Rejected

κ-Opioid receptors (KORs) play a predominant role in pain alleviation, itching skin diseases, depression and neurodegenerative disorders such as multiple sclerosis. Therefore, imaging of KOR by a fluorinated PET tracer was envisaged. Two strategies were followed to introduce a F atom into the very potent class of cis,trans-configured perhydroquinoxalines. Whereas the synthesis of fluoroethyltriazole 2 has already been reported, fluoropyrrolidines 14 (1-[2-(3,4-dichlorophenyl)acetyl]-8-[(R)-3-fluoropyrrolidin-1-yl]-perhydroquinoxalines) were prepared by S2 substitution of a cyclic sulfuric acid derivative with hydroxypyrrolidine and subsequent transformation of the OH moiety into a F substituent. Fluoropyrrolidines 14 showed similar low-nanomolar KOR affinity and selectivity to the corresponding pyrrolidines, but the corresponding alcohols were slightly less active. In the cAMP and β-arrestin assay, 14b (proton at the 4-position) exhibited similar KOR agonistic activity as U-50,488. The fluoro derivatives 14b and 14c (COCH at the 4-position) revealed KOR-mediated anti-inflammatory activity as CD11c and the IFN-γ production were reduced significantly in mouse and human dendritic cells. Compounds 14b and 14-c also displayed anti-inflammatory and immunomodulatory activity in mouse and human T cells. The PET tracer [F]-2 was prepared by 1,3-dipolar cycloaddition. In vivo, [F]-2 did not label KOR due to very fast elimination kinetics. Nucleophilic substitution of a mesylate precursor provided [F]-14c. Unfortunately, defluorination of [F]-14c occurred in vivo, which was analyzed in detail by in vitro studies.

Chronic shoulder pain is a complex and multidimensional phenomenon with multiple causative factors involved in its perpetuation. Alteration of central nervous system processing along with the central sensitization is a predominant feature in chronic pain. Reduction in physical function has an impact on the psychological well-being of an individual. The aim of the study was to compare pain, kinesiophobia, catastrophizing, disability and quality of life in chronic shoulder pain patients with and without central sensitization. Eighty chronic unilateral shoulder pain patients in the age group of 40 to 60 years were recruited. Of them, 38 were chronic shoulder pain with central sensitization and 42 without central sensitization, classified on the basis of central sensitization inventory. Pain catastrophizing was measured using the pain catastrophizing scale, kinesiophobia using Tampa scale of kinesiophobia, disability using Shoulder pain and disability index and quality of life using 36-Item Short Form Health Survey questionnaire was evaluated in both the groups. Increased pain catastrophizing (p=0.000), kinesiophobia (p=0.000) and disability (p=0.000) was observed in centrally sensitized chronic shoulder pain patients. Also, physical component summary (p=0.000) and mental component summary (p=0.000) of SF-36 quality of life were reduced in chronic shoulder pain with central sensitization as compared to without central sensitization. Hence, these components should be included during assessment which will provide a holistic and multimodal approach towards the understanding, planning and management of chronic shoulder pain patients.

Pediatric Chiari I malformation decompression is a common neurosurgical procedure. Liposomal bupivacaine (LB) is a novel formulation that can have an impact on postoperative recovery for particular procedures, but its potential role in pediatric neurosurgery is largely unexplored. The authors sought to describe and assess their initial experience with LB in pediatric Chiari I malformation decompression to better define its potential role as an analgesic agent in a procedure for which the postoperative course is often remarkably painful.

Opioids are effective analgesics in the management of chronic pain. However, their clinical use is hindered by adverse side effects such as addiction and analgesic tolerance. Naringenin is a common polyphenolic constituent of the citrus fruits and is one of the most commonly consumed flavonoids within our regular diet. However, its influences on opioid tolerance and addiction have not yet been clarified.

Superficial fungal infections (SFI) are common diseases affecting the skin, hair, nails, and mucosal membranes. They are often caused by dermatophytes and yeasts, e.g. Trichophyton, Candida, and Malassezia . Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease of the intertriginous areas associated with minor infections , peripheral vascular disease, diabetes, and smoking , the last three of which are risk factors for the development of SFI . Despite this, and the anatomical overlap between HS and types of SFI e.g. intertriginous candidiasis and tinea cruris, the possibility of an association between HS and SFI has never been investigated.

Benzodiazepines (BZDs) and related drugs (Z-drugs) are mainly taken chronically, and older people are much more likely to take them on a chronic basis despite recommendations. Withdrawal symptoms could be an obstacle to stopping BZD/Z-drug administration. The main objective of this study is to estimate the prevalence of withdrawal symptoms in patients aged 65 years and older who have experience a stop of BZD/Z-drug. The secondary objectives are to describe the withdrawal symptoms and identify factors associated.

