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Anti-digoxin antibody fragments (ADAF, 80 mg) were infused intravenously to successfully treat severe digoxin toxicity in an 82 year old woman. During treatment, total and free digoxin were determined using an Abbot TDX analyser and an ultrafiltration technique. ADAF were measured by an enzyme-linked immunosorbent assay. By 1 h after ADAF, total serum digoxin concentrations had risen 12-fold from a pretreatment level of 15.4 nmol l-1 but free digoxin fell from 10 to 0.1 nmol l-1, indicating greater than 99.9% digoxin binding to ADAF. However, the low free levels had rebounded to 7.7 nmol l-1 by 12 h, but despite this rise the patient's condition had improved. A serum ADAF/digoxin molar ratio of around five was associated with the low concentration of free digoxin at 1 h, while at later times with ratios roughly between 3 and 4, the free digoxin concentrations ranged between 2.0 and 7.7 nmol l-1. ADAF were mainly confined to the plasma during the first hour, but subsequently distributed into an apparent volume of 193 ml kg-1. The elimination half-lives of ADAF and total digoxin were 96 and 55 h, respectively. More than 50% of the estimated digoxin load had been excreted in the urine by 5 days; for ADAF the equivalent figure was only about 3%. Renal and/or bacterial degradation may have contributed to the low detection of urinary ADAF. [ABSTRACT FROM AUTHOR]

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.)

There is a tremendous interest in developing hydrogels as tunable in vitro cell culture platforms to study cell response to mechanical cues in a controlled manner. However, little is known about how common cell culture techniques, such as serial expansion on tissue culture plastic, affect subsequent cell behavior when cultured on hydrogels. In this work, a methacrylated hyaluronic acid hydrogel platform is leveraged to study stromal cell mechanotransduction. Hydrogels are first formed through thiol-Michael addition to model normal soft tissue (e.g., lung) stiffness (E ≈ 1 kPa). Secondary cross-linking via radical photopolymerization of unconsumed methacrylates allows matching of early- (E ≈ 6 kPa) and late-stage fibrotic tissue (E ≈ 50 kPa). Early passage (P1) human bone marrow mesenchymal stromal cells (hMSCs) display increased spreading, myocardin-related transcription factor-A (MRTF-A) nuclear localization, and focal adhesion size with increasing hydrogel stiffness. However, late passage (P5) hMSCs show reduced sensitivity to substrate mechanics with lower MRTF-A nuclear translocation and smaller focal adhesions on stiffer hydrogels compared to early passage hMSCs. Similar trends are observed in an immortalized human lung fibroblast line. Overall, this work highlights the implications of standard cell culture practices on investigating cell response to mechanical signals using in vitro hydrogel models., (© 2023 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

Context: Total pancreatectomy with islet autotransplantation (TPIAT) is a definitive management for intractable pain in patients with chronic pancreatitis (CP). Islet autotransplantation (IAT) allows for the preservation of beta cells to prevent complications of long-term diabetes., Objective: Our study follows TPIAT recipients for up to 12 years to determine the efficacy of the procedure completed with an off-site islet isolation facility., Methods: Patient demographics, mixed meal tolerance test measures, glycosylated hemoglobin, insulin requirements, and homeostatic model assessment for insulin resistance values were collected prior to surgery and at the most recent follow-up assessment., Results: Forty-four patients (median age, 46.0 years; range, 20-78 years) underwent TPIAT for CP. At an overall median follow-up time of 845.5 days (range, 195-4470 days) 8 patients were insulin independent and 36 patients were insulin dependent. At the most recent follow-up time point, islet yield per kilogram was the strongest indicator of insulin independence. Homeostatic model assessment for insulin resistance values were comparable between insulin independent and dependent cohorts., Conclusions: Our long-term follow-up data suggest that IAT can effectively reduce insulin requirements and improve postoperative glycemic control., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cellular mechanotransduction plays a central role in fibroblast activation during fibrotic disease progression, leading to increased tissue stiffness and reduced organ function. While the role of epigenetics in disease mechanotransduction has begun to be appreciated, little is known about how substrate mechanics, particularly the timing of mechanical inputs, regulate epigenetic changes such as DNA methylation and chromatin reorganization during fibroblast activation. In this work, we engineered a hyaluronic acid hydrogel platform with independently tunable stiffness and viscoelasticity to model normal (storage modulus, G ' ∼ 0.5 kPa, loss modulus, G '' ∼ 0.05 kPa) to increasingly fibrotic ( G ' ∼ 2.5 and 8 kPa, G '' ∼ 0.05 kPa) lung mechanics. Human lung fibroblasts exhibited increased spreading and nuclear localization of myocardin-related transcription factor-A (MRTF-A) with increasing substrate stiffness within 1 day, with these trends holding steady for longer cultures. However, fibroblasts displayed time-dependent changes in global DNA methylation and chromatin organization. Fibroblasts initially displayed increased DNA methylation and chromatin decondensation on stiffer hydrogels, but both of these measures decreased with longer culture times. To investigate how culture time affected the responsiveness of fibroblast nuclear remodeling to mechanical signals, we engineered hydrogels amenable to in situ secondary crosslinking, enabling a transition from a compliant substrate mimicking normal tissue to a stiffer substrate resembling fibrotic tissue. When stiffening was initiated after only 1 day of culture, fibroblasts rapidly responded and displayed increased DNA methylation and chromatin decondensation, similar to fibroblasts on static stiffer hydrogels. Conversely, when fibroblasts experienced later stiffening at day 7, they showed no changes in DNA methylation and chromatin condensation, suggesting the induction of a persistent fibroblast phenotype. These results highlight the time-dependent nuclear changes associated with fibroblast activation in response to dynamic mechanical perturbations and may provide mechanisms to target for controlling fibroblast activation.

