The effect of prednisolone and a short-term prednisolone discontinuation for the diagnostic accuracy of FDG-PET/CT in polymyalgia rheumatica-a prospective study of 101 patients.

PURPOSE: 2-[18F]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia rheumatica (PMR). However, the applicability of FDG-PET/CT remains unclear, especially following glucocorticoid administration. This study aimed to investigate the diagnostic accuracy of FDG-PET/CT before and during prednisolone treatment, as well as following short-term prednisolone discontinuation. METHODS: Treatment naïve suspected PMR patients were clinically diagnosed at baseline and subsequently had an FDG-PET/CT performed. Patients diagnosed with PMR were administered prednisolone following the first FDG-PET/CT and had a second FDG-PET/CT performed after 8 weeks of treatment. Subsequently, prednisolone was tapered with short-term discontinuation at week 9 followed by a third FDG-PET/CT at week 10. An FDG-PET/CT classification of PMR/non-PMR was applied, utilizing both the validated Leuven score and a dichotomous PMR score. The final diagnosis was based on clinical follow-up after 1 year. RESULTS: A total of 68 and 27 patients received a final clinical diagnosis of PMR or non-PMR. A baseline FDG-PET/CT classified the patients as having PMR with a sensitivity/specificity of 86%/63% (Leuven score) and 82%/70% (dichotomous score). Comparing the subgroup of non-PMR with inflammatory diseases to the PMR group demonstrated a specificity of 39%/54% (Leuven/dichotomous score). After 8 weeks of prednisolone treatment, the sensitivity of FDG-PET/CT decreased to 36%/41% (Leuven/dichotomous score), while a short-term prednisolone discontinuation increased the sensitivity to 66%/60%. CONCLUSION: FDG-PET/CT has limited diagnostic accuracy for differentiating PMR from other inflammatory diseases. If FDG-PET/CT is intended for diagnostic purposes, prednisolone should be discontinued to enhance diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020.

The effect of vasoconstriction on intestinal perfusion is determined by preload dependency: A prospective observational study.

BACKGROUND: The effects of vasoconstriction on cardiac stroke volume (SV) and indices of peripheral and intestinal perfusion are insufficiently described. METHODS: In a non-randomized clinical study, 30 patients undergoing elective rectal surgery were exposed to modulation of preload. The primary endpoint was intestinal perfusion (flux), measured by single-point laser Doppler flowmetry. Secondary endpoints were central cardiovascular variables obtained by the LiDCO rapid monitor, the peripheral perfusion index (PPI) derived from the pulse oximetry signal and muscle (StO2 ) and cerebral oxygenation (ScO2 ) determined by near-infrared spectroscopy. RESULTS: For the whole cohort (n = 30), administration of Phenylephrine during HUT induced a median [IQR] increase in SV by 22% [14-41], p = .003 and in mean arterial pressure (MAP) by 54% [31-62], p < .001, with no change in PPI, StO2 and ScO2 or flux. In patients who were preload dependent during HUT (stroke volume variation; SSV >10%; n = 23), administration of phenylephrine increased SV by 29% [12-43], p = .01 and MAP by 54% [33-63], p < .001, followed by an increase in intestinal perfusion flux by 60% [15-289], p = .05, while PPI, StO2 and ScO2  remained unchanged. For non-preload dependent patients (SSV <10%; n = 7), no changes in hemodynamic indices were seen besides an increase in MAP by 54% [33-58], p = .002. CONCLUSION: The reflection of vasoconstrictive modulation of preload in systemic cardiovascular variables and indices of perfusion was dependent on preload responsiveness. Administration of phenylephrine to increase preload did not appear to compromise organ perfusion.

Tendoscopic peritendon shaving of midportion Achilles tendinopathy: A randomized, placebo-controlled study.

