused by sialolithiasis: diagnostic value in reference to direct visualization with sialendoscopy.

Dentomaxillofac Radiol 2021 Mar 8;50(3):20200261. Epub 2020 Oct 8.

Department of Otorhinolaryngology, Head and Neck Surgery, University of Erlangen-Nuremberg, Erlangen, Germany.

Objectives: The aim of this study was to evaluate the diagnostic value of ultrasound in the obstructive pathology of the parotic gland not caused by sialolithiasis using sialendoscopy as reference standard.

Methods: Retrospective analysis of all patients who presented with suspected diagnosis of obstructive ductal pathology of the parotid gland other than sialolithiasis between January 2011 and December 2017. 538 patients, for a total of 691 parotid glands were included in the study. Ultrasound was performed, followed by sialendoscopy in all cases. Duct diameter and parenchyma echogenicity were assessed. Direct sialendoscopic examination of the parotid duct was regarded as the reference standard.

Results: Parotid glands with normal sialendoscopic findings (21.6%, = 149) had a duct diameter of 0.3 mm (0-2.7 mm) and homogeneous hyperechoic parenchyma on ultrasound in 98.7%. Ductal inflammation/sialodochitis (32.9%, = 227) on sialendoscopy had significantly larger ductal diameter of 0.7 mm (0-4.3 mm, = 0.001) and hypoechoic parenchyma in 78.0% ( < 0.001). Parotid glands with stenosis (45.6%, = 315) had hypoechoic parenchyma in 52.6% and a ductal diameter of 4.1 mm (0-19.0 mm; = 0.001). The ductal diameter was ≥2.7 mm in 95.6% of the stenosis (AUC 0.886, = 0.001). Using 5.1 mm as benchmark ductal diameter, stenosis with ductal anomaly (68/315) were identifiable with a sensitivity of 92.6% and a specificity of 96.8% (AUC 0.986, = 0.001).

Conclusion: Ultrasound parameters can be used to distinguish different types of obstructive ductal pathology of the parotid gland, supporting the use of this imaging modality as diagnostic tool of first choice.
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http://dx.doi.org/10.1259/dmfr.20200261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923063PMC
March 2021

Mechanical decoupling of quantum emitters in hexagonal boron nitride from low-energy phonon modes.

Sci Adv 2020 Sep 30;6(40). Epub 2020 Sep 30.

Institute for Quantum Optics, Ulm University, D-89081 Ulm, Germany.

Quantum emitters in hexagonal boron nitride were recently reported to hold unusual narrow homogeneous linewidths of tens of megahertz within the Fourier transform limit at room temperature. This unique observation was traced back to decoupling from in-plane phonon modes. Here, we investigate the origins for the mechanical decoupling. New sample preparation improved spectral diffusion, which allowed us to reveal a gap in the electron-phonon spectral density for low phonon frequencies. This sign for mechanical decoupling persists up to room temperature and explains the observed narrow lines at 300 kelvin. We investigate the dipole emission directionality and reveal preferred photon emission through channels between the layers supporting the claim for out-of-plane distorted defect centers. Our work provides insights into the underlying physics for the persistence of Fourier transform limit lines up to room temperature and gives a guide to the community on how to identify the exotic emitters.
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http://dx.doi.org/10.1126/sciadv.aba6038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527221PMC
September 2020

Successful free flap salvage surgery with off-label use of Alteplase: A case report, review of the literature and our free flap salvage algorithm.

Int J Surg Case Rep 2020 18;75:398-402. Epub 2020 Sep 18.

Department of Otorhinolaryngology, Head and Neck Surgery, Waldstrasse 1, 91054, Erlangen, University of Erlangen-Nuremberg, Germany. Electronic address:

Introduction: Microvascular free tissue transfer is a technique for reconstruction of large defects in head and neck surgery. Failure due to microvascular thrombosis can lead to microvascular damage or flap loss. Recombinant tissue-type plasminogen activator (Alteplase) is still an off-label use but it can help to rescue free flaps when embedded in a salvage algorithm.

Presentation Of Case: A 39-year-old patient with received a tumor resection and reconstruction by a radial forearm flap of the left palate. Postoperatively a venous flap thrombosis occurred and immediate surgical revision was done. Initially eperfusion of the flap could not be achieved even after mechanical removal of the thrombus. Then a thrombolysis with Alteplase, which was applied directly into the radial artery, was done. The flap was salvaged and is now completely integrated into the mucosa. Flap salvage procedure was performed according to our free flap salvage algorithm.

