Search

Aggressive pituitary neuroendocrine tumors (PitNETs)/adenomas are characterized by progressive growth despite surgery and all standard medical therapies and radiotherapy. A subset will metastasize to the brain and/or distant locations and are termed metastatic PitNETs (pituitary carcinomas). Studies of potential prognostic markers have been limited due to the rarity of these tumors. A few recurrent somatic mutations have been identified, and epigenetic alterations and chromosomal rearrangements have not been explored in larger cohorts of aggressive and metastatic PitNETs. In this study, we performed genome-wide methylation analysis, including copy-number variation (CNV) calculations, on tumor tissue specimens from a large international cohort of 64 patients with aggressive (48) and metastatic (16) pituitary tumors. Twelve patients with non-invasive pituitary tumors (Knosp 0-2) exhibiting an indolent course over a 5 year follow-up served as controls. In an unsupervised hierarchical cluster analysis, aggressive/metastatic PitNETs clustered separately from benign pituitary tumors, and, when only specimens from the first surgery were analyzed, three separate clusters were identified: aggressive, metastatic, and benign PitNETs. Numerous CNV events affecting chromosomal arms and whole chromosomes were frequent in aggressive and metastatic, whereas benign tumors had normal chromosomal copy numbers with only few alterations. Genome-wide methylation analysis revealed different CNV profiles and a clear separation between aggressive/metastatic and benign pituitary tumors, potentially providing biomarkers for identification of these tumors with a worse prognosis at the time of first surgery. The data may refine follow-up routines and contribute to the timely introduction of adjuvant therapy in patients harboring, or at risk of developing, aggressive or metastatic pituitary tumors., (© 2024. The Author(s).)

Background: Revision anterior cruciate ligament (ACL) reconstruction has been documented to have inferior outcomes compared with primary ACL reconstruction. The reasons why remain unknown., Purpose: To determine whether surgical factors performed at the time of revision ACL reconstruction can influence a patient's outcome at 6-year follow-up., Study Design: Cohort study; Level of evidence, 2., Methods: Patients who underwent revision ACL reconstruction were identified and prospectively enrolled between 2006 and 2011. Data collected included baseline patient characteristics, surgical technique and pathology, and a series of validated patient-reported outcome instruments: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) subjective form, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx activity rating score. Patients were followed up for 6 years and asked to complete the identical set of outcome instruments. Regression analysis was used to control for baseline patient characteristics and surgical variables to assess the surgical risk factors for clinical outcomes 6 years after surgery., Results: A total of 1234 patients were enrolled (716 men, 58%; median age, 26 years), and 6-year follow-up was obtained on 79% of patients (980/1234). Using an interference screw for femoral fixation compared with a cross-pin resulted in significantly better outcomes in 6-year IKDC scores (odds ratio [OR], 2.2; 95% CI, 1.2-3.9; P = .008) and KOOS sports/recreation and quality of life subscale scores (OR range, 2.2-2.7; 95% CI, 1.2-4.8; P < .01). Use of an interference screw compared with a cross-pin resulted in a 2.6 times less likely chance of having a subsequent surgery within 6 years. Use of an interference screw for tibial fixation compared with any combination of tibial fixation techniques resulted in significantly improved scores for IKDC (OR, 1.96; 95% CI, 1.3-2.9; P = .001); KOOS pain, activities of daily living, and sports/recreation subscales (OR range, 1.5-1.6; 95% CI, 1.0-2.4; P < .05); and WOMAC pain and activities of daily living subscales (OR range, 1.5-1.8; 95% CI, 1.0-2.7; P < .05). Use of a transtibial surgical approach compared with an anteromedial portal approach resulted in significantly improved KOOS pain and quality of life subscale scores at 6 years (OR, 1.5; 95% CI, 1.02-2.2; P ≤ .04)., Conclusion: There are surgical variables at the time of ACL revision that can modify clinical outcomes at 6 years. Opting for a transtibial surgical approach and choosing an interference screw for femoral and tibial fixation improved patients' odds of having a significantly better 6-year clinical outcome in this cohort., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This project was funded by grant No. 5R01-AR060846 from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. All author disclosures are listed in the Appendix (available in the online version of this article). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Context: Head and neck paragangliomas (HNPGLs) are rare, usually benign, slow-growing tumours arising from neural crest-derived tissue. Definitive management pathways for HNPGLs have yet to be clearly defined., Objective: To review our experience of the clinical features and management of these tumours and to analyse outcomes of different treatment modalities., Methods: Demographic and clinical data were obtained from The Northern Ireland Electronic Care Record (NIECR) as well from a prospectively maintained HNPGL database between January 2011 through December 2023., Results: There were 87 patients; 50 females: 37 males with a mean age of 52.3 ± 14.2 years old (range 17-91 years old). 58.6% (n = 51) of patients had carotid body tumours, 25.2% (n = 22) glomus vagal tumours, 6.8% (n = 6) tumours in the middle ear, 2.2% (n = 2) in the parapharyngeal space and 1.1% (n = 1) in the sphenoid sinus. 5.7% (n = 5) of patients had multifocal disease. The mean tumour size at presentation was 3.2 ± 1.4 cm (range 0.5-6.9 cm). Pathogenic SDHD mutations were identified in 41.3% (n = 36), SDHB in 12.6% (n = 11), SDHC in 2.2% (n = 2) and SDHA in 1.1% (n = 1) of the patients. Overall treatment modalities included surgery alone in 51.7% (n = 45) of patients, radiotherapy in 14.9% (n = 13), observation in 28.7% (n = 25), and somatostatin analogue therapy with octreotide in 4.5% (n = 4) of patients. Factors associated with a significantly higher risk of recurrence included age over 60 years (p = .04), tumour size exceeding 2 cm (p = .03), positive SDHx variants (p = .01), and vagal and jugular tumours (p = .04)., Conclusion: The majority of our patients underwent initial surgical intervention and achieved disease stability. Our results suggest that carefully selected asymptomatic or medically unfit patients can be safely observed provided lifelong surveillance is maintained. We advocate for the establishment of a UK and Ireland national HNPGL registry, to delineate optimal management strategies for these rare tumours and improve long term outcomes., (© 2024 John Wiley & Sons Ltd.)

To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a durable increase in soluble PD1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV + N and BV + I + N) compared with BV + I (P < 0.05). Nonresponders and patients with short progression-free survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine-deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (P < 0.05). The results suggest a circulating tumor-immune-derived signature of BV ± I ± N treatment resistance that may be useful for patient stratification in combination checkpoint therapy., Significance: Identification of multi-omic immune markers from peripheral blood may help elucidate resistance mechanisms to checkpoint inhibitor and antibody-drug conjugate combinations with potential implications for treatment decisions in relapsed HL., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Meniscal and chondral damage is common in the patient undergoing revision anterior cruciate ligament (ACL) reconstruction., Purpose: To determine if meniscal and/or articular cartilage pathology at the time of revision ACL surgery significantly influences a patient's outcome at 6-year follow-up., Study Design: Cohort study; Level of evidence, 3., Methods: Patients undergoing revision ACL reconstruction were prospectively enrolled between 2006 and 2011. Data collection included baseline demographics, surgical technique, pathology, treatment, and scores from 4 validated patient-reported outcome instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx Activity Rating Scale. Patients were followed up at 6 years and asked to complete the identical set of outcome instruments. Regression analysis assessed the meniscal and articular cartilage pathology risk factors for clinical outcomes 6 years after revision ACL reconstruction., Results: An overall 1234 patients were enrolled (716 males, 58%; median age, 26 years). Surgeons reported the pathology at the time of revision surgery in the medial meniscus (45%), lateral meniscus (36%), medial femoral condyle (43%), lateral femoral condyle (29%), medial tibial plateau (11%), lateral tibial plateau (17%), patella (30%), and trochlea (21%). Six-year follow-up was obtained on 79% of the sample (980/1234). Meniscal pathology and articular cartilage pathology (medial femoral condyle, lateral femoral condyle, lateral tibial plateau, trochlea, and patella) were significant drivers of poorer patient-reported outcomes at 6 years (IKDC, KOOS, WOMAC, and Marx). The most consistent factors driving outcomes were having a medial meniscal excision (either before or at the time of revision surgery) and patellofemoral articular cartilage pathology. Six-year Marx activity levels were negatively affected by having either a repair/excision of the medial meniscus (odds ratio range, 1.45-1.72; P ≤ .04) or grade 3-4 patellar chondrosis (odds ratio, 1.72; P = .04). Meniscal pathology occurring before the index revision surgery negatively affected scores on all KOOS subscales except for sports/recreation ( P < .05). Articular cartilage pathology significantly impaired all KOOS subscale scores ( P < .05). Lower baseline outcome scores, higher body mass index, being a smoker, and incurring subsequent surgery all significantly increased the odds of reporting poorer clinical outcomes at 6 years., Conclusion: Meniscal and chondral pathology at the time of revision ACL reconstruction has continued significant detrimental effects on patient-reported outcomes at 6 years after revision surgery.

