Tigilanol tiglate is an oncolytic small molecule that induces immunogenic cell death and enhances the response of both target and non-injected tumors to immune checkpoint blockade.

BACKGROUND: Tigilanol tiglate (TT) is a protein kinase C (PKC)/C1 domain activator currently being developed as an intralesional agent for the treatment of various (sub)cutaneous malignancies. Previous work has shown that intratumoral (I.T.) injection of TT causes vascular disruption with concomitant tumor ablation in several preclinical models of cancer, in addition to various (sub)cutaneous tumors presenting in the veterinary clinic. TT has completed Phase I dose escalation trials, with some patients showing signs of abscopal effects. However, the exact molecular details underpinning its mechanism of action (MoA), together with its immunotherapeutic potential in oncology remain unclear. METHODS: A combination of microscopy, luciferase assays, immunofluorescence, immunoblotting, subcellular fractionation, intracellular ATP assays, phagocytosis assays and mixed lymphocyte reactions were used to probe the MoA of TT in vitro. In vivo studies with TT used MM649 xenograft, CT-26 and immune checkpoint inhibitor refractory B16-F10-OVA tumor bearing mice, the latter with or without anti-programmed cell death 1 (PD-1)/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) mAb treatment. The effect of TT at injected and non-injected tumors was also assessed. RESULTS: Here, we show that TT induces the death of endothelial and cancer cells at therapeutically relevant concentrations via a caspase/gasdermin E-dependent pyroptopic pathway. At therapeutic doses, our data demonstrate that TT acts as a lipotoxin, binding to and promoting mitochondrial/endoplasmic reticulum (ER) dysfunction (leading to unfolded protein responsemt/ER upregulation) with subsequent ATP depletion, organelle swelling, caspase activation, gasdermin E cleavage and induction of terminal necrosis. Consistent with binding to ER membranes, we found that TT treatment promoted activation of the integrated stress response together with the release/externalization of damage-associated molecular patterns (HMGB1, ATP, calreticulin) from cancer cells in vitro and in vivo, characteristics indicative of immunogenic cell death (ICD). Confirmation of ICD in vivo was obtained through vaccination and rechallenge experiments using CT-26 colon carcinoma tumor bearing mice. Furthermore, TT also reduced tumor volume, induced immune cell infiltration, as well as improved survival in B16-F10-OVA tumor bearing mice when combined with immune checkpoint blockade. CONCLUSIONS: These data demonstrate that TT is an oncolytic small molecule with multiple targets and confirms that cell death induced by this compound has the potential to augment antitumor responses to immunotherapy.

One bite or two? A comparison of single bite and double bite biopsy techniques in gastrointestinal endoscopy (BITES).

BACKGROUND AND AIM: Endoscopic biopsies can be taken using either single or double bite technique. In the single bite method, intubation time may be proportionately prolonged depending upon the number of biopsies taken. In contrast to this, double bite, though a greater number of biopsies may be taken per unit time, it may influence the quality of the biopsy specimen. The aim of the study was to compare these methods and to see if taking double bite has significant effect on the histological quality of the endoscopic biopsies. METHODS: A prospective, randomised and partly blind study (n = 135, M: 54%, age 21-91 years) divided into two equal arms to compare 144 procedures was conducted. Specimen were compared for time taken to size, depth, crush artefacts, necrosis, fragmentation, distortion, and epithelial stripping. Time taken to collect specimens was also recorded in the upper GI procedures. RESULTS: No significant difference was observed in the histological quality of single and double bite specimens (p < 0.05). However, DB took significantly less time (M = 88.5, SD ± 28.5) as compared to SB (M = 180, SD ± 55.9) (p < 0.05). CONCLUSIONS: There is no difference between the histological quality of DB and SB and the former technique takes less time, hence reducing intubation time.

Mapping a Danger Zone of the Dorsal Nerve of the Clitoris: Implications in Female Cosmetic Genital Surgery.