Discussion: Thrombolysis with Alteplase for free flap salvage is not a common method. Pedicle thrombosis cannot be predicted. Important procedures during surgical intervention when thrombosis occurs are careful reopening, removal of thrombus, flushing with heparin. Since these procedures failed, surgeons decided to employ Alteplase to optimally rescue the flap.

Conclusion: The present case shows that pharmacological thrombolysis with Alteplase is an effective ultima ratio in free flap salvage with venous thrombosis, although it is still considered offlabel use. Early detection of flap failure and a clear salvage algorithm are important for successful surgical revisions.
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http://dx.doi.org/10.1016/j.ijscr.2020.09.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522445PMC
September 2020

Intraductal Lithotripsy in Sialolithiasis Using the Calculase III™ Ho:YAG Laser: First Experiences.

Lasers Surg Med 2021 Apr 30;53(4):488-498. Epub 2020 Sep 30.

Department of Otorhinolaryngology and Head and Neck Surgery, University of Erlangen-Nuremberg, Erlangen, Germany.

Background And Objectives: To report the first experiences with a newly available Ho:YAG laser system for the treatment of salivary stones.

Study Design/materials And Methods: A retrospective study in a tertiary referral center was conducted. Patients diagnosed with sialolithiasis were treated in Erlangen using the Calculase III™ Ho:YAG laser (Karl Storz, Tuttlingen, Germany). Preset parameters had a frequency of 4 Hz and energy of 0.8-1.2 J, resulting in 3.2-4.8 W. Following total fragmentation, one to two serial sialendoscopies were performed to achieve complete fragment clearance.

Results: A total of 55 stones in 49 patients were treated; 17 stones in 15 submandibular glands and 38 in 34 parotids. In total, 61 laser lithotripsies (range 1-3 per stone) were performed using various modes (long, short, and burst) and with preset parameters of 4 Hz and energy of 0.8-1.2 J, resulting in effective power of 3.2-4.8 W. Complete fragmentation was achieved in all the accessible stones. Sialendoscopes, fibers, or the mode used had no significant influence on success rates. A multimodal therapy concept was employed to treat stones in 12.24% of the cases; 95.92% of the patients were ultimately stone-free, and all became symptom-free. All glands were preserved.

Conclusions: The new Calculase III™ Ho:YAG laser was effective in the treatment of sialolithiasis with no increased risk of complications in the patients or damage to the sialendoscopes. Clinical factors such as the type of gland involved, or the location and size of stones had a greater impact on success rates than the technical or preset parameters. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
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http://dx.doi.org/10.1002/lsm.23325DOI Listing
April 2021

Neutrophil Extracellular Traps Promote the Development and Growth of Human Salivary Stones.

Cells 2020 09 22;9(9). Epub 2020 Sep 22.

Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Internal Medicine 3, Universitätsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany.

Salivary gland stones, or sialoliths, are the most common cause of the obstruction of salivary glands. The mechanism behind the formation of sialoliths has been elusive. Symptomatic sialolithiasis has a prevalence of 0.45% in the general population, is characterized by recurrent painful periprandial swelling of the affected gland, and often results in sialadenitis with the need for surgical intervention. Here, we show by the use of immunohistochemistry, immunofluorescence, computed tomography (CT) scans and reconstructions, special dye techniques, bacterial genotyping, and enzyme activity analyses that neutrophil extracellular traps (NETs) initiate the formation and growth of sialoliths in humans. The deposition of neutrophil granulocyte extracellular DNA around small crystals results in the dense aggregation of the latter, and the subsequent mineralization creates alternating layers of dense mineral, which are predominantly calcium salt deposits and DNA. The further agglomeration and appositional growth of these structures promotes the development of macroscopic sialoliths that finally occlude the efferent ducts of the salivary glands, causing clinical symptoms and salivary gland dysfunction. These findings provide an entirely novel insight into the mechanism of sialolithogenesis, in which an immune system-mediated response essentially participates in the physicochemical process of concrement formation and growth.
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http://dx.doi.org/10.3390/cells9092139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564068PMC
September 2020

[Thrombosis of sewn vs. coupled anastomoses in microvascular head and neck reconstructions].

Laryngorhinootologie 2020 Sep 14. Epub 2020 Sep 14.

Hals-Nasen-Ohrenklinik, Kopf- und Halschirurgie, Universitätskliniken Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutschland.

Objective:  The Anastomotic Coupling Device for microvascular anastomoses has become widely used in free tissue transplantation. This study compares the thrombosis rate and flap failure as a function of the anastomosis technique at a large head and neck cancer center.

