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Background and objectivesWhile there are several published recommendations and guidelines for trainees undertaking subspecialty Fellowships in regional anesthesia, a similar document describing a core regional anesthesia curriculum for non-fellowship trainees is less well defined. We aimed to produce an international consensus for the training and teaching of regional anesthesia that is applicable for the majority of worldwide anesthesiologists.MethodsThis anonymous, electronic Delphi study was conducted over two rounds and distributed to current and immediate past (within 5 years) directors of regional anesthesia training worldwide. The steering committee formulated an initial list of items covering nerve block techniques, learning objectives and skills assessment and volume of practice, relevant to a non-fellowship regional anesthesia curriculum. Participants scored these items in order of importance using a 10-point Likert scale, with free-text feedback. Strong consensus items were defined as highest importance (score ≥8) by ≥70% of all participants.Results469 participants/586 invitations (80.0% response) scored in round 1, and 402/469 participants (85.7% response) scored in round 2. Participants represented 66 countries. Strong consensus was reached for 8 core peripheral and neuraxial blocks and 17 items describing learning objectives and skills assessment. Volume of practice for peripheral blocks was uniformly 16–20 blocks per anatomical region, while ≥50 neuraxial blocks were considered minimum.ConclusionsThis international consensus study provides specific information for designing a non-fellowship regional anesthesia curriculum. Implementation of a standardized curriculum has benefits for patient care through improving quality of training and quality of nerve blocks.

Summary Excess cortisol is associated with hypertrophy and redistribution of adipose tissue leading to central obesity which is classically seen in Cushing’s syndrome. Abnormal accumulation of fatty tissue in the spinal canal is most commonly associated with chronic steroid therapy and rarely reported with endogenous Cushing’s syndrome. Herein, we describe a case of spinal epidural lipomatosis (SEL) associated with Cushing’s disease. A 17-year-old man was referred with lower limb weakness, weight gain, multiple stretch marks, back pain and loss of height. He had clinical and biochemical features of Cushing’s syndrome. MRI and Inferior Petrosal Sinus Sampling (IPSS) confirmed a pituitary adenoma as the source. On day 1 post trans-sphenoidal adenectomy he developed spastic paraparesis with a sensory deficit to the level of T5. MRI spine showed increased fat deposition in the spinal canal from T2 to T9 consistent with a diagnosis of SEL. He was managed conservatively and made a good recovery following restoration of eucortisolism and a period of rehabilitation. Learning points: SEL is a serious complication of glucocorticoid excess and should be considered in any patient presenting with new lower limb neurological symptoms associated with hypercortisolism. It is important to distinguish symptomatic SEL from cortisol-induced proximal myopathy by good history and clinical examination. MRI of the spine is the gold standard investigation for making a diagnosis of SEL. Restoration of eucortisolism can lead to resolution of fat accumulation and good neurological outcome.

The clinical course of pituitary adenoma can be highly variable. Aggressive pituitary tumours may require multimodal therapy with multiple operations. Even standard pituitary adenomas exhibit relatively high long-term recurrence rates and delayed intervention is often required. The indications for revision surgery in the endoscopic era are expanding for both functioning and nonfunctioning tumours, including access to the cavernous sinus and intracranial compartments. Although revision surgery can be challenging, it has been demonstrated to be both safe and effective. The question of the use of early radiotherapy in pituitary adenoma remains controversial. Our increasing understanding of pituitary tumour biology facilitates individualized treatment and surveillance protocols, with early intervention in high-risk adenoma subtypes. In this review, we discuss the treatment options for recurring pituitary tumours and focus on the role of revision surgery.

