‘Free’ inhibin α subunit is expressed by bovine ovarian theca cells and its knockdown suppresses androgen production

Inhibins are ovarian dimeric glycoprotein hormones that suppress pituitary FSH production. They are synthesised by follicular granulosa cells as α plus βA/βB subunits (encoded by INHA, INHBA, INHBB, respectively). Inhibin concentrations are high in follicular fluid (FF) which is also abundant in ‘free’ α subunit, presumed to be of granulosal origin, but its role(s) remains obscure. Here, we report the unexpected finding that bovine theca cells show abundant INHA expression and ‘free’ inhibin α production. Thus, theca cells may contribute significantly to the inhibin α content of FF and peripheral blood. In vitro, knockdown of thecal INHA inhibited INSL3 and CYP17A1 expression and androgen production while INSL3 knockdown reduced INHA and inhibin α secretion. These findings suggest a positive role of thecal inhibin α on androgen production. However, exogenous inhibin α did not raise androgen production. We hypothesised that inhibin α may modulate the opposing effects of BMP and inhibin on androgen production. However, this was not supported experimentally. Furthermore, neither circulating nor intrafollicular androgen concentrations differed between control and inhibin α-immunized heifers, casting further doubt on thecal inhibin α subunit having a significant role in modulating androgen production. Role(s), if any, played by thecal inhibin α remain elusive

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Changes in treatment plan for carpal tunnel syndrome based on electrodiagnostic test results

This study evaluated how often the treatment plan for carpal tunnel syndrome (CTS) changed based on electrodiagnostic test results. Secondly, we assessed factors associated with a change in the treatment plan for CTS. One-hundred-and-thirty English-speaking adult patients underwent electrodiagnostic testing in a prospective cohort study. Treatment plan was recorded before and after testing. Treatment plan changed in 25 patients (19%) based on electrodiagnostic test results. The plan for operative treatment before testing decreased significantly after testing (83% versus 72%). The best logistic regression model for no change in treatment plan included a prolonged or non-recordable median distal sensory latency (normal, prolonged, or non-recordable), and explained 24% of the variation. For surgeons that manage CTS on the basis of objective pathophysiology rather than symptoms, electrodiagnostic test results often lead to changes in recommended treatmen

Is there variation in procedural utilization for lumbar spine disorders between a fee-for-service and salaried healthcare system?

Background: Whether compensation for professional services drives the use of those services is an important question that has not been answered in a robust manner. Specifically, there is a growing concern that spine care practitioners may preferentially choose more costly or invasive procedures in a fee-for-service system, irrespective of the underlying lumbar disorder being treated. Questions/purposes: (1) Were proportions of interbody fusions higher in the fee-for-service setting as opposed to the salaried Department of Defense setting? (2) Were the odds of interbody fusion increased in a fee-for-service setting after controlling for indications for surgery? Methods: Patients surgically treated for lumbar disc herniation, spinal stenosis, and spondylolisthesis (2006-2014) were identified. Patients were divided into two groups based on whether the surgery was performed in the fee-for-service setting (beneficiaries receive care at a civilian facility with expenses covered by TRICARE insurance) or at a Department of Defense facility (direct care). There were 28,344 patients in the entire study, 21,290 treated in fee-for-service and 7054 treated in Department of Defense facilities. Differences in the rates of fusion-based procedures, discectomy, and decompression between both healthcare settings were assessed using multinomial logistic regression to adjust for differences in case-mix and surgical indication. Results: TRICARE beneficiaries treated for lumbar spinal disorders in the fee-for-service setting had higher odds of receiving interbody fusions (fee-for-service: 7267 of 21,290 [34%], direct care: 1539 of 7054 [22%], odds ratio [OR]: 1.25 [95% confidence interval 1.20-1.30], p \u3c 0.001). Purchased care patients were more likely to receive interbody fusions for a diagnosis of disc herniation (adjusted OR 2.61 [2.36-2.89], p \u3c 0.001) and for spinal stenosis (adjusted OR 1.39 [1.15-1.69], p \u3c 0.001); however, there was no difference for patients with spondylolisthesis (adjusted OR 0.99 [0.84-1.16], p = 0.86). Conclusions: The preferential use of interbody fusion procedures was higher in the fee-for-service setting irrespective of the underlying diagnosis. These results speak to the existence of provider inducement within the field of spine surgery. This reality portends poor performance for surgical practices and hospitals in Accountable Care Organizations and bundled payment programs in which provider inducement is allowed to persis

Is there variation in procedural utilization for lumbar spine disorders between a fee-for-service and salaried healthcare system?