Achilles tendinopathy is among the most frequent tendon injuries in sport. Despite evidence-based management, a significant proportion of patients continue to experience symptoms. This is the first randomized trial to investigate the effect of tendoscopic treatment of midportion Achilles tendinopathy compared with placebo at baseline, 3, 6 and 12 months. Patients with midportion Achilles tendinopathy (non-responsive to more than 6 months of nonsurgical treatments) were randomly assigned to receive either tendoscopic peritendon shaving or placebo tendoscopic treatment. The primary outcome measure was the total score of the Victorian Institute of Sport Assessment Achilles (VISA-A) questionnaire. Due to three adverse events (sural nerve injuries), in the group receiving tendoscopic treatment, the trial was stopped short of the planned 48 participants. All 23 patients included completed 3 months' follow-up (100%), 22 (96%) 6 months' and 19 (83%) completed 12 months' follow-up. The between-group estimates favored endoscopic treatment and ranged from 19 points (95% confidence interval [CI]: 1-38) at 3 months, 14 points (-7 to 34) at 6 months and 5 points (95% CI: -19 to 28) at 12 months. After 12 months, the tendoscopic group improved 47 points (95% CI: 29-65) versus 40 points (95% CI: 22-57) in the placebo-operated group. Despite a smaller sample size due to adverse events, VISA-A indicate faster recovery from tendoscopic treatment compared to placebo. These data suggest that tendoscopic treatment of midportion Achilles tendinopathy should be tested in further research; however, the technique needs to be refined to avoid sural nerve injuries.

Fast track clinic for early diagnosis of polymyalgia rheumatica: Impact on symptom duration and prednisolone initiation.

OBJECTIVES: To evaluate the efficacy of a fast track clinic (FTC) for patients suspected of polymyalgia rheumatica (PMR) regarding symptom duration, prednisolone initiation before rheumatological assessment, number of hospital contacts before diagnosis, and cancer diagnosis. METHODS: It is a retrospective cohort study with a one year follow-up period. Patients referred to the FTC (1st August 2016 to 25th June 2019) were compared to a historical cohort of PMR patients (1st August 2014 to 1st August 2016). Referral criteria are: age over 50, symptoms of PMR but not cranial GCA, and increased C-reactive protein. Data were obtained from patient journals. RESULTS: Ninety-seven PMR patients in the historical cohort and 113 FTC patients, of whom 83 patients had PMR, were included. The median (interquartile range) number of days from symptom onset until PMR diagnosis were 53 (31-83) days in the FTC versus 80 (58-132) days in the historical cohort (P<0.001). Prednisolone was prescribed before rheumatological assessment to 11% in the FTC versus 42% in the historical cohort (P<0.001). Patients in the FTC had significantly fewer contacts with the hospital before the diagnosis compared with the historical cohort. Four patients in the FTC were diagnosed with a cancer, all of which were found by imaging. CONCLUSION: The FTC reduced the time from symptom onset until diagnosis, lowered prednisolone initiation before rheumatological assessment, and resulted in fewer hospital visits. The frequency of cancers was low in patients suspected of PMR and cancers were discovered by imaging.

Characterisation of patients with idiopathic olfactory dysfunction and plan for clinical follow-up.

INTRODUCTION: Characterisation and management of olfactory dysfunction (OD) can be challenging, especially in patients diagnosed with idiopathic OD. This group of patients is at risk of developing neurodegenerative diseases such as Parkinson's disease, wherefore appropriate guidelines for management of OD are needed. We aimed to identify and characterise patients suffering from idiopathic hyposmia/anosmia. METHODS: This prospective study included 515 consecutive patients referred to the Flavour Clinic, Holstebro, Denmark. Patients with idiopathic, sino-nasal or post-infectious OD were compared with regards to symptoms and clinical findings including endoscopy of the upper airways, sino-nasal CT, allergy testing, and olfactory and gustatory assessment. RESULTS: Patients with idiopathic OD were older and a preponderance of females was observed compared with the sino-nasal group (p = 0.0302, and p = 0.0549, respectively). The OD group had a lower prevalence of allergy and longer symptom duration than both the sino-nasal and the post-infectious groups (p Less than 0.0001 and p = 0.0014; p less than 0.0001 and p less than 0.0001, respectively). CONCLUSIONS: Patients suffering from idiopathic OD were predominantly females with a long symptom duration. Only few of these patients suffered from allergies or sino-nasal pathologies. Patient history, the Sino-Nasal Outcome Test and threshold discrimination identification scores from the Extended Sniffin Sticks test are the most valuable clinical tools for diagnosing the aetiology behind OD. An ideal workup for idiopathic OD is presented. FUNDING: none. TRIAL REGISTRATION: not relevant.

Ultrasound imaging in patients with hip pain and suspected hip osteoarthritis: an inter-rater and intra-rater reliability study.