Context Polycystic ovary syndrome (PCOS) is associated with increased sympathetic nervous system activation, but the cerebral pathways involved are unclear. Objective To compare cerebral [blood oxygen level–dependent (BOLD) functional MRI], pressor [blood pressure (BP), heart rate (HR], and muscle sympathetic nerve activity (MSNA) responses to isometric forearm contraction (IFC) in women with PCOS and matched control subjects. Design Case-control study. Setting Referral center. Participants Patients with PCOS (n = 20; mean ± SD data: age, 29.8 ± 4.8 years; body mass index (BMI), 26.1 ± 4.9 kg/ m2) and 20 age- and BMI-matched control subjects (age, 29.7 ± 5.0 years; BMI, 26.1 ± 4.8 kg/ m2). Main outcome measures BP, HR, catecholamine, and MSNA responses to 30% IFC. BOLD signal change was modeled for BP response to 30% IFC. Results Although HR and BP increased to a similar extent in both groups after IFC, MSNA burst frequency increased by 68% in the PCOS group compared with 11.9% in control subjects (n = 7 in both groups; P = 0.002). Brain activation indexed by the BOLD signal in response to IFC was significantly greater in the PCOS group (n = 15) compared with controls (n = 15) in the right orbitofrontal cortex (P < 0.0001). Adjustment for insulin sensitivity, but not hyperandrogenism, abolished these between-group differences. Conclusion Our study confirms enhanced sympathoexcitation in women with PCOS and demonstrates increased regional brain activation in response to IFC. The right orbitofrontal cortex BOLD signal change in women with PCOS is associated with insulin sensitivity. Additional studies are warranted to clarify whether this may offer a novel target for cardiovascular risk reduction.

Use of immune checkpoint inhibitors in cancer treatment has increased vastly over the past decade, as both single and combination agent therapies. While having a positive impact on survival rates, adverse effects have been noted, with endocrine effects in around 10% of patients. Thyroid disease and hypophysitis are the most commonly encountered, with diabetes mellitus and primary adrenal insufficiency also reported, as well as more rare endocrinopathies. Patient and clinician education to raise awareness of these effects, as well as regular monitoring to enable early recognition, diagnosis and prompt treatment of the immune side effects, are key. In this review, we discuss the aetiology, presentation and management of the endocrine complications of immunotherapies that are relevant to the general physician, as well as highlighting important areas where further research is still needed.

Objective Acromegaly is a rare condition and there is often a long path to diagnosis for many patients. We sought to explore patient’s perceptions and understanding of acromegaly, to examine the quality of communication and find gaps in the information provided at diagnosis. Design A prospective study using qualitative research methodology and grounded theory. A semi-structured interview was conducted with 18 patients treated for acromegaly in a single tertiary centre and verbatim transcripts were thematically analysed for overarching themes. Results Eighteen patients with acromegaly were interviewed. The mean age of participants was 52 (range 30–72). Four overarching themes emerged; (1) Patients rely on online resources to understand acromegaly in the time between diagnosis and tertiary care clinic; (2) There is not enough support available for patients; (3) Patients have a basic understanding of acromegaly and associated conditions, but the long-term impact is underestimated; and (4) Patients initially felt intimidated by the multidisciplinary team panel, but overall found it useful. Conclusion Acromegalic patients have a strong need for information at the point of initial diagnosis, in particular online resources and interaction with other experienced patients. Wider dissemination of patient educational resources into primary and secondary care settings may improve overall patient satisfaction, treatment adherence and subsequent health care provider–patient relationships.