Upon discovery of a thyroid nodule (or nodules), a patient is usually referred for evaluation by ultrasound, which is typically performed by a trained radiologist or sonographer. More recently, this technology has been used intraoperatively by endocrine surgeons and also by endocrinologists, often in the context of 'one-stop shops' or point of care ultrasound in the outpatient setting. Although thyroid nodules are common and most will be benign, the subsequent work up of these can cause anxiety for patients and place a burden on radiologists. In the UK, sonographic features of benign, suspicious or malignant nodules are classified by the British Thyroid Association U1-U5 criteria, which decide whether to biopsy the nodule (typically U3 and above). This article provides an overview of ultrasound in assessing the thyroid nodule in the context of this classification. This can be used as a guide to interpretation of thyroid ultrasonography for non-radiologists.

Introduction: This study investigated Northern Ireland Diabetic Eye Screening Programme (NIDESP) attendance and diabetic retinopathy (DR) prevalence/severity in patients with diabetes mellitus secondary to chronic pancreatitis (PwDMsCP)., Research Design and Methods: Medical/NIDESP records for all PwDMsCP attending the pancreatic diabetes clinic were analyzed in 2017 (n=78) and 2019 (n=94)., Results: Between 2017 and 2019, those without DR decreased (76% to 63%); mild non-proliferative DR (NPDR), severe NPDR and PDR were found in 30%, 2% and 5%, respectively (previously 18%, 4%, 2%); diabetic maculopathy (DMac) was present in 12% (previously 10%). There was no significant difference between worst-eye DR/DMac grade and HbA1c, gender, body mass index, pancreatitis etiology and screening attendance (p>0.05). Patients with proliferative DR had longer diabetes and pancreatitis duration than DR-free patients (both p=0.001)., Conclusions: DR prevalence was similar in PwDMsCP and patients with type 2 diabetes of similar disease duration. This work demonstrates the importance of reaching all patients for establishing DR severity reliably and to provide accessible, equitable care to PwDMsCP., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The pituitary gland is an unusual site for metastatic spread and has been associated with a poor prognosis. Clinical presentation is variable but can include visual field defects, cranial nerve palsies, anterior pituitary dysfunction and/ or diabetes insipidus. Management options include surgery or radiotherapy, chemotherapy/immunotherapy or a conservative approach. The pituitary should not be overlooked as a site for metastasis in patients with known cancer and can be the first presentation of neoplastic disease in some patients. Given that patients are now living longer with cancer, clinicians should be alert to the varied presentation of pituitary metastasis. We provide a clinical overview of pituitary metastasis with the aid of illustrative clinical cases., (Copyright © 2021 Ulster Medical Society.)

