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BACKGROUND: MR arthrography (MRA) has previously been the radiological gold standard for investigating labral and chondral lesions of the hip joint. In recent years, 3T MRI has demonstrated comparable accuracy, being adopted as the first-line imaging investigation in many institutions. AIMS: We compare the associated increased cost and radiation dose of the fluoroscopic component of the MRA compared to MRI. METHODS: In this retrospective review over 2 years, 120 patients (mean age 27.3 years ± 13.2, range 8-67) underwent 3T MRA or non-contrast 3T MRI. Three musculoskeletal radiologists reported the data independently. Primary objectives included cost-comparison between each and radiation dose of the fluoroscopic component of the MRA. Secondary objectives included comparing detection of pathology involving the acetabular labrum, femoral cartilage, and acetabular cartilage. RESULTS: Then, 58 (48%) underwent 3T MRA and 62 (52%) patients underwent 3T MRI. The added cost of the fluoroscopic injection prior to MRA was 116.31/patient, equating to 7211.22 savings/year. MRA was associated with a small radiation dose of 0.003 mSv. CONCLUSIONS: Transitioning from 3T MRA to 3T MRI in the investigation of intra-articular hip pathology increases cost savings and reduces radiation dose.
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OBJECTIVES: To assess if brake response times are altered pre and post CT-guided cervical spine nerve root injections. METHODS: Brake response times were assessed before and after CT-guided cervical spine nerve root injections in a cohort of patients. The average of 3 brake response times was recorded before and 30 min after injection. Statistical analysis was performed using GraphPad. A paired Student t-test was used to compare the times before and after the injections. RESULTS: Forty patients were included in this study. The mean age was 55 years. There were 17 male and 23 female patients. There was no significant difference in the mean pre and post CT-guided cervical spine nerve root injection brake response times; 0.94 s (range 0.4-1.2 s) and 0.93 s (range 0.5-1.25 s), respectively (P = .77). CONCLUSIONS: Brake response time did not significantly differ pre and 30 min post CT-guided cervical spine nerve root injections. ADVANCES IN KNOWLEDGE: To the authors' best knowledge, there are no current studies assessing brake response times post CT-guided cervical spine nerve root injections. While driving safety cannot be proven by a single metric, it is a useful study in demonstrating that this is not inhibited in a cohort of patients.
Subject(s)
Radiculopathy , Humans , Male , Female , Middle Aged , Reaction Time , Spinal Nerve Roots/diagnostic imaging , Cervical Vertebrae/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
OBJECTIVES: To describe the percutaneous image-guided treatment of mucoid degeneration of the ACL causing deep knee pain on flexion in patients with advanced knee osteoarthritis. METHODS: Five patients with mucoid degeneration of the ACL complicating knee osteoarthritis underwent percutaneous image-guided steroid bupivacaine ACL sleeve injections over a 3-year period. RESULTS: There were four males and one female of mean age 54 (range 48-59 years). Each patient had Kellgren and Lawrence grade 4 medial compartment knee osteoarthritis with coexistent mucoid degeneration of the ACL sleeve. Each patient complained of deep knee pain on flexion as a dominant symptom. Each patient underwent image-guided (CT or ultrasound) steroid bupivacaine injection of the ACL sleeve resulting in symptom resolution and improved mobility for a mean duration of 8 months, (range 6-15 months.) CONCLUSION: Mucoid degeneration of the ACL should be sought in patients with osteoarthritis presenting with deep knee pain on flexion. Image-guided ACL sleeve injection in affected patients may result in symptom resolution and potential deferral of planned knee replacement surgery. ADVANCES IN KNOWLEDGE: Emphasises Image guided percutaneous treatment of Mucoid degeneration of ACL in patients with knee osteoarthritis.