OBJECTIVES: The objectives of this study were to asses (1) inter-rater and intrarater reliability of ultrasound imaging in patients with hip osteoarthritis, and (2) agreement between ultrasound and X-ray findings of hip osteoarthritis using validated Outcome Measures in Rheumatology ultrasound definitions for pathology. DESIGN: An inter-rater and intrarater reliability study. SETTING: A single-centre study conducted at a regional hospital. PARTICIPANTS: 50 patients >39 years of age referred for radiography due to hip pain and suspected hip osteoarthritis were included. Exclusion criteria were previous hip surgery in the painful hip, suspected fracture or malignant changes in the hip. INTERVENTION: Bilateral ultrasound examinations (n=92) were performed continuously by two experienced operators blinded to clinical information and other imaging findings. After 4-6 weeks, one operator reassessed the images. X-rays were assessed by a third imaging specialist. PRIMARY AND SECONDARY OUTCOME MEASURES: Inter-rater and intrarater reliability and agreement between ultrasound imaging and X-ray were assessed using Cohen's ordinal kappa statistics for binary categorical variables and weighted kappa for ordered categorical variables. RESULTS: Kappa values (κ) for inter-rater reliability were 0.9 and 0.8 for hip effusion/synovitis and osteoarthritis grading, respectively. For acetabular and femoral osteophytes, femoral cartilage changes and labrum changes κ ranged from 0.4 to 0.7. Intrarater reliability had κ equal or higher compared with inter-rater reliability. Agreement between ultrasound and X-ray findings ranged from κ=0.2 to κ=0.5. CONCLUSION: This study demonstrated substantial to almost perfect reliability on the most common ultrasound findings related to hip osteoarthritis and osteoarthritis grading. Agreement on the grade of osteoarthritis between ultrasound and X-ray was moderate. Overall, these results support ultrasound imaging as a reliable tool in the assessment of hip osteoarthritis.

Impact of red and processed meat and fibre intake on treatment outcomes among patients with chronic inflammatory diseases: protocol for a prospective cohort study of prognostic factors and personalised medicine.

INTRODUCTION: Chronic inflammatory diseases (CIDs) are frequently treated with biological medications, specifically tumour necrosis factor inhibitors (TNFi)). These medications inhibit the pro-inflammatory molecule TNF alpha, which has been strongly implicated in the aetiology of these diseases. Up to one-third of patients do not, however, respond to biologics, and lifestyle factors are assumed to affect treatment outcomes. Little is known about the effects of dietary lifestyle as a prognostic factor that may enable personalised medicine. The primary outcome of this multidisciplinary collaborative study will be to identify dietary lifestyle factors that support optimal treatment outcomes. METHODS AND ANALYSIS: This prospective cohort study will enrol 320 patients with CID who are prescribed a TNFi between June 2017 and March 2019. Included among the patients with CID will be patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis), rheumatic disorders (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis. At baseline (pretreatment), patient characteristics will be assessed using patient-reported outcome measures, clinical assessments of disease activity, quality of life and lifestyle, in addition to registry data on comorbidity and concomitant medication(s). In accordance with current Danish standards, follow-up will be conducted 14-16 weeks after treatment initiation. For each disease, evaluation of successful treatment response will be based on established primary and secondary endpoints, including disease-specific core outcome sets. The major outcome of the analyses will be to detect variability in treatment effectiveness between patients with different lifestyle characteristics. ETHICS AND DISSEMINATION: The principle goal of this project is to improve the quality of life of patients suffering from CID by providing evidence to support dietary and other lifestyle recommendations that may improve clinical outcomes. The study is approved by the Ethics Committee (S-20160124) and the Danish Data Protecting Agency (2008-58-035). Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT03173144; Pre-results.

A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on Prognostic Factors and Personalised Medicine.

Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome.

Inflammatory and Metabolic Alterations of Kager's Fat Pad in Chronic Achilles Tendinopathy.

BACKGROUND: Achilles tendinopathy is a painful inflammatory condition characterized by swelling, stiffness and reduced function of the Achilles tendon. Kager's fat pad is an adipose tissue located in the area anterior to the Achilles tendon. Observations reveal a close physical interplay between Kager's fat pad and its surrounding structures during movement of the ankle, suggesting that Kager's fat pad may stabilize and protect the mechanical function of the ankle joint. AIM: The aim of this study was to characterize whether Achilles tendinopathy was accompanied by changes in expression of inflammatory markers and metabolic enzymes in Kager's fat pad. METHODS: A biopsy was taken from Kager's fat pad from 31 patients with chronic Achilles tendinopathy and from 13 healthy individuals. Gene expression was measured by reverse transcription-quantitative PCR. Focus was on genes related to inflammation and lipid metabolism. RESULTS: Expression of the majority of analyzed inflammatory marker genes was increased in patients with Achilles tendinopathy compared to that in healthy controls. Expression patterns of the patient group were consistent with reduced lipolysis and increased fatty acid ß-oxidation. In the fat pad, the pain-signaling neuropeptide substance P was found to be present in one third of the subjects in the Achilles tendinopathy group but in none of the healthy controls. CONCLUSION: Gene expression changes in Achilles tendinopathy patient samples were consistent with Kager's fat pad being more inflamed than in the healthy control group. Additionally, the results indicate an altered lipid metabolism in Kager's fat pad of Achilles tendinopathy patients.