Context: Inferior petrosal sinus sampling (IPSS) helps differentiate the source of ACTH-dependent hypercortisolism in patients with inconclusive biochemical testing and imaging, and is considered the gold standard for distinguishing Cushing disease (CD) from ectopic ACTH syndrome. We present a comprehensive approach to interpreting IPSS results by examining several real cases., Evidence Acquisition: We performed a comprehensive review of the IPSS literature using PubMed since IPSS was first described in 1977., Evidence Synthesis: IPSS cannot be used to confirm the diagnosis of ACTH-dependent Cushing syndrome (CS). It is essential to establish ACTH-dependent hypercortisolism before the procedure. IPSS must be performed by an experienced interventional or neuroradiologist because successful sinus cannulation relies on operator experience. In patients with suspected cyclical CS, it is important to demonstrate the presence of hypercortisolism before IPSS. Concurrent measurement of IPS prolactin levels is useful to confirm adequate IPS venous efflux. This is essential in patients who lack an IPS-to-peripheral (IPS:P) ACTH gradient, suggesting an ectopic source. The prolactin-adjusted IPS:P ACTH ratio can improve differentiation between CD and ectopic ACTH syndrome when there is a lack of proper IPS venous efflux. In patients who have unilateral successful IPS cannulation, a contralateral source cannot be excluded. The value of the intersinus ACTH ratio to predict tumor lateralization may be improved using a prolactin-adjusted ACTH ratio, but this requires further evaluation., Conclusion: A stepwise approach in performing and interpreting IPSS will provide clinicians with the best information from this important but delicate procedure., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We present the case of a previously healthy, immunocompetent male with Lemierre's Syndrome. He presented with headache, sore throat and pyrexia. Initial blood tests revealed raised inflammatory markers and electrolyte abnormalities. Blood cultured Fusobacterium necrophorum. He developed respiratory distress and imaging confirmed lung abscess and empyema due to septic emboli. He required surgical drainage and a prolonged course of antibiotics. This case highlights the rare, but life-threatening condition of Lemierre's Syndrome. We discuss the importance of prompt recognition and early antibiotic therapy.

Context: Signs and symptoms of Cushing's syndrome (CS) overlap with common diseases, such as the metabolic syndrome, obesity, osteoporosis, and depression. Therefore, it can take years to finally diagnose CS, although early diagnosis is important for prevention of complications., Objective: The aim of this study was to assess the time span between first symptoms and diagnosis of CS in different populations to identify factors associated with an early diagnosis., Data Sources: A systematic literature search via PubMed was performed to identify studies reporting on time to diagnosis in CS. In addition, unpublished data from patients of our tertiary care center and 4 other centers were included., Study Selection: Clinical studies reporting on the time to diagnosis of CS were eligible. Corresponding authors were contacted to obtain additional information relevant to the research question., Data Extraction: Data were extracted from the text of the retrieved articles and from additional information provided by authors contacted successfully. From initially 3326 screened studies 44 were included., Data Synthesis: Mean time to diagnosis for patients with CS was 34 months (ectopic CS: 14 months; adrenal CS: 30 months; and pituitary CS: 38 months; P < .001). No difference was found for gender, age (<18 and ≥18 years), and year of diagnosis (before and after 2000). Patients with pituitary CS had a longer time to diagnosis in Germany than elsewhere., Conclusions: Time to diagnosis differs for subtypes of CS but not for gender and age. Time to diagnosis remains to be long and requires to be improved., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Thyroid ultrasound is used for the assessment and characterisation of thyroid nodules/goitres and to guide diagnostic biopsy, it is normally performed by radiologists. Point of care ultrasound (POCUS) by trained non-radiologists, has the potential to reduce cost, expedite diagnosis and enhance patient satisfaction if embedded in an outpatient clinic setting., Aim: To perform a pilot of the use of point of care thyroid ultrasound in an endocrine outpatient setting for the assessment of thyroid nodules and goitres., Methods: Thyroid ultrasound was undertaken with consultant radiologist supervision, over a period of 16 months between January 2017 to April 2018. Using a GE Logic e7 portable thyroid ultrasound machine with 12 MHz linear probe. All scans were performed on patients attending for assessment of thyroid disorders at the Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast., Results: Thyroid ultrasound was performed on 40 patients (M:10,F30), mean age 52 years, range 23-77 years, median follow up 14 months, range 6-18 months. Twenty scans were performed to assess thyroid nodules, 13 for investigation of a goitre and the remaining 7 were for patient preference. 39 patients had benign thyroid disease, 1 patient had a confirmed newly diagnosed papillary thyroid carcinoma (PTC). The ultrasound 'U' classification was U1 and U2 (n=37), U3 and above (n=3). Fine needle biopsy (FNA) was performed on 9 patients with one confirmed as a thyroid carcinoma (Thy1;n=2, Thy2;n=6 and Thy 5;n=1). Thyroid ultrasound reporting was broadly similar between radiologist and non-radiologist (p< 0.01). Time to scan was reduced during the pilot from the existing model (n=40) of a mean of 52 days (range 7-95 days) to 1 day (p<0.01)., Conclusion: With appropriate training and radiology supervision, point of care thyroid ultrasound can be performed accurately and safely in outpatients by an endocrinologist. There are potential benefits in terms of cost savings, time to scan, reduction in clinic visits, and in expediting diagnosis., Competing Interests: Provenance: externally peer-reviewed, (Copyright © 2020 Ulster Medical Society.)