Background: Lytic or malpositioned tunnels may require bone grafting during revision anterior cruciate ligament reconstruction (rACLR) surgery. Patient characteristics and effects of grafting on outcomes after rACLR are not well described., Purpose: To describe preoperative characteristics, intraoperative findings, and 2-year outcomes for patients with rACLR undergoing bone grafting procedures compared with patients with rACLR without grafting., Study Design: Cohort study; Level of evidence, 3., Methods: A total of 1234 patients who underwent rACLR were prospectively enrolled between 2006 and 2011. Baseline revision and 2-year characteristics, surgical technique, pathology, treatment, and patient-reported outcome instruments (International Knee Documentation Committee [IKDC], Knee injury and Osteoarthritis Outcome Score [KOOS], Western Ontario and McMaster Universities Osteoarthritis Index, and Marx Activity Rating Scale [Marx]) were collected, as well as subsequent surgery information, if applicable. The chi-square and analysis of variance tests were used to compare group characteristics., Results: A total of 159 patients (13%) underwent tunnel grafting-64 (5%) patients underwent 1-stage and 95 (8%) underwent 2-stage grafting. Grafting was isolated to the femur in 31 (2.5%) patients, the tibia in 40 (3%) patients, and combined in 88 patients (7%). Baseline KOOS Quality of Life (QoL) and Marx activity scores were significantly lower in the 2-stage group compared with the no bone grafting group ( P ≤ .001). Patients who required 2-stage grafting had more previous ACLRs ( P < .001) and were less likely to have received a bone-patellar tendon-bone or a soft tissue autograft at primary ACLR procedure ( P ≤ .021) compared with the no bone grafting group. For current rACLR, patients undergoing either 1-stage or 2-stage bone grafting were more likely to receive a bone-patellar tendon-bone allograft ( P ≤ .008) and less likely to receive a soft tissue autograft ( P ≤ .003) compared with the no bone grafting group. At 2-year follow-up of 1052 (85%) patients, we found inferior outcomes in the 2-stage bone grafting group (IKDC score = 68; KOOS QoL score = 44; KOOS Sport/Recreation score = 65; and Marx activity score = 3) compared with the no bone grafting group (IKDC score = 77; KOOS QoL score = 63; KOOS Sport/Recreation score = 75; and Marx activity score = 7) ( P ≤ .01). The 1-stage bone graft group did not significantly differ compared with the no bone grafting group., Conclusion: Tunnel bone grafting was performed in 13% of our rACLR cohort, with 8% undergoing 2-stage surgery. Patients treated with 2-stage grafting had inferior baseline and 2-year patient-reported outcomes and activity levels compared with patients not undergoing bone grafting. Patients treated with 1-stage grafting had similar baseline and 2-year patient-reported outcomes and activity levels compared with patients not undergoing bone grafting.

Background: Patients with anterior cruciate ligament (ACL) revision report lower outcome scores on validated knee questionnaires postoperatively compared to cohorts with primary ACL reconstruction. In a previously active population, it is unclear if patient-reported outcomes (PROs) are associated with a return to activity (RTA) or vary by sports participation level (higher level vs. recreational athletes)., Hypotheses: Individual RTA would be associated with improved outcomes (ie, decreased knee symptoms, pain, function) as measured using validated PROs. Recreational participants would report lower PROs compared with higher level athletes and be less likely to RTA., Study Design: Cohort study; Level of evidence, 2., Methods: There were 862 patients who underwent a revision ACL reconstruction (rACLR) and self-reported physical activity at any level preoperatively. Those who did not RTA reported no activity 2 years after revision. Baseline data included patient characteristics, surgical history and characteristics, and PROs: International Knee Documentation Committee questionnaire, Marx Activity Rating Scale, Knee injury and Osteoarthritis Outcome Score, and the Western Ontario and McMaster Universities Osteoarthritis Index. A binary indicator was used to identify patients with same/better PROs versus worse outcomes compared with baseline, quantifying the magnitude of change in each direction, respectively. Multivariable regression models were used to evaluate risk factors for not returning to activity, the association of 2-year PROs after rACLR surgery by RTA status, and whether each PRO and RTA status differed by participation level., Results: At 2 years postoperatively, approximately 15% did not RTA, with current smokers (adjusted odds ratio [aOR] = 3.3; P = .001), female patients (aOR = 2.9; P < .001), recreational participants (aOR = 2.0; P = .016), and those with a previous medial meniscal excision (aOR = 1.9; P = .013) having higher odds of not returning. In multivariate models, not returning to activity was significantly associated with having worse PROs at 2 years; however, no clinically meaningful differences in PROs at 2 years were seen between participation levels., Conclusion: Recreational-level participants were twice as likely to not RTA compared with those participating at higher levels. Within a previously active cohort, no RTA was a significant predictor of lower PROs after rACLR. However, among patients who did RTA after rACLR, approximately 20% reported lower outcome scores. Most patients with rACLR who were active at baseline improved over time; however, patients who reported worse outcomes at 2 years had a clinically meaningful decline across all PROs.

Rationale and Objectives: To train and validate machine learning models capable of classifying suspicious thoracic lesions as benign or malignant and to further classify malignant lesions by pathologic subtype while quantifying feature importance for each classification., Materials and Methods: 796 patients who had undergone CT guided thoracic biopsy for a concerning thoracic lesion (79.3% lung, 11.4% mediastinum, 6.5% pleura, 2.7% chest wall) were retrospectively enrolled. Lesions were classified as malignant or benign based on ground-truth pathology result, and malignant lesions were classified as primary or secondary cancer. Clinical variables were extracted from EMR and radiology reports. Supervised binary and multiclass classification models were trained to classify lesions based on the input features and evaluated on a held-out test set. Model specific feature analyses were performed to identify variables most predictive of each class, as well as to assess the independent importance of clinical, and imaging features., Results: Binary classification models achieved a top accuracy of 80.6%, with predictive features included smoking history, age, lesion size, and lesion location. Multiclass classification models achieved a top weighted average f1-score of 0.73. Features predictive of primary cancer included smoking history, race, and age, while features predictive of secondary cancer included lesion location, and a history of cancer., Conclusion: Machine learning models enable classification of suspicious thoracic lesions based on clinical and imaging variables, achieving clinically useful performance while identifying importance of individual input features on a pathology-proven dataset. We believe models such as these are more likely to be trusted and adopted by clinicians., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

It is acknowledged that the COVID-19 pandemic has caused profound disruption to the delivery of healthcare services globally. This has affected the management of many long-term conditions including osteoporosis as resources are diverted to cover urgent care. Osteoporosis is a public health concern worldwide and treatment is required for the prevention of further bone loss, deterioration of skeletal micro-architecture, and fragility fractures. This review provides information on how the COVID-19 pandemic has impacted the diagnosis and management of osteoporosis. We also provide clinical recommendations on the adaptation of care pathways based on experience from five referral centres to ensure that patients with osteoporosis are still treated and to reduce the risk of fractures both for the individual patient and on a societal basis. We address the use of the FRAX tool for risk stratification and initiation of osteoporosis treatment and discuss the potential adaptations to treatment pathways in view of limitations on the availability of DXA. We focus on the issues surrounding initiation and maintenance of treatment for patients on parenteral therapies such as zoledronate, denosumab, teriparatide, and romosozumab during the pandemic. The design of these innovative care pathways for the management of patients with osteoporosis may also provide a platform for future improvement to osteoporosis services when routine clinical care resumes., (© 2021. The Author(s).)