BACKGROUND: The literature regarding the route of the dorsal nerve of the clitoris is sparse and lacks surgical focus. With an increasing number of procedures being performed on the labia, it is important to elucidate the route and note any variation from normal of the nerve. METHODS: Fifty-one cadavers were dissected to yield 97 dorsal nerve of the clitoris samples. Measurements were taken from (1) the dorsal nerve of the clitoris penetration point of the perineal membrane to the urethra, (2) the nerve's penetration point of the perineal membrane to the pubic bone, (3) the angle of the clitoris to the branch point of the dorsal nerve of the clitoris, and (4) the branch point of the nerve to the distalmost point of the glans clitoris. Any anomalous branching patterns of the dorsal nerve of the clitoris were recorded and classified. RESULTS: The means and standard deviations of each measurement were used to create a surgical danger zone. The mean of each measurement was (1) 34.63 mm, (2) 5.74 mm, (3) -3.07 mm, and (4) 30.40 mm, respectively. In addition, six distinct branching patterns were observed, organized, and classified based on the location and number of branches observed. CONCLUSIONS: The dorsal nerve of the clitoris has multiple branching patterns and typically travels along the same course in most women. Further investigation of the course and three-dimensional position of the dorsal nerve of the clitoris is warranted to preserve sexual sensation as the frequency of procedures involving the female pudendum increases.

Activation of PKC supports the anticancer activity of tigilanol tiglate and related epoxytiglianes.

The long-standing perception of Protein Kinase C (PKC) as a family of oncoproteins has increasingly been challenged by evidence that some PKC isoforms may act as tumor suppressors. To explore the hypothesis that activation, rather than inhibition, of these isoforms is critical for anticancer activity, we isolated and characterized a family of 16 novel phorboids closely-related to tigilanol tiglate (EBC-46), a PKC-activating epoxytigliane showing promising clinical safety and efficacy for intratumoral treatment of cancers. While alkyl branching features of the C12-ester influenced potency, the 6,7-epoxide structural motif and position was critical to PKC activation in vitro. A subset of the 6,7-epoxytiglianes were efficacious against established tumors in mice; which generally correlated with in vitro activation of PKC. Importantly, epoxytiglianes without evidence of PKC activation showed limited antitumor efficacy. Taken together, these findings provide a strong rationale to reassess the role of PKC isoforms in cancer, and suggest in some situations their activation can be a promising strategy for anticancer drug discovery.

Wound formation, wound size, and progression of wound healing after intratumoral treatment of mast cell tumors in dogs with tigilanol tiglate.

BACKGROUND: Tigilanol tiglate (TT) is a novel small molecule for intratumoral treatment of nonmetastatic mast cell tumors (MCTs) in dogs. In a randomized controlled clinical study, 75% of dogs that received a single TT treatment achieved complete resolution of the MCT by 28 days, with no recurrence in 93% of dogs at 84 days. Critical to TT's efficacy was the area of the wound (tissue deficit) after slough of the necrotic tumor relative to pretreatment tumor volume. OBJECTIVES: To analyze data collected during the previous study to (a) describe wounds after slough of treated MCTs and (b) identify determinants of wound area and speed of wound healing. METHODS: Wound presence, condition, and area were determined from clinical records of 117 dogs over 84 days after a single intratumoral TT treatment. RESULTS: Tumor slough occurred 3 to 14 days after treatment, exposing granulation tissue in the wound bed. Wound area after tumor slough in general was related to pretreatment tumor volume, with maximal recorded wound area fully evident in 89% of dogs by day 7. In dogs achieving complete tumor resolution, all wounds were left to heal by secondary intention. Bandaging and other wound management interventions only were required in 5 dogs. Time to healing (ie, full re-epithelialization of treatment site) depended on wound area and location on the body, with most wounds being fully healed between 28 and 42 days after treatment. CONCLUSIONS: Wound area and healing after slough of TT-treated tumors follow a consistent clinical pattern for most dogs.

