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Background: Meniscus root tears comprise 10% to 21% of all meniscal tears. These tears alter knee biomechanics, elevating contact pressure, akin to a meniscectomy. Consequently, they are linked to advanced joint degeneration and cartilage damage in the affected compartment., Purpose: To systematically evaluate and relate the current literature describing the diagnosis and treatment strategies for meniscus root tears., Study Design: Scoping review; Level of evidence, 4., Methods: This review was conducted following the guidelines of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) extension for scoping reviews. Inclusion criteria encompassed English-language clinical and preclinical research, technical notes, and narrative reviews on meniscus root tears. Exclusion criteria were studies on patellar tendon rupture, studies on medial patellofemoral ligament rupture with additional knee joint ligament injuries, studies of patients <16 years old, and studies involving open fractures. The data were summarized using a descriptive analysis and a thematic analysis., Results: After 1425 articles were identified, 461 studies were included; 17% (n = 78) were case reports or case series, 15% (n = 71) were technical notes, 9% (n = 41) addressed aspects of diagnosis, 7% (n = 32 ) were narrative reviews, and 5% (n = 21) were systematic reviews or meta-analyses. Studies presenting original data comprised 57% (n = 262) of all included studies, and 97% of the studies were of evidence levels 3 to 5. Contributions were mainly from the United States (n = 123; 27%), Republic of Korea (n = 102; 22%), and Japan (n = 99; 21%). Many studies (n = 216; 47%) focused on the treatment and outcomes of meniscus root tears. A significant chronological surge in the quantity of studies addressing the diagnosis and treatment of meniscus root tears was evident, particularly over the past 3 years. Consensus was found regarding the definition of meniscus root tears, the advantages of early repair, and postoperative rehabilitation protocols. The variations in surgical techniques and operative strategies created the greatest amount of contention, along with clinical assessment and imaging modalities., Conclusion: High-level evidence studies for diagnosing and managing meniscus root tears were scarce. A consensus has yet to be reached regarding the role of concomitant osteotomy, comparison of repair techniques, the use of a centralization stitch, patient factors affecting outcomes, and long-term outcomes of nonoperative management., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: A.G.G. has received education payments from Arthrex and nonconsulting fees from Ossur and Smith+Nephew. I.M. has received consulting fees from Arthrex and Stryker. N.N.V. has received research support from Breg and Ossur, consulting fees from Arthrex and Stryker, royalties from Graymont Professional Products and Smith+Nephew, and hospitality payments from Spinal Simplicity. R.F.L. has received research support from Linvatec and Ossur, education payments from Foundation Medical, consulting fees from Ossur, nonconsulting fees from ConMed and Smith+Nephew, and royalties from Arthrex and Ossur. J.C. has received grant support from Arthrex; education payments from Medwest Associates and Smith+Nephew; consulting fees from DePuy Synthes, RTI Surgical, Ossur, and Vericel; nonconsulting fees from Arthrex and CONMED; and hospitality payments from Stryker. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Background: While increased posterior tibial slope (PTS) is an established risk factor for anterior cruciate ligament tears, the association between tibial slope and meniscal posterior root tears is not well-defined., Purpose: To summarize the available literature evaluating the association between PTS and meniscus root injuries compared with patients without root tears., Study Design: Systematic review; Level of evidence, 4., Methods: A literature search was performed using the Scopus, PubMed, and Embase databases. Human clinical studies evaluating the associations between the medial tibial slope (MTS), lateral tibial slope (LTS), lateral-to-medial (L-to-M) slope asymmetry, and the risk of meniscus root tears were included. Patients with medial meniscus posterior root tears (MMPRTs) and lateral meniscus posterior root tears (LMPRTs) were compared with a control group without root injury. Study quality was assessed using the methodological index for non-randomized studies criteria., Results: Ten studies with 1313 patients were included (884 patients with root tears; 429 controls). The LMPRT subgroup (n = 284) had a significantly greater LTS (mean ± SD, 7.3°± 1.5° vs 5.7°± 3.91°; P < .001), MTS (5.26°± 1.2° vs 4.8°± 1.25°; P < .001), and increased L-to-M asymmetry (2.3°± 1.3° vs 0.65°± 0.5°; P < .001) compared with controls. The MMPRT group (n = 600) had significantly increased MTS relative to controls (8.1°± 2.5° vs 4.3°± 0.7°; P < .001). Furthermore, there was a higher incidence of noncontact injuries (79.3%) and concomitant ramp lesions (56%) reported in patients with LMPRT., Conclusion: Increased MTS, LTS, and L-to-M slope asymmetry are associated with an increased risk of LMPRTs, while increased MTS is associated with MMPRTs. Surgeons should consider how proximal tibial anatomy increases the risk of meniscus root injury., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: S.A. has received support for education from Smith & Nephew. J.C. has received education payments from Arthrex and Smith & Nephew; consulting fees from Arthrex, DePuy, Linvatec, Vericel, and Smith & Nephew; speaking fees from Linvatec; and hospitality payments from Medical Device Business Services, Medwest Associates, and Stryker. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Purpose: To compare the clinical outcomes, failure rates, surgical complications, and postoperative radiographic changes following partial meniscectomy versus meniscal repair for horizontal cleavage tears (HCTs)., Methods: A literature search was performed according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the Scopus, PubMed, and Embase computerized databases. Clinical studies evaluating partial meniscectomy or meniscal repair for HCTs were included. Demographic characteristics, surgical techniques, clinical outcomes, failure rates, complications, and radiographic assessments were recorded., Results: A total of 18 studies comprising of 833 patients with HCT were included, of which 562 patients (67.5%) were treated with partial meniscectomy and 271 (32.5%) with meniscal repair. Both types of treatments reported improved clinical outcomes, including IKDC, Lysholm, KOOS, and Tegner scores. Failure rates were reported to range between 0 to 15% following partial meniscectomy, and between 0 to 17.6% following repair; and complications were 7.5% after partial meniscectomy, and between 3.8 to 21.4% following meniscal repair. Patients undergoing meniscectomy demonstrated progression of degenerative changes on radiographic assessments., Conclusion: Repair of HCTs in the appropriately indicated patient can result in similar patient outcomes and failure rates compared to partial meniscectomy. However, especially in patients aged 42 years and younger, a greater complication rate can be expected with repair, while a greater degree of ipsilateral compartment degeneration is seen after partial meniscectomy., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To systematically investigate the influence of preoperative depression diagnosis and symptom severity on outcomes after anterior cruciate ligament reconstruction (ACLR)., Methods: A literature search was performed using the PubMed, Scopus, and Embase databases according to the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. Studies evaluating the impact of depression on clinical outcomes after ACLR were included. Clinical outcomes, changes in depression, and complications were aggregated., Results: Nine studies comprising 308,531 patients (mean age, 28.1 years; age range, 14-50 years) were included. The depression