The outcome for pituitary endocrine function following endoscopic transsphenoidal surgery remains unclear. This study aims to evaluate endocrine outcomes following endoscopic surgery in order to provide a benchmark to assist in the counselling of patients perioperatively. A prospectively held pituitary database was retrospectively analysed for all adult pituitary adenoma patients undergoing endoscopic surgery from May 2011 to May 2017. All operations were performed by a single neurosurgeon at a regional centre for pituitary surgery. Functioning and non-functioning adenomas were included. Hormonal status was assessed at most recent follow-up. One hundred forty-five patients (69 M, 76 F) were included in the study with a median age of 52 years. Median follow-up was 52 months. Eighty-eight patients (61%) were not taking any hormone replacement medications, whilst 57 patients (39%) required hormone replacement therapy (HRT) preoperatively. Preoperatively, 29 patients (20%) had hypothalamo-pituitary-adrenal (HPA) axis dysfunction, 39 patients (27%) had thyroid axis dysfunction, 11 males (16%) and 7 females (9%) had gonadal axis dysfunction, and one patient had preoperative diabetes insipidus. Postoperatively, 26 patients (18%) had a new deficiency in pituitary function, whilst 6 patients (11%) were able to cease HRT. Nineteen patients (13%) had new HPA axis deterioration, 12 (8%) had new thyroid axis dysfunction, 8 males (11%) and 4 females (5%) had gonadal axis deterioration, and 6 patients (4%) had new diabetes insipidus (DI). The ability to restore pituitary function following endoscopic surgery remains limited, whilst new deficits still occur. It is essential that patients are counselled accordingly as hormonal replacement therapy can have a significant impact on quality of life. Larger longer-term collaborative studies of endocrine outcome in endoscopic pituitary surgery are needed.

Background Adductor canal (AC) catheters are being used to provide continuous postoperative analgesia after total knee arthroplasty (TKA) surgery. There are anatomical arguments that most AC catheters are being inserted into the femoral triangle (FT) compartment of the thigh rather than the AC compartment. The clinical relevance of this is unknown with respect to motor weakness, quality of analgesia, and opioid consumption. We hypothesised that AC catheters provide superior functional mobilisation on postoperative Day 1 after TKA as measured using the Timed Up and Go (TUG) test. Methods In this multinational, multicentre, double-blinded RCT, catheters were inserted under ultrasound guidance into the anatomical AC and FT compartments. The standardised protocol included spinal anaesthesia without intrathecal morphine, fixed catheter infusion rates, and oral analgesia. Results Of 151 subjects recruited, 75 were in the AC group and 76 in the FT group. There was no statistically significant difference in TUG on postoperative Day 1 between AC (38 [29–55] s) and FT subjects (44 [32–64] s) (median [inter-quartile range]); P=0.11). There was no difference in TUG Day 2, AC (38 [27–53] s) vs FT (42 [31–59] s); P=0.66. There were no statistically significant differences for secondary endpoints of pain level, effectiveness of pain relief, interference of functional activities and interpersonal relationships by pain, and opioid consumption between groups. Conclusions There were no differences in immediate postoperative functional mobility, analgesia, and opioid consumption provided by catheters inserted into the AC vs FT locations for TKA surgery. Clinical trial registration ANZCTR12617001421325.

A 60-year-old man presented with right third nerve palsy and headaches. Neuroimaging showed a pituitary lesion. There was evidence of rapid enlargement on interval scans, invasion of the cavernous sinus and displacement of the pituitary stalk. He subsequently developed anterior hypopituitarism. CT thorax, abdomen and pelvis did not show any evidence of malignancy. This was thought to be an aggressive pituitary macroadenoma but histology post-trans-sphenoidal surgery surprisingly showed metastasis from an undiagnosed prostate primary. His prostate specific antigen was raised and MRI pelvis confirmed locally advanced prostate cancer.

To the editor, We read with interest the recently published article by Swenson et al [1][1] examining a new technique for adductor canal block (ACB). We note that their study is based on the premise that an ACB must rely solely on the injection of local anesthetic into the true adductor canal

