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Background: Primary aldosteronism (PA) is the most common secondary endocrine cause of hypertension with familial hyperaldosteronism type 1 (FH-1), a rare heritable subtype. Timely identification of FH-1 is important because of an increased risk of vascular events in affected individuals and because it provides the opportunity to guide appropriate treatment. Genetic testing is recommended if onset is at a young age (<20 years), there is a family history of PA or early cerebrovascular events occur., Aims: To assess national rates of testing for FH-1, whether this varied over time and by region., Methods: De-identified data were obtained on genetic testing performed for FH-1 from 1 April 2010 to 30 October 2023 (163 months) from the Canterbury Health Laboratories database, the sole national testing laboratory for FH-1., Results: A total of 147 tests were performed, of which 19 (12.9%) were positive. Eleven of the positive tests were requested by one region. Testing rates varied from 0.00 to 0.63 per 100 000 people per annum. Most tests were requested by endocrinology services. Testing increased over time from an average of 4.6 tests per annum in the first 5 years of the period studied to 17.7 tests in the most recent 5 years. Limitations include lack of ethnicity data, information on testing indications and testing rates for other familial PA subtypes., Conclusions: Testing for FH-1 has increased over time but remains low. Testing for familial forms of PA should be considered in those in whom PA was diagnosed at a young age or with a suggestive family history., (© 2024 The Author(s). Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Importance: Evidence-based treatment decisions for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) require individualized patient-centered decision-making that accounts for patient and cancer characteristics., Objective: To create an accessible guidance document to educate clinicians and patients on biomarkers informing prognosis and treatment in unresectable or metastatic GEP-NENs., Methods: A multidisciplinary panel in-person workshop was convened to define methods. English language articles published from January 2016 to January 2023 in PubMed (MEDLINE) and relevant conference abstracts were reviewed to investigate prognostic and treatment-informing features in unresectable or metastatic GEP-NENs. Data from included studies were used to form evidence-based recommendations. Quality of evidence and strength of recommendations were determined using the Grading of Recommendations, Assessment, Development and Evaluations framework. Consensus was reached via electronic survey following a modified Delphi method., Findings: A total of 131 publications were identified, including 8 systematic reviews and meta-analyses, 6 randomized clinical trials, 29 prospective studies, and 88 retrospective cohort studies. After 2 rounds of surveys, 24 recommendations and 5 good clinical practice statements were developed, with full consensus among panelists. Recommendations focused on tumor and functional imaging characteristics, blood-based biomarkers, and carcinoid heart disease. A single strong recommendation was made for symptomatic carcinoid syndrome informing treatment in midgut neuroendocrine tumors. Conditional recommendations were made to use grade, morphology, primary site, and urinary 5-hydroxyindoleacetic levels to inform treatment. The guidance document was endorsed by the Commonwealth Neuroendocrine Tumour Collaboration and the North American Neuroendocrine Tumor Society., Conclusions and Relevance: The study results suggest that select factors have sufficient evidence to inform care in GEP-NENs, but the evidence for most biomarkers is weak. This article may help guide management and identify gaps for future research to advance personalized medicine and improve outcomes for patients with GEP-NENs.

We introduce a proof-of-concept extended reality (XR) environment for discussing cancer, presenting genomic information from multiple tumour sites in the context of 3D tumour models generated from CT scans. This tool enhances multidisciplinary discussions. Clinicians and cancer researchers explored its use in oncology, sharing perspectives on XR's potential for use in molecular tumour boards, clinician-patient communication, and education. XR serves as a universal language, fostering collaborative decision-making in oncology., (© 2024. The Author(s).)