Subject(s)
Anterior Cruciate Ligament , Osteoarthritis, Knee , Humans , Female , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/surgery , Middle Aged , Male , Anterior Cruciate Ligament/surgery , Bupivacaine/therapeutic use , Bupivacaine/administration & dosage , Injections, Intra-Articular , Anesthetics, Local/administration & dosage , Anesthetics, Local/therapeutic useABSTRACT
BACKGROUND: Pulmonary embolism (PE) is a leading cause of pregnancy-related mortality. CT pulmonary angiogram (CTPA) is the first-line advanced imaging modality for suspected PE in pregnancy at institutes offering low-dose techniques; however, a protocol balancing safety with low dose remains undefined. The wide range of CTPA doses reported in pregnancy suggests a lack of confidence in implementing low-dose techniques in this group. PURPOSE: To define and validate the safety, radiation dose and image quality of a low-dose CTPA protocol optimised for pregnancy. MATERIALS AND METHODS: The OPTICA study is a prospective observational study. Pregnant study participants with suspected PE underwent the same CTPA protocol between May 2018 and February 2022. The primary outcome, CTPA safety, was judged by the reference standard; the 3-month incidence of venous thromboembolism (VTE) in study participants with a negative index CTPA. Secondary outcomes defined radiation dose and image quality. Absorbed breast, maternal effective and fetal doses were estimated by Monte-Carlo simulation on gestation-matched phantoms. Image quality was assessed by signal-to-noise and contrast-to-noise ratios and a Likert score for pulmonary arterial enhancement. RESULTS: A total of 116 CTPAs were performed in 113 pregnant women of which 16 CTPAs were excluded. PE was diagnosed on 1 CTPA and out-ruled in 99. The incidence of recurrent symptomatic VTE was 0.0% (one-sided 95% CI, 2.66%) at follow-up. The mean absorbed breast dose was 2.9 ± 2.1mGy, uterine/fetal dose was 0.1 ± 0.2mGy and maternal effective dose was 1.4 ± 0.9mSv. Signal-to-noise ratio (SNR) was 11.9 ± 3.7. Contrast-to-noise ratio (CNR) was 10.4 ± 3.5. CONCLUSION: The OPTICA CTPA protocol safely excluded PE in pregnant women across all trimesters, with low fetal and maternal radiation. CLINICAL RELEVANCE: OPTICA (Optimised CT Pulmonary Angiography in Pregnancy) is the first prospective study to define the achievable radiation dose, image-quality and safety of a low-dose CT pulmonary angiogram protocol optimised for pregnancy (NCT04179487). It provides the current benchmark for safe and achievable CT pulmonary angiogram doses in the pregnant population. KEY POINTS: ⢠Despite the increased use of CT pulmonary angiogram in pregnancy, an optimised low-dose protocol has not been defined and reported doses in pregnancy continue to vary widely. ⢠The OPTICA (Optimised CT Pulmonary Angiography in Pregnancy) study prospectively defines the achievable dose, image quality and safety of a low-dose CT pulmonary angiogram protocol using widely available technology. ⢠OPTICA provides a benchmark for safe and achievable CT pulmonary angiogram doses in the pregnant population.
Subject(s)
Computed Tomography Angiography , Pregnancy Complications, Cardiovascular , Pulmonary Embolism , Radiation Dosage , Humans , Female , Pregnancy , Computed Tomography Angiography/methods , Adult , Prospective Studies , Pulmonary Embolism/diagnostic imaging , Pregnancy Complications, Cardiovascular/diagnostic imaging , Signal-To-Noise RatioABSTRACT
OBJECTIVES: To assess the most common lower limb acute muscle injuries on MRI imaging in a national specialist centre for orthopaedics and sports medicine and to explore potential gender differences. METHODS: Over a 3-year time period, all MRI lower limb studies with acute muscle injury (AMI) were reviewed. A British Athletics muscle injury classification (BAMIC) was given and a statistical analysis was performed. RESULTS: A total of 195 AMIs were diagnosed: 177 (91%) male and 18 (9%) female injuries (M to F = 9.8:1). The most common lower limb AMIs were BAMIC grade 1a injuries (n = 48, 25%). The most commonly injured muscle was biceps femoris (n = 87, 45%), specifically grade 1b and grade 2b injuries. There was no significant difference in age between men and women with acute lower limb muscle injuries (p = 0.19). Females were 1.5 times more likely to have a lower grade AMI than males, although this did not reach statistical significance (p = 0.7) owing to a striking lower number of female patients. There was no significant difference between genders in the likelihood of sustaining a hamstring or quadricep AMI (hamstrings OR = 2.47, p = 0.14 and quadriceps OR = 0.926, p 0.99). CONCLUSIONS: Grade 1a is the most common lower limb AMI grade in our institution, accounting for 25%. Biceps femoris is the most commonly injured muscle (45%) with grade 1b and grade 2b being the most frequently encountered grades of biceps femoris injuries. Lower-grade injuries are more common in females compared to males, although not significantly so. Further studies are required to explore possible reasons for this gender gap.
