Intrabursal Injection Research Articles

Intrabursal Doxycycline Sclerotherapy for Recurrent Olecranon Bursitis of the Elbow: A Case Control Study

This study aimed to determine the efficacy and safety of intrabursal injection of doxycycline sclerotherapy to treat olecranon bursitis (OB) refractory to conservative management. We retrospectively reviewed 27 patients with recurrent OB who were treated over 11 years with intrabursal injections of doxycycline. They were compared with a control group of 18 patients with recurrent OB who underwent surgical bursectomy. Patients were re-evaluated by the treating physician for recurrence of bursitis and treatment complications and completed a questionnaire to assess satisfaction, pain, and other patient-reported outcomes. Eight patients (29.6%) undergoing doxycycline sclerotherapy had recurrence, requiring one more doxycycline lavage within the first 4 weeks of initial doxycycline treatment. Three patients (16.7%) undergoing surgery had recurrence after surgery, requiring repeat aspiration. There were no patients in either doxycycline or surgical groups with recurrence of bursitis at the final follow-up (median= 195 and 1,055 days, respectively). No patients in the doxycycline group ultimately required surgical bursectomy, and no patients undergoing surgery required repeat surgeries. A regression model controlling for covariates did not find a significant difference between groups in the likelihood of physician-identified complication or repeat aspiration after doxycycline lavage or surgical bursectomy. Of patients undergoing doxycycline sclerotherapy, 85.7% of patients reported high satisfaction (Likert score: 8-10), and 95.2% reported that they would pursue this treatment again. Use of intrabursal doxycycline as a sclerosing agent for recurrent OB was safe and effective, with high patient satisfaction and no ultimate recurrence of bursitis at the final follow-up. This may be an effective alternative to surgical bursectomy for patients with recurrent OB refractory to conservative management. Therapeutic IV.

Autophagy in the corpus luteum correlates with tissue growth in pregnant rats.

The developmental activation of the corpus luteum (CL) structurally and functionally is critical for the temporally regulated establishment, maintenance, and termination of pregnancy in rats. In this study, we have investigated the possible involvement of autophagy in the regulation of the CL during pregnancy in rats. The expression ratio of microtubule-associated protein light chain 3 (LC3)-II/-I, a widely used indicator of autophagic activity, in the CL remained relatively stable until day 15 of pregnancy. Subsequently, it progressively increased until day 21, and then declined until day 3 postpartum. This fluctuation was closely associated with the tissue weight of the CL rather than progesterone (P4) production activity. Light and electron microscopy revealed the presence of immunoreactive LC3 aggregates and irregularly shaped autolysosome-like microstructures in the cytoplasm of luteal cells during late pregnancy. Notably, a bolus intrabursal injection of the autophagy inhibitor bafilomycin A1 on day 15 of pregnancy resulted in a significant reduction in luteal cell size and disrupted the normal alteration of circulating P4 levels. Consequently, treatment with this inhibitor increased the likelihood of the varied timing (both advanced and delayed) of delivery and led to reduced body weight in neonates when compared with the vehicle-treated control group. Our findings suggest that autophagy in the rat CL contributes to luteal tissue growth, influences P4 production, and thereby fine-tunes the regulation of gestation length in rats.

Non-surgical treatment of aseptic olecranon bursitis: A systematic review

ObjectiveOlecranon bursitis (OB), characterized by inflammation and fluid collection in the olecranon bursa is a commonly encountered out-patient condition. The data is heterogeneous regarding a stepwise and standardized approach to aseptic OB treatment and the efficacy of intra-bursal corticosteroid injections (CSI). The objective of this review is to systematically evaluate the non-surgical treatment options for aseptic OB. MethodsThis systematic review was conducted in accordance with PRISMA recommendations. The English and non-English literature search was performed in 5 medical databases to identify studies evaluating the treatment of OB. All included studies were evaluated for risk of bias (RoB) using the revised Cochrane RoB tool for randomized control trials (RCTs) and the Newcastle-Ottawa Scale (NOS) for case–control and cohort studies. ResultsFor the final analyses, 2 RCTs and 2 observational studies were included. The RoB for the RCTs was high and both failed to demonstrate a significant difference in terms of the resolution of OB and bursal tenderness among various invasive and non-invasive treatment options. Corticosteroid injection (CSI) was associated with a significant decline in the duration of symptoms. However, it was associated with a higher number of complications including bursal infection and skin atrophy. ConclusionBased on the available data, it appears that the clinical resolution of aseptic OB can occur with conservative methods if implemented earlier in the disease course. Although CSI is more effective than other treatments, it should be reserved for refractory cases because of a higher complication rate.