Key Anatomical Clarifications for the Marginal Mandibular Branch of the Facial Nerve: Clinical Significance for the Plastic Surgeon.

BACKGROUND: The marginal mandibular branch (MMBr) of the facial nerve is the least likely to recover from injury due to infrequent anastomosis with other branches. The MMBr has been described as coursing superior to the inferior border of the mandible. However, studies have reported variations in its location in embalmed and fresh specimens. It has been postulated that the embalming process may effect its anatomic position. OBJECTIVES: The aim of this study was to re-evalulate the location of the MMBr relative to the inferior border of the mandible in both fresh and embalmed cadavers, and investigate variation in its position with sex, side of the face, and age. METHODS: Superficial fascial planes were dissected to reveal the MMBr and its anatomic relations. Distance between the most inferior branch of the MMBr and the antegonial notch were measured bilaterally. The most inferior position of the MMBr between the antegonial notch and gonion was measured. Fresh heads were used as a comparison, with an additional measurement taken of the distance between the MMBr and the gonial angle. RESULTS: The MMBr was located inferior to the border of the mandible (90.3%) more often than above (9.6%). No significant differences were found between fresh and embalmed cadavers, sex, side of body, or age (P > 0.05). No significant difference was found between intact cadavers and fresh heads (P > 0.05). CONCLUSIONS: This study confirms and describes reliable landmarks for safety zones for the MMBr during plastic and reconstructive surgery of the lower face and upper neck. These data add reliability to studies that have investigated nerve locations in embalmed cadavers.

Randomized controlled clinical study evaluating the efficacy and safety of intratumoral treatment of canine mast cell tumors with tigilanol tiglate (EBC-46).

OBJECTIVE: To evaluate the efficacy and safety of tigilanol tiglate (TT) for local intratumoral treatment of mast cell tumors (MCTs) in dogs. METHODS: A randomized controlled clinical study in 2 phases involving 123 dogs with cytologically diagnosed MCT. Phase 1 compared 81 TT-treated dogs with 42 control dogs; phase 2 allowed TT treatment of control dogs and retreatment of dogs that failed to achieve tumor resolution after TT treatment in phase 1. Tigilanol tiglate (1 mg/mL) was injected intratumorally with dose based on tumor volume. Concomitant medications were used to minimize potential for MCT degranulation. Modified response evaluation criteria in solid tumors were used to evaluate treatment response at 28 and 84 days. Adverse events and quality of life were also assessed. RESULTS: A single TT treatment resulted in 75% complete response (CR) (95% confidence interval [CI] = 61-86) by 28 days, with no recurrence in 93% (95% CI = 82-97) of dogs by 84 days. Eight TT-treated dogs that did not achieve CR in phase 1 achieved CR after retreatment, increasing the overall CR to 88% (95% CI = 77-93). Control dogs had 5% CR (95% CI = 1-17) at 28 days. Wound formation after tumor slough and wound size relative to tumor volume were strongly associated with efficacy. Adverse events typically were low grade, transient, and directly associated with TT's mode of action. CONCLUSIONS: Tigilanol tiglate is efficacious and well tolerated, providing a new option for the local treatment of MCTs in dogs.

Etiology and Comorbidity Diagnoses Effect on Outcomes for Patients Undergoing Endoscopic Retrograde Cholangiopancreatography.