Background: Although graft choice may be limited in the revision setting based on previously used grafts, most surgeons believe that graft choice for anterior cruciate ligament (ACL) reconstruction is an important factor related to outcome., Hypothesis: In the ACL revision setting, there would be no difference between autograft and allograft in rerupture rate and patient-reported outcomes (PROs) at 6-year follow-up., Study Design: Cohort study; Level of evidence, 2., Methods: Patients who had revision surgery were identified and prospectively enrolled in this cohort study by 83 surgeons over 52 sites. Data collected included baseline characteristics, surgical technique and pathology, and a series of validated PRO measures. Patients were followed up at 6 years and asked to complete the identical set of PRO instruments. Incidence of additional surgery and reoperation because of graft failure were also recorded. Multivariable regression models were used to determine the predictors (risk factors) of PROs, graft rerupture, and reoperation at 6 years after revision surgery., Results: A total of 1234 patients including 716 (58%) men were enrolled. A total of 325 (26%) underwent revision using a bone-patellar tendon-bone (BTB) autograft; 251 (20%), soft tissue autograft; 289 (23%), BTB allograft; 302 (25%), soft tissue allograft; and 67 (5%), other graft. Questionnaires and telephone follow-up for subsequent surgery information were obtained for 809 (66%) patients, while telephone follow-up was only obtained for an additional 128 patients for the total follow-up on 949 (77%) patients. Graft choice was a significant predictor of 6-year Marx Activity Rating Scale scores ( P = .024). Specifically, patients who received a BTB autograft for revision reconstruction had higher activity levels than did patients who received a BTB allograft (odds ratio [OR], 1.92; 95% CI, 1.25-2.94). Graft rerupture was reported in 5.8% (55/949) of patients by their 6-year follow-up: 3.5% (16/455) of patients with autografts and 8.4% (37/441) of patients with allografts. Use of a BTB autograft for revision resulted in patients being 4.2 times less likely to sustain a subsequent graft rupture than if a BTB allograft were utilized ( P = .011; 95% CI, 1.56-11.27). No significant differences were found in graft rerupture rates between BTB autograft and soft tissue autografts ( P = .87) or between BTB autografts and soft tissue allografts ( P = .36). Use of an autograft was found to be a significant predictor of having fewer reoperations within 6 years compared with using an allograft ( P = .010; OR, 0.56; 95% CI, 0.36-0.87)., Conclusion: BTB and soft tissue autografts had a decreased risk in graft rerupture compared with BTB allografts. BTB autografts were associated with higher activity level than were BTB allografts at 6 years after revision reconstruction. Surgeons and patients should consider this information when choosing a graft for revision ACL reconstruction.

We introduced virtual fracture liaison clinics during the COVID-19 pandemic in order to support clinical care while DXA services were down-turned. We observed that virtual FLS clinics are effective in delivering fracture risk assessment, health promotion, and clinical management and are well received by patients with positive patient experience., Introduction: We examined the impact of virtual FLS telephone clinics, as an alternative to face-to-face clinics during the COVID-19 lockdown., Methods: Patients presenting with low trauma fracture were recruited according to standard criteria. A structured telephone clinic appointment was offered, which included fracture risk and health promotion assessment and a treatment plan. Risk factors, demographics, fracture type, FRAX scores, and outcomes were analysed. We assessed patient experience with an anonymised patient survey., Results: Clinical outcomes from virtual clinics were assessed (77F/33M; mean age 65.7 years). The mean 10-year observed fracture risk for major osteoporotic fracture was 18.2% and 7.0% for hip fracture. We observed high 'attendance' rates at 79%; however, a significant number were still not available for telephone review (11%) or cancelled their appointment (10%). A recommendation for bisphosphonate treatment was made in 54% of the cohort based on National Osteoporosis Guidelines Group (NOGG) criteria. Follow-up DXA assessment is planned for 64%, according to fracture risk and NOGG guidance. We received 60 responses from the initial patient survey. Ninety percent rated their overall experience of service at 4 or 5 (very good to excellent). Ninety-eight indicated they would recommend the service to others., Conclusions: Virtual clinics are effective in delivery of fracture risk assessment and clinical management with positive patient experience. While a significant proportion will require DXA follow-up to complete the clinical assessment, virtual clinics have mitigated delays in fracture prevention interventions during the COVID-19 pandemic.

Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors., Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs., Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored., Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs., Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.)

We introduced a standardised reporting system in the radiology department to highlight vertebral fractures and to signpost fracture prevention services. Our quality improvement project achieved improved fracture reporting, access to the FLS service, bone density assessment and anti-fracture treatment., Purpose: Identification of vertebral fragility fractures (VF) provides an opportunity to identify individuals at high risk who might benefit from secondary fracture prevention. We sought to standardise VF reporting and to signpost fracture prevention services. Our aim was to improve rates of VF detection and access to our fracture liaison service (FLS)., Methods: We introduced a standardised reporting tool within the radiology department to flag VFs with signposting for referral for bone densitometry (DXA) and osteoporosis assessment in line with Royal Osteoporosis Society guidelines. We monitored uptake of VF reporting during a quality improvement phase and case identification within the FLS service., Results: Recruitment of individuals with VF to the FLS service increased from a baseline of 63 cases in 2017 (6%) to 95 (8%) in 2018 and 157 (8%) in 2019 and to 102 (12%) in the first 6 months of 2020 (p = 0.001). One hundred fifty-three patients with VFs were identified during the QI period (56 males; 97 females). Use of the terminology 'fracture' increased to 100% (mean age 70 years; SD 13) in computed tomography (n = 110), plain X-ray (n = 37) or magnetic resonance imaging (n = 6) reports within the cohort. Signposting to DXA and osteoporosis assessment was included in all reports (100%). DXA was arranged for 103/153; 12 failed to attend. Diagnostic categories were osteoporosis (31%), osteopenia (36%) or normal bone density (33%). A new prescription for bone protection therapy was issued in 63/153. Twelve of the series died during follow-up., Conclusions: Standardisation of radiology reporting systems facilitates reporting of prevalent vertebral fractures and supports secondary fracture prevention strategies.