Material And Methods:  Retrospective analysis of all patients receiving free flap reconstructions in the period 2001-2019. Reconstruction type, recipient vessels, number of venous anastomoses, coupler size, and operation time were investigated. We compared the rates of venous thrombosis between hand sewn and coupled anastomoses, as well as the rate of flap failure.

Results:  A total of 403 free flap reconstructions were performed for over 17 years. The venous anastomosis was sewn in 113 flaps in single suture technique, and in 290 cases, coupler device was used. The rate of venous thrombosis requiring immediate surgical revision was 6.2 % (7/113) in the sewn group compared to 7.6 % in the coupled group (22/290; p = 0.627). With an overall success rate of 95.0 % (383/403), the rate of flap failure was 3.6 % (4/113) and 5.5 % (16/290; p = 0.421), respectively. Surgical time is comparable with 680 ± 144 minutes in the hand-sewn group and 688 ± 167 minutes in the coupled group (p = 0.678).

Conclusions:  With similar success rates, the coupler device is an effective alternative to venous anastomosis in single suture technique. Due to the generally low rate of pedicle thrombosis in both groups, we cannot separate the influence of the anastomosis technique from possible interfering variables.
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http://dx.doi.org/10.1055/a-1253-8392DOI Listing
September 2020

Considerations for Continuing Semielective and Emergency Otolaryngological Procedures During the COVID-19 Pandemic.

Ear Nose Throat J 2021 Jan 7;100(1):19-25. Epub 2020 Sep 7.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Erlangen, 9171Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

Introduction: During the COVID-19 pandemic, worldwide over 600,000 human beings died due to the cause of the disease. In order to deescalate the transmission rate and to avoid crush loading the countries medical health systems social distancing, face masks, and lockdowns have been considered essential by the majority of governments. Whereas some countries have highly reduced or completely stopped otorhinolaryngological procedures, other countries have continued selected surgeries. The objective of this study was to analyze procedures and outcomes of continuing semielective and emergency surgeries during the COVID-19 pandemic.

Methods: Retrospective analysis of n = 750 patients who received semi-elective or emergency surgery between March 26 and June 16, 2020, in the Otolaryngology Department of the Friedrich-Alexander-University of Erlangen-Nürnberg. All patients were screened for COVID symptoms and swabbed for SARS-CoV-2 prior to surgery.

Results: Of the n = 750 patients, n = 699 patients received semielective surgery and n = 51 emergency surgery. For 27 patients, the swab result could not be awaited due to a life-threatening condition. In these cases, surgery was performed in full protective equipment. No patient was tested positive during or after the surgery (follow-up 45 to 127 days). No member of the medical personnel showed symptoms or was tested positive after contact with patients. Due to the continuation of surgeries, patients' lives were saved and improvement of long-term quality-of-life and outcomes is anticipated.

Conclusions: Continuing selected otorhinolaryngological surgeries is crucial for patients' health, survival, and long-time quality of life, yet, the protection of the medical personnel has to be granted.
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http://dx.doi.org/10.1177/0145561320952506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477481PMC
January 2021

Role of Neoadjuvant Chemotherapy in Squamous Variant Histology in Urothelial Bladder Cancer: Does Presence and Percentage Matter?

Clin Genitourin Cancer 2021 Feb 19;19(1):47-52. Epub 2020 Jun 19.

Department of Urology, Indiana University School of Medicine, Indianapolis, IN.

Background: The purpose of this study was to evaluate the effect of neoadjuvant chemotherapy (NACT) on squamous variant (SV) bladder cancer by investigating patients presenting with SV histology at the time of transurethral resection (TUR), stratified by their receipt of NACT.

Materials And Methods: The records of 71 patients with muscle-invasive bladder cancer and SV in the TUR specimen who underwent cystectomy between 2008 and 2018 were reviewed. Our primary outcome was pathologic response at time of cystectomy. Secondary outcomes included recurrence-free survival and overall survival stratified by receipt of NACT. A subgroup analysis was then conducted on the patients with defined SV% on TUR stratified by % involvement (< 50% SV vs. ≥ 50% SV).

Results: The median age of the NACT and no-NACT groups was 60.2 and 70 years, respectively (P = .003). The complete response rate at cystectomy was 60% versus 13.7% for the NACT and no-NACT groups, respectively (P < .001). The non-organ-confined disease rate at time of radical cystectomy was 35% for the NACT group and 68.6% for the no-NACT group (P = .01). The NACT group had fewer recurrences than the no-NACT group (10% vs 47.1%; P = .003). In the subgroup analysis, the lower rate of non-organ-confined disease persisted for the patients who underwent NACT at the lower SV percentage but failed to remain significant at greater percentage involvement. This was also true for overall survival.