Objective: This study investigated the seroprevalence of SARS-CoV-2 antibodies among adults over 18 years., Design: Prospective cohort study., Settings: A large public university., Participants: This study took volunteers over 5 days and recruited 1064 adult participants., Primary Outcome Measures: Seroprevalence of SARS-CoV-2-specific antibodies due to previous exposure to SARS-CoV-2 and/or vaccination., Results: The seroprevalence of the antireceptor binding domain (RBD) antibody was 90% by a lateral flow assay and 88% by a semiquantitative chemiluminescent immunoassay. The seroprevalence for antinucleocapsid was 20%. In addition, individuals with previous natural COVID-19 infection plus vaccination had higher anti-RBD antibody levels compared with those who had vaccination only or infection only. Individuals who had a breakthrough infection had the highest anti-RBD antibody levels., Conclusion: Accurate estimates of the cumulative incidence of SARS-CoV-2 infection can inform the development of university risk mitigation protocols such as encouraging booster shots, extending mask mandates or reverting to online classes. It could help us to have clear guidance to act at the first sign of the next surge as well, especially since there is a surge of COVID-19 subvariant infections., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Familial hyperaldosteronism type 1 (FH1), previously known as glucocorticoid-remediable aldosteronism, was the first identified monogenic cause of primary aldosteronism. Patients classically develop hypertension at a young age and are at risk of premature vascular complications. A systematic review of FH1 was performed to determine long-term treatment outcomes., Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted searches with a patient/population, intervention, comparison and outcomes (PICO) framework using Embase, Medline, PubMed, Scopus, and Web of Science databases to identify patients with FH1 prescribed either no treatment with a minimum 3 months follow-up or medical treatment of at least 3 months duration., Results: A total of 99 FH1 cases were identified from 42 studies. Most had early-onset hypertension but variable hypokalemia, hyperaldosteronism, and hyporeninemia. Of the 62 cases with a reported age of FH1 diagnosis, median age was 18 ± 17.6 years old. Of those treated, 72% received a glucocorticoid for long-term treatment compared with 22% receiving a potassium-sparing diuretic. Data on long-term treatment and disease side effects, complications, and outcomes were seldom reported. However, of 20 patients with reported complications, premature vascular complications were evident with the median age of diagnosis for left ventricular hypertrophy and hypertensive retinopathy 15 and 16.5 years old respectively, the youngest age of aortic dissection age 10 years, and those with reported cerebrovascular history had strokes or transient ischemic attacks before age 40 years., Conclusions: Major gaps in the literature around FH1 patients' long-term treatment and disease outcomes still exist. Long-term outcome data are required to help inform clinicians of the best long-term treatment for FH1., Competing Interests: Disclosures None.

