Immediate versus delayed urinary catheter removal following non-hysterectomy benign gynaecological laparoscopy: a randomised trial.

OBJECTIVE: To compare rates of urinary retention and postoperative urinary tract infection between women with immediate versus women with delayed removal of indwelling catheter following benign non-hysterectomy gynaecological laparoscopic surgery. DESIGN: This randomised clinical trial was conducted between February 2012 and December 2019, with follow-up to 6 weeks. SETTING: Two university-affiliated teaching hospitals in Sydney, Australia. POPULATION: Study participants were 693 women aged 18 years or over, undergoing non-hysterectomy laparoscopy for benign gynaecological conditions, excluding pelvic floor or concomitant bowel surgery. METHODS: Three hundred and fifty-five participants were randomised to immediate removal of urinary catheter and 338 participants were randomised to delayed removal of urinary catheter. MAIN OUTCOME MEASURES: The co-primary outcomes were urinary retention and urinary tract infection. Secondary outcomes included hospital readmission, analgesia requirements, duration of hospitalisation and validated bladder function questionnaires. RESULTS: Urinary retention was higher after immediate compared with delayed removal of the urinary catheter (8.2% vs 4.2%, RR 1.8, 95% CI 1.0-3.0, p = 0.04). Although urinary tract infection was 7.2% following delayed removal of the urinary catheter and 4.7% following immediate removal of the urinary catheter, the difference was not statistically significant (RR 0.7, 95% CI 0.3-1.2, p = 0.2). CONCLUSIONS: There is an increased risk of urinary retention with the immediate compared with the delayed removal of the urinary catheter following benign non-hysterectomy gynaecological laparoscopic surgery. The difference in urinary tract infection was not significant. There is 1/12 risk of re-catheterisation after immediate urinary catheter removal. It is important to ensure that patients report normal voiding and emptying prior to discharge, to reduce the need for readmission for the management of urinary retention.

Bone metastases induce metabolic changes and mitophagy in mice.

NEW FINDINGS: What is the central question of this study? Cachexia causes severe changes in skeletal muscle metabolism and function and is a key predictor of negative outcomes in cancer patients: what are the changes in whole animal energy metabolism and mitochondria in skeletal muscle? What is the main finding and its importance? There is decreased whole animal energy expenditure in mice with cachexia. They displayed highly dysmorphic mitochondria and mitophagy in skeletal muscle. ABSTRACT: Cachexia causes changes in skeletal muscle metabolism. Mice with MDA-MB-231 breast cancer bone metastases and cachexia have decreased whole animal energy metabolism and increased skeletal muscle mitophagy. We examined whole animal energy metabolism by indirect calorimetry in mice with MDA-MB-231 breast cancer bone metastases, and showed decreased energy expenditure. We also examined skeletal muscle mitochondria and found that mitochondria in mice with MDA-MB-231 bone metastases are highly dysmorphic and have altered protein markers of mitochondrial biogenesis and dynamics. In addition, LC3B protein was increased in mitochondria of skeletal muscle from cachectic mice, and colocalized with the mitochondrial protein Tom20. Our data demonstrate the importance of mitophagy in cachexia. Understanding these changes will help contribute to defining treatments for cancer cachexia.

Clinical and neurohormonal characteristics in African Americans with neurogenic orthostatic hypotension.

PURPOSE: Neurogenic orthostatic hypotension (nOH) is the hallmark of neurodegenerative forms of autonomic failure, including pure autonomic failure, multiple system atrophy, and Parkinson's disease. Studies have shown autonomic physiological differences in Africans Americans (AA) such as lower heart rate variability, enhanced blood pressure reactivity, and blunted sympathetic neural response compared to non-Hispanic whites. However, the clinical characteristics and neurohormonal profile of autonomic failure in AA is unknown. METHODS: A total of 65 patients with nOH participated in this study (9 AA and 56 non-Hispanic whites). Both groups were of similar age and comorbidity status, and they underwent standardized autonomic testing and assessment of neurohormonal levels and renin activity and aldosterone in supine and upright positions. RESULTS: There were no significant differences in baseline autonomic clinical characteristics between non-Hispanic whites and AA with nOH. Non-Hispanic whites demonstrated a significant increase in upright renin activity compared to AA (295 ± 88% vs. 13 ± 13%, respectively). AA showed a blunted increase in aldosterone compared to non-Hispanic whites (188 ± 27% vs. 59 ± 38%, respectively). These results indicated persistent suppression of the renin-angiotensin system in AA, particularly during upright posture. CONCLUSION: Our findings demonstrate that AA with nOH have similar clinical characteristics and hemodynamic autonomic profiles, but lower upright renin activity and aldosterone levels, compared to non-Hispanic whites. Renin suppression persists in AA with severe autonomic failure and can potentially contribute to postural changes and supine hypertension.