incidence ranged from 3.8% to 42%. Seven studies showed postoperative improvement in depression scores, with 5 reporting statistical significance. Assessment of depression exhibited substantial variability, with Patient-Reported Outcomes Measurement Information System (PROMIS) scores being the most common method. Patients with depression, despite showing greater improvements in scores, experienced significantly higher PROMIS Pain Interference scores preoperatively (range, 59.1-65.7 vs 56.8-59.2) and postoperatively (range, 46.3-52.3 vs 46.3-47.4) than patients without depression. They also showed significantly lower preoperative (range, 33-38.1 vs 39.7-41.5) and postoperative (range, 51.6-56.7 vs 56.7-57.6) PROMIS Physical Function scores, regardless of greater score improvement. Patients affected by depression had significantly higher rates of minimal clinically important difference achievement for the PROMIS Physical Function score (71%-100% vs 80%) and similar rates for the PROMIS Pain Interference score (71%-81% vs 68%) compared with patients without depression in 3 studies. Depression was associated with reduced adherence to rehabilitation protocols and increased postoperative complications, including infection, graft failure, arthrofibrosis, and readmission., Conclusions: ACLR yields favorable outcomes for patients with and without preoperative depression. Individuals with preoperative depression may report inferior outcomes in terms of pain and functionality; nevertheless, despite these challenges, they exhibit significant improvements across all outcome measures after surgery, including reductions in depression levels., Level of Evidence: Level IV, systematic review of Level II to IV studies., Competing Interests: Disclosures The authors report the following potential conflicts of interest or sources of funding: J.C. reports other from Arthrex, Inc, other from CONMED Linvatec, other from Smith & Nephew, outside the submitted work. All authors (J.R.G, S.A.B., J.S, S.G.A., A.A.W., F.A., N.N.V.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: This study examines failure rates, complication rates and patient-reported outcome measures (PROMs) for meniscal all-inside (AI) and inside-out (IO) repair techniques., Methods: A systematic search was conducted on PubMed, Embase and Cochrane (inception to January 2024) assessing for Level I-III studies evaluating outcomes after meniscal repair. The primary outcome regarded differences in failure rates between AI and IO repair techniques. Secondary outcomes included a comparison of complication rates and PROMs. Quality assessment was performed using the Grading of Recommendations Assessment, Development and Evaluation and Methodological Index for Non-Randomized Studies criteria. A meta-analysis was conducted for outcomes reported by more than three comparative studies., Results: A total of 24 studies (13 studies and 912 menisci for AI vs. 17 studies and 1,117 menisci for IO) were included. The mean follow-up ranges were 22-192 months (AI) and 18.5-155 months (IO). The overall reported AI failure rate ranged from 5% to 35% compared to 0% to 25% within the IO group. When comparing meniscal repair failure rates in the setting of concomitant anterior cruciate ligament reconstruction, the AI group had a failure rate (AI: 5%-34%; IO: 0%-12.9%). The complication rate ranged from 0% to 40% for AI and 0% to 20.5% for IO. Post-operative PROM scores ranged from 81.2 to 93.8 (AI) versus 89.6 to 94 (IO) for IKDC and 4.0-7.02 (AI) versus 4.0-8.0 (IO) for Tegner. Upon pooling of six comparative studies, a significantly lower failure rate favouring the IO technique was observed (15.9% AI vs. 11.1% IO; p = 0.02), although this result was influenced by a study with a predominantly elite athlete population. Moreover, no significant differences were found regarding complication rates between cohorts (7.3% AI vs. 4.8% IO; p = 0.86)., Conclusion: The present study underscores comparable clinical success between AI and IO meniscal repair techniques, with both techniques demonstrating similar complication rates. However, the AI repair technique was associated with 1.77 times higher odds of failure compared to the IO cohort., Level of Evidence: Level III., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background: It has been postulated that chronic kidney disease (CKD) is a state of relative 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) insufficiency, resulting in increased cortisol-mediated mineralocorticoid receptor (MR) activation. We hypothesized that relative 11βHSD2 insufficiency manifests across a wide spectrum of progressively declining kidney function, including within the normal range., Methods: Adult participants were recruited at two academic centers. A discovery cohort (n=500) enrolled individuals with estimated glomerular filtration rate (eGFR) ranging from normal to CKD stage 5, in whom serum cortisol-to-cortisone (F/E) was measured as a biomarker of 11βHSD2 activity. A validation cohort (n=101) enrolled only individuals with normal kidney function (eGFR ≥ 60 mL/min/1.73 m2) in whom 11βHSD2 activity was assessed via serum F/E and 11-hydroxy-to-11-keto androgen (11OH/K) ratios following multiple maneuvers: oral sodium suppression test (OSST), dexamethasone suppression test (DST), and ACTH-stimulation test (ACTHstim)., Results: In the discovery cohort, lower eGFR was associated with higher F/E (P-trend<0.001). Similarly, in the validation cohort, with normal eGFR, an inverse association between eGFR and both F/E and 11OH/K ratios was observed (P-trend<0.01), which persisted following DST (P-trend<0.001) and ACTHstim (P-trend< 0.05). The fractional excretion of potassium, a marker of renal MR activity, was higher with higher F/E (P-trend < 0.01) and with lower eGFR (P-trend<0.0001)., Conclusions: A continuum of declining 11βHSD2 activity was observed with progressively lower eGFR in individuals spanning a wide spectrum of kidney function, including those with apparently normal kidney function. These findings implicate cortisol-mediated MR activation in the pathophysiology of hypertension and cardiovascular disease in CKD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background: The emergence of artificial intelligence (AI) has allowed users to have access to large sources of information in a chat-like manner. Thereby, we sought to evaluate ChatGPT-4 response's accuracy to the 10 patient most frequently asked questions (FAQs) regarding anterior cruciate ligament (ACL) surgery., Methods: A list of the top 10 FAQs pertaining to ACL surgery was created after conducting a search through all Sports Medicine Fellowship Institutions listed on the Arthroscopy Association of North America (AANA) and American Orthopaedic Society of Sports Medicine (AOSSM) websites. A Likert scale was used to grade response accuracy by two sports medicine fellowship-trained surgeons. Cohen's kappa was used to assess inter-rater agreement. Reproducibility of the responses over time was also assessed., Results: Five of the 10 responses received a 'completely accurate' grade by two-fellowship trained surgeons with three additional replies receiving a 'completely accurate' status by at least one. Moreover, inter-rater reliability accuracy assessment revealed a moderate agreement between fellowship-trained attending physicians (weighted kappa = 0.57, 95% confidence interval 0.15-0.99). Additionally, 80% of the responses were reproducible over time., Conclusion: ChatGPT can be considered an accurate additional tool to answer general patient questions regarding ACL surgery. None the less, patient-surgeon interaction should not be deferred and must continue to be the driving force for information retrieval. Thus, the general recommendation is to address any questions in the presence of a qualified specialist., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘J.C. reports a relationship with American Orthopaedic Society for Sports Medicine that includes board membership, a relationship with Arthrex Inc that includes consulting or advisory, a relationship with Arthroscopy Association of North America that includes board membership, a relationship with CONMED Corp that includes consulting or advisory, a relationship with International Society of Arthroscopy Knee Surgery and Orthopaedic Sports Medicine that includes board membership, a relationship with Ossur Americas that includes consulting or advisory, a relationship with Smith and Nephew Inc that includes consulting or advisory and speaking and lecture fees. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.’., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To compare patient-reported outcomes (PROs), failure, and healing rates after all-inside (AI) repair versus inside-out (IO) repair for the treatment of meniscal radial tears., Methods: A literature search was performed according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using the Scopus, PubMed, and Embase computerized databases. Level of Evidence I through IV human clinical studies evaluating PROs and/or the incidence of failure and healing after AI versus IO repairs for meniscal radial tears were included. Clinical failure was defined by the presence of joint-line tenderness; a positive McMurray test; and mechanical symptoms, such as locking, catching, or giving way. Study quality was assessed using the Methodological Index for Non-Randomized Studies criteria and the Modified Coleman Methodology Score., Results: Ten studies published from 2008 to 2023 comprising 205 patients were identified, including 142 patients who underwent AI repair and 63 patients who underwent IO repair for radial meniscus tears. Postoperative Lysholm and Tegner scores ranged from 90.8 to 95.6 and 5.7 to 8.2, respectively, in the AI repair group, compared with 86.9 to 94.2 and 6 to 7.5, respectively, in the IO repair group. All patients exceeded published values for minimal clinically important difference for the Lysholm score. Clinical failure ranged from 0% to 40% in the AI group and 0% to 62.5% in the IO group. Healing assessments on second-look arthroscopy revealed failure rates ranging from 0% to 13.3% in the AI group and 0% to 39% in the IO group. Complete and partial healing ranged from 28.6% to 92.3% in the AI group and from 25% to 70% in the IO group. Chondral damage on second-look arthroscopy ranged from 0% to 95% in the IO group and 0% to 57.7% in the AI group. Postoperative complications ranged from 0% to 2% within the AI group, whereas no complications were reported in the IO group. No implant-related complications were reported in any study group., Conclusions: Both all-inside and inside-out repairs for meniscal radial tears demonstrated improved PROs; however, current literature suggests that the IO technique may have higher failure rates both clinically and on second-look arthroscopy., Level of Evidence: Level IV, systematic review of Level III and IV studies., Competing Interests: Disclosures The authors (L.D., G.R.J. F.A., E.S.M., S.A.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. J.C. reports personal fees from Smith & Nephew, personal fees from Arthrex, personal fees from CONMED Linvatec, personal fees from Ossur, other from American Orthopaedic Society for Sports Medicine, other from Arthroscopy Association of North America, other from International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine, outside the submitted work., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To describe the proposed classification systems for meniscal ramp lesions (RLs) in the literature and evaluate their accuracy and reliability., Methods: A systematic search was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analyses guidelines utilising PubMed, Embase and Cochrane Library databases. Level I-IV studies referencing RLs along with either an arthroscopic- or magnetic resonance imaging (MRI)-based classification system used to describe RL subtypes were included., Results: In total, 21 clinical studies were included. Twenty-seven (79%) of the included studies were published in 2020 or later. There were four main classification systems proposed within the literature (two arthroscopic-, two MRI-based), describing tear patterns, mediolateral extent, associated ligament disruption and stability of the lesion. The first classification was proposed in 2015 by Thaunat et al. and is referenced in 22 (64.7%) of the included studies. The application of the Thaunat et al. criteria to MRI showed variable sensitivity (31.70%-93.8%) and interobserver agreement (k = 0.55-0.80). The Greif et al. modification to the Thaunat et al. system was referenced in 32.4% of the included studies and had a substantial interobserver agreement (k = 0.8). Stability to probing and specific tear location were each used to classify RLs in 28.6% and 23.8% of the included clinical studies, respectively., Conclusion: Although there has been a recent increase in the recognition and treatment of meniscal RLs, there is limited consistency in descriptive classifications used for this pathology. Current RL classification systems based on preoperative MRI have variable reliability, and arthroscopic examination remains the gold standard for diagnosis and classification., Level of Evidence: Level IV., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Purpose: To systematically review the available literature on patients with discoid lateral meniscus (DLM) with the goal of elucidating the rates and types of meniscal tears, clinical symptoms, treatment strategies, and postoperative clinical and radiographic outcomes in adult patients compared with a pediatric population., Methods: A literature search was performed using the PubMed, Embase, and Scopus databases from database inception to October 2023 according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Level of evidence I through IV human clinical studies evaluating rate and type of meniscal tears, clinical symptoms, patient-reported outcome measures, and postoperative radiographical assessments in patients with DLM were included. Comparisons were made by age younger and older than 16 years. Study quality was assessed using the Methodological Index for Non-Randomized Studies criteria., Results: Thirteen studies comprising 1,772 adult patients (>16 years old) with DLM (n = 1,856 knees) and 8 studies conducted in 304 pediatric patients (≤16 years old, n = 353 knees) were included. The reported mean age ranged from 22.4 to 45 years (mean follow-up, 24-157.5 months) in the adult group and from 5 to 12.9 years (mean follow-up, 37-234 months) in the pediatric DLM group. Among studies that reported on tear patterns, the majority of adult (n = 553; 96.5%) and pediatric (n = 163; 71.8%) patients had tears of the DLM. Complete DLM was the predominant type of DLM in both study groups (range in adults, 49.6% to 88%; range in pediatric patients, 19%-100%) with complex (46.1%; range, 5.3%-100%) and horizontal tears (18.2%; range, 20%-37.5%) being the most frequently described tear patterns in the adult and pediatric DLM groups, respectively. Pain was the predominant reported symptom in both study groups (range in adults, 12.1%-99.3%; range in pediatric patients, 32.4%-100%). Partial meniscectomy was the most frequently reported treatment option conducted in 334 adult knees (39.5%; range, 24.2%-100%) and 66 pediatric knees (63.5%; range, 15%-100%). Overall, improved postoperative clinical outcomes were reported in both study groups; however, radiographic progression of degenerative changes after subtotal meniscectomy was noted., Conclusions: More adult patients with DLM present with tears in the literature compared with the pediatric population. Complex and horizontal tear patterns are the most frequently reported tears in adult and pediatric patients, respectively. Pain was the most relevant symptom in both study groups. There was generally significant improvement in postoperative clinical outcome scores; partial meniscectomy, however, remains the most frequently reported treatment option and is associated with fewer degenerative changes than in subtotal meniscectomy., Level of Evidence: Level IV, systematic review of Level I to IV studies., Competing Interests: Disclosures The authors report no conflicts of interest in the authorship and publication of this article. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: Anterior cruciate ligament reconstruction (ACLR) is one of the most frequently performed procedures in sports medicine, and undesirable outcomes still may range from 3-18%. One technique that has been explored to improve outcomes is preservation of the ACL remnant tibial stump, as opposed to stump debridement, at the time of reconstruction., Purpose: To review current high-level evidence and compare remnant-preserving anterior cruciate ligament reconstruction (ACLR) versus standard ACLR in terms of clinical outcomes and measures of knee stability., Hypothesis: ACLR with remnant preservation would result in improved clinical outcomes and knee stability measures., Study Design: Systematic review; Level of evidence, 2., Methods: A systematic review of randomized controlled trials (RCTs) and cohort studies comparing remnant-preserving ACLR with standard ACLR with a minimum level of evidence of 2 was performed. Extracted data were summarized as general information, surgical characteristics, postoperative clinical outcomes, knee stability, graft evaluation, tunnel assessment, and postoperative complications. When feasible, a meta-analysis was performed., Results: Seven RCTs and 5 cohort studies met the inclusion criteria. In total, 518 patients underwent remnant-preserving ACLR and 604 patients underwent standard ACLR. Ten studies performed the reconstruction with hamstring tendon (HT) autografts, 1 study with HT and bone-patellar tendon-bone autografts, and 1 study with HT and tibialis anterior allografts. On meta-analysis, remnant-preserving ACLR provided comparable outcomes with respect to International Knee Documentation Committee grades or Tegner scores. Even though there was a significant improvement in Lysholm scores (mean difference, -1.9; 95% CI, -2.89 to -0.91; P = .0002) with the remnant-preserving technique, this did not exceed previously reported minimal clinically important difference values. Remnant-preserving ACLR demonstrated superior knee stability in terms of patients achieving negative pivot shift when compared with the control group (88.89% vs 79.92%; P = .006). Although there was a significant improvement in the side-to-side difference in anterior tibial translation favoring remnant preservation ( P = .004), the mean difference was 0.51 mm., Conclusion: Remnant-preserving ACLR, primarily with HT autografts, results in comparable clinical outcome scores and significantly improved knee stability relative to standard ACLR without remnant preservation without increasing the complication rate. Further studies will help clarify if remnant-preserving ACLR also has benefits in terms of enhancing graft integration and maturation, improving proprioception, limiting tunnel enlargement, and reducing complications., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: S.A. has received support for education from Smith & Nephew. R.F.L. has received research support from Arthrex, Linvatec, Ossur, and Smith & Nephew; consulting fees from Ossur and Smith & Nephew; royalties from Arthrex, Ossur, and Smith & Nephew; and support for education from Foundation Medical. J.C. has received consulting fees from Arthrex, CONMED Linvatec, Ossur, Smith & Nephew, DePuy Synthes Products, and Vericel; support for education from Arthrex, Smith & Nephew, and Medwest Associates; and hospitality payments from Medical Device Business Services. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: The association between congenital heart disease and chronic kidney disease is well known. Various mechanisms of kidney damage associated with congenital heart disease have been established. The etiology of kidneydisease has commonly been considered to be secondary to focal segmental glomerulosclerosis (FSGS), however, this has only been demonstrated in case reports and not in observational or clinical trials., Aim: To identify baseline and clinical characteristics, as well as the findings in kidney biopsies of patients with congenital heart disease in our hospital., Methods: This is a retrospective observational study conducted at the Nephrology Department of the National Institute of Cardiology "Ignacio Chávez". All patients over 16 years old who underwent percutaneous kidney biopsy from January 2000 to January 2023 with congenital heart disease were included in the study., Results: Ten patients with congenital heart disease and kidney biopsy were found. The average age was 29.00 years ± 15.87 years with pre-biopsy proteinuria of 6193 mg/24 h ± 6165 mg/24 h. The most common congenital heart disease was Fallot's tetralogy with 2 cases (20%) and ventricular septal defect with 2 (20%) cases. Among the 10 cases, one case of IgA nephropathy and one case of membranoproliferative glomerulonephritis associated with immune complexes were found, receiving specific treatment after histopathological diagnosis, delaying the initiation of kidney replacement therapy. Among remaining 8 cases (80%), one case of FSGS with perihilar variety was found, while the other 7 cases were non-specific FSGS., Conclusion: Determining the cause of chronic kidney disease can help in delaying the need for kidney replacement therapy. In 2 out of 10 patients in our study, interventions were performed, and initiation of kidney replacement therapy was delayed. Prospective studies are needed to determine the usefulness of kidney biopsy in patients with congenital heart disease., Competing Interests: Conflict-of-interest statement: None of the authors have any conflict-of-interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

A large proportion of patients with low-renin hypertension (LRH) correspond to primary aldosteronism (PA). However, some of these subjects have low to normal aldosterone. Since low renin is driven by excessive mineralocorticoids or glucocorticoids acting on mineralocorticoid receptors (MRs), we hypothesize that a low-cortisone condition, associated classically with 11βHSD2 deficiency, is a proxy of chronic MR activation by cortisol, which can also lead to low renin, elevated blood pressure, and renal and vascular alterations., Objective: To evaluate low cortisone as a predictor of low renin activity and its association with parameters of kidney and vascular damage., Methods: A cross-sectional study was carried out in 206 adult subjects. The subjects were classified according to low plasma renin activity (<1 ng/mL × hours) and low cortisone (<25th percentile)., Results: Plasma renin activity was associated with aldosterone (r = 0.36; P < .001) and cortisone (r = 0.22; P = .001). A binary logistic regression analysis showed that serum cortisone per ug/dL increase predicted the low-renin phenotype (OR 0.4, 95% CI 0.21-0.78). The receiver operating characteristic curves for cortisone showed an area under the curve of 0.6 to discriminate subjects with low renin activity from controls. The low-cortisone subjects showed higher albuminuria and PAI-1 and lower sodium excretion. The association study also showed that urinary cortisone was correlated with blood pressure and serum potassium ( P < .05)., Conclusion: This is the first study showing that low cortisone is a predictor of a low-renin condition. Low cortisone also predicted surrogate markers of vascular and renal damage. Since the aldosterone to renin ratio is used in the screening of PA, low cortisone values should be considered additionally to avoid false positives in the aldosterone-renin ratio calculation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Appropriate management of radial meniscal tears is complex, with continued efforts focused on optimizing diagnostic methods for identification to help dictate treatment, especially as surgical indications for repair have expanded, coupled with improvements in surgical techniques and instrumentation. Currently, no standardized classification system for radial meniscal tears exists, limiting the ability to accurately characterize injury patterns and guide surgical decision-making., (© 2023 The Authors.)