Diabetes secondary to chronic pancreatitis (CP) or type 3cDM refers to a brittle form of diabetes and is often characterised by hypoglycaemic episodes, erratic glycaemic control, and impaired quality of life. It differs from other forms of diabetes and is typically characterised by concurrent pancreatic endocrine and exocrine insufficiency which can present as malabsorption and nutritional deficiencies. In this review, we discuss the pathogenesis, epidemiology, and the practicalities of diagnosis, screening, and management of this condition., Competing Interests: All authors have no conflict of interest., (Copyright © 2019 Philip C. Johnston et al.)

Introduction: Patient portals are online electronic medical record applications that allow patients greater control of their own health and encourage meaningful interaction with their healthcare providers. The uptake of this technology is commonplace throughout developed healthcare economies and is on the Northern Ireland Electronic Healthcare Record (NIECR) roadmap., Aim: To assess patients' perceptions and proposed provision of a patient portal in endocrinology outpatients., Methods: Patients (n=75) attending three endocrinology outpatient clinics were eligible to participate. After discussion at clinic, invited patients were contacted via e-mail to complete a confidential and anonymised online survey. There were a total of 23 questions in the survey which included a mix of free text and categorical responses. The survey duration was conducted over a 6-month period., Results: The survey response rate was 51/75 (68%), M33:F18. 46/51 (90%) had access to smart phones, 45/51 (88%) used the internet daily. 31/51 (60%) of respondents were aged between 18-45, 20/51 (40%) were aged ≥ 45 years. 50/51 (98%) reported they would use the technology if available. 47/51 (92%) felt engaging with a patient portal would enhance communication with their doctor and improve understanding of their medical issues. Reported perceived applications of use included; remote access and advice for test results and medical questions, arranging appointments, requesting prescriptions and health promotion. 90% of respondents said they would be content to access results even if abnormal. Possible barriers to adoption of this technology included data protection and understanding medical terminology., Conclusions: The overall response to the provision of this technology was positive, although concerns regarding data protection remain prevalent. Perceived benefits included enhanced doctor-patient communication, optimizing workflow and improving patient engagement., Competing Interests: Provenance: externally peer reviewed, (Copyright © 2019 Ulster Medical Society.)

Context: Transsphenoidal surgery (TSS) to resect a pituitary adenoma is considered first-line treatment for patients with Cushing's disease (CD). Early, post-operative remission rates >80% are expected for patients with a microadenoma (≤ 10 mm) visible on magnetic resonance (MR) imaging., Objective: To report surgical outcomes and predictors of remission in a specialist center for patients with CD., Patients and Methods: Clinical data was obtained from a prospective CD database in addition to review of all electronic medical, laboratory and surgical patient records. Patients who underwent their first TSS by one neurosurgeon between 2004 and 2013, and had a minimum 1 year follow up, were evaluated., Results: One hundred and one consecutive patients with CD (73F, 28M) underwent TSS. Median (range) age and follow-up were 47 (15-87) and 4.33 (1-9.8) years, respectively. At surgery, 74 (73.2%) patients had a microadenoma, 27 a macroadenoma; six of the latter patients had a planned, subtotal resection to control neurological signs due to mass effect. Initial remission rates were: microadenoma, 89% (66/74); macroadenoma, 63% (17/27); and 81% (17/21) in those macroadenomas where complete surgical removal was anticipated. Initial non-remission occurred in 18 patients, ten macro- and eight microadenoma; six of 18 had residual disease on most recent follow up. Six (2 macro, 4 micro) of the 83 patients with initial remission have had late (>12 months) recurrence of hypercortisolism that required either repeat TSS or adjunctive therapy, three of whom have persistent hypercortisolism. Macroadenoma (p = 0.003) and tumor invasion beyond the pituitary and sella (p < 0.001) were associated with failure to obtain remission with the initial TSS and greater likelihood of late recurrence. Patients in whom no lesion was seen on neuroimaging had rates of initial remission (21/25 or 84%) and a similar late recurrence rate of 4% (1/25) in comparison with those with MR-visible microadenomas (3/49, or 6%)., Conclusions: A team-based approach, in a specialized pituitary center, can lead to initial and durable, long-term remission in patients with CD. The presence of a macroadenoma and tumor extension beyond the pituitary and sella were predictive of initial non-remission as well as risk of late recurrence.