A comparison of health-related quality of life in autonomic disorders: postural tachycardia syndrome versus vasovagal syncope.

PURPOSE: Postural tachycardia syndrome (POTS) and vasovagal syncope (VVS) are two disorders of orthostatic intolerance which are often misdiagnosed as the other. In each case, patients experience a reduced health-related quality of life (HRQoL) compared to healthy populations. This study was conducted to test the hypothesis that HRQoL is worse in POTS. METHODS: POTS patients were recruited from the Dysautonomia International Annual Patient and Caregiver Conference. VVS patient data came from those enrolled in the Second Prevention of Syncope Trial. Participants aged ≥ 18 years (177 POTS and 72 VVS) completed the RAND 36-Item Health Survey, a generic and coherent health-related quality of life survey. RESULTS: POTS patients reported reduced HRQoL compared to VVS patients in physical functioning (42.5 ± 1.7 vs. 76.5 ± 2.9, p < 0.001), role limitations due to physical health (11.4 ± 1.9 vs. 33.0 ± 5.0, p < 0.001), energy and fatigue (27.2 ± 1.3 vs. 50.7 ± 2.6, p < 0.001), social functioning (45.2 ± 1.8 vs. 71.2 ± 2.9, p < 0.001), pain (48.8 ± 1.9 vs. 67.7 ± 2.9, p < 0.001), and general health (31.2 ± 1.5 vs. 60.5 ± 2.6, p < 0.001) domains. Scores did not differ significantly in the role limitations due to emotional health (p = 0.052) and emotional well-being (p = 0.271) domains. Physical and general health composite scores were lower in the POTS population, while mental health composite scores were not different. CONCLUSION: Differences in HRQoL exist between these patient populations. POTS patients report lower scores in physical and general health domains than VVS patients, but emotional health domains do not differ significantly. Targeting physical functioning in these patients may help improve quality of life.

Long-COVID postural tachycardia syndrome: an American Autonomic Society statement.

COVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization. While the acute impacts of COVID-19 were the initial focus of concern, it is becoming clear that in the wake of COVID-19, many patients are developing chronic symptoms that have been called Long-COVID. Some of the symptoms and signs include those of postural tachycardia syndrome (POTS). Understanding and managing long-COVID POTS will require a significant infusion of health care resources and a significant additional research investment. In this document from the American Autonomic Society, we outline the scope of the problem, and the resources and research needed to properly address the impact of Long-COVID POTS.

The Arcuate Nucleus of the Hypothalamus and Metabolic Regulation: An Emerging Role for Renin-Angiotensin Pathways.

Obesity is a chronic state of energy imbalance that represents a major public health problem and greatly increases the risk for developing hypertension, hyperglycemia, and a multitude of related pathologies that encompass the metabolic syndrome. The underlying mechanisms and optimal treatment strategies for obesity, however, are still not fully understood. The control of energy balance involves the actions of circulating hormones on a widely distributed network of brain regions involved in the regulation of food intake and energy expenditure, including the arcuate nucleus of the hypothalamus. While obesity is known to disrupt neurocircuits controlling energy balance, including those in the hypothalamic arcuate nucleus, the pharmacological targeting of these central mechanisms often produces adverse cardiovascular and other off-target effects. This highlights the critical need to identify new anti-obesity drugs that can activate central neurocircuits to induce weight loss without negatively impacting blood pressure control. The renin-angiotensin system may provide this ideal target, as recent studies show this hormonal system can engage neurocircuits originating in the arcuate nucleus to improve energy balance without elevating blood pressure in animal models. This review will summarize the current knowledge of renin-angiotensin system actions within the arcuate nucleus for control of energy balance, with a focus on emerging roles for angiotensin II, prorenin, and angiotensin-(1-7) pathways.