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A 34-year-old female presented to the emergency department with neck pain, dysphonia and dysphagia ten days after a fall from an electric scooter. Subsequent computed tomography of the neck revealed bilateral vertebral artery and unilateral internal carotid artery non-occlusive dissections, which were managed with antiplatelet therapy. This case describes mechanisms of injury, clinical presentation, imaging appearances, and subsequent management of cervical artery dissection.
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AIM: The purpose of our study was to review a large cohort of athletes of all levels presenting with groin pain who underwent investigation with MRI and to determine what the commonest patterns of injury were. We aimed to explore whether particular findings were commonly found in association and whether measurable gender differences exist in the incidence of specific injuries. MATERIALS AND METHODS: Imaging records were reviewed to identify MRI studies of the pelvis performed for the investigation of groin pain in patients who were active in sports/athletic pursuits. Findings were classified and recorded as follows: injury to the common rectus abdominis/adductor longus origin, injury to the short adductor muscles, pubic bone oedema, pubic symphysis degenerative changes, hip joint injury and 'other'. The prevalence of specific injuries in female athletes compared to males was analysed using relative risk ratios. RESULTS: A total of 470 athletes underwent MRI for the investigation of groin pain during the study period. Forty-six were female, and 424 were male. Female athletes were significantly less likely to have rectus abdominis-adductor longus (RR = 0.31, p = .017), short adductor (RR = 0.14, p = .005) or hip (RR = 0.41, p = .003) injuries. Pubic bone degenerative changes were much more common in female athletes (RR = 7.37, p = .002). CONCLUSION: Significant gender differences exist in the frequency with which specific injuries are observed. Female athletes are also significantly underrepresented; this is likely a multifactorial phenomenon; however, the possibility of unconscious referrer bias must be considered.
Subject(s)
Athletic Injuries , Humans , Male , Female , Athletic Injuries/diagnostic imaging , Athletic Injuries/epidemiology , Athletic Injuries/complications , Groin/diagnostic imaging , Groin/injuries , Sex Factors , Magnetic Resonance Imaging/methods , Athletes , Pain/etiologyABSTRACT
OBJECTIVE: Acetabular paralabral cysts are common and are almost always associated with labral tears. Uncommonly, they extend into the periacetabular soft tissues or may propagate along peripheral nerves causing pain and hip dysfunction. The aim was to evaluate the clinical and MRI presentations of such cases including perineural propagation. METHODS: Retrospective cross-sectional study with a search of electronic health records for cases of acetabular paralabral cysts demonstrating perineural propagation was performed. Clinical and MR imaging features were tabulated after re-review by experienced musculoskeletal radiologists, and available outcomes were recorded. Descriptive statistics were performed. RESULTS: 14 cases were recorded. The mean age was 56.9 years (range = 30-79 years) and female:male ratio was 1:2.6. The commonest presenting complaint was hip pain (10/14, 71.4%). Other complaints included groin pain, perineal pain and hip dysfunction. No symptoms were attributed to the acetabular paralabral cyst in 3/14 patients (21.4%). None had foot drop. The cysts were multilocular in all cases and were homogenously T2 hyperintense in 13/14 (92.9%). Labral tears were identified in 11/14 cases (78.6%). The sciatic nerve was most commonly involved in 5/14 cases (35.7%) with the obturator, medial femoral cutaneous nerve, femoral nerve, superior and inferior gluteal nerves also affected.No intervention was undertaken in 9/14 cases (64.3%). 5/14 (35.7%) underwent image guided aspiration and corticosteroid injection. 4/5 such patients reported reduced pain following the procedure. CONCLUSION: Paralabral cysts demonstrating perineural propagation are uncommon and exhibit varied presentations. Most patients who underwent image-guided or surgical interventions reported an improvement in symptoms. ADVANCES IN KNOWLEDGE.: This is the first description of a series of patients with acetabular paralabral cysts demonstrating perineural propagation in the literature. A comprehensive description of their clinical and imaging characteristics and interventions/outcomes where relevant is provided.