Context: Spontaneous hypoglycemia has been reported in patients after total pancreatectomy (TP) and islet autotransplantation (IAT) with maintained insulin independence. Details surrounding these events have not been well described., Objective: The objective of the study was to determine the frequency and characteristics of spontaneous hypoglycemia in patients undergoing TP-IAT and/or to ascertain predictive or protective factors of its development., Design: This was an observational cohort study in 40 patients who underwent TP-IAT from August 2008 to May 2014, with a median follow-up of 34 months., Setting: The study was conducted at a single institution (Cleveland Clinic)., Patients: Patients included recipients of TP-IAT., Intervention: The intervention included small, frequent meals in those patients who developed spontaneous hypoglycemia., Main Outcome Measures: Incidence of spontaneous hypoglycemia development, characteristics of the patients developing hypoglycemia, and their response to small, frequent meals were measured., Results: Six of 12 patients, who maintained insulin independence, developed spontaneous hypoglycemia. The episodes could be fasting, postprandial, and/or exercise associated, with the frequency ranging from two to three times daily to once every 1-2 weeks. All patients experienced at least one episode that required external assistance, glucagon administration, and/or emergent medical attention. Patients who developed hypoglycemia had a lower median age and tended to have a lower median islet equivalent/kg body weight but a higher median total islet equivalent, body mass index, and homeostatic model assessment for insulin resistance score. All patients who received small, frequent meal intervention had improvement in severity and/or frequency of the hypoglycemic episodes., Conclusions: Spontaneous hypoglycemia is prevalent after TP-IAT. Although the underlying pathophysiology responsible for these hypoglycemia events remains to be elucidated, small, frequent meal intervention is helpful in ameliorating this condition.

Aim: In view of the increased rates of pre-eclampsia observed in diabetic pregnancy and the lack of ex vivo data on placental biomarkers of oxidative stress in T1 diabetic pregnancy, the aim of the current investigation was to examine placental antioxidant enzyme status and lipid peroxidation in pregnant women with type 1 diabetes. A further objective of the study was to investigate the putative impact of vitamin C and E supplementation on antioxidant enzyme activity and lipid peroxidation in type 1 diabetic placentae., Methods: The current study measured levels of antioxidant enzyme [glutathione peroxidase (Gpx), glutathione reductase (Gred), superoxide dismutase (SOD) and catalase] activity and degree of lipid peroxidation (aqueous phase hydroperoxides and 8-iso-prostaglandin F2α) in matched central and peripheral samples from placentae of DAPIT (n=57) participants. Levels of vitamin C and E were assessed in placentae and cord blood., Results: Peripheral placentae demonstrated significant increases in Gpx and Gred activities in pre-eclamptic in comparison to non-pre-eclamptic women. Vitamin C and E supplementation had no significant effect on cord blood or placental levels of these vitamins, nor on placental antioxidant enzyme activity or degree of lipid peroxidation in comparison to placebo-supplementation., Conclusion: The finding that maternal supplementation with vitamin C/E does not augment cord or placental levels of these vitamins is likely to explain the lack of effect of such supplementation on placental indices including antioxidant enzymes or markers of lipid peroxidation., (Copyright © 2016. Published by Elsevier Inc.)

Lymphocytic infundibulo-neurohypophysitis is an uncommon inflammatory disorder postulated to be autoimmune in origin. Because of the location of inflammation, it selectively affects the posterior lobe of the pituitary (neurohypophysis) and pituitary stalk (infundibulum). The most common presentation is central diabetes insipidus. Although the definitive diagnosis is established histologically by a pituitary biopsy, radiological imaging can be valuable in diagnosing this condition. In this paper, we provide an overview of the pathophysiology, investigations, management, and outcomes of lymphocytic infundibulo-neurohypophysitis.

Background: Cushing's disease is a condition rarely encountered during pregnancy. It is known that hypercortisolism is associated with increased maternal and fetal morbidity and mortality. When hypercortisolism from Cushing's disease does occur in pregnancy, the impact of achieving biochemical remission on fetal outcomes is unknown. We sought to clarify the impact of successful surgical treatment by presenting such a case report., Case Description: A 38-year-old pregnant woman with recurrent Cushing's disease after 8 years of remission. The patient had endoscopic transsphenoidal of her pituitary adenoma in her 18(th) week of pregnancy. The patient had postoperative biochemical remission and normal fetal outcome with no maternal complications., Conclusion: Transsphenoidal surgery for Cushing's disease can be performed safely during the second trimester of pregnancy.