Background: Meniscal preservation has been demonstrated to contribute to long-term knee health. This has been a successful intervention in patients with isolated tears and tears associated with anterior cruciate ligament (ACL) reconstruction. However, the results of meniscal repair in the setting of revision ACL reconstruction have not been documented., Purpose: To examine the prevalence and 2-year operative success rate of meniscal repairs in the revision ACL setting., Study Design: Case-control study; Level of evidence, 3., Methods: All cases of revision ACL reconstruction with concomitant meniscal repair from a multicenter group between 2006 and 2011 were selected. Two-year follow-up was obtained by phone and email to determine whether any subsequent surgery had occurred to either knee since the initial revision ACL reconstruction. If so, operative reports were obtained, whenever possible, to verify the pathologic condition and subsequent treatment., Results: In total, 218 patients (18%) from 1205 revision ACL reconstructions underwent concurrent meniscal repairs. There were 235 repairs performed: 153 medial, 48 lateral, and 17 medial and lateral. The majority of these repairs (n = 178; 76%) were performed with all-inside techniques. Two-year surgical follow-up was obtained on 90% (197/218) of the cohort. Overall, the meniscal repair failure rate was 8.6% (17/197) at 2 years. Of the 17 failures, 15 were medial (13 all-inside, 2 inside-out) and 2 were lateral (both all-inside). Four medial failures were treated in conjunction with a subsequent repeat revision ACL reconstruction., Conclusion: Meniscal repair in the revision ACL reconstruction setting does not have a high failure rate at 2-year follow-up. Failure rates for medial and lateral repairs were both <10% and consistent with success rates of primary ACL reconstruction meniscal repair. Medial tears underwent reoperation for failure at a significantly higher rate than lateral tears.

We introduced an electronic triage system into our osteoporosis service to actively manage referral demand in a busy outpatient service. Our study demonstrated the effectiveness of e-triage in supporting alternative management pathways, through use of virtual advice and direct to investigation services, to improve patient access., Purpose: Osteoporosis referrals are increasing with awareness of the potential for prevention of fragility fracture and with complex decision making around management with long-term bisphosphonate therapy. We examined whether active triage of referrals might improve referral management processes and patient access to osteoporosis services., Methods: We implemented electronic triage (e-triage) of referrals to our osteoporosis service using the Northern Ireland electronic health care record. This included the option of 'advice only', direct to investigation with DXA or face-to-face appointments at the consultant-led complex osteoporosis service. We anticipated that there was scope to manage patient flow direct to investigation, or to provide referring clinicians with clinical advice without the need for a face-to-face assessment, at the consultant-led specialist service., Results: We reviewed e-triage outcomes of 809 referrals (692 F; 117 M) to osteoporosis specialist services (mean age 65 ± 16.5 years) over a 12-month period. There was a high degree of agreement for the triage category between the referring clinician and specialist services (741/809). 73.3% attended a face-to-face appointment at the consultant-led clinic, while active triage enabled direct to investigation (18.4%) or discharge (8.3%) in the remainder. The mean time between receipt of an electronic referral and e-triage was 3 days over the 12-month period as compared with 2.1 days (median 1.1 days) when annual leave periods were excluded., Conclusion: E-triage supports effective referral management in a busy osteoporosis service. Efficiency is limited by reliance on a sole clinician and 5 day working at present. There is scope to further improve systems access through multidisciplinary team working, virtual clinics and future information technology developments.

Osteoporosis is a significant global health and economic burden associated with bone fracture, morbidity and mortality. Denosumab, a novel human monoclonal antibody second-line treatment, inhibits osteoclast-mediated bone resorption and increases bone mineral density (BMD). Treatment achieves reductions in vertebral, non-vertebral and hip fracture risk. We undertook a service evaluation to review clinical outcomes of patients treated with denosumab in an osteoporosis department that provides regional services. We identified 529 patients (95% female; mean age 72.8 years; 35-98 years), who had at least one dose of denosumab administered for the treatment of osteoporosis. The mean number of denosumab doses administered was 4.9 (range: 1 to 12). 330/529 patients had completed a baseline and post-treatment bone densitometry scan (DXA). The mean observed BMD change at around 18 months at the lumbar spine was +8.4% and at the hip was +3.5%. While the majority have transitioned to shared care administration of treatment within primary care (53%), 20% continue to attend hospital clinics to receive treatment. During follow-up, there were 66 deaths (12%). 15% switched to an alternative treatment or were discharged. This retrospective cohort study demonstrates the clinical effectiveness of denosumab in improving bone mineral density in a real life setting in an ageing, co-morbid population. There has been recent progress with adoption of shared care administration in primary care. As part of a quality improvement programme we have recently developed a dedicated denosumab database and day-case treatment clinic for those receiving treatment in secondary care., Competing Interests: Provenance: externally peer reviewed., (Copyright © 2019 Ulster Medical Society.)

Background: Patient-reported outcomes (PROs) are a valid measure of results after revision anterior cruciate ligament (ACL) reconstruction. Revision ACL reconstruction has been documented to have worse outcomes when compared with primary ACL reconstruction. Understanding positive and negative predictors of PROs will allow surgeons to modify and potentially improve outcome for patients., Purpose/hypothesis: The purpose was to describe PROs after revision ACL reconstruction and test the hypothesis that patient- and technique-specific variables are associated with these outcomes., Study Design: Cohort study; Level of evidence, 2., Methods: Patients undergoing revision ACL reconstruction were identified and prospectively enrolled by 83 surgeons over 52 sites. Data included baseline demographics, surgical technique and pathology, and a series of validated PRO instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index, and Marx Activity Rating Scale. Patients were followed up at 2 years and asked to complete the identical set of outcome instruments. Multivariate regression models were used to control for a variety of demographic and surgical factors to determine the positive and negative predictors of PRO scores at 2 years after revision surgery., Results: A total of 1205 patients met the inclusion criteria and were successfully enrolled: 697 (58%) were male, with a median cohort age of 26 years. The median time since their most recent previous ACL reconstruction was 3.4 years. Two-year questionnaire follow-up was obtained from 989 patients (82%). The most significant positive predictors of 2-year IKDC scores were a high baseline IKDC score, high baseline Marx activity level, male sex, and having a longer time since the most recent previous ACL reconstruction, while negative predictors included having a lateral meniscectomy before the revision ACL reconstruction or having grade 3/4 chondrosis in either the trochlear groove or the medial tibial plateau at the time of the revision surgery. For KOOS, having a high baseline score and having a longer time between the most recent previous ACL reconstruction and revision surgery were significant positive predictors for having a better (ie, higher) 2-year KOOS, while having a lateral meniscectomy before the revision ACL reconstruction was a consistent predictor for having a significantly worse (ie, lower) 2-year KOOS. Statistically significant positive predictors for 2-year Marx activity levels included higher baseline Marx activity levels, younger age, male sex, and being a nonsmoker. Negative 2-year activity level predictors included having an allograft or a biologic enhancement at the time of revision surgery., Conclusion: PROs after revision ACL reconstruction are associated with a variety of patient- and surgeon-related variables. Understanding positive and negative predictors of PROs will allow surgeons to guide patient expectations as well as potentially improve outcomes.

Background: Anterior cruciate ligament (ACL) revision cohorts continually report lower outcome scores on validated knee questionnaires than primary ACL cohorts at similar time points after surgery. It is unclear how these outcomes are associated with physical activity after physician clearance for return to recreational or competitive sports after ACL revision surgery., Hypotheses: Participants who return to either multiple sports or a singular sport after revision ACL surgery will report decreased knee symptoms, increased activity level, and improved knee function as measured by validated patient-reported outcome measures (PROMs) and compared with no sports participation. Multisport participation as compared with singular sport participation will result in similar increased PROMs and activity level., Study Design: Cross-sectional study; Level of evidence, 3., Methods: A total of 1205 patients who underwent revision ACL reconstruction were enrolled by 83 surgeons at 52 clinical sites. At the time of revision, baseline data collected included the following: demographics, surgical characteristics, previous knee treatment and PROMs, the International Knee Documentation Committee (IKDC) questionnaire, Marx activity score, Knee injury and Osteoarthritis Outcome Score (KOOS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). A series of multivariate regression models were used to evaluate the association of IKDC, KOOS, WOMAC, and Marx Activity Rating Scale scores at 2 years after revision surgery by sports participation category, controlling for known significant covariates., Results: Two-year follow-up was obtained on 82% (986 of 1205) of the original cohort. Patients who reported not participating in sports after revision surgery had lower median PROMs both at baseline and at 2 years as compared with patients who participated in either a single sport or multiple sports. Significant differences were found in the change of scores among groups on the IKDC ( P < .0001), KOOS-Symptoms ( P = .01), KOOS-Sports and Recreation ( P = .04), and KOOS-Quality of Life ( P < .0001). Patients with no sports participation were 2.0 to 5.7 times more likely than multiple-sport participants to report significantly lower PROMs, depending on the specific outcome measure assessed, and 1.8 to 3.8 times more likely than single-sport participants (except for WOMAC-Stiffness, P = .18), after controlling for known covariates., Conclusion: Participation in either a single sport or multiple sports in the 2 years after ACL revision surgery was found to be significantly associated with higher PROMs across multiple validated self-reported assessment tools. During follow-up appointments, surgeons should continue to expect that patients who report returning to physical activity after surgery will self-report better functional outcomes, regardless of baseline activity levels.