Background: Whether compensation for professional services drives the use of those services is an important question that has not been answered in a robust manner. Specifically, there is a growing concern that spine care practitioners may preferentially choose more costly or invasive procedures in a fee-for-service system, irrespective of the underlying lumbar disorder being treated.Questions/purposes: (1) Were proportions of interbody fusions higher in the fee-for-service setting as opposed to the salaried Department of Defense setting? (2) Were the odds of interbody fusion increased in a fee-for-service setting after controlling for indications for surgery?Methods: Patients surgically treated for lumbar disc herniation, spinal stenosis, and spondylolisthesis (2006-2014) were identified. Patients were divided into two groups based on whether the surgery was performed in the fee-for-service setting (beneficiaries receive care at a civilian facility with expenses covered by TRICARE insurance) or at a Department of Defense facility (direct care). There were 28,344 patients in the entire study, 21,290 treated in fee-for-service and 7054 treated in Department of Defense facilities. Differences in the rates of fusion-based procedures, discectomy, and decompression between both healthcare settings were assessed using multinomial logistic regression to adjust for differences in case-mix and surgical indication.Results: TRICARE beneficiaries treated for lumbar spinal disorders in the fee-for-service setting had higher odds of receiving interbody fusions (fee-for-service: 7267 of 21,290 [34%], direct care: 1539 of 7054 [22%], odds ratio [OR]: 1.25 [95% confidence interval 1.20-1.30], p \u3c 0.001). Purchased care patients were more likely to receive interbody fusions for a diagnosis of disc herniation (adjusted OR 2.61 [2.36-2.89], p \u3c 0.001) and for spinal stenosis (adjusted OR 1.39 [1.15-1.69], p \u3c 0.001); however, there was no difference for patients with spondylolisthesis (adjusted OR 0.99 [0.84-1.16], p = 0.86).Conclusions: The preferential use of interbody fusion procedures was higher in the fee-for-service setting irrespective of the underlying diagnosis. These results speak to the existence of provider inducement within the field of spine surgery. This reality portends poor performance for surgical practices and hospitals in Accountable Care Organizations and bundled payment programs in which provider inducement is allowed to persist.Level of evidence: Level III, economic and decision analysis

Evaluation of the scratch collapse test for the diagnosis of carpal tunnel syndrome

This prospective study measured and compared the diagnostic performance characteristics of various clinical signs and physical examination manoeuvres for carpal tunnel syndrome (CTS), including the scratch collapse test. Eighty-eight adult patients that were prescribed electrophysiological testing to diagnose CTS were enrolled in the study. Attending surgeons documented symptoms and results of standard clinical manoeuvres. The scratch collapse test had a sensitivity of 31%, which was significantly lower than the sensitivity of Phalen's test (67%), Durkan's test (77%), Tinel's test (43%), CTS-6 lax (88%), and CTS-6 stringent (54%). The scratch test had a specificity of 61%, which was significantly lower than the specificity of thenar atrophy (96%) and significantly higher than the specificity of Durkan's test (18%) and CTS-6 lax (13%). The sensitivity of the scratch collapse test was not superior to other clinical signs and physical examination manoeuvers for CTS, and the specificity of the scratch collapse test was superior to that of Durkan's test and CTS-6 lax. Further studies should seek to limit the influence of a patient's clinical presentation on scratch test performance and assess the scratch test's inter-rater reliabilit

Elevated expression of activins promotes muscle wasting and cachexia

Fulltext embargoed for: 12 months post date of publicationIn models of cancer cachexia, inhibiting type IIB activin receptors (ActRIIBs) reverse muscle wasting and prolongs survival, even with continued tumor growth. ActRIIB mediates signaling of numerous TGF-β proteins; of these, we demonstrate that activins are the most potent negative regulators of muscle mass. To determine whether activin signaling in the absence of tumor-derived factors induces cachexia, we used recombinant serotype 6 adeno-associated virus (rAAV6) vectors to increase circulating activin A levels in C57BL/6 mice. While mice injected with control vector gained ~10% of their starting body mass (3.8±0.4 g) over 10 wk, mice injected with increasing doses of rAAV6:activin A exhibited weight loss in a dose-dependent manner, to a maximum of -12.4% (-4.2±1.1 g). These reductions in body mass in rAAV6:activin-injected mice correlated inversely with elevated serum activin A levels (7- to 24-fold). Mechanistically, we show that activin A reduces muscle mass and function by stimulating the ActRIIB pathway, leading to deleterious consequences, including increased transcription of atrophy-related ubiquitin ligases, decreased Akt/mTOR-mediated protein synthesis, and a profibrotic response. Critically, we demonstrate that the muscle wasting and fibrosis that ensues in response to excessive activin levels is fully reversible. These findings highlight the therapeutic potential of targeting activins in cachexia