Subject(s)
Acetabulum , Cysts , Acetabulum/diagnostic imaging , Adult , Aged , Arthralgia , Arthroscopy/methods , Cross-Sectional Studies , Cysts/diagnosis , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Retrospective StudiesABSTRACT
Complications in musculoskeletal interventions are rare and where they do occur tend to be minor, and often short-lived or self-limiting. Nonetheless, the potential for significant complications exists, and a thorough understanding of both the mechanisms which contribute and the manner in which they may clinically present is of critical importance for all musculoskeletal radiologists involved in performing procedures, both to mitigate against the occurrence of complications and to aid rapid recognition. The purpose of this review is to analyse the relevant literature to establish the frequency with which complications occur following musculoskeletal intervention. Furthermore, we highlight some of the more commonly discussed and feared complications in musculoskeletal intervention, such as the risk of infection, potential deleterious articular consequences including accelerated joint destruction and the poorly understood and often underestimated systemic effects of locally injected corticosteroids. We also consider both extremely rare but emergent scenarios such as anaphylactic reactions to medications, and much more common but less significant complications such as post-procedural pain. We suggest that meticulous attention to detail including strict adherence to aseptic technique and precise needle placement may reduce the frequency with which complications occur.
Subject(s)
Adrenal Cortex Hormones , Needles , Adrenal Cortex Hormones/adverse effects , Humans , InjectionsABSTRACT
Voriconazole is a broad-spectrum triazole antifungal used to treat invasive fungal infections. It is commonly used prophylactically in immunocompromized patient cohorts, including transplant recipients. Diffuse periostitis is a very rare complication of chronic voriconazole use. It is associated with diffuse bone pain, elevated serum alkaline phosphatase and fluorine levels. Characteristic imaging findings include periosteal thickening with a dense, nodular, irregular and often bilateral pattern. We describe the case of a 71-year-old female who presented with multifocal bone pain six years following double lung transplantation. Her post transplantation course had been complicated by a life threatening episode of sepsis secondary to Scedosporium apiospermum, a rare invasive fungal infection following which lifelong prophylaxis with oral Voriconazole was commenced. We discuss the characteristic clinical and imaging manifestations of this rare condition.
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Denervation pseudohypertrophy is an uncommon cause of limb swelling, which may be overlooked. It is an important diagnosis to arrive at, as it instructs the search for an underlying cause which may itself require intervention. We present the case of a 32-year-old male rugby player with a 2-year history of left calf swelling and intermittent pain and tightness. He described a previous history of 2 left sided lumbar micro-discectomy surgeries. There was no tenderness or sensory deficit on examination. MRI of the left calf revealed muscular enlargement, with fat interspersed between the muscle fibers, in keeping with pseudohypertrophy. This has a number of causes, in this cause attributed to lumbar radiculopathy. This case highlights a rare but important cause of limb swelling which should be considered in the workup of a unilateral swollen limb.
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This paper demonstrates a case of multiple glomangiomas, or glomangiomatosis, including clinical presentation, imaging appearances, and subsequent management. Differentiating features from typical glomus tumors are described. To the best of our knowledge, this is the first reported case of a glomangioma involving the distal tibiofibular syndesmosis.
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Rotator cuff tears are the most likely source of shoulder pain in adults and may cause protracted disability. Management of rotator cuff tears is associated with considerable costs. Accurate diagnosis can guide surgical planning and help achieve a favorable clinical outcome. Although radiography remains the initial imaging test for shoulder injury, the roles of MRI and ultrasound (US) as first-line imaging after radiography are evolving. This article leverages current literature and the practical experience of subspecialty musculoskeletal radiologists from different institutions in describing a practical approach to imaging rotator cuff pathology. Both MRI and US are accurate for identifying rotator cuff tears, but each has advantages and shortcomings. As both modalities currently represent reasonable first-line approaches, considerable practice variation has evolved. Given the low cost of US, imagers should strive to optimize the quality of shoulder US examinations and to build referrer confidence in this modality. The roles of direct CT and MR arthrography as well as imaging evaluation of the postoperative rotator cuff are also considered. Through careful selection among the available imaging modalities and optimal performance and interpretation of such examinations, radiologists can positively contribute to the diagnosis and treatment of patients with rotator cuff injuries.