Catheter-guided interventional implantation of cardiac valves is one of the main developments in cardiology over the past 15 years. It is characterized by a close interdisciplinary cooperation in the heart team (H-team), which consists of cardiac anesthesiologists, cardiologists and heart surgeons. This co-responsibility for anesthesia, which is demanded by the legislator (Federal Joint Committee, G‑BA, July 2015), includes not only qualified training for the cardiac anesthesiologist, including transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) but also several years of experience in cardiac anesthesia and correlates with the recommendations of the German Society for Anaesthesiology and Intensive Care Medicine. In accompaniment with the demographic development, the number of heart valve diseases increases with age. More than 50% of all heart operations are performed on patients over the age of 70 years and nearly 20% on patients over the age of 80 years. Minimally invasive procedures are outstanding opportunities for patients who were initially classified as inoperable. Therefore, anesthesiologists must have precise knowledge of the possible complications related to the procedure itself. Additionally, it challenges the anesthesiologist with unconventional situations in the care of older patients who are exposed to a higher risk. The aforementioned risks are organic functional restrictions, increasing number of comorbidities and more severe exposure due to malnutrition and frailty; however, monitoring methods are also being developed aiming for patient-specific anesthesia management and analgesia treatment. This article discusses the interventional procedures of heart valvular diseases as well as the hemodynamic changes associated with the procedures from the anesthesiologist's point of view. To present examples, we have selected transcatheter aortic valve replacement (TAVR) and the interventional procedure of mitral and tricuspid valve insufficiency called MitraClip and TricaClip. A thorough examination of the procedural risk rate shows that despite minimizing the surgical intervention by miniaturizing the devices, the presence of an experienced cardiac anesthesiologist is obligatory.

Sizing of iliac vein stents remains controversial. We present the first Venovo venous stent (BD/Bard) that was explanted because of worsening of back and leg pain post treatment and analyze data from the first 50 consecutive Venovo venous stents from our center. Stent size was obtained with intravascular ultrasound of the ipsilateral common iliac vein. The data indicate that there is no statistical relationship between the stent size and worsening or emergence of low back and leg pain. Patient-specific factors may be contributing to this extremely rare and persistent pain beyond the 30-day follow-up.

In pre-surgical patients with chronic rhinosinusitis with nasal polyps (CRSwNPs), positive findings on computed tomography (CT) scans and an exacerbation of symptoms are two possible factors that indicate surgery. However, the relationship between these factors remains unclear. Confirmed CRSwNP patients ready for sinus surgery were consecutively enrolled. The Sino-Nasal Outcome Test 22 (SNOT-22) and visual analog scale (VAS) scoring were completed by these patients, and scores were subjected to factor analysis using a principal component analysis (PCA) to evaluate subjective symptom components related to CRS. Patient CT scores, measured by the Lund-Mackay score (LMS), together with their demographics, medical treatment, and atopy status, were collected and analyzed. A total of 288 patients who met the criteria for CRSwNP and underwent CT scanning prior to surgery in the Eye, Ear, Nose, and Throat Hospital of Fudan University were enrolled. Five components were identified from the PCA of the SNOT-22 results and VAS scores related to subjective symptoms. More severe 'nasal' symptoms (P=0.03; 95% CI, 0.092-1.824), loss of smell and taste (P<0.001; 95% CI, 0.961-1.767) and lower facial pain (P=0.001; 95% CI 1.811 to -0.475), derived from the SNOT-22, were significantly associated with total CT score. For the VAS PCA components, less severe 'ocular' symptoms (P=0.004; 95% CI -1.852 to -0.352), a reduced 'pain' component (P<0.001; 95% CI -2.133 to -0.715), a higher 'nasal' symptom component (P<0.001; 95% CI 0.752-2.257) and, again, loss of smell and taste (P<0.001; 95% CI 0.437-0.811) showed an association with total CT score. 'Allergy-associated symptoms' in both the SNOT-22 and VAS scores and 'loss of smell or taste' and 'hyposmia' were significantly more severe in patients with ethmoid sinus/maxillary sinus (E/M) ratios of >2.59 compared with patients with E/M ratios <2.59. Loss of smell and taste alone was correlated with the LMS in patients with highly positive CT scores. The present study demonstrated associations between several subjective symptoms and objective severity in preoperative CRSwNP patients. Nasal symptoms, including olfaction loss, were correlated positively with CT scores, while ocular- and pain-related symptoms showed an opposite pattern. However, this relationship was not confirmed in patients with highly positive CT scores. A subset analysis confirmed, in terms of symptoms, the value of the E/M ratio for indicating eosinophilic chronic rhinosinusitis.