Objectives: The objective of this study was to compare the diurnal variations in cortisol and cortisone concentrations in serum and saliva among extremely preterm (EPT), very preterm (VPT), and full-term (FT) children, all born appropriate for gestational age (AGA)., Methods: EPT, VPT, and FT children, all born AGA, were recruited from two healthcare centers. Cortisol and cortisone concentrations in serum and saliva were measured by liquid chromatography-mass spectrometry (LC‒MS). Statistical analysis was performed using nonparametric tests., Results: A total of 101 children (5.0-8.9 years old) were included in this study: EPT=18, VPT=43 and FT=40. All groups had similar distributions in terms of age, birth weight standard deviation score (SDS) and BMI (SDS), showing no differences in serum ACTH, cortisol, or cortisone levels. Additionally, salivary cortisol and cortisone concentrations decreased significantly throughout the day (p-values<0.0001). Salivary cortisol concentrations were below the limit of detection (0.55 nmol/L) before dinner and before bedtime in approximately one-third and two-thirds of all children, respectively. Salivary cortisone was detectable in all but one sample., Conclusions: The diurnal cortisol rhythm was preserved in all preterm children, regardless of their gestational age, and no differences in cortisol concentrations among the groups were found. This may have significant implications for the clinical management and follow-up of preterm individuals., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Patients with pathologic genu recurvatum may present with complaints regarding anterior knee pain, instability, loss of range of motion, or locking episodes of the knee. Symptomatic genu recurvatum refractory to conservative measures may require surgical treatment. In this Technical Note, the authors describe a surgical technique involving an anterior opening-wedge high tibial osteotomy for a patient with symptomatic genu recurvatum from a knee hyperextension injury resulting in posterior soft-tissue laxity. The surgical technique aims to correct the limb sagittal alignment and provide stability to the knee joint, with the ultimate goal of improving patient outcomes., (© 2023 The Authors.)

Interdisciplinary teamwork is essential for the rehabilitation of patients with cleft lip and palate, and therefore, the application of treatment techniques for velopharyngeal insufficiency, both surgical and prosthetic, depends on the experience of each rehabilitation team. For this reason, the following study consisting of the cooperation between interdisciplinary cleft lip and palate teams from Chile and Argentina, which succeeded in correcting velopharyngeal insufficiency in an adolescent, initially using a pharyngeal bulb prosthesis and speech therapy, and finally through pharyngeal flap surgery, is presented. This shows that international cooperation is a valuable tool for training, implementation, and follow-up of different treatment techniques for teams in formation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Interdisciplinary evaluation is essential to diagnose and define clinical conduct for children and adults presenting with an altered lingual frenulum; however, there are few reports on the subject in the literature. In this context, the following study exemplifies a proposed protocol for the surgical and SLT treatment of a lingual frenulum based on a review of the literature and the experience of speech and language therapists and maxillofacial surgeons from hospitals in Santiago de Chile. After its application, a history of breastfeeding with difficulties and a maintained preference for soft foods was reported. Upon anatomic examination, the lingual apex was heart-shaped, and the lingual frenulum was fixed in the upper third of the ventral side of the tongue, with a pointed shape, submerged up to the apex, and of adequate thickness. Meanwhile, upon functional examination, the tongue was descended at rest, performed tongue protrusion with restrictions (raising and clicking), did not achieve attachment or vibration, and presented distortion of the sounds / r/ and /rr/. With this information, an altered lingual frenulum was diagnosed, with the indication for surgery and postoperative speech and language therapy. The constructed instrument allowed for the standardization of the evaluation in different teams but should be validated in future research., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Objective: Describe and compare the results of speech and velopharyngeal function in children with classic and occult submucous cleft palate undergoing interdisciplinary treatment at the Gantz Foundation., Methods: The clinical history of all patients born between 2012 and 2017 with a diagnosis of classic or occult submucous cleft palate was retrospectively reviewed. Preoperative and postoperative medical, surgical, and speech and language history were collected., Results: Twenty-eight cases diagnosed at the age of 44.8±23.9 months were included. Of these, 71.4% presented classic submucous cleft, and 28.6% occult. Before primary surgery, 7.1% had a diagnosis of the syndrome, and 21.4% were under study. A total of 39.3% had hearing difficulties and 21.4% used tympanic ventilation tubes. A total of 60.7% had language problems, 39.3% had compensatory articulation, 17.9% had absent hypernasality, and 21.4% had absent nasal emission. The team indicated primary palate surgery in 71.4%, of which 85% performed the surgery at the mean age of 61.7±24.7 months. The surgical technique was Furlow in 88.2% of the cases and intravelar veloplasty in the remaining 11.8%. Then, 3 cases underwent velopharyngeal insufficiency surgery; 2 of them eliminated hypernasality and reduced nasal emission. The age of diagnosis ( P =0.021) and the performance of velopharyngeal insufficiency surgery ( P =0029) of the occult submucous cleft palate group was significatively later than the classic cleft palate group., Conclusions: Language, hearing, compensatory articulation, hypernasality, and nasal emission problems were recorded. A high percentage required primary surgery. Of these, a low proportion also required a velopharyngeal insufficiency surgery, which improved the velopharyngeal function of the children but did not completely adapt it. In this regard, early diagnosis is essential, as well as an analysis of each center primary closure protocol., (Copyright © 2023 by Mutaz B. Habal, MD.)

The common peroneal nerve (CPN) runs laterally around the fibular neck and enters the peroneal tunnel, where it divides into the deep, superficial, and recurrent peroneal nerves. CPN entrapment is the most common neuropathy of the lower extremity and is vulnerable at the fibular neck because of its superficial location. Schwannomas are benign, encapsulated tumors of the nerve sheath that can occur sporadically or in cases of neurocutaneous conditions, such neurofibromatosis type 2. In cases with compressive neuropathy resulting in significant or progressive motor loss, decompression and neurolysis should be attempted. We present a technical note for the treatment of CPN compressive neuropathy in the setting of a previous ipsilateral schwannoma removal with a minimally invasive surgical approach and neurolysis of the CPN at the fibular neck., (© 2022 The Authors.)