Limited success in patients treated with transanal haemorrhoidal dearterialisation.

INTRODUCTION: Transanal haemorrhoidal dearterialisation (THD) is a novel non-excisional technique based on suture closure of the haemorrhoidal arterial flow feeding the haemorrhoidal plexus. The primary objective of this study was to report the first Danish experience with THD. METHODS: The study was a single-centre, non-controlled retrospective study that comprised consecutive patients from a two-year period. Prior to the study start, THD was introduced in our surgical department as the standard treatment of Grade III-IV haemorrhoids. All patients were clinically examined 4-6 weeks post-operatively. Additionally, a structured telephone interview was conducted within two years after the THD operation. RESULTS: During the study period (from January 2011 to January 2013), 93 patients underwent a THD procedure. Twenty patients were exluded from the study which left 73 patients for analysis. Treatment success was obtained in 47 patients (64%) after a median follow-up period of nine months (range 1-24 months). CONCLUSION: We found a relatively low success rate of 64% in patients undergoing THD. Our findings may, in part, reflect a learning curve, patient selection, or that a low success rate is associated with the use of THD per se. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Stereological quantification of immune-competent cells in baseline biopsy specimens from achilles tendons: results from patients with chronic tendinopathy followed for more than 4 years.

BACKGROUND: Limited data exist on the presence and function of immune-competent cells in chronic tendinopathic tendons and their potential role in inflammation and tissue healing as well as in predicting long-term outcome. PURPOSE: To quantify subtypes of immune-competent cells in biopsy specimens from nonruptured chronic tendinopathic Achilles tendons and healthy control tendons. In addition, to examine whether findings in baseline cell biopsy specimens can predict the long-term presence of Achilles tendon symptoms. STUDY DESIGN: Cross-sectional and case-control study; Level of evidence, 3. METHODS: Fifty patients with nonruptured chronic Achilles tendinopathy and 15 healthy participants were included. At time of inclusion, an ultrasound examination was performed immediately before an ultrasound-guided Achilles tendon biopsy specimen was obtained. Tissue samples were evaluated immunohistochemically by quantifying the presence of macrophages (CD68-PGM1(+), CD68-KP1(+)), hemosiderophages (Perls blue), T lymphocytes (CD2(+), CD3(+), CD4(+), CD7(+), CD8(+)), B lymphocytes (CD20(+)), natural killer cells (CD56(+)), mast cells (NaSDCl(+)), Schwann cells (S100(+)), and endothelial cells (CD34(+)) using a stereological technique. A follow-up examination was conducted more than 4 years (range, 4-9 years) after the biopsy procedure to evaluate the long-term presence of Achilles tendon symptoms. RESULTS: Macrophages, T lymphocytes, mast cells, and natural killer cells were observed in the majority (range, 52%-96%) of biopsy specimens from nonruptured chronic tendinopathic Achilles tendons. CD68-KP1(+) macrophages (0.29% vs 0; P = .005) and CD34(+) endothelial cells (3% vs 0.97%; P = .04) were significantly more numerous in tendinopathic tendons compared with healthy tendons. The presence of iron(+) hemosiderophages was more frequently observed in biopsy specimens obtained from the group who was asymptomatic at follow-up compared with the symptomatic group (42% vs 5%; P = .02). CONCLUSION: This study provides evidence for the presence of immune-competent cells in the majority of biopsy specimens from nonruptured chronic tendinopathic Achilles tendons. Macrophages and endothelial cells were significantly more numerous in tendinopathic tendons than in healthy tendons. The presence of iron(+) hemosiderophages in baseline biopsy specimens was associated with a good prognosis. CLINICAL RELEVANCE: New insight into the role of immune-competent cells in chronic Achilles tendinopathy.

PTH(1-84) replacement therapy in hypoparathyroidism: a randomized controlled trial on pharmacokinetic and dynamic effects after 6 months of treatment.