Objective: Venous thoracic outlet syndrome (VTOS) is most commonly treated by transaxillary, supraclavicular, or paraclavicular approaches, based on surgeon preference. However, we have adopted an infraclavicular approach to VTOS as the surgical pathology is in the anterior costoclavicular space. We hypothesize that this approach, combined with catheter-directed thrombolysis (CDT) with venoplasty as needed, provides safe and effective treatment of patients with an acute presentation of VTOS., Methods: We retrospectively reviewed all consecutive patients that underwent infraclavicular thoracic outlet decompression for an acute presentation of VTOS from July 2005 to February 2014 by a single surgeon. Acute presentation was defined as less than 14 days between the onset of symptoms and CDT. Demographics, primary and secondary subclavian vein patency, perioperative outcomes, and reinterventions were recorded., Results: There were 33 patients that underwent an infraclavicular approach for treatment of VTOS. Average age was 35 years, and 61% were male. All patients underwent CDT, subsequent infraclavicular first rib resection, and intraoperative venography. Intraoperative subclavian vein angioplasty was performed in 70%. Median postoperative length of stay was 2 days (range, 2-6 days), blood loss was 78 mL (range, 20-200 mL), and operative time was 120 minutes (range, 76-166 minutes). Median follow-up was 78 days (range, 2-483 days). Follow-up ultrasound showed all patients having a patent subclavian vein at last follow-up. Reinterventions included two cases for rethrombosis and one case of hemothorax. Primary patency was 91%, and secondary patency was 100%. There were no complications of brachial plexus or phrenic nerve injury. All patients at last follow-up were symptom-free, and subclavian veins were patent., Conclusions: An infraclavicular approach is a safe and effective treatment for acute VTOS. It provides excellent access to the costoclavicular space for first rib resection and subclavian venolysis while at the same time minimizing the risk of brachial plexus and phrenic nerve injury., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Opinion Statement: Patients with chronic pancreatitis should be screening at least annually for diabetes. Lifestyle modifications remain to be an important part of treatment for diabetic control. Unless contraindicated or not tolerated, metformin can be initiated and continued concurrently with other anti-diabetic agents or insulin. All anti-diabetic agents should be used based on their physiology and adverse effect profiles, along with the metabolic status of patients. Insulin therapy should be initiated without delay for any of the following: symptomatic or overt hyperglycemia, catabolic state secondary to uncontrolled diabetes, history of diabetic ketoacidosis, hospitalization or acute exacerbation of pancreatitis, or hyperglycemia that cannot be otherwise controlled. Dose adjustment should be done conservatively as these patients are more likely to be insulin sensitive and have loss of counter regulatory hormones. Insulin pump and continuous glucose monitoring should be considered early during therapy in selected patients. For patients undergoing total pancreatectomy or extensive partial pancreatectomy, evaluations to determine the eligibilities for islet cell autotransplantation should be considered.

We review the etiology, investigations, management and outcomes of pituitary tumor apoplexy. Pituitary tumor apoplexy is a clinical syndrome which typically includes the acute onset of headache and/or visual disturbance, cranial nerve palsy and partial or complete endocrine dysfunction. It is associated with either infarction or hemorrhage of a pre-existing pituitary adenoma and is associated with significant morbidity and potential fatality. Not all patients will present with classic signs and symptoms, therefore it is pertinent to appreciate the clinical spectrum in which this condition can present., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Context: Total pancreatectomy (TP) with islet cell autotransplantation (IAT) can reduce or prevent diabetes by preserving beta cell function and is normally performed with on-site isolation laboratory facilities., Objective: We examined factors associated with islet yield and metabolic outcomes in patients with chronic pancreatitis undergoing TP-IAT. We report our experience of TP-IAT with an off-site islet isolation laboratory., Patients and Methods: Data (August 2008 to February 2014) were obtained from a TP-IAT database which included information from medical records, clinic visits, questionnaires, and follow-up telephone calls. Each patient was assessed with pre- and postoperative 5-hour mixed-meal tolerance tests for metabolic measurements and with serial glycosylated hemoglobin (HbA1c) determinations., Results: Thirty-six patients with a mean age of 38 years (range, 16-72 y) underwent TP-IAT for different etiologies. At a median follow-up time of 28 months (range, 3-66 mo), 12 patients were insulin independent and 24 patients were on at least one insulin injection a day. Postoperatively, C-peptide levels ≥0.3 ng/mL were present in 23/33 (70%) of the patients, with a median fasting C-peptide value of 0.8 ng/mL (range, <0.2-1.5 ng/mL). Those who were insulin independent were more likely to be female (P = .012), have normal morphology on pre-operative pancreatic imaging (P = .011), and have significantly higher median islet yield (6845 islet equivalent numbers [IEQ]/kg, n = 12 vs 3333 IEQ/kg, n = 24; P < .001)., Conclusions: IAT after TP performed in our facility with an off-site islet isolation laboratory shows islet yield and rates of insulin independence that are comparable to other large centers with on-site laboratories.