Nocardiosis, a rare infection occurring mostly in immunosuppressed patients can present with neurological complications including cerebral abscess formation, and is associated with high morbidity and mortality. We describe the case of a 54-year-old immunocompetent man with cerebral nocardiosis, who presented with sudden onset hemiparesis in an acute medicine unit. He required three craniotomies with excision, following failure to respond to antimicrobial therapy, with subsequent clinical improvement and radiological resolution of multiple cerebral abscesses. Challenges in diagnosis and management of hemiparesis in the acute medical unit are discussed. Successful management of cerebral nocardiosis require early communication with a neurosurgical unit, neuropathology and microbiology services to optimise management with targeted antimicrobial therapy.

Background: The occurrence of physiologic knee hyperextension (HE) in the revision anterior cruciate ligament reconstruction (ACLR) population and its effect on outcomes have yet to be reported. Hypothesis/Purpose: The prevalence of knee HE in revision ACLR and its effect on 2-year outcome were studied with the hypothesis that preoperative physiologic knee HE ≥5° is a risk factor for anterior cruciate ligament (ACL) graft rupture., Study Design: Cohort study; Level of evidence, 2., Methods: Patients undergoing revision ACLR were identified and prospectively enrolled between 2006 and 2011. Study inclusion criteria were patients undergoing single-bundle graft reconstructions. Patients were followed up at 2 years and asked to complete an identical set of outcome instruments (International Knee Documentation Committee, Knee injury and Osteoarthritis Outcome Score, WOMAC, and Marx Activity Rating Scale) as well as provide information regarding revision ACL graft failure. A regression model with graft failure as the dependent variable included age, sex, graft type at the time of the revision ACL surgery, and physiologic preoperative passive HE ≥5° (yes/no) to assess these as potential risk factors for clinical outcomes 2 years after revision ACLR., Results: Analyses included 1145 patients, for whom 2-year follow-up was attained for 91%. The median age was 26 years, with age being a continuous variable. Those below the median were grouped as "younger" and those above as "older" (age: interquartile range = 20, 35 years), and 42% of patients were female. There were 50% autografts, 48% allografts, and 2% that had a combination of autograft plus allograft. Passive knee HE ≥5° was present in 374 (33%) patients in the revision cohort, with 52% being female. Graft rupture at 2-year follow-up occurred in 34 cases in the entire cohort, of which 12 were in the HE ≥5° group (3.2% failure rate) and 22 in the non-HE group (2.9% failure rate). The median age of patients who failed was 19 years, as opposed to 26 years for those with intact grafts. Three variables in the regression model were significant predictors of graft failure: younger age (odds ratio [OR] = 3.6; 95% CI, 1.6-7.9; P = .002), use of allograft (OR = 3.3; 95% CI, 1.5-7.4; P = .003), and HE ≥5° (OR = 2.12; 95% CI, 1.1-4.7; P = .03)., Conclusion: This study revealed that preoperative physiologic passive knee HE ≥5° is present in one-third of patients who undergo revision ACLR. HE ≥5° was an independent significant predictor of graft failure after revision ACLR with a >2-fold OR of subsequent graft rupture in revision ACL surgery. Registration: NCT00625885 ( ClinicalTrials.gov identifier).

Background: Articular cartilage health is an important issue following anterior cruciate ligament (ACL) injury and primary ACL reconstruction. Factors present at the time of primary ACL reconstruction may influence the subsequent progression of articular cartilage damage., Hypothesis: Larger meniscus resection at primary ACL reconstruction, increased patient age, and increased body mass index (BMI) are associated with increased odds of worsened articular cartilage damage at the time of revision ACL reconstruction., Study Design: Case-control study; Level of evidence, 3., Methods: Subjects who had primary and revision data in the databases of the Multicenter Orthopaedics Outcomes Network (MOON) and Multicenter ACL Revision Study (MARS) were included. Reviewed data included chondral surface status at the time of primary and revision surgery, meniscus status at the time of primary reconstruction, primary reconstruction graft type, time from primary to revision ACL surgery, as well as demographics and Marx activity score at the time of revision. Significant progression of articular cartilage damage was defined in each compartment according to progression on the modified Outerbridge scale (increase ≥1 grade) or >25% enlargement in any area of damage. Logistic regression identified predictors of significant chondral surface change in each compartment from primary to revision surgery., Results: A total of 134 patients were included, with a median age of 19.5 years at revision surgery. Progression of articular cartilage damage was noted in 34 patients (25.4%) in the lateral compartment, 32 (23.9%) in the medial compartment, and 31 (23.1%) in the patellofemoral compartment. For the lateral compartment, patients who had >33% of the lateral meniscus excised at primary reconstruction had 16.9-times greater odds of progression of articular cartilage injury than those with an intact lateral meniscus ( P < .001). For the medial compartment, patients who had <33% of the medial meniscus excised at the time of the primary reconstruction had 4.8-times greater odds of progression of articular cartilage injury than those with an intact medial meniscus ( P = .02). Odds of significant chondral surface change increased by 5% in the lateral compartment and 6% in the medial compartment for each increased year of age ( P ≤ .02). For the patellofemoral compartment, the use of allograft in primary reconstruction was associated with a 15-fold increased odds of progression of articular cartilage damage relative to a patellar tendon autograft ( P < .001). Each 1-unit increase in BMI at the time of revision surgery was associated with a 10% increase in the odds of progression of articular cartilage damage ( P = .046) in the patellofemoral compartment., Conclusion: Excision of the medial and lateral meniscus at primary ACL reconstruction increases the odds of articular cartilage damage in the corresponding compartment at the time of revision ACL reconstruction. Increased age is a risk factor for deterioration of articular cartilage in both tibiofemoral compartments, while increased BMI and the use of allograft for primary ACL reconstruction are associated with an increased risk of progression in the patellofemoral compartment.

The emotional distress associated with adjusting to and living with diabetes has been termed diabetes distress. Diabetes distress is associated with glycaemic control but interventions to reduce diabetes distress have failed to consistently improve diabetes control. Various illness perceptions have previously been linked with both diabetes distress and glycaemic control but interrelationships between these features have not been previously investigated. We hypothesised that illness perceptions mediate the relationship between diabetes distress and glycaemia. Participants with type 2 diabetes attending diabetes outpatient clinics (n = 84) provided demographic and clinical information and completed the Diabetes Distress Scale-17 and the Brief Illness Perceptions Questionnaire. Using regression analysis we demonstrated that the illness perceptions of personal control, regimen-related distress, socioeconomic status and insulin use were significant contributors in the final model predicting HbA 1c . Higher levels of personal control were associated with better glycaemic control. Conversely, regimen-related distress was associated with hyperglycaemia. Mediation analyses showed that the relationship between regimen-related distress and HbA 1c was mediated by personal control. Our work suggests that psychological interventions designed to reduce diabetes distress may be more efficacious in improving glycaemic control if they address an individual's perception of personal control.