Conclusions: The effect of NACT in variant histology bladder cancer is variable. In patients with SV, these results favor the recommendation in favor of NACT administration, particularly when the primary tumor has < 50% involvement by the variant histology.
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http://dx.doi.org/10.1016/j.clgc.2020.06.004DOI Listing
February 2021

Postoperative management of antithrombotic medication in microvascular head and neck reconstruction: a comparative analysis of unfractionated and low-molecular-weight heparin.

Eur Arch Otorhinolaryngol 2020 Jul 24. Epub 2020 Jul 24.

Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich Alexander University of Erlangen-Nuremberg, Waldstrasse 1, 91054, Erlangen, Germany.

Purpose: Free flap reconstruction is a valuable technique to preserve function in oncological head and neck surgery. Postoperative graft thrombosis is a dreaded risk. This study aims to compare low-dose unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in perioperative thrombosis prophylaxis.

Methods: This is a retrospective analysis of 266 free flaps performed at our academic center. A comparison was made between 2 patient groups, based on their respective postoperative prophylaxis protocols either with UFH (n = 87) or LMWH (n = 179). Primary endpoints were the frequency of transplant thrombosis and the number of flap failures. Secondary endpoints were the occurrence of peri- and postoperative complications.

Results: The flap survival rate was 96.6% and 93.3% for the groups UFH and LMWH, respectively (P = 0.280). The rate of postoperative bleeding requiring revision was 4.6% and 6.7% for each group, respectively (P = 0.498). We found a hematoma formation in 4.6% and 3.9% (P = 0.792).

Conclusion: The free-flap survival rate using low-dose UFH seems to be equivalent to LMWH regimens without compromising the postoperative outcome. Consequently, for risk-adapted thrombosis prophylaxis, either LMWH or UFH can be administrated.
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http://dx.doi.org/10.1007/s00405-020-06219-wDOI Listing
July 2020

Stenosis and stenosis-like lesions in the submandibular duct: Detailed clinical and sialendoscopy-based analysis and proposal for a classification.

Oral Surg Oral Med Oral Pathol Oral Radiol 2020 Nov 5;130(5):486-495. Epub 2020 Jun 5.

Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich Alexander University of Erlangen-Nuremberg, Germany.

Objective: The aim of this study was to perform a detailed analysis of submandibular duct stenoses and propose a classification for them.

Study Design: This retrospective study covering the period 2001-2019 included 314 patients with 370 submandibular duct stenoses, assessed sialendoscopically for number, grade of narrowing, length, tissue type, and underlying main cause/associated diseases.

Results: In the included patients, 58.9% of the stenoses were at the papilla, 89.2% were short, and 61.6% were of high grade. Predominantly inflammatory stenoses (type 1) differed from fibrotic stenoses (type 2). Detailed analysis identified stenosis-like lesions caused by anatomic duct narrowing and/or duct variations (type 3), differing significantly from type 2 stenoses in location, length, and bilaterality (each P = .0001) and from type 1 stenoses in location (P = .0001). Compared with type 2, type 1 stenoses were bilateral significantly more often and shorter (each P = .0001). Frequencies of the main causes of stenosis-anatomic narrowness/duct variation and chronic sialadenitis-differed significantly in the different locations (P = .0001). There were no significant differences in frequencies of associated diseases/conditions for the different stenosis types.

Conclusions: Three types of stenosis/stenosis-like lesions were distinguished. In view of these results and the findings from a review of the literature, the location and type of stenoses were found to be more important parameters, whereas number, grade, and length were less important. The underlying cause may be useful for assessing the prognosis.
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http://dx.doi.org/10.1016/j.oooo.2020.05.015DOI Listing
November 2020

Predictors of Prostate-specific Membrane Antigen (PSMA/FOLH1) Expression in a Genomic Database.

Urology 2020 Oct 30;144:117-122. Epub 2020 Jun 30.

Department of Urology, Indiana University, Indianapolis, IN.

Objective: To assess predictors of prostate-specific membrane antigen (PSMA) expression in a genomic database; positron emission tomography with PSMA-targeted radiopharmaceuticals is increasingly being utilized.

Methods: The de-identified Decipher Biosciences database, which includes expression for more than 46,000 coding and noncoding genes per patient, was queried for expression of FOLH1 (PSMA). Prostate cancer patients who underwent radical prostatectomy and received the Decipher Test were included in the analysis. PSMA expression was compared to the Gleason Grade Group, Decipher risk category (a validated 22 biomarker genomic score), basal versus luminal molecular subtype, and androgen receptor activity. Multivariable regression analyses were performed.