Background: Clinical and biochemical follow up after surgery for phaeochromocytoma is essential with long term studies demonstrating recurrence frequencies between 6% and 23%., Aim: To examine the characteristics and frequency of tumour recurrence in a regional endocrine referral centre, in patients with surgical resection of phaeochromocytoma (P) and abdominal paraganglioma (AP)., Methods: We identified a cohort of 52 consecutive patients who attended our Regional Endocrinology & Diabetes Centre and retrospectively reviewed their clinical, biochemical and radiological data (between 2002 and 2013). After confirmation of early post-operative remission by negative biochemical testing, tumour recurrence was defined by demonstration of catecholamine excess with confirmatory imaging., Results: Phaeochromocytoma was confirmed histologically in all cases (43:P, 9:AP, mean-age:53 years). Open adrenalectomy was performed in 20 cases and laparoscopically in 32. Hereditary phaeochromocytoma was confirmed by genetic analysis in 12 (23%) patients. Median follow up time from initial surgery was 47 months, (range: 12 - 296 months), 49 patients had no evidence of tumour recurrence at latest follow-up. Three patients (6%) demonstrated tumour development, one in a patient with VHL which occurred in a contralateral adrenal gland, one sporadic case had local recurrence, and an adrenal tumour occurred in a patient with a SDHB gene mutation who had a previous bladder tumour. After initial surgery, the tumours occurred at 8.6, 12.0 and 17.7 years respectively., Conclusion: In this study tumour development occurred in 6% of patients. Although tumour rates were low, careful and sustained clinical and biochemical follow up is advocated, as new tumour development or recurrence may occur long after the initial surgery is performed.

The use of intra-articular (IA) glucocorticoids for reducing pain and inflammation in patients with osteoarthritis, rheumatoid arthritis, and other inflammatory arthropathies is widespread among primary care physicians, specialists, and non-specialists in the United States. Injectable glucocorticoids have anti-inflammatory and analgesic properties which can be effective in improving clinical parameters such as pain, range of motion, and quality of life. After injection into the IA space, glucocorticoids may be systemically absorbed; the degree of absorption can depend on the size of the joint injected, the injectable glucocorticoid preparation used, the dosage, and the frequency of the injection. The adverse effects of intra-articular glucocorticoid injections (IAGC) can often be overlooked by both the patient and physicians who administer them, in particular the potential deleterious effect on the hypothalamic-pituitary-adrenal (HPA)-axis which can result in adrenal suppression and/or iatrogenic Cushing syndrome. In this paper we provide an overview on the often under-recognized effects of IAGC on HPA-axis function.

Unlabelled: A 54-year-old woman presented with bi-temporal hemianopia, palpitations, and diaphoresis. An invasive pituitary macroadenoma was discovered. The patient had biochemical evidence of secondary hyperthyroidism and GH excess; however, she did not appear to be acromegalic. Surgical removal of the pituitary mass revealed a plurihormonal TSH/GH co-secreting pituitary adenoma. TSH-secreting adenomas can co-secrete other hormones including GH, prolactin, and gonadotropins; conversely, co-secretion of TSH from a pituitary adenoma in acromegaly is infrequent., Learning Points: This case highlights an unusual patient with a rare TSH/GH co-secreting pituitary adenoma with absence of the clinical features of acromegaly.Plurihormonality does not always translate into the clinical features of hormonal excess.There appears to be a clinical and immunohistochemical spectrum present in plurihormonal tumors.

Ectopic pituitary adenomas are defined by the presence of adenomatous pituitary tissue outside the sella and distinctly separate from the pituitary gland. Ectopic ACTH-secreting pituitary adenomas (EAPAs) are a rare cause of Cushing's syndrome. Detecting these radiologically can prove difficult, in part, due to their typically small size and unpredictable anatomical location. In ACTH-dependent Cushing's syndrome, if, despite comprehensive testing, the source of excess ACTH remains occult (including negative work up for ectopic ACTH syndrome) thought should be given to the possibility of the patient harboring an EAPA. In most cases, ectopic ACTH pituitary adenomas within the sphenoid sinus will manifest with symptoms of hormonal excess, have an obvious sphenoid sinus mass on pre-operative imaging and will demonstrate resolution of hypercortisolism after surgical excision if located and removed. Twenty cases of EAPAs have been reported in the literature to date. This paper will review the current literature on all previously reported EAPAs within the sphenoid sinus in addition to the current case.