Background: Māori have an increased incidence of thyrotoxicosis when compvared to non-Māori, however there are limited data on benign non-toxic nodular thyroid disease., Aims: The aims of this study were to determine the rates of non-toxic multinodular goitre (NTMNG) surgery for Māori and non-Māori and to determine if there were differences in thyroid size between Māori and non-Māori undergoing total thyroidectomy for NTMNG., Methods: Single centre study of patients undergoing thyroidectomy for NTMNG from 1 December 2006 to 30 November 2016., Results: Māori were overrepresented amongst the 427 patients who underwent surgery for NTMNG at 34% compared to the expected ~17% of the background Māori adult population in the region. At the time of surgery, Māori were younger (P = 0.004) and had a larger thyroid gland (P < 0.001) when compared to non-Maori also undergoing total/near total thyroidectomy. Complication rates were low across all ethnic groups., Conclusion: Māori have increased rates of surgery for NTMNG compared to non-Māori and thyroid size is larger at the time of surgery. The reasons for this are currently unknown and more research is required., (© 2022 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Context: Pheochromocytomas and paragangliomas (PPGLs) are known to be rare. However, there is scant literature reporting their epidemiology, particularly whether the diagnosis of PPGL has increased with advances in medical imaging and biochemical and genetic testing., Objective: The primary objective of this systematic review was to determine the annual incidence of PPGLs and change over time., Design: A systematic review was performed. Medline, Embase, PubMed, and Web of Science Core Collection databases were searched to identify studies reporting PPGL incidence. Studies were eligible for inclusion from the database's inception until August 30, 2021., Results: A total of 6109 manuscripts were identified; 2282 duplicates were excluded, and a further 3815 papers were excluded after abstract and/or full text review. Twelve studies were included in the final review. The incidence of PPGL ranged from 0.04 to 0.95 cases per 100 000 per year. Incidence increased over time, from approximately 0.2/100,000 individuals in studies performed before 2000, to approximately 0.6/100,000 in studies undertaken after 2010. The mode of diagnosis changed over the same time period, with more patients diagnosed from incidental imaging findings, and fewer at autopsy or from symptoms., Conclusion: The annual incidence of PPGL has increased over time. Much of this increase is likely from incidental identification of tumors on imaging. However, the epidemiology of PPGL remains understudied, in particular, in associations with altitude, ethnicity, and genetics. To improve early detection and management guidelines, these gaps should be addressed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Objectives: This study aimed to assist practitioners in performing an accurate assessment of the external and internal pelvic musculoskeletal (MSK) systems to improve appropriate diagnosis and referral of patients with pelvic floor disorders or pelvic pain and to improve understanding of physical therapy (PT) treatment principles, thereby improving communication between practitioners and encouraging a multidisciplinary approach., Methods: A referenced review of the anatomy of the pelvic floor muscles, pelvis, and surrounding structures, followed by a detailed assessment of anatomy, posture, and gait, is presented. A thorough description of PT assessment and treatment is included with clinical relevance., Results: When proper assessments are routinely performed, MSK conditions can be recognized, allowing for prompt and appropriate referrals to PT. Assessment and treatment by qualified physical therapists are integral to pelvic health care. After efficient medical assessment, MSK dysfunction can be addressed expeditiously, thereby avoiding further decline. Left unaddressed, pelvic dysfunction may become chronic., Conclusions: We propose a guide for MSK assessment of the pelvis and associated structures that can be used for both clinical and research purposes. This guide is designed for health care providers caring for women with pelvic floor disorders, including physicians, advanced practice providers, and nurses. This guide serves to improve communication among multidisciplinary practitioners to refine MSK assessment and treatment approaches and thereby advance clinical care and research., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2021 American Urogynecologic Society. All rights reserved.)