Results: The Decipher de-identified Decipher Biosciences database contained 16,807 men who underwent prostatectomy with the average age being 65-year old and most being Gleason Grade Group 2 (35%) or 3 (27%). Higher Grade Group was associated with higher PSMA expression except in Grade Group 5 [Grade group: 1 (0.66), 2 (0.84), 3 (0.99), 4 (1.07), 5 (0.99), P <.001]. Luminal subtype was found to have much higher PSMA expression when compared to basal (1.01 vs 0.68, P <.001). The androgen receptor activity signature demonstrated a dramatic difference between basal (0.19) and luminal (0.62) subtypes (P <.001). In the multivariable model, luminal patients, high androgen receptor activity scores, and high Grade Groups were significantly associated with higher FOLH1 percentile rank (P <.001).

Conclusion: High PSMA expression (FOLH1) was associated with high androgen receptor activity and luminal subtype. Genomic tests could aid in predicting, interpreting, and/or directing PSMA theranostics.
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http://dx.doi.org/10.1016/j.urology.2020.06.025DOI Listing
October 2020

Semi-Minimal Invasive Method to Induce Myocardial Infarction in Rats and the Assessment of Cardiac Function by an Isolated Working Heart System.

J Vis Exp 2020 06 11(160). Epub 2020 Jun 11.

Ludwig-Boltzmann-Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna;

Myocardial infarction (MI) remains the main contributor to morbidity and mortality worldwide. Therefore, research on this topic is mandatory. An easily and highly reproducible MI induction procedure is required to obtain further insight and better understanding of the underlying pathological changes. This procedure can also be used to evaluate the effects or potency of new and promising treatments (as drugs or interventions) in acute MI, subsequent remodeling and heart failure (HF). After intubation and pre-operative preparation of the animal, an anesthetic protocol with isoflurane was performed, and the surgical procedure was conducted quickly. Using a minimally invasive approach, the left anterior descending artery (LAD) was located and occluded by a ligature. The occlusion can be performed acutely for subsequent reperfusion (ischemia/reperfusion injury). Alternatively, the vessel can be ligated permanently to investigate the development of chronic MI, remodeling or HF. Despite common pitfalls, the drop-out rates are minimal. Various treatments such as remote ischemic conditioning can be examined for their cardioprotective potential pre-, peri- and post-operatively. The post-operative recovery was quick as the anesthesia was precisely controlled and the duration of the operation was short. Post-operative analgesia was administered for three days. The minimally invasive procedure reduces the risk of infection and inflammation. Furthermore, it facilitates rapid recovery. The "working heart" measurements were performed ex vivo and enabled precise control of preload, afterload and flow. This procedure requires specific equipment and training for adequate performance. This manuscript provides a detailed step-by-step introduction for conducting these measurements.
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http://dx.doi.org/10.3791/61033DOI Listing
June 2020

Sociability and extinction of conditioned social fear is affected in neuropeptide S receptor-deficient mice.

Behav Brain Res 2020 09 22;393:112782. Epub 2020 Jun 22.

Institute for Pharmacology and Toxicology, Otto von Guericke University Magdeburg, Leipziger Straße 44, D-39120 Magdeburg, Germany; Center for Behavioral Brain Sciences, Otto von Guericke University Magdeburg, Leipziger Straße 44, D-39120 Magdeburg, Germany. Electronic address:

Being cautious of unfamiliar conspecifics is adaptive because sick or aggressive conspecifics may jeopardize survival and well-being. However, prolonged or excessive caution, i.e. fear related to social situations, is maladaptive and may result in social anxiety disorder. Some anxiety disorders in humans are associated with polymorphisms of the neuropeptide S receptor (NPSR) gene. In line with this finding, animal studies showed an important role of NPS and NPSR in anxiety and fear. The present study investigated the role of NPSR deficiency in social behavior under non-aversive and aversive conditions. For this, female and male NPSR-deficient mice were tested for (1) sociability and social novelty and (2) acquisition, expression, and extinction of conditioned social fear. The present study revealed very particular effects of the NPSR genotype: Sociability was reduced in female heterozygous NPSR-deficient mice, but was unaffected in males and the other genotypes. Furthermore, the NPSR genotype did not affect the acquisition and expression of conditioned social fear, but its extinction was impaired in heterozygous and facilitated in homozygous NPSR-deficient mice. This indicates that the NPS system plays a role in social behavior under non-aversive and aversive conditions, partly in a sex-dependent manner. The present findings may help to explain social symptoms in anxiety disorders associated with the NPSR genotype.
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http://dx.doi.org/10.1016/j.bbr.2020.112782DOI Listing
September 2020