Introduction Endoscopic retrograde cholangiopancreatography (ERCP) is now the first-line approach to treating choledocholithiasis. As a minimally invasive procedure, it is considered relatively safe but still entails a higher risk than other routine endoscopic procedures. This study aims to look at possible patient etiologies and comorbidities that may affect patient outcomes.  Methods This study used the Nationwide Inpatient Sample (NIS) from the years 2012 - 2015 to collect anonymous patient data through the use of International Classification of Diseases, Ninth Revision (ICD-9) codes. Specific codes were used to determine the top five etiologies (or presenting diagnosis) for patients who had this surgery and to separate outpatients with specific comorbidity diagnoses. The IBM Statistical Package for Social Sciences (SPSS) (IBM SPSS Statistics, Armonk, NY) was then used to compare patients with these diagnoses or etiologies to those without to measure differences in patient outcomes, such as mortality, length of stay, and total charges. Results Patients who had an etiological diagnosis of acute kidney failure had worse outcomes than patients who were admitted for ERCP without that etiological diagnosis. There were also specific comorbidity diagnoses that were noted to have worse patient outcomes, including congestive heart failure, diabetes mellitus with complications, a coagulopathy disorder, anemia, or chronic liver disease. Additionally, patients who had both acute kidney disease and chronic liver disease had the worst outcomes. Conclusions This study highlights the need to understand all patient risk factors before having them undergo ERCP, especially in the setting of scheduled surgery. Working to control these factors before surgery can increase the possibility of avoiding negative outcomes like mortality, increased patient costs, and increased length of stay.

Anatomic Variations From 120 Mental Nerve Dissections: Lessons for Transoral Thyroidectomy.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a promising technique for eliminating a neck incision. A new risk of TOETVA is the potential for injury to the mental nerves during placement of three oral endoscopic ports. A better understanding of the variations in mental nerve anatomy is needed to inform safer TOETVA technique. MATERIALS AND METHODS: We performed 120 dissections of mental nerve branches exiting the mental foramen in 60 human cadavers. Anatomic distances and relationships of the foramen to the midline were evaluated. Mental nerve branching patterns were studied and compared with previously reported classification systems to determine surgical safe zones free of nerve branches. RESULTS: The mean midline-to-mental foramen distance was 29.2 ± 3.3 mm, with high variability across individuals (18.8-36.8 mm). There were differences in this distance between the left and right foramina (29.8 ± 3.2 versus 28.8 ± 3.3 mm, P = 0.03). All mental nerve branches exiting the mental foramen distributed medially. The branching patterns were classified into eight distinct categories, three of which are previously undescribed. One of these novel patterns, occurring in 9.2% of cases, had a dense and wide clustering of branches traveling toward the midline. CONCLUSIONS: The location of the mental foramen and mental nerve branching patterns demonstrate high variability. To avoid mental nerve injury in TOETVA, we identify a safe zone for lateral port placement lateral to the plane of the mental foramen. Placement and extension of the middle port incision should proceed with caution, as clustering of mental nerve branches in this area can frequently be present.

Novel epoxy-tiglianes stimulate skin keratinocyte wound healing responses and re-epithelialization via protein kinase C activation.

Epoxy-tiglianes are a novel class of diterpene esters. The prototype epoxy-tigliane, EBC-46 (tigilanol tiglate), possesses potent anti-cancer properties and is currently in clinical development as a local treatment for human and veterinary cutaneous tumors. EBC-46 rapidly destroys treated tumors and consistently promotes wound re-epithelialization at sites of tumor destruction. However, the mechanisms underlying these keratinocyte wound healing responses are not completely understood. Here, we investigated the effects of EBC-46 and an analogue (EBC-211) at 1.51 nM-151 µM concentrations, on wound healing responses in immortalized human skin keratinocytes (HaCaTs). Both EBC-46 and EBC-211 (1.51 nM-15.1 µM) accelerated G0/G1-S and S-G2/M cell cycle transitions and HaCaT proliferation. EBC-46 (1.51-151 nM) and EBC-211 (1.51 nM-15.1 µM) further induced significant HaCaT migration and scratch wound repopulation. Stimulated migration/wound repopulation responses were even induced by EBC-46 (1.51 nM) and EBC-211 (1.51-151 nM) with proliferation inhibitor, mitomycin C (1 µM), suggesting that epoxy-tiglianes can promote migration and wound repopulation independently of proliferation. Expression profiling analyses showed that epoxy-tiglianes modulated keratin, DNA synthesis/replication, cell cycle/proliferation, motility/migration, differentiation, matrix metalloproteinase (MMP) and cytokine/chemokine gene expression, to facilitate enhanced responses. Although epoxy-tiglianes down-regulated established cytokine and chemokine agonists of keratinocyte proliferation and migration, enhanced HaCaT responses were demonstrated to be mediated via protein kinase C (PKC) phosphorylation and significantly abrogated by pan-PKC inhibitor, bisindolylmaleimide-1 (BIM-1, 1 µM). By identifying how epoxy-tiglianes stimulate keratinocyte healing responses and re-epithelialization in treated skin, our findings support the further development of this class of small molecules as potential therapeutics for other clinical situations associated with impaired re-epithelialization, such as non-healing skin wounds.