Tips and tricks in ultrasound-guided musculoskeletal interventional procedures.

Ultrasound visualization affords proceduralists versatile and accurate guidance for a variety of percutaneous, minimally invasive procedures in the musculoskeletal system including joint (intra-articular) injections or aspirations, intra-bursal injections, peritendinous, and perineural injections. A variety of percutaneous procedures are traditionally performed blindly, but may be more easily or more accurately performed with the real-time assistance of ultrasound guidance. Other procedures are only possible utilizing image-guidance, due to the required precision of the injection because of delicate local anatomy or depth of the injection; ultrasound is a safe, portable, and widespread modality that can be used to assist the proceduralist in localizing the needle tip in such cases, to ensure safe and accurate delivery of the medication, most frequently a solution of steroid and anesthetic. This review aims to provide a foundational approach to ultrasound-guided procedures in the musculoskeletal system, offering tips and tricks that can be employed in many different procedures including intra-articular, juxta-articular, and perineural injections for a multitude of clinical scenarios. Technical considerations regarding ultrasound transducer selection, sonographic technique, as well as common indications, contraindications, and complications of these procedures, are presented. Additionally, a variety of pharmacologic considerations for proceduralists contemplating ultrasound-guided injections are discussed.

A prospective study of 100 patients with rotator cuff tendinopathy showed no correlation between subacromial bursitis and the efficacy of ultrasound-guided corticosteroid injection.

The objective of this study was to determine whether the presence of subacromial bursitis in patients with rotator cuff tendinopathy (RCT) was associated with a better outcome after ultrasound (US)-guided subacromial corticosteroid injection. A single-center prospective study was performed including patients referred for subacromial injection to manage RCT. At baseline, all patients received an US-guided intra-bursal injection of betamethasone (1ml). The primary endpoint was reduced pain 3months (M3) after the procedure: a good responder was defined by a decrease in Visual Analogue Scale pain of more than 30%. Secondary endpoints included functional recovery assessed by the Oxford Shoulder Score (OSS) and clinical success at 6weeks (W6). We also explored the association between good clinical response and other factors, such as US or X-ray features. One hundred patients were included and 49 presented with subacromial bursitis. At M3, 60% of patients (54/100) were considered good responders. The rate of good responders did not differ between the bursitis and non-bursitis groups (p = 0.6). During follow-up, OSS improved over time whether bursitis was present or not. We did not find any US or X-ray features significantly associated with a favorable clinical outcome. The presence of subacromial bursitis did not influence clinical outcomes at 3months post-subacromial injection in patients suffering from RCT. The presence of subacromial bursitis did not influence clinical outcomes at 3months post-subacromial corticosteroid injection in patients with rotator cuff tendinopathy. For patient management, looking for ultrasonographic signs of bursitis does not appear relevant for the indication of the injection. • Ultrasound-guided subacromial corticosteroid injections led to a significant improvement in 60% of patients suffering from rotator cuff tendinopathy. • The presence of subacromial bursitis was not associated with better improvement at 3months post-injection. • Except for the Minnesota score referring to job satisfaction, we did not find any baseline clinical, X-ray, or ultrasound characteristics associated with a successful outcome.

O-246 The molecular mechanism of miR-96-5p in the pathogenesis and treatment of polycystic ovary syndrome