Aims: To determine the proportion of cases of childhood Type 1 diabetes that present with ketoacidosis and any temporal trend. To assess the impact of a publicity campaign promoting earlier diagnosis. Methods: We used an all-Wales register of incident cases with data on 2046 children from 1991 to 2009. The proportion with ketoacidosis at diagnosis was compared with the Yorkshire Childhood Diabetes Register. On World Diabetes Day posters were sent to every pharmacy, school and general practitioner surgery across Wales and radio interviews given. A questionnaire survey was conducted in Gwent to assess penetrance of the campaign. Results: Annually, in 1991–2009 the proportion presenting with ketoacidosis varied between 20% and 33% (mean 25%) with no change over time. Similar proportions occurred in Yorkshire. Ketoacidosis was more common before age 5 years (37% of cases) than at age 5–9 years (20%) or 10–14 years (23%) (P < 0.001). From November 2006–2007 30% of cases presented with ketoacidosis and from November 2007–2008 25% cases presented with ketoacidosis. After the campaign (November 2008–2009) 26% presented with ketoacidosis (P = 0.72). The information had reached a low proportion of families. General practitioners referred immediately cases that presented to them. Conclusions: Over 20 years in Wales there has been no change in the proportion of children with Type 1 diabetes initially presenting with ketoacidosis. This presentation occurs in a higher proportion of new cases aged under 5 years. Publicity to increase awareness did not reduce the proportion with DKA ketoacidosis at diagnosis in Wales. We need to get the educational message through to parents to reduce ketoacidosis at presentation.

Aims Metformin is associated with lowering of vitamin B12 levels. We hypothesise that holotranscobalamin (holoTC) and methylmalonic acid (MMA) are more sensitive indicators of B12 deficiency in patients receiving metformin therapy, and that these correlate with declining peripheral neurological function. Methods Patients with type 2 diabetes were recruited and divided into those receiving metformin for greater than 6 months and a non-metformin group. Baseline characteristics were measured in both groups including vitamin B12, holoTC and MMA concentrations. Neurological function was assessed using neurothesiometry, monofilament, Neuropathy Total Symptom Score-6 questionnaire and the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs questionnaire. Results In total, 202 patients were recruited: 152 in the metformin group and 50 in the non-metformin group. Vitamin B12 levels were lower in the metformin group (219.1±105.4 ng/L, 281.4±95.1 ng/L, pConclusion Although metformin therapy is associated with lower vitamin B12 status there does not appear to be any significant effect on peripheral neuropathy in those receiving metformin. We do not recommend changing current practice to routinely monitor or replace patients receiving metformin with vitamin B12 unless clinically indicated.

Endocrine tumours occur rarely in pregnant women but present clinicians with unique challenges. A high index of suspicion is often required to make a diagnosis since the symptoms and signs associated with many of these tumours, including insulinoma, adrenocortical carcinoma and phaeochromocytoma, mimic those of normal pregnancy or its complications, such as pre-eclampsia. The evidence base which informs management is very limited hence decisions on investigation and therapy must be individualised and undertaken jointly by the multidisciplinary medical team and the patient. The optimal strategy will depend on the nature and stage of the endocrine tumour, gestational stage, treatments available and patient wishes. Thus, surgical intervention, appropriately timed, may be considered in pregnancy for resectable adrenocortical carcinoma or phaeochromocytoma, but delayed until the postpartum period for well-differentiated thyroid cancer. Medical therapy may be required to reduce the drive to tumour growth, control symptoms of hormone excess and to minimise the risks of surgery, anaesthesia or labour.