We report a case of a 58-year-old male presenting with confusion and hypoglycaemia. There had been no prior exposure to oral hypoglycaemic agents or insulin. He was found to have inappropriate endogenous hyperinsulinaemia. Insulinoma was excluded by detailed endocrine assessment. Insulin antibodies were positive in keeping with a diagnosis of insulin autoimmune syndrome (IAS). He was treated with prednisolone 5mg once daily and nutritional supplements leading to resolution of acute confusion and hypoglycaemic episodes. The patient also had severe psoriasis and following discharge was treated with a variety of immunosuppressant therapies. This was associated with disappearance of insulin antibodies after twelve months of follow up. While it is possible that there was spontaneous resolution of insulin antibodies, we speculate that his prednisolone and immunosuppressant therapy may have suppressed insulin antibody production. There are several well recognised associations with IAS and autoimmune conditions, including Grave's disease, systemic lupus erythematous and rheumatoid arthritis. To our knowledge this is the first reported case of insulin autoimmune syndrome, resolving with immunosuppressant treatment of psoriasis., Competing Interests: Provenance: externally peer-reviewed.

Background: Revision anterior cruciate ligament (ACL) reconstruction has been documented to have worse outcomes compared with primary ACL reconstruction., Hypothesis: Certain factors under the control of the surgeon at the time of revision surgery can both negatively and positively affect outcomes., Study Design: Case-control study; Level of evidence, 3., Methods: Patients undergoing revision ACL reconstruction were identified and prospectively enrolled between 2006 and 2011. Data collected included baseline demographics, intraoperative surgical technique and joint disorders, and a series of validated patient-reported outcome instruments (International Knee Documentation Committee [IKDC] subjective form, Knee Injury and Osteoarthritis Outcome Score [KOOS], Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC], and Marx activity rating scale) completed before surgery. Patients were followed up for 2 years and asked to complete an identical set of outcome instruments. Regression analysis was used to control for age, sex, body mass index (BMI), activity level, baseline outcome scores, revision number, time since last ACL reconstruction, and a variety of previous and current surgical variables to assess the surgical risk factors for clinical outcomes 2 years after revision ACL reconstruction., Results: A total of 1205 patients (697 male [58%]) met the inclusion criteria and were successfully enrolled. The median age was 26 years, and the median time since their last ACL reconstruction was 3.4 years. Two-year follow-up was obtained on 82% (989/1205). Both previous and current surgical factors were found to be significant contributors toward poorer clinical outcomes at 2 years. Having undergone previous arthrotomy (nonarthroscopic open approach) for ACL reconstruction compared with the 1-incision technique resulted in significantly poorer outcomes for the 2-year IKDC ( P = .037; odds ratio [OR], 2.43; 95% CI, 1.05-5.88) and KOOS pain, sports/recreation, and quality of life (QOL) subscales ( P ≤ .05; OR range, 2.38-4.35; 95% CI, 1.03-10.00). The use of a metal interference screw for current femoral fixation resulted in significantly better outcomes for the 2-year KOOS symptoms, pain, and QOL subscales ( P ≤ .05; OR range, 1.70-1.96; 95% CI, 1.00-3.33) as well as WOMAC stiffness subscale ( P = .041; OR, 1.75; 95% CI, 1.02-3.03). Not performing notchplasty at revision significantly improved 2-year outcomes for the IKDC ( P = .013; OR, 1.47; 95% CI, 1.08-1.99), KOOS activities of daily living (ADL) and QOL subscales ( P ≤ .04; OR range, 1.40-1.41; 95% CI, 1.03-1.93), and WOMAC stiffness and ADL subscales ( P ≤ .04; OR range, 1.41-1.49; 95% CI, 1.03-2.05). Factors before revision ACL reconstruction that increased the risk of poorer clinical outcomes at 2 years included lower baseline outcome scores, a lower Marx activity score at the time of revision, a higher BMI, female sex, and a shorter time since the patient's last ACL reconstruction. Prior femoral fixation, prior femoral tunnel aperture position, and knee flexion angle at the time of revision graft fixation were not found to affect 2-year outcomes in this revision cohort., Conclusion: There are certain surgical variables that the physician can control at the time of revision ACL reconstruction that can modify clinical outcomes at 2 years. Whenever possible, opting for an anteromedial portal or transtibial surgical exposure, choosing a metal interference screw for femoral fixation, and not performing notchplasty are associated with significantly better 2-year clinical outcomes.

Background: While revision anterior cruciate ligament reconstruction (ACLR) can be performed to restore knee stability and improve patient activity levels, outcomes after this surgery are reported to be inferior to those after primary ACLR. Further reoperations after revision ACLR can have an even more profound effect on patient satisfaction and outcomes. However, there is a current lack of information regarding the rate and risk factors for subsequent surgery after revision ACLR., Purpose: To report the rate of reoperations, procedures performed, and risk factors for a reoperation 2 years after revision ACLR., Study Design: Case-control study; Level of evidence, 3., Methods: A total of 1205 patients who underwent revision ACLR were enrolled in the Multicenter ACL Revision Study (MARS) between 2006 and 2011, composing the prospective cohort. Two-year questionnaire follow-up was obtained for 989 patients (82%), while telephone follow-up was obtained for 1112 patients (92%). If a patient reported having undergone subsequent surgery, operative reports detailing the subsequent procedure(s) were obtained and categorized. Multivariate regression analysis was performed to determine independent risk factors for a reoperation., Results: Of the 1112 patients included in the analysis, 122 patients (11%) underwent a total of 172 subsequent procedures on the ipsilateral knee at 2-year follow-up. Of the reoperations, 27% were meniscal procedures (69% meniscectomy, 26% repair), 19% were subsequent revision ACLR, 17% were cartilage procedures (61% chondroplasty, 17% microfracture, 13% mosaicplasty), 11% were hardware removal, and 9% were procedures for arthrofibrosis. Multivariate analysis revealed that patients aged <20 years had twice the odds of patients aged 20 to 29 years to undergo a reoperation. The use of an allograft at the time of revision ACLR (odds ratio [OR], 1.79; P = .007) was a significant predictor for reoperations at 2 years, while staged revision (bone grafting of tunnels before revision ACLR) (OR, 1.93; P = .052) did not reach significance. Patients with grade 4 cartilage damage seen during revision ACLR were 78% less likely to undergo subsequent operations within 2 years. Sex, body mass index, smoking history, Marx activity score, technique for femoral tunnel placement, and meniscal tearing or meniscal treatment at the time of revision ACLR showed no significant effect on the reoperation rate., Conclusion: There was a significant reoperation rate after revision ACLR at 2 years (11%), with meniscal procedures most commonly involved. Independent risk factors for subsequent surgery on the ipsilateral knee included age <20 years and the use of allograft tissue at the time of revision ACLR.

Objective: Diabetes is highly prevalent in individuals with acute coronary syndrome (ACS). Current NICE guidelines recommend diabetes screening of hyperglycaemic patients using a fasting plasma glucose after 4 days from admission. In 2012 the World Health Organisation (WHO) approved the use of HbA1c in the diagnosis and targeted screening for type 2 diabetes. We introduced a service improvement project using HbA1c for diabetes screening in patients with no previous diagnosis of diabetes admitted with ACS regardless of glycaemic state., Method: An initial retrospective audit utilised 21 months of data from the MINAP database to identify patients meeting current NICE criteria for diabetes screening. A prospective service improvement project was undertaken over a 4 month period using HbA1c as a universal screening test to categorise ACS patients based on WHO criteria., Results: The retrospective audit identified 93 of 420 (22%) patients with pre-existing diabetes and 8 of the remaining 327 (2.4%) were hyperglycaemic, thus meeting NICE criteria for diabetes screening. In the service improvement project 2/49 patients (4%) met NICE criteria for diabetes screening. Twenty six of these 49 patients had a HbA1c test on admission and 17/26 (65.4%) were classified as probable diabetes or high risk., Conclusion: A significant proportion of ACS patients have diabetes, which may be undetected by current NICE criteria. Universal HbA1c testing offers utility as a simple and effective screening test for diabetes in the ACS population.