Abstract Study question Polycystic ovary syndrome, characterized by the androgen excess and arrest of antral follicles, is lacking novel specific diagnostic biomarkers and therapeutic targets. Summary answer Study of the molecular mechanisms of microRNAs in the etiology and its potential applications in PCOS provides the insight. What is known already Some of molecular mechanisms of microRNAs have been demonstrated involved in the etiology of PCOS Study design, size, duration Clinically, we collected the samples of serum, follicular fluid (FF) and primary human granulosa cells (hGCs) of PCOS patients (n = 70) vs. non-PCOS women (n = 60). Experimentally, we carried out studies with 3-types of induced PCOS-like mice. Participants/materials, setting, methods By analysing the expression levels of miR-96-5p in serum, follicular fluid (FF) and primary human granulosa cells (hGCs) of PCOS patients (n = 70) vs. non-PCOS women (n = 60). as well as in ovaries from 3-types of induced PCOS-like mice. Main results and the role of chance Clinically, we demonstrated that the elevated circulating miR-96-5p levels were significantly correlated with the PCOS disordered endocrine clinical features, and the area under the curve of receiver operating characteristic was 0.8344, with 75.71% specificity and 80% sensitivity. Mechanically, we identified miR-96-5p as an androgen-regulated miRNA that directly targets the forkhead transcription factor FOXO1. Inhibition of miR-96-5p decreased estrogen synthesis, while decreasing the cell proliferation index of KGN via regulating the expression of FOXO1 and its downstream genes. Inversely, inhibition of FOXO1 abrogated the effect of miR-96-5p on estrogen synthesis and proliferation index. Of note, ovarian intra-bursal injection of miR-96-5p agomir rescued the phenotypes of dehydroepiandrosterone-induced PCOS like mice. Limitations, reasons for caution This study needs a large-scale clinical investigation to confirm the specificity and sensitivity of miR-96-5p as a clinical biomaker. Wider implications of the findings In conclusion, our results clarified a vital role of miR-96-5p in the pathogenesis of PCOS and might serve as a novel diagnostic biomarker and therapeutic target for PCOS. Trial registration number no

Obesity-induced inflammatory miR-133a mediates apoptosis of granulosa cells and causes abnormal folliculogenesis.

Obesity has been reported to promote disordered folliculogenesis, but the exact molecular mechanisms are still not fully understood. In this study, we find that miR-133a is involved in obesity-induced follicular development disorder. After feeding with a high-fat diet (HFD) and fructose water for nine weeks, the mouse body weight is significantly increased, accompanied by an inflammatory state and increased expression of miR-133a in the adipose tissues and ovaries as well as accelerated follicle depletion. Although miR-133a is increased in the fat and ovaries of HFD mice, the increased miR-133a in the HFD ovaries is not derived from exosome transferred from obese adipose tissues but is synthesized by ovarian follicular cells in response to HFD-induced inflammation. In vivo experiments show that intrabursal injection of miR-133a agomir induces a decrease in primordial follicles and an increase in antral follicles and atretic follicles, which is similar to HFD-induced abnormal folliculogenesis. Overexpression of miR-133a modestly promotes granulosa cell apoptosis by balancing the expression of anti-apoptotic proteins such as C1QL1 and XIAP and pro-apoptotic proteins such as PTEN. Overall, this study reveals the function of miR-133a in obesity-induced ovarian folliculogenesis dysfunction and sheds light on the etiology of female reproductive disorders.

The molecular mechanism of miR-96-5p in the pathogenesis and treatment of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS), characterized by the androgen excess and arrest of antral follicles, is a common endocrine disorder among women lacking specific diagnostic biomarkers and therapeutic targets. Herein, we studied the molecular mechanism of miR-96-5p in the process of PCOS and its potential applications in PCOS. Clinically, we found that miR-96-5p significantly decreased in serum, follicular fluid and primary human granulosa cells (hGCs) of PCOS patients (n = 70) vs non-PCOS women (n = 60), as well as in the ovaries of 3-types of induced PCOS-like mice. Furthermore, we demonstrated that the elevated circulating miR-96-5p levels were significantly correlated with the PCOS disordered endocrine clinical features, and the area under the curve of receiver operating characteristic was 0.8344, with 75.71% specificity and 80% sensitivity. Mechanically, we identified miR-96-5p as an androgen-regulated miRNA that directly targets the forkhead transcription factor FOXO1. Inhibition of miR-96-5p decreased estrogen synthesis, while decreasing the cell proliferation index of KGN via regulating the expression of FOXO1 and its downstream genes. Inversely, inhibition of FOXO1 abrogated the effect of miR-96-5p on estrogen synthesis and proliferation index. Of note, ovarian intra-bursal injection of miR-96-5p agomir rescued the phenotypes of dehydroepiandrosterone-induced PCOS like mice. In conclusion, our results clarified a vital role of miR-96-5p in the pathogenesis of PCOS and might serve as a novel diagnostic biomarker and therapeutic target for PCOS.