Sex differences in cardiovascular actions of the renin-angiotensin system.

Cardiovascular disease (CVD) remains a worldwide public health concern despite decades of research and the availability of numerous targeted therapies. While the intrinsic physiological mechanisms regulating cardiovascular function are similar between males and females, marked sex differences have been established in terms of CVD onset, pathophysiology, manifestation, susceptibility, prevalence, treatment responses and outcomes in animal models and clinical populations. Premenopausal females are generally protected from CVD in comparison to men of similar age, with females tending to develop cardiovascular complications later in life following menopause. Emerging evidence suggests this cardioprotection in females is, in part, attributed to sex differences in hormonal regulators, such as the renin-angiotensin system (RAS). To date, research has largely focused on canonical RAS pathways and shown that premenopausal females are protected from cardiovascular derangements produced by activation of angiotensin II pathways. More recently, a vasodilatory arm of the RAS has emerged that is characterized by angiotensin-(1-7) [(Ang-(1-7)], angiotensin-converting enzyme 2 and Mas receptors. Emerging studies provide evidence for a shift towards these cardioprotective Ang-(1-7) pathways in females, with effects modulated by interactions with estrogen. Despite well-established sex differences, female comparison studies on cardiovascular outcomes are lacking at both the preclinical and clinical levels. Furthermore, there are no specific guidelines in place for the treatment of cardiovascular disease in men versus women, including therapies targeting the RAS. This review summarizes current knowledge on sex differences in the cardiovascular actions of the RAS, focusing on interactions with gonadal hormones, emerging data for protective Ang-(1-7) pathways and potential clinical implications for established and novel therapies.

Angiotensin-(1-7) Improves Integrated Cardiometabolic Function in Aged Mice.

Angiotensin (Ang)-(1-7) is a beneficial renin-angiotensin system (RAS) hormone that elicits protective cardiometabolic effects in young animal models of hypertension, obesity, and metabolic syndrome. The impact of Ang-(1-7) on cardiovascular and metabolic outcomes during aging, however, remains unexplored. This study tested the hypothesis that Ang-(1-7) attenuates age-related elevations in blood pressure and insulin resistance in mice. Young adult (two-month-old) and aged (16-month-old) male C57BL/6J mice received Ang-(1-7) (400 ng/kg/min) or saline for six-weeks via a subcutaneous osmotic mini-pump. Arterial blood pressure and metabolic function indices (body composition, insulin sensitivity, and glucose tolerance) were measured at the end of treatment. Adipose and cardiac tissue masses and cardiac RAS, sympathetic and inflammatory marker gene expression were also measured. We found that chronic Ang-(1-7) treatment decreased systolic and mean blood pressure, with a similar trend for diastolic blood pressure. Ang-(1-7) also improved insulin sensitivity in aged mice to levels in young mice, without effects on glucose tolerance or body composition. The blood pressure-lowering effects of Ang-(1-7) in aged mice were associated with reduced sympathetic outflow to the heart. These findings suggest Ang-(1-7) may provide a novel pharmacological target to improve age-related cardiometabolic risk.

Perinatal high-fat diet alters development of GABAA receptor subunits in dorsal motor nucleus of vagus.