Diabetes distress is a rational emotional response to the threat of a life-changing illness. Distinct from depression, it is conceptually rooted in the demands of diabetes management and is a product of emotional adjustment. Diabetes distress has been found to be significantly associated with glycated haemoglobin (HbA1c) level and the likelihood of an individual adopting self-care behaviours. The lack of perceived support from family, friends and healthcare professionals significantly contributes to elevated diabetes distress, and this issue tends to be overlooked when designing interventions. Pioneering large-scale research, DAWN2, gives voices to the families of those with diabetes and reaffirms the need to consider psychosocial factors in routine diabetes care. Structured diabetes education programmes are the most widely used in helping individuals cope with diabetes, but they tend not to include the psychological or interpersonal aspects of diabetes management in their curricula. The need for health practitioners, irrespective of background, to demonstrate an understanding of diabetes distress and to actively engage in discussion with individuals struggling to cope with diabetes is emphasised., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Context: Selective adenomectomy via transsphenoidal surgery induces remission of Cushing's disease (CD) in most patients. Although an undetectable postoperative serum cortisol (<2 μg/dl) has been advocated as an index of remission, there is no consensus on predictors of recurrence., Objective: We hypothesized that patients with subnormal cortisol (2-4.9 μg/dl) might achieve long-term remission and that postoperative responses to CRH might predict recurrence., Design, Setting, and Participants: We prospectively studied CD patients with initial remission after adenomectomy or hemihypophysectomy (n = 14). Long-term recurrence (n = 39) or remission (n = 293) was assigned by laboratory results, glucocorticoid dependence, or patient survey at a mean of 10.6 yr after surgery., Intervention and Main Outcome Measures: Postoperatively, morning cortisol was measured on d 3-5, and cortisol and ACTH responses to ovine CRH were assessed around d 10., Results: Follow-up duration was median 11 yr (range 1-22.8 yr). Fewer patients achieved a cortisol nadir below 2 μg/dl (87%) than below 5 μg/dl (98%), yet recurrence rates were similar (<2 μg/dl, 9.5%; <5 μg/dl, 10.4%; 2-4.9 μg/dl, 20%; not significant). CRH-stimulated cortisol (P < 0.002) and ACTH (P = 0.04) values were higher for the recurrence than the remission group. However, no basal or stimulated ACTH or serum or urine cortisol cutoff value predicted all who later recurred., Conclusions: A postoperative cortisol below 2 μg/dl predicts long-term remission after transsphenoidal surgery in CD. Remission in those with intermediate d 3-5 postoperative cortisol values (2-4.9 μg/dl) suggests that these patients do not require immediate reoperation. However, because no single cortisol cutoff value excludes all patients with recurrence, all require long-term clinical follow-up.

Tuberculosis (TB) is a major health issue in both developing and developed countries such as the UK. Healthy individuals who contract the infection have only 5-10% chance of converting to the active disease over their lifetime. We present the clinical history of a 76 year old female who attended the emergency department complaining of wrist pain, and was only diagnosed with TB after three years. This case report emphasises the importance of including TB in the differential diagnosis when treating patients with an infection resistant to conventional antibiotics, even though risk factors for TB may not be evident or special stains for TB are negative., (© JSCR.)

Resonance Raman and UV-visible diffuse reflectance spectra were recorded from samples of cotton, viscose, polyester, nylon, and acrylic textile swatches dyed black with one of seven single dyes, a mixture of two dyes, or one of seven mixtures of three dyes. The samples generally gave characteristic Raman spectra of the dyes, demonstrating that the technique is applicable for the forensic analysis of dyed black textiles. Survey studies of the widely used dye Reactive Black 5 show that essentially the same Raman spectrum is obtained on bulk sampling from the dye in solution, on viscose, on cotton at different uptakes, and on microscope sampling from the dye in cotton threads and single fibres. The effects of laser irradiation on the Raman bands and emission backgrounds from textile samples with and without dye are also reported., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Nateglinide restores early-phase insulin secretion to feeding and reduces postprandial hyperglycaemia in type 2 diabetes. This study evaluated the effects of nateglinide on dipeptidyl peptidase-IV (DPP-IV) activity and glucose-dependent insulinotropic polypeptide (GIP) degradation. Research design and methods Blood samples were collected from type 2 diabetic subjects (n=10, fasting glucose 9.36+/-1.2 mmol/l) following administration of oral nateglinide (120 mg) 10 min prior to a 75 g oral glucose load in a randomised crossover design., Results: Plasma glucose reached 18.2+/-1.7 and 16.7+/-1.7 mmol/l at 90 min in control and placebo groups (P<0.001). These effects were accompanied by prompt 32% inhibition of DPP-IV activity after 10 min (19.9+/-1.6 nmol/ml per min, P<0.05), reaching a minimum of 1.9+/-0.1 nmol/ml per min at 120 min (P<0.001) after nateglinide. Insulin and C-peptide levels increased significantly compared with placebo, to peak after 90 min at 637.6+/-163.9 pmol/l (P<0.05) and 11.8+/-1.4 mg/l (P<0.01) respectively. DPP-IV-mediated degradation of GIP was significantly less in patients receiving nateglinide compared with placebo. Inhibition of DPP-IV activity corresponded with a time- and concentration-dependent inhibitory effect of nateglinide on DPP-IV-mediated truncation of GIP(1-42) to GIP(3-42) in vitro. Comparison of in vitro inhibition of DPP-IV by nateglinide and vildagliptin revealed IC(50) values of 17.1 and 2.1 microM respectively., Conclusions: Although considerably less potent than specified DPP-IV inhibitors, the possibility that some of the beneficial actions of nateglinide are indirectly mediated through DPP-IV inhibition and increased bioavailability of GIP and other incretins merits consideration.

Copper(i) (+/-)-N,N'-bis(2,4,6-trimethylbenzylidene)-1,2-diaminocyclohexane reacts with either ethene or butadiene to give the corresponding alkene complexes. In each case crystallographic studies show that the alkene coordinates in an eta(2) fashion. In the butadiene complex a dimer is formed where the butadiene bridges two copper complexes. Variable temperature NMR spectroscopy of the ethene adduct demonstrates fluxional behaviour, which is attributed to the rotation of the coordinated ethene relative to the complex, DeltaG(double dagger)(255) = 50 +/- 2 kJ mol(-1).

Objective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing's syndrome, because there is no recent consensus on the management of this rare disorder., Participants: Thirty-two leading endocrinologists, clinicians, and neurosurgeons with specific expertise in the management of ACTH-dependent Cushing's syndrome representing nine countries were chosen to address 1) criteria for cure and remission of this disorder, 2) surgical treatment of Cushing's disease, 3) therapeutic options in the event of persistent disease after transsphenoidal surgery, 4) medical therapy of Cushing's disease, and 5) management of ectopic ACTH syndrome, Nelson's syndrome, and special patient populations., Evidence: Participants presented published scientific data, which formed the basis of the recommendations. Opinion shared by a majority of experts was used where strong evidence was lacking., Consensus Process: Participants met for 2 d, during which there were four chaired sessions of presentations, followed by general discussion where a consensus was reached. The consensus statement was prepared by a steering committee and was then reviewed by all authors, with suggestions incorporated if agreed upon by the majority., Conclusions: ACTH-dependent Cushing's syndrome is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. Generally, the treatment of choice for ACTH-dependent Cushing's syndrome is curative surgery with selective pituitary or ectopic corticotroph tumor resection. Second-line treatments include more radical surgery, radiation therapy (for Cushing's disease), medical therapy, and bilateral adrenalectomy. Because of the significant morbidity of Cushing's syndrome, early diagnosis and prompt therapy are warranted.