Ultrasound-Guided Iliopsoas Bursal Injections for Management of Iliopsoas Bursitis After Total Hip Arthroplasty

BackgroundIliopsoas tendonitis can cause persistent pain after total hip arthroplasty (THA). Nonoperative management of iliopsoas tendonitis includes anti-inflammatory drugs and image-guided corticosteroid injections. This study evaluated the efficacy of ultrasound-guided corticosteroid injections (US-CSIs) for iliopsoas tendonitis following THA. MethodsWe retrospectively reviewed 42 patients who received an US-CSI for iliopsoas tendonitis after primary THA between 2009 and 2020 at a single institution. Outcomes including reoperation, groin pain at last follow-up, additional intrabursal injection, and Harris Hip Score (HHS) were evaluated at a minimum of 1 year. Cross-table lateral radiographs (36 patients) or computed tomography scans (6 patients) were reviewed to determine if anterior cup overhang was present, indicating a mechanical etiology of iliopsoas tendonitis. Descriptive statistics and univariate comparison of HHS preinjection and postinjection were performed, with alpha < 0.05. ResultsAmong the 22 patients who did not have cup overhang, four (18.2%) had persistent groin pain at mean follow-up of 40 months (range, 14-94) after US-CSI. Three patients had a second injection; none had groin pain at most recent follow-up. No patients required acetabular revision. Mean HHS improved from 74 points (range, 52-94 points) to 91 points (range, 76-100 points; P < .001) at last follow-up. Among the 20 patients who had anterior cup overhang, five underwent acetabular revision after only temporary pain relief from injection. Groin pain was resolved in all revised patients at mean follow-up of 43 months (range, 12-60) after revision. Of the remaining 15 patients, five had persistent groin pain at mean follow-up of 35 months (range, 12-83). Mean HHS improved from 69 points (range, 50-96 points) preinjection to 81 (range, 56-98 points; P = .007) at last follow-up. ConclusionResolution of groin pain was demonstrated in 78.6% of patients in the cohort; however, those who did not have acetabular overhang had higher rates of success. The overall revision rate was 11.9%. US-CSI appears to be safe and effective in the diagnosis and treatment of iliopsoas tendonitis following primary THA. Level of EvidenceLevel IV, Therapeutic Study.

Role and mechanism of miR-335-5p in the pathogenesis and treatment of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of unknown etiology that occurs in women of reproductive age. Despite being considered to affect up to one-fifth of women in this cohort, the condition lacks generally accepted diagnostic biomarkers and options for targeted therapy. Hereby, we analyzed the diagnostic, therapeutic, and functional potential of a recently discovered miR-335-5p that was observed to be reduced in the follicular fluid (FF) of PCOS patients as compared with healthy women. We found miR-335-5p to be significantly decreased in the serum and FF samples of PCOS patients (n=40) vs healthy women (n=30), as well as in primary human granulosa cells (hGCs), and in 3 different hormonally induced PCOS-like murine models vs. wild-type (WT) mice. The level of circulating miR-335-5p was found to significantly correlate with the impaired endocrine and clinical features associated with PCOS in human patients. Ovarian intrabursal injection of the miR-335-5p antagomir in WT mice ovaries induced a PCOS-like reproductive phenotype. Treatment with the miR-335-5p agomir rescued the dihydrotestosterone-induced PCOS-phenotype in mice, thereby providing a functional link between miR-335-5p and PCOS. We identified SP1 as a miR-335-5p target gene by using the dual-luciferase reporter assay. Both the luciferase reporter assay and chromatin immunoprecipitation assay showed that SP1 bound to the promoter region of human CYP19A1 and inhibited its transcription. miR-335-5p increased the production of estradiol via the SP1/CYP19A1 axis in hGCs, thereby suggesting its mechanistic pathway of action. In conclusion, these results provide evidence that miR-335-5p may function as a mediator in the etiopathogenesis of PCOS, as well as has the potential as both a novel diagnostic biomarker and therapeutic target for PCOS.

Ultrasound-guided Treatments for the Painful Shoulder.

Shoulder pain is an extremely common condition. The painful shoulder may be the result of a wide spectrum of underlying pathological conditions, including calcific tendinopathy of the rotator cuff, subacromial-subdeltoid bursitis, acromioclavicular or glenohumeral arthritis, tenosynovitis of the long biceps tendon, rotator cuff lesions, and many other less common conditions. Ultrasound imaging is an effective tool for the diagnosis and also for the image guidance of treatment of the majority of these conditions. Several ultrasound-guided procedures are effective for pain relief, such as percutaneous irrigation, intra-bursal or intra-articular drugs injection, fluid aspiration, neural block. This review article aims to summarize and discuss the most common treatment possibilities with ultrasound guidance for the painful shoulder.