Perinatal high-fat diet (pHFD) exposure increases the inhibition of dorsal motor nucleus of the vagus (DMV) neurons, potentially contributing to the dysregulation of gastric functions. The aim of this study was to test the hypothesis that pHFD increases the inhibition of DMV neurons by disrupting GABAA receptor subunit development. In vivo gastric recordings were made from adult anesthetized Sprague-Dawley rats fed a control or pHFD (14 or 60% kcal from fat, respectively) from embryonic day 13 (E13) to postnatal day 42 (P42), and response to brainstem microinjection of benzodiazepines was assessed. Whole cell patch clamp recordings from DMV neurons assessed the functional expression of GABAA α subunits, whereas mRNA and protein expression were measured via qPCR and Western blotting, respectively. pHFD decreased basal antrum and corpus motility, whereas brainstem microinjection of L838,417 (positive allosteric modulator of α2/3 subunit-containing GABAA receptors) produced a larger decrease in gastric tone and motility. GABAergic miniature inhibitory postsynaptic currents in pHFD DMV neurons were responsive to L838,417 throughout development, unlike control DMV neurons, which were responsive only at early postnatal timepoints. Brainstem mRNA and protein expression of the GABAA α1,2, and 3 subunits, however, did not differ between control and pHFD rats. This study suggests that pHFD exposure arrests the development of synaptic GABAA α2/3 receptor subunits on DMV neurons and that functional synaptic expression is maintained into adulthood, although cellular localization may differ. The tonic activation of slower GABAA α2/3 subunit-containing receptors implies that such developmental changes may contribute to the observed decreased gastric motility. NEW & NOTEWORTHY Vagal neurocircuits involved in the control of gastric functions, satiation, and food intake are subject to significant developmental regulation postnatally, with immature GABAA receptors expressing slower α2/3-subunits, whereas mature GABAA receptor express faster α1-subunits. After perinatal high-fat diet exposure, this developmental regulation of dorsal motor nucleus of the vagus (DMV) neurons is disrupted, increasing their tonic GABAergic inhibition, decreasing efferent output, and potentially decreasing gastric motility.

The renin-angiotensin system in cardiovascular autonomic control: recent developments and clinical implications.

Complex and bidirectional interactions between the renin-angiotensin system (RAS) and autonomic nervous system have been well established for cardiovascular regulation under both physiological and pathophysiological conditions. Most research to date has focused on deleterious effects of components of the vasoconstrictor arm of the RAS on cardiovascular autonomic control, such as renin, angiotensin II, and aldosterone. The recent discovery of prorenin and the prorenin receptor have further increased our understanding of RAS interactions in autonomic brain regions. Therapies targeting these RAS components, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers, are commonly used for treatment of hypertension and cardiovascular diseases, with blood pressure-lowering effects attributed in part to sympathetic inhibition and parasympathetic facilitation. In addition, a vasodilatory arm of the RAS has emerged that includes angiotensin-(1-7), ACE2, and alamandine, and promotes beneficial effects on blood pressure in part by reducing sympathetic activity and improving arterial baroreceptor reflex function in animal models. The role of the vasodilatory arm of the RAS in cardiovascular autonomic regulation in clinical populations, however, has yet to be determined. This review will summarize recent developments in autonomic mechanisms involved in the effects of the RAS on cardiovascular regulation, with a focus on newly discovered pathways and therapeutic targets for this hormone system.

Angiotensin-(1-7) contributes to insulin-sensitizing effects of angiotensin-converting enzyme inhibition in obese mice.

Angiotensin-converting enzyme (ACE) inhibitors reduce body weight, lower blood pressure (BP), and improve insulin sensitivity in animal models of cardiometabolic syndrome. These effects are generally attributed to reduced angiotensin (ANG) II formation; however, these therapies also increase levels of ANG-(1-7), a beneficial hormone opposing ANG II actions. We hypothesized that this ANG-(1-7) generation contributes to the insulin-sensitizing effects of ACE inhibition in obese mice. Adult male C57BL/6J mice were placed on a 60% high-fat diet for 11 wk. During the last 3 wk of diet, mice received normal water or water containing the ACE inhibitor captopril (50 mg/l) as well as the ANG-(1-7) mas receptor antagonist A779 (400 or 800 ng·kg-1·min-1) or saline vehicle via subcutaneous osmotic minipumps. At the end of treatment, arterial BP was measured, and hyperinsulinemic-euglycemic clamps were performed in conscious obese mice receiving vehicle, captopril, captopril plus A779, or A779 ( n = 6-13/group). Captopril reduced body weight (28 ± 2 vs. 41 ± 2 g saline; P = 0.001), lowered systolic BP (109 ± 6 vs. 144 ± 7 mmHg saline; P = 0.041), and improved whole-body insulin sensitivity (steady-state glucose infusion rate: 31 ± 4 vs. 16 ± 2 mg·kg-1·min-1 saline; P = 0.001) in obese mice. A779 attenuated captopril-mediated improvements in insulin sensitivity (23 ± 2 mg·kg-1·min-1; P = 0.042), with no effect on body weight (32 ± 2 g; P = 0.441) or BP (111 ± 7 mmHg; P = 0.788). There was no effect of A779 alone on cardiometabolic outcomes. These data suggest that insulin-sensitizing effects of ACE inhibition are in part due to activation of ANG-(1-7)/ mas receptor pathways and provide new insight into mechanisms underlying the positive metabolic effects of these therapies.