Untreated, hypoparathyroidism (hypoPT) is a state of hypocalcemia with inappropriately low plasma parathyroid hormone (PTH) levels and hyperphosphatemia. PTH administration normalizes plasma calcium and phosphate levels and reduces the doses of calcium and active vitamin D analogues needed. To develop an evidence-based clinical algorithm to monitor hypoPT patients treated with recombinant human PTH (rhPTH[1-84]) injected subcutaneously in the thigh, we performed a 24-hour monitoring study of pharmacokinetic and pharmacodynamic effects in a group of 38 patients who had completed a 6-month randomized study on effects of treatment with a fixed rhPTH(1-84) dose of 100 µg/d or similar placebo as an add-on to conventional treatment. PTH levels rose immediately, reaching a median peak level of 26.5 (interquartile range [IQR], 20.1-42.5) pmol/L 15 minutes following injection. Thereafter, levels gradually decreased until reaching predosing levels after 16 hours, with a plasma half-life of 2.2 (1.7-2.5) hours. rhPTH(1-84) changed the diurnal rhythms of ionized calcium levels and 1,25-dihydroxyvitamin D (1,25[OH]2 D) levels, with rising levels following injection. Ionized calcium peaked after 7.0 (5.0-10.0) hours. Asymptomatic hypercalcemia was present in 71% of the rhPTH(1-84)-treated patients. Compared with placebo, 24-hour urinary calcium, phosphate, and magnesium did not change, although the diurnal variation in renal excretion rates changed significantly in response to treatment. In conclusion, as a safety precaution, we recommend occasionally measuring calcium levels at approximately 7 hours after administration in order to reveal episodes of hypercalcemia. A 100-µg daily dose of rhPTH(1-84) appears to be too high in some patients, suggesting a need for a device allowing for individual dose adjustments.

Ultrasound-guided drainage of subcutaneous abscesses on the trunk is feasible.

INTRODUCTION: Subcutaneous trunk abscesses are frequent, and current treatment options generally involve incision. By contrast, the standard care for breast abscesses is ultrasound-guided drainage. The aim of this study was to evaluate the feasibility of ultrasound-guided drainage combined with antibiotics in the treatment of subcutaneous abscesses on the trunk. MATERIAL AND METHODS: In this prospective study, 27 patients were treated with ultrasound-guided needle aspiration and oral antibiotics. Follow-up was performed at a 3-6-day interval, and the procedure was repeated if the abscess was not obliterated. RESULTS: Treatment was initially successful in 25 of the 27 participants (93%); two patients went on to surgery. The median time from first treatment to the final control visit was nine days. The 25 patients with initial successful treatment were contacted after a median of 84 days, and six (24%) of these reported recurrence of an abscess at the puncture site. 88% of the patients reported that they were satisfied or very satisfied with ultrasound-guided drainage. CONCLUSION: Our results indicate that ultrasound-guided drainage combined with antibiotics is feasible in the treatment of small subcutaneous abscesses on the trunk. Ultrasound-guided drainage was well-tolerated, had a high degree of success and short healing times. Additional randomised studies are needed to verify our findings. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

[HCG in the treatment of cryptorchidism. The effect of age and position of the testis]. / Humant choriongonadotropin-behandling af kryptorkisme. Effekt af alder og testisplacering.

In a recent study, the effect of human chorionic gonadotropin (HCG) in the treatment of children with cryptorchidism aged less than four years was questioned. The purpose of the present study was to determine, on the basis of a retrospective examination of patients' records, the effect of HCG treatment, whether outcomes are age-dependent and whether the effects of treatment are related to the position of the testis. Patients diagnosed with undescended testis who had been treated at the Department of Urology at Gentofte Hospital (Copenhagen) in the period from 1 November 1998 to 31 May 2003 were identified. Patients who had been treated with HCG were included in the sample. Boys who at an earlier stage had been operated on in the inguinal or scrotal region, or who had suffered from inguinal hernia, were excluded, and clinical retractile testes were separated from true undescended testes. The criterion of success for efficient treatment was complete descent to the bottom of the scrotum. In the 306 records examined, 121 patients met the inclusion criteria. In total, there were 170 undescended testes. The patients' median age at time of treatment was 3.6 years. The overall success rate was 34.7%. The success rates in the individual age categories were: 1-2 years, 36.7%; 3-4 years, 33.4%; and 5-13 years, 35%. The position of the testis at the beginning of treatment showed that the lower the pretreatment position, the better the success rate. The overall success of HCG treatment of cryptorchidism was 34.7%. No age dependency of HCG effects was found, but the position of the testis before treatment influenced the success rate.