Deficiency of C1QL1 Reduced Murine Ovarian Follicle Reserve Through Intraovarian and Endocrine Control.

Ovarian aging is associated with depletion of the ovarian follicle reserve, which is the key determinant of fertility potential in females. In this study, we found that the small, secreted protein complement 1Q-like (C1QL1) is involved in the regulation of follicle depletion through intraovarian and endocrine control in a multidimensional collaborative manner. C1ql1 was detected to be conserved in the ovary and showed high transcript levels during folliculogenesis. Blockade of C1QL1 by IP and ovarian intrabursal injection of C1QL1 antiserum into prepubertal mice impaired folliculogenesis accompanied by reductions in body weight, fat mass, and intraovarian lipid accumulation. An elevation of circulating estradiol levels, reduction of hypothalamic KISS1 and GnRH expression, and a decrease in serum FSH levels were found in C1QL1-deficient mice. In C1QL1-deficient ovaries, many primordial follicles were recruited and developed into medium follicles but underwent atresia at the large follicle stages, which resulted in depletion of follicle reserve. Depletion of C1QL1 alleviated the inhibitory effect of C1QL1 on granulosa cell apoptosis and the stimulatory effect of C1QL1 on granulosa cell autophagy, which resulted in accumulation in the preantral and early antral follicles and an increase in the atretic follicles. The abnormal profile of endocrine hormones accelerated the intraovarian effect of C1QL1 deficiency and further led to depletion of ovarian reserve. Altogether, this study revealed the expression patterns and the mechanism of action of C1QL1 during folliculogenesis and demonstrated that deficiency of C1QL1 caused ovarian follicular depletion.

Oncogenic Events Dictate the Types and Locations of Gynecological Malignancies Originating from Krt8+ Mesothelial and Müllerian-Derived Epithelial Cells.

Simple SummaryOvarian and uterine cancers are the most common gynecological malignancies in women. The early detection, prevention, and treatment of these gynecological cancers can benefit from a better understanding of how tumor-initiating cells in them are formed from their corresponding target cell populations in the female reproductive system. To study this, we utilized a genetic approach in mice to introduce driver mutations commonly found in these cancers to Keratin 8 positive (K8+) mesothelial and epithelial cells in the ovary, fallopian tube, and uterus. We found that p53-loss appears to preferentially affect K8+ epithelial cells, leading to the development of uterine and ovarian malignancies, whereas PTEN-loss may preferentially affect mesothelial cells, leading to the development of ovarian endometrioid malignancies or adenoma on the fallopian tube surface. Collectively, our data suggest that oncogenic driver mutations may dominantly determine the locations and types of gynecological malignancies developed from K8+ mesothelial and epithelial cells in the female reproductive system.Ovarian and uterine cancers are the most prevalent types of gynecological malignancies originating from mesothelial and/or Müllerian-derived epithelial cells. Recent genomic studies have identified common mutations in them that affect signaling pathways such as p53, PTEN/PI3K, RAS, and WNT pathways. However, how these mutations and their corresponding deregulated pathways affect gynecological cancer development from their cells-of-origin remains largely elusive. To address this, we performed the intrabursal injection of Cre-expressing adenovirus under the control of Krt8 promoter (Ad-K8-Cre) to mice carrying combinations of various conditional alleles for cancer genes. We found that Ad-K8-Cre specifically targeted mesothelial cells, including ovarian surface epithelial (OSE) cells (mainly the LGR5+ subset of OSE cells) and mesothelial cells lining the fallopian tube (FT) serosa; the injected Ad-K8-Cre also targeted Müllerian-derived epithelial cells, including FT epithelial cells and uterine endometrial epithelial cells. The loss of p53 may preferentially affect Müllerian-derived epithelial cells, leading to the development of uterine and ovarian malignancies, whereas PTEN-loss may preferentially affect mesothelial cells, leading to the development of ovarian endometrioid malignancies (upon KRAS-activation or APC-loss) or adenoma on the FT surface (upon DICER-loss). Overall, our data suggest that different Krt8+ mesothelial and epithelial cell types in the female reproductive system may have different sensitivities toward oncogenic mutations and, as a result, oncogenic events may dominantly determine the locations and types of the gynecological malignancies developed from them.