Background: Cushing's syndrome (CS) is a severe condition with excess mortality and significant morbidity necessitating control of hypercortisolemia. There are few data documenting use of the steroidogenesis inhibitor metyrapone for this purpose. Objective: The objective was to assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with CS. Design: This was designed as a retrospective, multicenter study. Setting: Thirteen University hospitals were studied. Patients: We studied a total of 195 patients with proven CS: 115 Cushing's disease, 37 ectopic ACTH syndrome, 43 ACTH-independent disease (adrenocortical carcinoma 10, adrenal adenoma 30, and ACTH-independent adrenal hyperplasia 3). Measurements: Measurements included biochemical parameters of activity of CS: mean serum cortisol “day-curve” (CDC) (target 150–300 nmol/L); 9 am serum cortisol; 24-hour urinary free cortisol (UFC). Results: A total of 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 mo, range 3 d to 11.6 y). There were significant improvements on metyrapone, first evaluation to last review: CDC (91 patients, 722.9 nmol/L [26.2 μg/dL] vs 348.6 nmol/L [12.6 μg/dL]; P < .0001); 9 am cortisol (123 patients, 882.9 nmol/L [32.0 μg/dL] vs 491.1 nmol/L [17.8 μg/dL]; P < .0001); and UFC (37 patients, 1483 nmol/24 h [537 μg/24 h] vs 452.6 nmol/24 h [164 μg/24 h]; P = .003). Overall, control at last review: 55%, 43%, 46%, and 76% of patients who had CDCs, UFCs, 9 am cortisol less than 331 nmol/L (12.0 μg/dL), and 9 am cortisol less than upper limit of normal/600 nmol/L (21.7 μg/dL). Median final dose: Cushing's disease 1375 mg; ectopic ACTH syndrome 1500 mg; benign adrenal disease 750 mg; and adrenocortical carcinoma 1250 mg. Adverse events occurred in 25% of patients, mostly mild gastrointestinal upset and dizziness, usually within 2 weeks of initiation or dose increase, all reversible. Conclusions: Metyrapone is effective therapy for short- and long-term control of hypercortisolemia in CS. Cushing's syndrome (CS) is a severe condition with excess mortality and significant morbidity necessitating effective biochemical control (1). Where a cause amenable to surgical intervention is identified, surgery at a center with appropriate expertise is the optimum management. Nevertheless, many patients need urgent control of severe or persisting hypercortisolemia. Options for medical treatment include steroidogenesis enzyme inhibitors suitable for all causes of CS (ketoconazole, metyrapone, mitotane), agents to suppress ACTH in Cushing's disease (CD), such as dopamine agonists and pasireotide, and the glucocorticoid receptor antagonist, mifepristone (2, 3). The modern use of ketoconazole has recently been reported in a multicenter French Study (4), although its availability in the United States has been restricted after an Food and Drug Administration safety warning for hepatotoxicity in 2013 (5, 6), but it is widely available in Europe in 2015 (7).The cortisol-lowering effect of metyrapone was described as early as 1958 by Liddle et al (8), with later reports confirming metyrapone as a potent inhibitor of the steroidogenesis enzyme 11β-hydroxylase (8, 9). Since then, it has been used as a diagnostic test of adrenal reserve and to treat the hypercortisolism of CS. Despite its widespread use, data on metyrapone are scarce, with the largest study to date (including 91 patients) being published over 25 years ago (10). Here, we have assessed the effectiveness of metyrapone therapy in a contemporary series of patients with CS, by performing a retrospective study of patients treated in the United Kingdom.

Background and Objectives Checklists and global rating scales (GRSs) are used for assessment of anesthesia procedural skills. The purpose of this study was to evaluate the reliability and validity of a recently proposed assessment tool comprising a checklist and GRS specific for ultrasound-guided regional anesthesia. Methods In this prospective, fully crossed study, we videotaped 30 single-target nerve block procedures performed by anesthesia trainees. Following pilot assessment and observer training, videos were assessed in random order by 6 blinded, expert observers. Interrater reliability was evaluated with intraclass correlation coefficients (ICCs) based on a 2-way random-effects model that took into account both agreement and correlation between observer results. Construct validity and feasibility were also evaluated. Results The ICC between assessors’ total scores was 0.44 (95% confidence interval, 0.27–0.62). All 6 observers scored “experienced trainees” higher than “inexperienced trainees” (median total score 76.7 vs 54.2, P = 0.01), supporting the test’s construct validity. The median time to assess the videos was 4 minutes 29 seconds. Conclusions This is the first study to evaluate the reliability and validity of a combined checklist and GRS for ultrasound-guided regional anesthesia using multiple observers and taking into account both absolute agreement and correlation in determining the ICC of 0.44 for interrater reliability. There was evidence to support construct validity.