Dose Characterization of the Investigational Anticancer Drug Tigilanol Tiglate (EBC-46) in the Local Treatment of Canine Mast Cell Tumors.

Mast cell tumor (MCT) is the most common cutaneous neoplasm in dogs and wide surgical resection is the current first-line treatment. However, recurrence is common and often requires more specialist and expensive therapies. Tigilanol tiglate is a novel small molecule drug delivered by intratumoral injection that is currently under development to provide a new option for treating MCT. The aim of this study was to characterize a safe and effective dose of tigilanol tiglate for canine MCT and to gather preliminary data on the drug's pharmacokinetics. A multicenter, open-label, uncontrolled, non-randomized, dose de-escalation design was used. Eligibility was MCT stage I/IIa and a tumor size of 0.1-6.0 cm3. Dosing was based on tumor size (50% v/v tumor) and 3 drug concentrations (1.0, 0.5, 0.2 mg/mL) were evaluated. Twenty-seven dogs were treated in 3 dose de-escalation cohorts (10, 10, and 7 dogs, respectively). Efficacy at 21 days was defined using international accepted solid tumor response criteria (RECIST). Greatest efficacy (90% complete response) was observed at the highest drug concentration (1.0 mg/mL) and adverse events were generally low grade, mild and transient, and directly associated with the mode of action of the drug. Hematological and serum biochemistry were generally unremarkable with plasma concentration curves typical of a non-intravenous parenteral medication. Intratumoral treatment of MCT with tigilanol tiglate at a concentration of 1.0 mg/mL was highly efficacious and well-tolerated. These results support the drug's further development for the treatment of MCT and other solid tumors.

New Casbanes and the First trans-Cyclopropane seco-Casbane from the Australian Rainforest Plant Croton insularis.

Investigation of the Australian rainforest plant Croton insularis revealed seven new cis-, two new trans-cyclopropane casbanes, and the first trans-cyclopropane seco-casbane. The relative configuration of the cyclopropane moiety for all compounds (EBC-182, 217, 218, 220, 343, 357, 358, 361, 365, 373; EBC=EcoBiotics Compound) was assigned using 13 C NMR data. Comparison of the experimental electronic circular dichroism (ECD) spectra with the theoretical curves, calculated by TD-DFT at the B3LYP/6-31+G**//B3LYP/6-31+G** level, in conjunction with NOE data afforded the absolute configuration. EBC-180, 181 and 220 displayed potent activity against cervical carcinoma (HeLa cells).

The First Casbane Hydroperoxides EBC-304 and EBC-320 from the Australian Rainforest.

Investigation of the Australian rainforest plant Croton insularis led to isolation of the first casbane hydroperoxide diterpenes EBC-304 and EBC-320. Extensive DFT and electronic circular dichroism (ECD) calculations in combination with 2D NMR spectroscopy determined the absolute configurations. EBC-304 and EBC-320 both display significant cytotoxicity.

Using Plate Osteosynthesis to Treat Isolated Greater Tuberosity Fractures.