Purpose: The present study is aimed towards determining and comparing normative nasalance scores in Chilean Spanish-speaking adult men and women., Methods: 40 women (age range 18 to 35, X = 25.79, SD = 5.83) and 36 men (age range 18 to 35, X = 26.45, SD = 4.08) were invited to participate, all of them without any previous speech therapy, neurological pathologies, intellectual deficits, hearing loss, syndromes, or other diagnosed pathologies that could impact speech production.A study of proper velopharyngeal function was performed, using a perceptual resonance evaluation. Nasalance was determined using a model 6450 Nasometer, during the reading of three standardized speech samples in Spanish: a nasal passage (NP), an oronasal passage (ONP), and an oral passage (OP). Also, the nasalance distance was calculated. Genders were compared using Wilcoxon tests for independent samples., Results: The NP presented the highest percentage of nasalance, with 52.13% (± 4.73), followed by the ONP with 25.38% (± 3.7), and finally the OP, which presented the lowest value of 14.15% (± 5.03). Meanwhile, nasalance distance was 37.98% (± 5.32). Finally, no significant differences were observed when comparing the nasalance between genders (p >0.05)., Conclusion: The nasalance values obtained were similar to those observed for other Spanish speakers. Also, male and women showed similar scores. The results of this study are a contribution to the indirect assessment of velopharyngeal function in Chilean adults.

Background: Familial hyperaldosteronism type I is caused by the generation of a chimeric aldosterone synthase enzyme (ASCE) which is regulated by ACTH instead of angiotensin II. We have reported that in vitro, the wild-type (ASWT) and chimeric aldosterone synthase (ASCE) enzymes are inhibited by progesterone and estradiol does not affect their activity., Aim: To explore the direct action of testosterone on ASWT and ASCE enzymes., Material and Methods: HEK-293 cells were transiently transfected with vectors containing the full ASWT or ASCE cDNAs. The effect of testosterone on AS enzyme activities was evaluated incubating HEK-cells transfected with enzyme vectors and adding deoxycorticosterone (DOC) alone or DOC plus increasing doses of testosterone. Aldosterone production was measured by HPLC-MS/MS. Docking of testosterone within the active sites of both enzymes was performed by modelling in silico., Results: In this system, testosterone inhibited ASWT (90% inhibition at five pM, 50% inhibitory concentration (IC50) =1.690 pM) with higher efficacy andpotency than ASCE (80% inhibition at five pM, IC50=3.176 pM). Molecular modelling studies showed different orientation of testosterone in ASWT and ASCE crystal structures., Conclusions: The inhibitory effect of testosterone on ASWT or ASCE enzymes is a novel non-genomic testosterone action, suggesting that further clinical studies are needed to assess the role of testosterone in the screening and diagnosis of primary aldosteronism.

Objective: To assess pulmonary embolism incidence, its relationship with D-dimer levels and other possible associated factors in addition to anticoagulation and contrast medium adverse effects., Methods: A retrospective observational cohort study at a Chilean public hospital was performed. Intensive care unit mechanically ventilated COVID-19 patients older than 18 years old between March and June 2020 were included. All patients received heparin thromboprophylaxis, which was increased to the anticoagulation dose with D-dimer greater than 3µg/mL., Results: A total of 127 patients were followed up, of whom 73 underwent pulmonary computed tomography angiography (mean age, 54 ± 12 years; 49 men). Sixty-two of the 73 patients (84.9%) received full anticoagulation before computed tomography angiography. In addition, 18 of the 73 patients had pulmonary embolism (24.7%). When comparing patients with and without pulmonary embolism, no significant differences were observed in age, sex, obesity, smoking, Wells and revised Geneva scores, D-dimer or mortality. Anticoagulant use was similar in both groups. Days from the start of anticoagulation until computed tomography angiography were significantly lower in the pulmonary embolism group (p = 0.002). Three patients presented post contrast-acute kidney injury (4.1%), and one patient had major bleeding., Conclusion: Despite anticoagulation, one in four COVID-19 patients connected to mechanical ventilation and evaluated with pulmonary computed tomography angiography had pulmonary embolism. With a longer the delay in performing computed tomography angiography once empirical anticoagulation was started, significantly less pulmonary embolism was identified.

Background: Due to the lockdown and quarantines caused by the COVID-19 pandemic, the need to study and use telepractice for providing speech pathology interventions for children with cleft palate has arisen., Objective: To carry out a systematic review of the use of telepractice during the COVID-19 pandemic for providing speech pathology interventions for Spanish-speaking children with cleft palate., Methods: In July and August 2020, the authors searched the electronic databases Medline, LILACS, SciELO, and the Cochrane Library using the following keywords in English (MeSH): Cleft palate combined with Early intervention, Speech therapy, Rehabilitation of speech and language disorders, Speech production measurement, Speech articulation tests and Telemedicine. Original articles were selected and analyzed, complemented by an analysis of flowcharts and recommendations by the GES Clinical Guide of Cleft Lip and Palate of Chile's Government and the authors' expert opinions., Results: A total of 2680 articles were retrieved, of which 23 were critically analyzed and used to adapt the early stimulation, evaluation, and treatment of children with CP to speech therapy telepractice at the Gantz Foundation, a Hospital in Santiago de Chile., Limitations: Only three researchers carried out a quick review, which limited the depth of individual analysis of the studies included. Also, the suggestions and material presented should be evaluated in future investigations., Conclusion: This systematic review provides useful guidelines for providing speech pathology interventions through telepractice for children with cleft palate. Audiovisual materials seem to be extremely useful for families receiving the interventions. The use of interactive videos for Spanish-speaking children and educational videos for parents is manifest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Factors that contribute to the development of juvenile osteochondritis dissecans (JOCD) of the talus are poorly understood. Some authors suggest that a higher loading of the affected zone may be a cofactor in osteochondral lesions. Therefore, the purpose