Effects of Ultrasound-Guided Peritendinous and Intrabursal Corticosteroid Injections on Shoulder Tendon Elasticity: A Post Hoc Analysis of a Randomized Controlled Trial

ObjectivesThe study aimed to investigate whether the shoulder tendons changed their elasticity after ultrasound-guided peritendinous or intrabursal corticosteroid injections. DesignPost hoc secondary analysis of a double-blinded, randomized controlled study with 3 months of follow-up. SettingOutpatient rehabilitation clinic. ParticipantsPatients with subacromial impingement syndrome (N=60). InterventionsPatients with unilateral shoulder pain were randomly assigned to receive standard ultrasound-guided subacromial or dual-target corticosteroid injections. The supraspinatus tendons were exposed to 40 mg triamcinolone acetonide in the formal group, whereas the long head of the biceps brachii tendons (LHBT) and supraspinatus tendons were individually infiltrated by 20 mg triamcinolone acetonide in the latter group. Patients’ bilateral shoulders were divided into group 1 (n=30, receiving standard subacromial injections), group 2 (n=30, receiving dual-target injections), and group 3 (n=60, without injections). Main Outcome MeasuresStrain ratio of LHBT and supraspinatus tendons using ultrasound elastography. ResultsThe repeated-measures analysis of variance revealed no intragroup difference of the strain ratio of the LHBT (P=.412 for group 1, P=.936 for group 2, P=.131 for group 3) and supraspinatus tendon (P=.309 for group 1, P=.067 for group 2, P=.860 for group 3) across the 3 time points. Treating group 3 as the reference, the linear mixed model revealed no significant changes in tendon elasticity after either the standard subacromial injection (P=.205 for the LHBT and P=.529 for the supraspinatus tendon) or the dual-target injection (P=.961 for the LHBT and P=.831 for the supraspinatus tendon). ConclusionsElasticity of the LHBT and supraspinatus tendons is unlikely to change after a single dose of peritendinous or intrabursal corticosteroid injections. Future studies with a shorter follow-up interval are needed to validate whether corticosteroid injections can cause transient changes of the tendon’s elasticity.

Botulinum Toxin Injections for Shoulder and Upper Limb Pain: A Narrative Review

Botulinum toxin (BoNT) has been widely employed to treat poststroke spasticity, cervical dystonia and muscle hyperactivity. Recently, BoNT injections are increasingly used in treating musculoskeletal pain. The mechanism of BoNT in pain relief comprises relaxation of overused muscles and inhibition of inflammatory nociceptive cytokines/neurotransmitters. As BoNT injections seem promising in treating painful musculoskeletal disorders, we aimed to investigate its effectiveness in shoulder and upper limb pain. Although the present article is a narrative review, we employed a systematic approach to search for relevant articles in PubMed. A total of 19 clinical studies were included. Here, we observed that intramuscular BoNT injections were helpful in stroke patients with hemiplegic shoulder pain. In shoulder joint pain, intra-articular and intrabursal BoNT injections achieved a longer period of pain relief than corticosteroid injections. Similarly, a more durable effect of intramuscular BoNT than saline injections was seen in shoulder myofascial pain. Its use in complex regional pain syndrome and persistent upper limb pain in breast cancer survivors was insufficient, necessitating more studies. Since not all of the included studies could provide Class I of evidence based on the efficacy criteria used by American Academy of Neurology, controlled clinical trials in a larger number of patients are necessary to verify validity of these findings in the future.

Ultrasound-guided percutaneous irrigation of calcific tendinopathy: redefining predictors of treatment outcome.