Isolated greater tuberosity fractures make up a small subset of proximal humerus fractures. We conducted a study to evaluate the radiologic and clinical outcomes of patients who underwent a novel use of plate osteosynthesis in the treatment of displaced greater tuberosity fractures. Eleven consecutive patients with a displaced greater tuberosity fracture were treated. Mean age at surgery was 60.3 years old (range, 37-71 years). Mean follow-up was 27 months (range, 16-44 months). All 11 patients experienced radiographic union. Three of the 11 had a loss of anatomical reduction. Mean Penn Shoulder Score was 79, and mean Single Assessment Numeric Evaluation score was 72. At most recent follow-up, mean forward elevation was 147°, and mean external rotation was 25°. Plate osteosynthesis is a novel technique for the treatment of displaced greater tuberosity fractures. This technique resulted in excellent fracture reduction, a 100% union rate, minimal fracture migration, and good return of range of motion.

Use of reverse total shoulder arthroplasty in the Medicare population.

BACKGROUND: Reverse shoulder arthroplasty (RSA) has been Food and Drug Administration approved in the United States since 2004 but did not obtain a unique code until 2010. Therefore, the use of this popular procedure has yet to be reported. The purpose of this study was to examine the use and reimbursement of RSA compared with total shoulder arthroplasty (TSA) and shoulder hemiarthroplasty (SHA). METHODS: We analyzed the 100% sample of the 2011 Medicare Part A claims data for patients aged 65 years or older. Patient demographic characteristics, diagnoses, provider information, reimbursements, and lengths of stay were extracted from the claims data. RESULTS: In 2011, a total of 31,002 shoulder arthroplasty procedures were performed; 37% were RSAs, 42% were TSAs, and 21% were SHAs. Osteoarthritis was the primary diagnosis code in 91% of TSAs, 37% of SHAs, and 45% of RSAs. A primary diagnosis of osteoarthritis with no secondary code for rotator cuff tear was found in 22% of patients undergoing RSA. The mean length of stay for RSA (2.6 days; SD, 2.1 days) was longer than that for TSA (2.1 days; SD, 1.5 days) and shorter than that for SHA (3.5 days; SD, 3.6 days) (P < .001). Lower-volume surgeons (<10 arthroplasties per year) performed most shoulder arthroplasties: 57% of RSAs, 65% of TSAs, and 97% of SHAs. Seventy percent of RSAs were implanted by surgeons who performed more RSAs than TSAs and SHAs combined. CONCLUSIONS: RSA is performed with similar frequency to TSA and almost twice as much as SHA in the Medicare population. Lower-volume surgeons perform most RSAs, and a majority of surgeons perform more RSAs than all anatomic shoulder arthroplasties combined.

Intra-lesional injection of the novel PKC activator EBC-46 rapidly ablates tumors in mouse models.

Intra-lesional chemotherapy for treatment of cutaneous malignancies has been used for many decades, allowing higher local drug concentrations and less toxicity than systemic agents. Here we describe a novel diterpene ester, EBC-46, and provide preclinical data supporting its use as an intra-lesional treatment. A single injection of EBC-46 caused rapid inflammation and influx of blood, followed by eschar formation and rapid tumor ablation in a range of syngeneic and xenograft models. EBC-46 induced oxidative burst from purified human polymorphonuclear cells, which was prevented by the Protein Kinase C inhibitor bisindolylmaleimide-1. EBC-46 activated a more specific subset of PKC isoforms (PKC-ßI, -ßII, -α and -γ) compared to the structurally related phorbol 12-myristate 13-acetate (PMA). Although EBC-46 showed threefold less potency for inhibiting cell growth than PMA in vitro, it was more effective for cure of tumors in vivo. No viable tumor cells were evident four hours after injection by ex vivo culture. Pharmacokinetic profiles from treated mice indicated that EBC-46 was retained preferentially within the tumor, and resulted in significantly greater local responses (erythema, oedema) following intra-lesional injection compared with injection into normal skin. The efficacy of EBC-46 was reduced by co-injection with bisindolylmaleimide-1. Loss of vascular integrity following treatment was demonstrated by an increased permeability of endothelial cell monolayers in vitro and by CD31 immunostaining of treated tumors in vivo. Our results demonstrate that a single intra-lesional injection of EBC-46 causes PKC-dependent hemorrhagic necrosis, rapid tumor cell death and ultimate cure of solid tumors in pre-clinical models of cancer.