The need for further surgical intervention following primary hysteroscopic morcellation of submucosal leiomyomas in women with abnormal uterine bleeding.

BACKGROUND: Intrauterine hysteroscopic morcellators have been studied as an alternative method for removing submucosal leiomyomas. AIMS: To assess the long-term efficacy of hysteroscopic morcellation of submucosal leiomyomas in women with abnormal uterine bleeding (AUB). MATERIALS AND METHODS: We conducted a prospective cohort study including all women with AUB who underwent a hysteroscopic resection with mechanical morcellation of a benign submucosal leiomyoma confirmed at histopathology. Need for further surgery, patient satisfaction, symptom resolution and post-operative complications were documented by direct patient contact after a minimum of six months of follow-up. RESULTS: A total of 73 women were included in the study with a mean length of follow-up of 32 ± 13 months. Mean total size of pathology at the time of index surgery was of 42 ± 20 mm. A total of 9/73 (12%) women required subsequent hysterectomy and 20/73 (27%) any subsequent related surgery (operative hysteroscopy, abdominal myomectomy or hysterectomy) with the estimated three-year cumulative incidence being 30 ± 6%. Satisfaction rate of participants was 84%. In multivariate Cox proportional analyses, only a total size of pathology of 50 mm or more was found to be significantly associated with the risk of requiring further surgical procedures (hazard ratio = 2.9, P = 0.02). CONCLUSIONS: Hysteroscopic morcellation of submucosal leiomyomas is an effective method to manage women with AUB, although women with larger pathology have an increased risk of requiring subsequent surgical procedures.

Pelvic examination may be meaningfully taught to novices and be used to predict operating times for laparoscopic excision of endometriosis in one surgical procedure.

OBJECTIVE: To investigate whether pelvic examination may be meaningfully taught to novice medical students and its accuracy in predicting operating times for laparoscopic excision of endometriosis at a single surgical procedure. METHODS: Women with suspected endometriosis scheduled for laparoscopy underwent pelvic examination to estimate operative time by medical students (novices), trainees, senior clinicians with <10 years surgical experience (experts) and ≥10 years (masters). Examination and intraoperative findings were compared and stage of disease recorded. RESULTS: There were 138 estimations of operating time at the initial assessment and 251 estimations of operating time prior to surgery. The median surgical duration was 44 min (range 12-398) and increased progressively with revised American Society for Reproductive Medicine disease stage. Clinical predictions exceeded actual operating times by a median of 18 min (range overestimating by 180 min and underestimating by 120 min) with 80% of procedures completed in less time than predicted and none requiring a second procedure. There was no statistical difference in operative time estimations between the groups with students and trainees underestimating surgical duration by a median of two and five minutes, respectively, experts having a median time difference of zero minutes, and masters overestimating by 4.5 min. CONCLUSION: Targeted pelvic examining may be taught to novices (medical students) and can be used to predict operating time at one surgical procedure. Less experienced examiners have a tendency to underestimate surgical duration, with masters overestimating surgical time when scheduling laparoscopies for endometriosis, and increasing disease stage is associated with a less precise estimation of surgical duration.

Monogenic diabetes syndromes: Locus-specific databases for Alström, Wolfram, and Thiamine-responsive megaloblastic anemia.