To identify prognostic factors affecting the clinical outcome in patients treated with rotator cuff ultrasound-guided percutaneous irrigation of calcific tendinopathy (US-PICT), by evaluating the degree of calcium removal, the size and consistency of calcific deposits, and baseline level of shoulder pain and functionality. From January 2017 to December 2019, 79 patients (23 males, 56 females; mean age, 45.7 years) who underwent US-PICT were prospectively enrolled. The calcifications' location, consistency, and size were evaluated. For US-PICT, local anesthesia, lavage of calcific material, and intrabursal steroid injection were performed. The degree of calcium removal was graded as total/partial. Shoulder pain and functionality were assessed with the visual analogue scale (VAS) in all and Constant score (CS) in a subset of patients, respectively, at 4 time-points. Mann-Whitney U test, Fisher's test, and linear and binary logistic regression were utilized for analysis. Pain improvement correlated with the presence of larger calcifications and lower baseline VAS score, at 1 week (p = 0.001, p < 0.001, respectively) and 1 year (p < 0.001, p = 0.002, respectively). Improved functionality correlated with total calcification retrieval, higher baseline CS, and fluid/soft calcific consistency at 1 week (p = 0.013, p = 0.003, p = 0.019, respectively). Increased calcification size, cystic appearance, and lower baseline VAS scores independently predicted complete pain resolution at 1 year. Large calcifications and low-grade pain at baseline correlated with short- and long-term pain improvement. The degree of calcium removal did not impact pain or functional improvement beyond 1 week. Increased calcification size, cystic appearance, and low-grade baseline pain predicted complete pain recovery at 1 year. • The presence of larger calcifications and lower-grade baseline pain appear to correlate with pain improvement at 1 week and 1 year after ultrasound-guided irrigation of rotator cuff calcific tendinopathy (US-PICT). • Total calcification retrieval, less affected baseline shoulder functionality, and presence of fluid/soft consistency of calcific deposits appear to correlate with improved shoulder functionality at 1 week post-treatment. • Baseline pain intensity and calcifications' morphologic characteristics, but not the degree of calcium retrieval, represent predictors of complete pain recovery at 1 year after US-PICT.

LY75 Suppression in Mesenchymal Epithelial Ovarian Cancer Cells Generates a Stable Hybrid EOC Cellular Phenotype, Associated with Enhanced Tumor Initiation, Spreading and Resistance to Treatment in Orthotopic Xenograft Mouse Model.

The implications of the epithelial–mesenchymal transition (EMT) mechanisms in the initiation and progression of epithelial ovarian cancer (EOC) remain poorly understood. We have previously shown that suppression of the antigen receptor LY75 directs mesenchymal–epithelial transition (MET) in EOC cell lines with the mesenchymal phenotype, associated with the loss of Wnt/β-catenin signaling activity. In the present study, we used the LY75-mediated modulation of EMT in EOC cells as a model in order to investigate in vivo the specific role of EOC cells, with an epithelial (E), mesenchymal (M) or mixed epithelial plus mesenchymal (E+M) phenotype, in EOC initiation, dissemination and treatment response, following intra-bursal (IB) injections of SKOV3-M (control), SKOV3-E (Ly75KD) and a mixed population of SKOV3-E+M cells, into severe combined immunodeficiency (SCID) mice. We found that the IB-injected SKOV3-E cells displayed considerably higher metastatic potential and resistance to treatment as compared to the SKOV3-M cells, due to the acquisition of a Ly75KD-mediated hybrid phenotype and stemness characteristics. We also confirmed in vivo that the LY75 depletion directs suppression of the Wnt/β-catenin pathway in EOC cells, suggestive of a protective role of this pathway in EOC etiology. Moreover, our data raise concerns regarding the use of LY75-targeted vaccines for dendritic-cell EOC immunotherapy, due to the possible occurrence of undesirable side effects.

Identification of ovarian high-grade serous carcinoma cell lines that show estrogen-sensitive growth as xenografts in immunocompromised mice

Ovarian cancer remains a significant challenge in women worldwide. Tumors of the high-grade serous carcinoma (HGSC) type represent the most common form of the disease. Development of new therapies for HGSC has been hampered by a paucity of preclinical models in which new drugs could be tested for target engagement and anti-tumor efficacy. Here, we systematically assessed in vivo growth of ovarian cancer cells, including six validated HGSC cell lines, in highly immunocompromised NSG mice by varying the injection site. We found that, with the exception of OVCAR3, HGSC cell lines COV318, COV362, KURAMOCHI, OVCAR4, and OVSAHO, generally demonstrate poor growth as either subcutaneous or intraperitoneal xenografts. Intrabursal injections performed with KURAMOCHI and COV362 cells did not improve tumor growth in vivo. Additional analysis revealed that OVSAHO and COV362 express moderate levels of estrogen receptor (ERα), which translated into improved growth of xenografts in the presence of 17β-Estradiol. Surprisingly, we also found that the growth of the widely used non-HGSC ovarian cell line SKOV3 could be significantly improved by estrogen supplementation. By describing successful establishment of estrogen-sensitive HGSC xenograft models, OVSAHO and COV362, this work will enable testing of novel therapies for this aggressive form of ovarian cancer.