Relative rate constants have been measured for the oxidation of aryl methyl sulfides and sulfoxides by dimethyldioxirane in acetone, in mixtures of acetone with aprotic co-solvents of both higher and lower relative permittivity, and in aqueous acetone mixtures. Correlation analyses of the effects of substituents in the different solvents show that, with one exception, reactions take place via a single step mechanism in which the formation of the new SO bond and the elimination of acetone occur concertedly. The exception was oxidation of the sulfides in aqueous acetone containing the highest proportion of water of those studied (20% v/v). Here, the behaviour of the reaction is consistent with a two-step mechanism in which the oxidant reversibly attacks the sulfide to form an open-chain sulfonium betaine that subsequently fragments to sulfoxide and acetone. There is no evidence for the participation of an intermediate dioxathietane as has been found in the case of sulfide oxidations by (trifluoromethyl)methyldioxirane in CH(2)Cl(2) and similar aprotic solvents. It is not justified to generalise a mechanism involving a betaine, with or without a derived dioxathietane, to the reactions of dimethyldioxirane in acetone.

Routine aspiration thrombectomy (AT) in percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction (STEMI) has not proved effective in randomized trials. However, in patients undergoing primary percutaneous coronary intervention with severely reduced flow or visible thrombus, AT remains an intuitively attractive option. The use of adjunctive AT in a high-risk cohort of 158 consecutive patients with STEMI and Thrombolysis In Myocardial Infarction (TIMI) 0 to 1 flow or visible thrombus on baseline angiography was examined. Of these, 80 patients underwent AT as an adjunct to primary percutaneous coronary intervention, and 78 underwent percutaneous coronary intervention without AT (non-AT). TIMI 3 flow rates, residual thrombus after percutaneous coronary intervention, and major adverse cardiac events (mortality and nonfatal Q-wave myocardial infarction) at 30 days, 6 months, and 1 year were compared. Baseline characteristics were similar between groups. The AT group more frequently achieved TIMI 3 flow after the intervention (91.3% AT vs 67.9% non-AT; p <0.001) and had less residual thrombus (7.5% AT vs 19.2% non-AT; p = 0.03). AT was associated with reduced major adverse cardiac events at 6 months (6.8% AT vs 24.0% non-AT; p = 0.004) and 1 year (16.6% AT vs 29.2% non-AT; p = 0.009), and decreased mortality rates in the AT group at 6 months (5.4% AT vs 21.3% non-AT; p = 0.004) and 1 year (7.7% AT vs 26.2% non-AT; p = 0.005). In conclusion, for patients with STEMI and TIMI 0 or 1 flow or visible thrombus on baseline angiography, AT was associated with increased TIMI 3 flow rates, decreased residual thrombus, and decreased clinical events, including mortality.

Dipeptidyl peptidase (DPP-IV) rapidly metabolizes hormones such as glucagon-like peptide-1(7-36)amide. This study evaluated circulating DPP-IV activity in type 2 diabetic patients in relation to GLP-1 degradation and metabolic control. Blood samples were collected from type 2 diabetic patients in three main categories: good glycaemic control (HbA(1c) <7%, upper limit of non-diabetic range), moderate glycaemic control (HbA(1c) 7-9%) and poor glycaemic control (HbA(1c) >9%). Age- and sex-matched non-diabetic subjects were used as controls. Circulating DPP-IV activity of healthy control subjects was 22.5+/-0.7 nmol/ml/min (n=70). In the combined groups of type 2 diabetic subjects, circulating DPP-IV activity was significantly decreased at 18.1+/-0.7 nmol/ml/min (p<0.001, n=54). DPP-IV activity was negatively correlated with both glucose (p<0.01) and HbA(1c) (p<0.01) in this population. Furthermore, DPP-IV activity was reduced 1.2-fold (p<0.01, n=25), 1.3-fold (p<0.001, n=19) and 1.3-fold (p<0.05, n=10) in good, moderate and poorly controlled diabetic groups, 18.7+/-1.0, 17.4+/-1.4 and 18.0+/-1.5 nmol/ml/min, respectively. Degradation of GLP-1 by in vitro incubation with pooled plasma samples from healthy and type 2 diabetic subjects revealed decreased degradation to the inactive metabolite, GLP-1(9-36), in the diabetic group. These data indicate decreased DPP-IV activity and GLP-1 degradation in type 2 diabetes. DPP-IV enzyme activity appears to be depressed in response to poor glycaemic control.

Half the patients who survive ST-segment elevation anterior myocardial infarction continue to have ST elevation (STE) 6 months after the event. The mechanism for this and its clinical significance are unclear. There are data to suggest that larger infarcts are more likely to have persistent changes in the ST segment. This study is designed to test this association further using a novel means of assessing the presence and magnitude of myocardial scar using cardiac magnetic resonance imaging (MRI). Delayed imaging by MRI after injection of gadolinium is commonly used to detect myocardial scar through the appearance of delayed contrast hyperenhancement. Consecutive patients referred for myocardial viability imaging were reviewed. The volume of scar as a percentage of anterior wall volume was calculated, and the 26 patients with scar involving >or=10% of the anterior wall were selected for inclusion. All had an electrocardiogram recorded within 15 days of MRI, and none had an intervening cardiac event. Observers unaware of MRI findings independently measured ST-segment changes. Nine patients had STE >1 mm and 17 did not. Mean anterior scar volume in the group without STE was 31.9 +/- 17.1% of the anterior wall volume compared with 50.3 +/- 15.9% in the group with STE >1 mm (p = 0.01). The larger the myocardial scar, the more likely STE was to be present. Only 1 of 10 patients (10%) with scar in the anterior wall <30% had such an elevation compared with 3 of 9 (33%) with scar size of 30% to 49% and 5 of 7 (78%) with scars >or=50%. In conclusion, persistent anterior STE is associated with the size of myocardial scar detected using MRI.

Objective: Measurement of plasma ACTH levels by radioimmunoassay (RIA) is used to identify adrenal causes (AA) of Cushing's syndrome (CS) and to distinguish ectopic CS (EAS) from Cushing's disease (CD) using CRH stimulation testing and inferior petrosal sinus sampling (IPSS). We wished to determine whether diagnostic criteria developed with RIA would also be applicable for immunoradiometric (IRMA) or immunochemiluminescent (ICMA) assays., Subjects and Methods: ACTH was measured by RIA, immunoradiometric and/or immunochemiluminescent assay on samples obtained during three types of diagnostic testing in a tertiary referral setting: a) basally (63 CD, 5 AA, 2 EAS and 37 non-CS patients); b) in 44 CD patients following CRH; c) in 6 ectopic CS and 17 CD patients during IPSS. The primary outcome was comparison of diagnostic utility., Results: a) IRMA results, while lower, correlated highly with RIA (r=0.9, p<0.0001) and had similar sensitivity (100 vs 80%) and specificity (89 vs 94%) for the diagnosis of AA (p=0.3); b) the sensitivity for CD of CRH testing using IRMA was similar to that of RIA (85 vs 83%, p=1.0); c) during IPSS, IRMA had similar sensitivity (100%) and specificity (100 vs 83%) compared with ICMA or RIA (p=1.0)., Conclusions: ACTH immunometric assays correlate closely to RIA and offer similar diagnostic utility.