We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease-associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alström, and Thiamine-responsive megaloblastic anemia syndromes, respectively; and included 23 previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1. We then investigated genotype-phenotype relations for the WFS1 gene. The presence of biallelic loss-of-function variants predicted Wolfram syndrome defined by insulin-dependent diabetes and optic atrophy, with a sensitivity of 79% (95% CI 75%-83%) and specificity of 92% (83%-97%). The presence of minor loss-of-function variants in WFS1 predicted isolated diabetes, isolated deafness, or isolated congenital cataracts without development of the full syndrome (sensitivity 100% [93%-100%]; specificity 78% [73%-82%]). The ability to provide a prognostic prediction based on genotype will lead to improvements in patient care and counseling. The development of the database as a repository for monogenic diabetes gene variants will allow prognostic predictions for other diabetes syndromes as next-generation sequencing expands the repertoire of genotypes and phenotypes. The database is publicly available online at https://lovd.euro-wabb.org.

Toward interprofessional learning and education: Mapping common outcomes for prequalifying healthcare professional programs in the United Kingdom.

INTRODUCTION: Interprofessional education (IPE) continues to be a key component in prequalifying health professional education, with calls for regulators to publish a joint statement regarding IPE outcomes. To date, the regulatory documents for healthcare education in the United Kingdom have not been examined for common learning outcomes; information that could be used to inform such a statement and to identify opportunities for interprofessional learning. METHODS: A mapping of the outcomes/standards required by five, UK, health profession regulatory bodies was undertaken. This involved the identification of common outcomes, a keyword search and classification of common outcomes/standards; presented as themes and subthemes. RESULTS: Seven themes were identified: knowledge for practice, skills for practice, ethical approach, professionalism, continuing professional development (CPD), patient-centered approach and teamworking skills, representing 22 subthemes. Each subtheme links back to the outcomes/standards in the regulatory documents. CONCLUSIONS: This study identifies the key areas of overlap in outcomes/standards expected of selected healthcare graduates in the United Kingdom. The mapping provides a framework for informing prequalifying IPE curricula, for example, identifying possible foci for interprofessional education outcomes and associated learning opportunities. It allows reference back to the standards set by regulatory bodies, a requirement for all institutions involved in health profession education.

The ergonomics of laparoscopic surgery: a quantitative study of the time and motion of laparoscopic surgeons in live surgical environments.

BACKGROUND: Laparoscopic surgery presents multiple ergonomic difficulties for the surgeon, requiring awkward body postures and prolonged static muscle loading that increases risk of musculoskeletal strain and injury. This prospective study quantitatively measures the biomechanical movements of surgeons during laparoscopic procedures to determine at-risk movements from prolonged static muscle loading and repetitive motions that may lead to injury. METHODS: A total of 150 video recordings of 18 surgeons, standing at the patient's left, were captured from three fixed camera positions during live gynecological laparoscopic surgery. Postoperative processing quantified surgeon movements at the neck, shoulders and elbows using computer software to measure extreme joint angles and time spent within defined joint angle ranges. RESULTS: Surgeons spent a median of 98 % (range 77-100 %) of surgical time with their neck rotated at 21° (range 0°-52°). The non-dominant arm was subjected to more extreme positions for significantly longer periods of time compared to the dominant, with shoulder flexion at 45°-90° for 35 vs. 0 % (p < 0.001) and elbow flexion at >120° for 31 vs. 0 % (p < 0.001) of total surgical time. Procedures involving power morcellation required significantly greater number of instrument insertion/removals-119 (range 56-182) compared with 12 (range 2-122) when morcellation was not used (p < 0.001). Shorter surgeons maintained significantly greater degrees of neck rotation when viewing the monitor (p < 0.003) and surgeons with shorter arm lengths spent longer in extreme positions with their non-dominant shoulder at >90° (p = 0.04) and elbow at >120° (p < 0.001) compared with taller surgeons. No significant correlations were found between BMI or surgical experience and more extreme joint positions. CONCLUSIONS: Four primary areas have been identified where surgeons are consistently demonstrating movements that increase their risk of harm: (1) extended periods of neck rotation; (2) asymmetrical loading between the dominant and non-dominant shoulders; (3) power morcellation and frequent insertions/removals of laparoscopic instruments resulting in repetitions of the most extreme shoulder positions and (4) a negative correlation between height and percentage time spent in more extreme positions.