Ultrasound-Guided Percutaneous Irrigation of Rotator Cuff Calcific Tendinopathy (US-PICT): Patient Experience.

Purpose To assess patients' experience of ultrasound-guided percutaneous irrigation of rotator cuff calcific tendinopathy (US-PICT). Methods Ninety-one patients (58 females; mean age: 50.5 ± 8.3 years) treated by US-PICT (local anesthesia, single-needle lavage, and intrabursal steroid injection) answered to a list of questions regarding their experience of the procedure before treatment, immediately after treatment, and three months later. The Borg CR10 scale was used to evaluate perceived pain, discomfort during anesthetic injection, and anxiety. The Wilcoxon, Spearman's rho, linear regression, and chi-square statistics were used. Results 81/91 patients complained mild discomfort during the injection of anesthetics (2, 1-2). Pain scores during US-PICT were very low (0, 0-1), with 70% patients having not experienced pain. After treatment, we found a significant reduction of pain (before: 8, 7-8; 3-month: 3, 1-6; p < .001) and anxiety (before: 5, 2-7; during treatment: 2, 1-7; p = 0.010), with high overall satisfaction (immediately after: 10, 9-10; 3-month: 9, 7-10) and confidence in the possibility of recovery (immediately after: 9, 8-10; 3-month: 10, 8-10), respectively. Treatments performed before US-PICT were not statistically associated with pain relief (p = 0.389) and clinical improvement (p = 0.937). We found a correlation between satisfaction immediately postprocedure and confidence in the possibility of recovery (p = 0.002) and between satisfaction three months after treatment and clinical improvement (p < 0.001) and patients' reminds about the description of the procedure (p = 0.005) and of the potential complications (p = 0.035). Conclusions US-PICT is a mildly painful, comfortable, and well-tolerated procedure, regardless of any previous treatments. Patients' satisfaction is correlated with clinical benefit and full explanation of the procedure and its complications.

US-guided percutaneous irrigation of calcific tendinopathy of the rotator cuff in patients with or without previous external shockwave therapy.

To compare the outcome of US-guided percutaneous irrigation of calcific tendinopathy (US-PICT) of the rotator cuff in patients with or without previous external shockwave therapy (ESWT). We analyzed all patients treated with US-PICT from March 1, 2016, to October 1, 2019, with shoulder pain refractory to conservative management for rotator cuff calcific tendinopathy, diagnosed with ultrasound. Each patient was examined using the Constant-Murley Score (CMS) questionnaire (score 0-100) before and after treatment. We tested CMS differences using the Mann-Whitney U (Wilcoxon rank-sum) test in the two groups. US-PICT was performed placing two or multiple 14G needles, according to the calcification size, inserted under US guidance to create a circuit of irrigation in the calcified tendon. NaCl solution at 38°C was then injected from the entry needle in a variable amount to hydrate and fragment the calcification, finally allowing for its expulsion through the exit needle. All patients also received an intrabursal steroid injection. From 2016 to 2019, 72 US-PICT treatments were performed on 70 patients (females = 46; males = 26) with a mean age of 49.7years (SD = 8.7. Thirty-three (47%) underwent previous ESWT, while thirty-seven (53%) had no previous treatments. No treatment-related complications were observed. Follow-up was averagely 14.4months (median = 11.6, SD = 11.9, range 1-45); 37 patients had a follow-up shorter than 12months (1-11.6); 35 patients were visited after more than 1year (12.2-45.6, Table W). Before treatment, the mean CMS was 35 (SD = 21); after treatment, it reached 75.4, with an average CMS improvement of 40.3 points (SD = 23.7, p < 0.001). The comparison of improvement between the ESWT and non-ESWT group yielded no significant difference (p = 0.3). US-PICT of the rotator cuff is an effective procedure to reduce shoulder pain and increase mobility in patients with calcific tendinopathy, both in short- and long-term time intervals. Previous unsuccessful ESWT does not affect the outcome of US-PICT.