Subject(s)
Magnetic Resonance Imaging/methods , Rotator Cuff Injuries/diagnostic imaging , Ultrasonography/methods , Humans , Rotator Cuff/diagnostic imagingABSTRACT
Rationale: Much is known about the acute infective process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of the coronavirus disease (COVID-19) pandemic. The marked inflammatory response and coagulopathic state in acute SARS-CoV-2 infection may promote pulmonary fibrosis. However, little is known about the incidence and seriousness of post-COVID-19 pulmonary pathology. Objectives: To describe the respiratory recovery and self-reported health after infection at the time of outpatient attendance. Methods: Infection severity was graded into three groups: 1) not requiring admission, 2) requiring hospital admission, and 3) requiring intensive care unit care. Participants underwent chest radiography and a 6-minute walk test (6MWT). Fatigue and subjective return to health were assessed, and concentrations of CRP (C-reactive protein), IL-6 (interleukin-6), sCD25 (soluble CD25), and D-dimer were measured. The associations between initial illness and abnormal chest X-ray findings, 6MWT distance, and perception of maximal exertion were investigated. Results: A total of 487 patients were offered an outpatient appointment, of whom 153 (31%) attended for assessment at a median of 75 days after diagnosis. A total of 74 (48%) had required hospital admission during acute infection. Persistently abnormal chest X-ray findings were seen in 4%. The median 6MWT distance covered was 460 m. A reduced distance covered was associated with frailty and length of inpatient stay. A total of 95 (62%) patients believed that they had not returned to full health, whereas 47% met the case definition for fatigue. Ongoing ill health and fatigue were associated with an increased perception of exertion. None of the measures of persistent respiratory disease were associated with initial disease severity. Conclusions: This study highlights the rates of objective respiratory disease and subjective respiratory symptoms after COVID-19 and the complex multifactorial nature of post-COVID-19 ill health.
Subject(s)
COVID-19/complications , Fatigue/physiopathology , Frailty/physiopathology , Lung/physiopathology , Recovery of Function , Adult , Aged , Ambulatory Care , COVID-19/diagnostic imaging , COVID-19/physiopathology , Dyspnea/physiopathology , Female , Health Status , Hospitalization , Humans , Intensive Care Units , Length of Stay/statistics & numerical data , Lung/diagnostic imaging , Male , Middle Aged , Physical Exertion , Radiography, Thoracic , SARS-CoV-2 , Severity of Illness Index , Walk Test , Post-Acute COVID-19 SyndromeABSTRACT
OBJECTIVE: To establish the incidence and define the nature of complications occurring following image-guided musculoskeletal injections at our institution. MATERIALS AND METHODS: All patients undergoing image-guided musculoskeletal injection during the study period (16/3/2016 to 24/01/2020) were included. Departmental records were reviewed to identify all patients describing possible complications following injection, what therapy was required (if any) and what the outcome was. No patients were excluded. Complications were classified as minor or major. Injections were categorised as follows: cervical spine, lumbar facet joint, lumbar nerve root, caudal epidural and 'other'. The complication rate for each individual category of procedure was compared with the combined complication rate for all other categories by constructing contingency tables and using Fisher's exact test. RESULTS: A total of 8226 patients underwent image-guided musculoskeletal injections within the study period. Exactly 100 patients were identified as having reported a complication, producing an overall complication rate of 1.2%. One complication was categorised as 'major', with the patient requiring expedited surgery. The remainder (99 patients) were categorised as having experienced minor complications. The incidence of complications after 'other' injections was significantly greater than for other categories of injection (1.86%, p = 0.028). There was no significant difference in the complication rate for cervical spine (0.93%, p = 0.257), lumbar nerve root (0.85%, p = 0.401), lumbar facet joint (0.67%, p = 0.326) or caudal epidural (1.29%, p = 0.687) injections. 'Other' injections were subsequently further sub-categorised by anatomical site and imaging modality used. Glenohumeral (2.97%, p = 0.0361) and sacro-iliac (3.51%, p = 0.0498) joint injections were associated with a significantly increased risk of complications. There was no difference in the incidence of complications with fluoroscopic or ultrasound guidance. CONCLUSION: In conclusion, image-guided musculoskeletal injections are safe and well-tolerated procedures. Complications are rare, occurring in just 1.2% of patients. 99% of complications are minor, either not requiring intervention or resolving with simple supportive treatment.