A Prospective Analysis of Hysteroscopic Morcellation in the Management of Intrauterine Pathologies.

OBJECTIVE: To determine the effectiveness of the MyoSure intrauterine mechanical morcellator device for removal of intrauterine pathology. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). INTERVENTION: This study was performed at the Royal Hospital for Women and Prince of Wales Private Hospital, Sydney, Australia. All women undergoing hysteroscopic removal of intrauterine pathology using the MyoSure device between January 2013 and June 2015 were included. RESULTS: A total of 255 MyoSure procedures were performed, with 61% performed by trainees. Resection of leiomyomas occurred in 40% or cases, polyps in 39%, combination pathology in 9%, pregnancy products in 6%, and preinvasive or invasive disease in 5% of cases. Complete resection of pathology was achieved in 92% of polyps, 66% of leiomyomas, and 87% of pregnancy tissue. Leiomyomas were more likely to be completely resected when surgery was performed by an attending physician or senior resident, however there was no statistically significant difference in clinical outcomes. When leiomyomas were stratified according to size, 87% of leiomyomas ≤40 mm were completely resected with only 48% of leiomyomas >40 mm completely resected with the index surgery. No intraoperative complications occurred. Postoperative outcomes included symptom resolution in 76%, further surgery (repeat hysteroscopy or hysterectomy) in 10%, pregnancy in 2%, and medical/conservative management in 12% of patients. CONCLUSION: The MyoSure device is very effective when used to resect endometrial polyps. Leiomyomas >40 mm are unlikely to be completely resected at a single operation when using the MyoSure device. Similar clinical outcomes were obtained when procedures were performed by trainees compared to senior clinicians.

Sympathetic activation is associated with increased IL-6, but not CRP in the absence of obesity: lessons from postural tachycardia syndrome and obesity.

Sympathetic activation is thought to contribute to the inflammatory process associated with obesity, which is characterized by elevated circulating C-reactive protein (hsCRP) and interleukin-6 (IL-6). To evaluate whether sympathetic activation is associated with inflammation in the absence of obesity, we studied patients with postural tachycardia syndrome (POTS), a condition characterized by increased sympathetic tone in otherwise healthy individuals. Compared with 23 lean controls, 43 lean female POTS had greater vascular sympathetic modulation (low-frequency blood pressure variability, LFSBP, 3.2 ± 0.4 vs. 5.5 ± 0.6 mmHg(2), respectively, P = 0.006), lower cardiac parasympathetic modulation (high-frequency heart rate variability, 1,414 ± 398 vs. 369 ± 66 ms(2), P = 0.001), and increased serum IL-6 (2.33 ± 0.49 vs. 4.15 ± 0.54 pg/ml, P = 0.011), but this was not associated with increases in hsCRP, which was low in both groups (0.69 ± 0.15 vs. 0.82 ± 0.16 mg/l, P = 0.736). To explore the contribution of adiposity to inflammation, we then compared 13 obese female POTS patients and 17 obese female controls to matched lean counterparts (13 POTS and 11 controls). Compared with lean controls, obese controls had increased LFSBP (3.3 ± 0.5 vs. 7.0 ± 1.1 mmHg(2); P = 0.016), IL-6 (2.15 ± 0.58 vs. 3.92 ± 0.43 pg/ml; P = 0.030) and hsCRP (0.69 ± 0.20 vs. 3.47 ± 0.72 mg/l; P = 0.001). Obese and lean POTS had similarly high IL-6 but only obese POTS had increased hsCRP (5.76 ± 1.99 mg/l vs. 0.65 ± 0.26; P < 0.001). In conclusion, sympathetic activation in POTS is associated with increased IL-6 even in the absence of obesity. The coupling between IL-6 and CRP, however, requires increased adiposity, likely through release of IL-6 by visceral fat.