Unprecedented 1,14-seco-crotofolanes from Croton insularis: oxidative cleavage of crotofolin C by a putative homo-Baeyer-Villiger rearrangement.

EBC-162 isolated from Croton insularis, obtained from the northern rainforest of Australia, was structurally affirmed as crotofolin C (4). Novel oxidative degradation products, EBC-233 and EBC-300, which are the first crotofolane endoperoxides, were also isolated. Both endoperoxides were found to be stable intermediates, which are proposed to undergo an unprecedented homo-Baeyer-Villiger biosynthetic rearrangement to give a new class of 1,14-seco-crotofolane diterpenes. Prolonged storage of all isolates assisted in authenticating their natural product status. Anticancer activities of reported compounds are presented.

EBC-219: a new diterpene skeleton, crotinsulidane, from the Australian rainforest containing a bridgehead double bond.

EBC-219 (4), isolated from Croton insularis (Baill), was established by spectroscopic and DFT methods as the first member of a new diterpene skeletal class, uniquely defined by the presence of a bicyclo[10.2.1] bridgehead olefin. The proposed biogenetic pathway to 4 from the co-isolated natural products EBC-131 (1), EBC-180 (2) and EBC-181 (3) is highly likely. EBC-180 (2) and EBC-181 (3) showed moderate to strong cytotoxic activity against various cancer cell lines.

Diagnostic accuracy of noncontrast MRI for detection of glenohumeral cartilage lesions: a prospective comparison to arthroscopy.

BACKGROUND: The purpose of this study was to determine the prevalence of glenohumeral articular cartilage lesions in patients with rotator cuff tendinopathy and to assess the accuracy of noncontrast magnetic resonance imaging (MRI) in detecting these defects compared with the "gold standard" of arthroscopy. METHODS: Noncontrast MRI studies obtained in 84 consecutive patients undergoing shoulder arthroscopy for rotator cuff tendinopathy (mean age, 54.8 years; range, 17-82 years) were prospectively evaluated for glenohumeral cartilage lesions. Two fellowship-trained, experienced musculoskeletal radiologists were blinded from the arthroscopic findings and independently evaluated the glenoid and humeral head cartilage on 2 separate occasions. RESULTS: At arthroscopy, cartilage lesions of the humeral head were detected in 23 patients (frequency, 27.4%), and glenoid cartilage lesions were found in 20 patients (frequency, 23.8%). For detection of a humeral lesion on MRI, the radiologists' combined accuracy was 78%, sensitivity was 43%, and specificity was 91%. The combined accuracy for detection of glenoid lesions on MRI was 84%, sensitivity was 53%, and specificity was 93%. Combining the readers, low-grade lesions (International Cartilage Repair Society grades 1 and 2) of the glenoid and humerus were read as negative on MRI in 63% and 86% of cases, respectively. CONCLUSION: Overall accuracy of noncontrast MRI for detection of glenohumeral articular cartilage lesions is good; however, interpretation is reader dependent, and accuracy is significantly reduced for detection of low-grade lesions. On the basis of these findings, we recommend that patients with rotator cuff tendinopathy undergoing arthroscopy be informed that the presence and severity of cartilage lesions may be underestimated on MRI.

Os acromiale: a review and an introduction of a new surgical technique for management.

Os acromiale is a common finding in shoulder surgery. We review the anatomy, prevalence, pathophysiology, and treatment options for this diagnosis. In addition, we report on a case series of 6 patients with a symptomatic meso os acromiale who were treated with a new technique involving arthroscopic acromioplasty in conjunction with the excision of the acromial nonunion site. We have demonstrated this novel treatment method to be a safe and effective technique in this case series. This arthroscopic partial resection of an os acromiale is considered to be an alternative option for treating a symptomatic meso os acromiale.