Subject(s)
Cervical Vertebrae , Zygapophyseal Joint , Fluoroscopy , Humans , Injections, Epidural/adverse effects , Injections, Intra-Articular , Spinal Nerve RootsABSTRACT
The use of the unprecedented annulating reagents methyl N-(tert-butylsulfinyl)-4-chlorobutanimidate and methyl N-(tert-butylsulfinyl)-5-bromopentanimidate enables the diastereoselective preparation of 5- and 6-membered carbocycles bearing three contiguous stereocenters. These synthons undergo cycloaddition with a variety of Michael acceptors to form cyclopentane/cyclohexane rings with excellent stereochemical control, generating only one of the eight possible diastereomers. This novel methodology has enabled the highly enantioselective and high yielding synthesis of novel chemotypes of pharmacological relevance.
ABSTRACT
Scaffold hopping and structure-based drug design were employed to identify substituted 4-aminoquinolines and 4-aminonaphthyridines as potent, small molecule inhibitors of tumor necrosis factor alpha (TNFα). Structure-activity relationships in both the quinoline and naphthyridine series leading to the identification of compound 42 with excellent potency and pharmacokinetic profile are discussed. X-ray co-crystal structure analysis and ultracentrifugation experiments clearly demonstrate that these inhibitors distort the TNFα trimer upon binding, leading to aberrant signaling when the trimer binds to TNF receptor 1 (TNFR1). Pharmacokinetic-pharmacodynamic activity of compound 42 in a TNF-induced IL-6 mouse model and in vivo activity in a collagen antibody-induced arthritis model, where it showed biologic-like in vivo efficacy, will be discussed.
Subject(s)
Naphthyridines/pharmacology , Quinolines/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/drug therapy , Drug Design , Female , Humans , Mice, Inbred C57BL , Microsomes, Liver/metabolism , Molecular Structure , Naphthyridines/chemical synthesis , Naphthyridines/pharmacokinetics , Naphthyridines/therapeutic use , Proof of Concept Study , Quinolines/chemical synthesis , Quinolines/pharmacokinetics , Quinolines/therapeutic use , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/metabolismABSTRACT
In order to rapidly develop C6 and C8 SAR of our reported tricyclic sulfone series of RORγt inverse agonists, a late-stage bromination was employed. Although not regioselective, the bromination protocol allowed us to explore new substitution patterns/vectors that otherwise would have to be incorporated at the very beginning of the synthesis. Based on the SAR obtained from this exercise, compound 15 bearing a C8 fluorine was developed as a very potent and selective RORγt inverse agonist. This analog's in vitro profile, pharmacokinetic (PK) data and efficacy in an IL-23 induced mouse acanthosis model will be discussed.
Subject(s)
Heterocyclic Compounds, 3-Ring/therapeutic use , Melanosis/drug therapy , Nuclear Receptor Subfamily 1, Group F, Member 3/antagonists & inhibitors , Sulfones/therapeutic use , Animals , Crystallography, X-Ray , Drug Inverse Agonism , Female , Heterocyclic Compounds, 3-Ring/chemical synthesis , Heterocyclic Compounds, 3-Ring/pharmacokinetics , Interleukin-18 , Male , Melanosis/chemically induced , Mice, Inbred BALB C , Mice, Inbred C57BL , Molecular Structure , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Protein Binding , Structure-Activity Relationship , Sulfones/chemical synthesis , Sulfones/pharmacokineticsABSTRACT
RORγt is the master regulator of the IL-23/IL-17 axis, a pathway that is clinically validated for the treatment of various immunological disorders. Over the last few years, our group has reported different chemotypes that potently act as inverse agonists of RORγt. One of them, the tricyclic pyrrolidine chemotype, has demonstrated biologic-like preclinical efficacy and has led to our clinical candidate BMS-986251. In this letter, we discuss the invention of an annulation reaction which enabled the synthesis of a tricyclic exocyclic amide chemotype and the identification of compounds with RORγt inverse agonist activity. Preliminary structure activity relationships are disclosed.