of the study is to evaluate any association between ankle morphology and talus JOCD using morphologic parameters from magnetic resonance images. Our hypothesis is that ankles with JOCD lesions would have differences in the anatomy compared with age and sex-matched unaffected ankles., Methods: We evaluated a total of 75 extremities. There were 22 patients (25 ankles) with talus JOCD lesions, and 50 patients (50 ankles) sex and age-matched individuals with healthy ankles served as controls. Two examiners conducted independent measurements of 8 magnetic resonance images parameters: tibial anterior surface angle, tibial shaft both malleoli angle (TBM), tibial axis-medial malleolus angle, anterior opening angle of the talus, malleolar width, tibial lateral surface angle, Maximal tibial thickness, length of trochlea tali arc, and height of trochlea tali arc. Measurement reliability was assessed using intraclass correlation coefficients. Differences in parameters between JOCD patients and controls were evaluated using independent t test. The level of significance was taken to be P<0.05., Results: Intraclass correlation coefficients demonstrated good to excellent consistency for all measurements. Sagittal parameters demonstrated a significant length of trochlea tali arc increase in ankles with JOCD lesions compared with normal ankles (P=0.015). There was no statistical difference in any of the axial or coronal parameters., Conclusions: Ankle morphology may have a relationship with JOCD lesions. Future larger studies will be useful for further clarifying our findings, and detecting other potential predisposing factors with clinical relevance and how they can be modified., Study Design: Cross-sectional study (Level of evidence III)., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The main role of Vitamin D is to regulate calcium metabolism, whose main source is vitamin D3 ob tained mostly from the action of ultraviolet (UV) light on the skin., Objective: To evaluate the seaso nal differences in the concentrations of 25-hydroxy-vitamin D3 (25OHVitD3), parathyroid hormone (PTH), alkaline phosphatase (ALP), and calcium in school-age children., Subjects and Method: The concentrations of 25OHVitD3, PTH, ALP, and calcium were measured in children from Santiago, Chile (latitude -33.4372), aged 5 to 8 years, without Vitamin D supplementation, in different seasons of the year. VitD status was defined as sufficient with concentrations of 25OHVitD3 >20 ng/mL (50 nmol/L), insufficient 12-20 ng/mL (30-50 nmol/L) and deficient <12 ng/mL (30 nmol/L) based on the recommendations of the expert group of the "Global Consensus for the Prevention and Mana gement of Nutritional Rickets"., Results: 133 children participated (89 preterms under or equal to 32 weeks), 41 during summer, 28 in fall, 35 in winter, and 29 in spring. The difference of means between summer and winter was 9.6 ng/mL for 25OHVitD3 (p <0.0001), -11.1 pg/mL for PTH (p <0.0001), and -47.5 IU/mL for ALP (p= 0.01). There were no differences in calcium concentrations. In sum mer, 97.6% of the subjects were classified with sufficiency status (> 20 ng/mL), which decreased significantly in winter to 54.3% (p <0.0001)., Conclusions: In winter, 25OHVitD3 concentrations decreased in approximately half of the children, which was associated with an increase in PTH and ALP, and normal calcium concentrations. According to our results, children may need VitD supple mentation during fall and winter.

Objectives: To identify associations among the plasma renin concentration (PRC), plasma aldosterone and urinary sodium (Na)/potassium (K) ratio, and to integrate these variables into a nomogram with the aim of estimating the expected versus observed aldosterone concentration., Methods: We studied 40 healthy normotensive children (5-8 years old, 57.5% girls) who were born at term and were adequate for their gestational age. Following overnight fasting, the PRC and plasma aldosterone in blood samples were measured, and the Na/K ratio was calculated from a simultaneously obtained urinary spot sample. A mathematical function was defined with these three variables, and a nomogram was built that would return the expected aldosterone concentration from the obtained plasma renin and urinary Na/K ratio values., Results: The PRC (B =  5.9, P < 0.001) and urinary Na/K ratio (B = -98.1, P = 0.003) were significant independent predictors of plasma aldosterone. The correlation between the observed plasma aldosterone and the expected plasma aldosterone, as obtained from the nomogram, was r = 0.88, P < 0.001. The average difference between the observed and expected plasma aldosterone was -0.89, with a standard deviation of ±30%., Conclusion: The strong correlation between the urinary Na/K ratio, from urine samples taken at the same as the blood samples, and plasma renin and aldosterone concentrations allowed us to build a nomogram to predict aldosterone levels. This approach may be useful for evaluating the renin-angiotensin-aldosterone system (RAAS) in pediatric patients with hypertension and RAAS dysfunction.

Background: The "nonclassic" apparent mineralocorticoid excess (NC-AME) has been identified in approximately 7% of general population. This phenotype is characterized by low plasma renin activity (PRA), high serum cortisol (F) to cortisone (E) ratio, low cortisone, high Fractional Excretion of potassium (FEK) and normal-elevated systolic blood pressure (SBP). An early detection and/or identification of novel biomarkers of this phenotype could avoid the progression or future complications leading to arterial hypertension. Isolation of extracellular vesicles, such as exosomes, in specific biofluids support the identification of tissue-specific RNA and miRNA, which may be useful as novel biomarkers. Our aim was to identify miRNAs within urinary exosomes associated to the NC-AME phenotype., Methods: We perform a cross-sectional study in a primary care cohort of 127 Chilean subjects. We measured BP, serum cortisol, cortisone, aldosterone, PRA. According to the previous reported, a subgroup of subjects was classified as NC-AME (n = 10). Urinary exosomes were isolated and miRNA cargo was sequenced by Illumina-NextSeq-500., Results: We found that NC-AME subjects had lower cortisone (p < 0.0001), higher F/E ratio (p < 0.0001), lower serum potassium (p = 0.009) and higher FEK 24 h (p = 0.03) than controls. We found miR-204-5p (fold-change = 0.115; p 0.001) and miR-192-5p (fold-change = 0.246; p 0.03) are both significantly downregulated in NC-AME. miR-192-5p expression was correlated with PRA (r = 0.45; p 0.028) and miR-204-5p expression with SBP (r = - 0.48, p 0.027) and F/E ratio (r = - 0.48; p 0.026)., Conclusions: These findings could support a potential role of these miRNAs as regulators and novel biomarkers of the NC-AME phenotype.