Peptide receptor radionuclide therapy (PRRT) is an increasingly used treatment for unresectable neuroendocrine tumours (NETs) that express somatostatin receptors. Normal pituitary tissue expresses somatostatin receptors so patients receiving PRRT may be at risk of developing hypopituitarism. The aim was to assess the prevalence of clinically significant hypopituitarism a minimum of 2 years following radioisotope therapy for metastatic NET. This was a multicentre study (Australia and New Zealand). Sixty-six patients with unresectable NETs were included-34 had received PRRT and 32 comparison patients. Median follow-up after PRRT was 68 months. Male hypogonadism was the most common hormonal abnormality (16 of 38 men [42%]) from the total cohort. Of these, seven men had primary hypogonadism (five from PRRT group) and nine had secondary hypogonadism (six in PRRT group). There was no difference in either male hypogonadism or other hormonal dysfunction between patients who had received PRRT and those that had not. Patients who have received PRRT out to 68 months following treatment do not show concerning hypopituitarism although there may be the suggestion of growth hormone deficiency developing. However, hypogonadism is common in men with NETs so the gonadal axis should be assessed in men with suggestive symptoms as the treatment of testosterone deficiency may improve the quality of life., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: One in four diabetes patients will develop a foot ulcer over their lifetime. The role of glycaemic control in the healing of foot ulcers in diabetes patients is not supported by randomised controlled trial (RCT) data., Objectives: To determine the feasibility of an RCT of glycaemic control with intensive insulin therapy in diabetic foot ulcer, by assessing: entry criteria, fasting capillary blood glucose (FCBG) medication satisfaction and sensitivity of different ulcer-healing endpoints to glycaemic control., Design: Two substudies: one cross-sectional and one single-arm prospective., Setting: Single-centre secondary care diabetic foot clinic in New Zealand., Participants: Substudy 1: 78 participants consisting of all people ≥18 years with a diabetic foot ulcer presenting to the clinic over 35 weeks in 2015.Substudy 2: 15 participants from Substudy 1 consenting to intensive insulin therapy., Intervention: Substudy 1: None.Substudy 2: Intensive insulin therapy with standard podiatry care over 24 weeks., Outcome: Substudy 1: Proportion of participants satisfying potential RCT entry criteria; medication satisfaction (Diabetes Medication Satisfaction).Substudy 2: FCBG, index ulcer healing time, index ulcer size, health-related quality of life (HRQoL; EuroQol 5 Dimensions 5 Levels and Diabetic Foot Ulcer Scale-Short Form)., Results: Proportion in Substudy 1 satisfying all entry criteria was 31% (95% CI 21 to 42). FCBG values decreased between baseline and study end (difference -3.7 mmol/L, 95% CI -6.5 to -0.8); 83% (95% CI 44 to 95) of ulcers healed by 24 weeks. FCBG correlated negatively with medication satisfaction. Ulcer area logarithm was most sensitive to FCBG changes, displaying significant negative correlation with HRQoL outcomes. Detecting a 30% between-group difference in this outcome (80% power, α=5%) requires 220 participants per arm, achievable within 1 year with 15 centres similar to study setting., Conclusions: An adequately powered RCT requires cooperation between a large number of centres. Ulcer area logarithm should be primary endpoint., Trial Registration Number: ANZCTR ACTRN12617001414303., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Gas Chromatography-Mass Spectrometry (GC-MS) has long been used for metabolite profiling of a wide range of biological samples. Many derivatisation protocols are already available and among these, trimethylsilyl (TMS) derivatisation is one of the most widely used in metabolomics. However, most TMS methods rely on off-line derivatisation prior to GC-MS analysis. In the case of manual off-line TMS derivatisation, the derivative created is unstable, so reduction in recoveries occurs over time. Thus, derivatisation is carried out in small batches. Here, we present a fully automated TMS derivatisation protocol using robotic autosamplers and we also evaluate a commercial software, Maestro available from Gerstel GmbH. Because of automation, there was no waiting time of derivatised samples on the autosamplers, thus reducing degradation of unstable metabolites. Moreover, this method allowed us to overlap samples and improved throughputs. We compared data obtained from both manual and automated TMS methods performed on three different matrices, including standard mix, wine, and plasma samples. The automated TMS method showed better reproducibility and higher peak intensity for most of the identified metabolites than the manual derivatisation method. We also validated the automated method using 114 quality control plasma samples. Additionally, we showed that this online method was highly reproducible for most of the metabolites detected and identified (RSD < 20) and specifically achieved excellent results for sugars, sugar alcohols, and some organic acids. To the very best of our knowledge, this is the first time that the automated TMS method has been applied to analyse a large number of complex plasma samples. Furthermore, we found that this method was highly applicable for routine metabolite profiling (both targeted and untargeted) in any metabolomics laboratory.