Objective: The optimal role for bare metal stents (BMS) or stent grafts (SG) in femoropopliteal occlusive disease (FPOD) is as of yet undefined. Understanding the clinical consequences of failure can help guide initial treatment decisions. The goal of this study was to define the nature, frequency, and risk factors for adverse clinical events related to BMS and SG failure in FPOD., Methods: This is a single-institution retrospective review of primary endovascular interventions for FPOD using either a BMS or SG, from September 2007 through October 2011. Patients were excluded if they had any previous lower extremity interventions. Patient demographics, indications for intervention, anatomic characteristics, procedural details, clinical outcomes, and reintervention details were reviewed. Clinical outcomes included the composite end point of any reintervention, amputation, or stenosis, acute limb ischemia (ALI), and the composite end point of major adverse limb events, which included a need for bypass, thrombolysis, or major amputation., Results: Seventy-one limbs were treated with BMS and 63 with SG. Although patient demographics were largely similar between cohorts, key differences included indication for intervention (percent claudication BMS vs SG, 34/71 (48%) vs 42/63 (67%); P < .05) and the TransAtlantic Inter-Society Consensus II classification of lesions in the claudicant subgroup (TransAtlantic Inter-Society Consensus D BMS vs SG, 4/34 (12%) vs 17/42 (40%); P < .01). Freedom from reintervention at 1 year was better in the SG group (75% vs 64%; hazard ratio, 0.46; 95% confidence interval, 0.25-0.78; P < .01). Freedom from major adverse limb events was not different between groups; however, SG thrombosis resulted in a more frequent need for thrombolysis. On multivariate analysis, treating with a BMS vs SG was a significant predictor for freedom from thrombolysis (hazard ratio, 0.53; confidence interval, 0.37-0.76; P < .01). ALI during follow-up was seen only in the SG group (nine vs zero events, log- rank; P < .02)., Conclusions: Failure modes of BMS and SG used to treat FPOD differ, and the clinical consequences may not be benign. Claudicants may not revert back to claudication with treatment failure. Although the overall reintervention rate at 1 year is lower for SG compared to BMS, we observed a higher rate of ALI and need for thrombolysis with SG failure. In light of these differential risks of treatment failure, we believe that the use of SG as initial therapy for FPOD should be carefully deliberated and mandates close postoperative surveillance., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Aim: To examine the role of placental protein tyrosine nitration and p38-Mitogen-Activated Protein Kinase α (p38-MAPKα), Extra Cellular-Signal Regulated Kinase (ERK) and c-Jun NH2-Terminal Kinase (JNK) activity, in the pathogenesis of type 1 diabetic pre-eclampsia, and the putative modulation of these indices by maternal vitamin C and E supplementation., Methods: Placental samples were obtained from a sub-cohort of the DAPIT trial: a randomised placebo-controlled trial of antioxidant supplementation to reduce pre-eclampsia in type 1 diabetic pregnancy. Placenta from placebo-treated: normotensive (NT) [n=17], gestational hypertension (GH) [n=7] and pre-eclampsia (PE) [n=6] and vitamin-treated: NT (n=20), GH (n=4) and PE (n=3) was analysed. Protein tyrosine nitration was assessed by immunohistochemistry in paraffin-embedded tissue. Catalytic activities of placental p38-MAPKα, ERK and JNK were measured by enzyme-linked immunosorbent assay (ELISA)., Results: Nitrotyrosine immunostaining was present in placebo-treated NT, GH and PE placentae, with no significant difference observed between the groups. There was a non-significant trend towards decreased p38-MAPKα activity in PE vs NT control placentae. ERK and JNK were similar among the three outcome placebo groups and vitamin supplementation did not significantly alter their activity., Conclusion: Nitrotyrosine immunopositivity in normotensive diabetic placentae indicates some degree of tyrosine nitration in uncomplicated diabetic pregnancy, possibly due to inherent oxidative stress and peroxynitrite production. Our results suggest that p38-MAPKα, ERK and JNK are not directly involved in the pathogenesis of type 1 diabetic pre-eclampsia and are not modulated by vitamin-supplementation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Mesenteric prosthetic graft infection is a rare and challenging clinical scenario. A patient is described who developed recurrent abdominal pain after occlusion of an iliomesenteric prosthetic bypass. Endovascular recanalization of the native superior mesenteric artery, which had been occluded for more than 10 years, was accomplished using axillofemoral through-wire access and a steerable guiding catheter. The infected prosthetic was then explanted and his graft-enteric fistula repaired. Technical and strategic considerations are discussed., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)