Introduction: Aim of this study is to evaluate if regeneration in repair of nerve defects can be improved by combination of a poly-dl-lactide-ɛ-caprolactone conduit (PLC) with long-term release of anti-inflammatory Interleukin 10 (IL10), which is known to reduce intraneural scarring in nerve regeneration through its anti-inflammatoric properties., Method: Experiments were performed at 30 female Lewis rats. Conduits filled with fibrin (PLC-group n = 10) and fibrin loaded with IL10 (IL10-group n = 10) were compared to autologs nerve grafts (NG-group n = 10) in a 15 mm sciatic nerve gap lesion. Sciatic function index (SFI) and electrophysiological analyses were performed 16 weeks after surgery prior to histological evaluation. In histological analyses total nerve count, total nerve area, myelination index, and N-ratio were measured. Additionally, gastrocnemius muscle was weighed., Results: SFI (NG-group:-50.68 ± 7.03%; PLC-group:-56.48  ± 2.30%; IL10-group:-56.54  ± 8.22%) and nerve conduction velocity (NG-group: 92.52  ± 4.64 m/s; PLC-group: 92.77  ± 5.07 m/s; IL10-group: 93.78  ±3.63 m/s) showed no significant differences after 16 weeks (P > 0.05). Significant higher axon count (17.592  ± 483) were observed in the NG-group compared to PLC- (6.722 ± 553) and IL10-group (6.842 ± 681) (P < 0.001). NG-group had significant highest nerve cross sections (604.214  ± ±15.217 µm 2 ) as compared to PLC- (245.669  ± ±28.034 µm 2 ) and IL10-group (244.698 ± 26.772 µm 2 ) (P < 0.001). Comparison of myelination index showed significant higher values for NG-group (0.46  ± 0.02) than PLC- (0.64  ± 0.01) and IL10-group (0.62  ± 0.01) (P < 0.001). N-ratios in PLC-group (0.21  ± 0.01) and IL10-group (0.24 ± 0.01) were lower than in NG-group (0.51  ± 0.03) (P < 0.001). Between PLC- and IL10-group no differences were observed (P > 0.05). Gastrocnemius muscle was heavier in NG-group (0.86 ± 0.21g) as compared to PLC- (0.26 ± 0.05g) and IL-10 group (0.29 ± 0.06 g) (P < 0.05)., Conclusion: Bridging critical nerve defects through fibrin-filled PLC conduits is possible. Although, autologs nerve graft showed superior histological results. Long-term release of IL10 in the conduit did not improve regeneration of critical nerve defects. © 2015 Wiley Periodicals, Inc. Microsurgery 36:410-416, 2016., (© 2015 Wiley Periodicals, Inc.)

Introduction: Peripheral nerve regeneration over longer distances through conduits is limited. In the presented study, critical size nerve gap bridging with a poly-DL-lactide-ε-caprolactone (PLC) conduit was combined with application of C3 toxin to facilitate axonal sprouting., Materials and Methods: The PLC filled with fibrin (n = 10) and fibrin gel loaded with 1-μg C3-C2I and 2-μg C2II (n = 10) were compared to autologous nerve grafts (n = 10) in a 15-mm sciatic nerve gap lesion model of the rat. Functional and electrophysiological analyses were performed before histological evaluation., Results: Evaluation of motor function and nerve conduction velocity at 16 weeks revealed no differences between the groups. All histological parameters and muscle weight were significantly elevated in nerve graft group. No differences were observed in both PLC groups., Conclusions: The PLCs are permissive for nerve regeneration over a 15-mm defect in rats. Intraluminal application of C3 toxin did not lead to significant enhancement of nerve sprouting.

Aim: Medical schools must select and educate to meet anticipated health needs. Factors influencing career choice include those of the student and their background as well as subsequent experience. Women have comprised over 50% of medical classes for over 20 years. This study describes gender patterns of current specialty interest among medical students at the University of Auckland, and models the predictive effect of gender compared to other career influencing factors., Method: The study analysed career intention survey data from 711 graduating medical students (response rate, 79%) from 2006 to 2011., Results: Interest level was highest for medicine, followed by subspecialty surgery, general practice and paediatrics. There were differences by gender for most specialties, but not for general practice. Women were more likely than men to be interested in Obstetrics and Gynaecology, Paediatrics, Geriatrics, Public Health or General Medicine, and less interested in Surgery, Anaesthesia, Emergency Medicine or post graduate study. Each specialty had a different pattern of influencing factors with the most important factor being the experience on a clinical attachment., Conclusion: Factors in career choice are complex and vary by gender and specialty. General practice levels of interest are too low for workforce needs. Predictive models need to be validated in longer term studies but may help guide selection and curriculum design.

Background and Objectives: Medical schools and residencies lack training in communication skills with patients with disabilities, thereby creating potential barriers to care. To address this shortcoming, the Department of Family Medicine at Lehigh Valley Health Network developed an innovative program in which the patients themselves serve as medical educators. The P-DAT (Patients With Disabilities as Teachers) program is designed to teach basic communication skills and disability etiquette to promote sensitivity to issues unique to this patient population. As such, it conforms to the established principles of the patient-centered medical home., Methods: Two persons with disabilities who were patients of the residency-affiliated clinic underwent training to become educators. In the resulting interactive education session with medical students, the P-DAT educators describe their daily routines and health care experiences while encouraging their learners to ease anxieties in interacting with patients with disabilities by asking questions., Results: The 44 student participants evaluated the program by responding to a series of Likert scale and open-ended questions. Tallies of the post-program survey results reveal that prior to the disability etiquette training a majority (89%) felt uncomfortable in communicating with patients with disabilities. The survey revealed that 98% of respondents found the program beneficial because it increased overall awareness and sensitivity (52%) and improved competency for future interactions with patients (46%)., Conclusions: Although these evaluation results reflect the early stages of P-DAT implementation, the preliminary feedback indicates that medical students are eager to close the gap in their knowledge about disability etiquette so they can improve their care of this patient population.

End-to-side (ETS) neurorrhaphy is an option in peripheral nerve surgery. The aim of this study was to investigate whether the application of the anti-inflammatory cytokine interleukin-10 (IL-10) reduces scarring and thus enhances nerve regeneration in an ETS peroneal/tibial nerve lesion model of the rat. Twenty rats with a peroneal to tibial ETS neurorrhaphy were divided into two groups: (1) control group and (2) IL-10 group with intrafascicular application of 0.125 µg/100 µl IL-10. Survival time was 8 weeks. Nerve conduction velocities (NCVs) and motor function were analyzed and histomorphological evaluation with measurement of intraneural collagen level, axon count, total nerve area, and myelination index followed. Evaluation of motor function and nerve conduction did not show any statistical differences. Histological analyses revealed thicker myelin sheaths and higher myelination index in the IL-10 group (p < 0.001). Axon count showed no difference. The IL-10 group revealed lower collagen levels (p < 0.001). Comparison of total nerve area showed no statistical significance. At this dose, IL-10 evaluated at 8 weeks was not significantly different than placebo in functional, NCVs, and most morphological measures. However, there was a significant difference in thicker myelin sheaths and higher myelination index and lower collagen levels. This suggests that future experiments of IL-10 at different doses or longer periods of evaluation would be of interest., (© 2011 Peripheral Nerve Society.)

Severity of illness or injury should be the primary justification for aeromedical transport. To determine whether differences in patient severity were detectable in air transport programs, helicopter-transported patients were examined by three established physiologic scores: the Trauma Score, the Acute Physiology and Chronic Health Evaluation Score, and the Rapid Acute Physiology Score. These scores were obtained prospectively on 1,868 consecutive patient transfer requests from six air medical services for periods ranging from two to six months. A patient meeting strict physiologic criteria was considered critically ill. Overall, 42.6% of the patients (range, 34.8% to 53.3%) were considered critically ill. Patients transported from inpatient hospital units and patients with cardiac disease were less likely to be critically ill than those transported emergently from scenes of accident or from emergency departments. There were also significant differences between programs with regard to the percentage of critically ill patients transported. This study suggests that physiologic scoring may be useful in comparing air ambulance programs and that a majority of patients transported by these services may not be critically ill.

The linear, crosslinked amylose-succinate hemostatic agent, IP760, has been evaluated for its interaction with aminoglycosidic antibiotics. The highly structured polymer appears to act as a cationic exchange resin which binds the basic aminoglycosides. Binding of these agents to IP760 is reversed by increased pH and/or increased ionic strength. Dialysis experiments demonstrated that 85 and 90% of the bound gentamicin was released at pH 7.5 and 8.0, respectively, over a period of 36 hr. Formation of the IP760-antibiotic complexes suggests potential medicinal use for hemostatis and slow release of the antibiotic for prophylaxis of postsurgical contamination or infection