Background: Aldosterone has been linked with obesity, metabolic syndrome (MetS), pro-inflammatory, and prothrombotic states; however, most studies relate these indicators with primary aldosteronism (PA), excluding non-PA patients., Objective: To determine whether aldosterone, renin, or the plasma aldosterone/renin ratio (ARR) are associated with metabolic disorders and inflammatory/vascular biomarkers in a non-PA population., Methods: We studied 275 patients including adolescents and adults of both genders and measured plasma and urinary aldosterone and determined the plasma renin activity. In all subjects, the presence of MetS was determined according to Adult Treatment Panel III. Renal, vascular, inflammatory, and mineralocorticoid activity biomarkers were evaluated., Results: The ARR correlated with the number of variables of MetS (r = 0.191, P = 0.002), body mass index (BMI; r = 0.136, P = 0.026), systolic blood pressure (r = 0.183, P = 0.002), diastolic blood pressure (r = 0.1917, P = 0.0014), potassium excreted fraction (r = 0.174, P = 0.004), low-density lipoprotein (r = 0.156, P = 0.01), plasminogen activator inhibitor type 1 (r = 0.158, P = 0.009), microalbuminuria (r = 0.136, P = 0.029), and leptin (r = 0.142, P = 0.019). In a linear regression model adjusted by age, BMI, and gender, only the ARR was still significant (r = 0.108, P = 0.05). In a logistic regression analysis, the ARR predicted MetS index (odds ratio (OR) = 1.07 [95% confidence interval (CI) = 1.011-1.131], P= 0.02) even after adjusting for age, BMI, and gender. On the other hand, aldosterone showed no association with MetS or inflammatory markers., Conclusion: These results suggest a continuum of cardiometabolic risk beyond the classic PA threshold screening. The ARR could be a more sensitive marker of obesity, MetS, and endothelial damage in non-PA patients than aldosterone or renin alone. Prospective studies are needed to develop future screening cutoff values., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Context: Classical apparent mineralocorticoid excess (AME) is a rare recessive disorder, caused by severe 11β-hydroxysteroid dehydrogenase type 2 enzyme (11β-HSD2) deficiency. AME manifests as low-renin pediatric hypertension, hypokalemia and high cortisol/cortisone (F/E) ratio., Objective: To evaluate nonclassic AME (NC-AME) due to partial 11β-HSD2 insufficiency and its association with hypertension, mineralocorticoid receptor (MR) activation, and inflammatory parameters., Design: Cross-sectional study., Setting: Primary care cohort., Participants: We recruited 127 adolescents and adults. Subjects with secondary hypertension were excluded. We measured clinical, biochemical, renal, vascular, and inflammatory variables. Sequencing of HSD11B2 gene was performed in all subjects., Main Outcome Measure: NC-AME., Results: Serum F/E ratio was positively associated with systolic blood pressure (BP), microalbuminuria, and high-sensitivity C-reactive protein (hs-CRP). Serum cortisone correlated with MR activation parameters even when adjusted for age, body mass index, and sex: lower cortisone with higher potassium excretion (partial r = -0.29, P = 0.002) and with lower plasma renin activity (PRA) (partial r = 0.29, P = 0.001). Consistently, we identified 9 in 127 subjects (7.1%) with high F/E ratios (first quartile) and low cortisone (last quartile), suggestive of NC-AME. These subjects had higher systolic BP, 141.4 ± 25.7 mm Hg vs 127.3 ± 18.1 mm Hg, P = 0.03; lower PRA, 0.36 ± 0.19 ng/L*s vs 0.64 ± 0.47 ng/L*s, P < 0.0001; and greater potassium excretion, microalbuminuria, hs-CRP, and plasminogen activator inhibitor. We only found in 2 out of 9 subjects with NC-AME heterozygous mutations in the HSD11B2 gene., Conclusions: These findings suggest a spectrum of partial 11β-HSD2 insufficiency in a primary care cohort without the classic phenotype and genotype of AME. NC-AME may represent a phenotype of MR activation and cardiovascular risk, suggesting that these subjects could be treated with MR antagonists.

Background: Cortisol dysregulation has a potential role in depression., Aim and Methods: We evaluated depressive symptoms using the Hamilton Rating Scale for Depression in 48 primary care subjects without history of previous or current depression and its association with cortisol dysregulation (morning plasma cortisol, 24-hour urinary free cortisol and cortisol metabolites). Presence of metabolic syndrome and inflammatory parameters were also assessed., Results: Hamilton Rating Scale for Depression correlated significantly with morning cortisol, but not with urinary free cortisol or metabolites. A significant increase in morning cortisol by Hamilton groups (asymptomatic ≤8; mild to moderate: 9-18; moderate to severe: ≥19) was observed even when adjusted by age/gender. We observed no association of depressive symptoms with metabolic or inflammatory parameters., Conclusion: Depressive symptoms in primary care subjects not consulting for their mood are associated with higher morning plasma cortisol, but not urinary cortisol or its metabolites. These observations suggest that systemic hypercortisolism and related metabolic disorders are not observed in mild/initial states of depressive disorders.

Background: Mounting evidence has associated high sodium (HS) intake with hypertension, cardiovascular disease, and stroke. We investigated whether HS intake modulates the parameters of endothelial damage, inflammation, and oxidative stress., Methods: We used a cross-sectional study design including 223 Chilean subjects (6.9-65.0 years old). We measured aldosterone, renin activity, cortisol, cortisone, adiponectin, leptin, hsCRP, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor type 1 (PAI-1), metalloproteinase (MMP)-9 and MMP-2 activity, and malondialdehyde. Sodium and creatinine were measured in 24-hour urine samples. The subjects were divided by sodium intake, high sodium (HS): ≥150 mEq/day, n = 118, and adequate sodium (AS): <150 mEq/day, n = 105., Results: We observed a positive correlation between urinary sodium excretion and blood pressure (r = 0.1669, P = 0.0124 for systolic and r = 0.2416, P = 0.0003 for diastolic), glycemia (r = 0.2660, P < 0.0001), and triglycerides (r = 0.1604, P = 0.0175) and a highly significant correlation between sodium excretion and PAI-1 (r = 0.2701, P < 0.0001). An inverse correlation was observed between urinary sodium and HDL-cholesterol (r = -0.2093, P = 0.0018) and adiponectin (r = -0.2679, P < 0.0001). In a linear regression model, urinary sodium excretion remained significantly associated with PAI-1 values even after adjusting for age, gender, and BMI. The HS group had higher blood pressure, glycemia, HOMA-IR, atherogenic index of plasma, and PAI-1 values than the group with AS intake., Conclusions: HS intake is associated with endothelial damage (high PAI-1) and metabolic dysregulation. On the other hand, inflammation and oxidative stress parameters are not modified by sodium intake.

Background: Pathogenic variations in HSD11B2 gene triggers the apparent mineralocorticoid excess syndrome (AME). There is scarce information regarding the phenotypes of subjects carrying heterozygous pathogenic variants in HSD11B2 gene. We investigated if serum cortisol/cortisone (F/E) ratio and cortisone are useful for identifying partial 11βHSD2 deficiency in those heterozygous subjects., Methods: We studied two patients diagnosed with AME and their families carrying either D223N or R213C mutation. We also evaluated 32 healthy control subjects (13 children and 19 adults) to obtain normal references ranges for all measured variables. Case 1: A boy carrying D223N mutation in HSD11B2 gene and Case 2: A girl carrying R213C mutation. We assessed serum F/E ratio and cortisone by HPLC-MS/MS, aldosterone, plasma-renin-activity(PRA), electrolytes, and HSD11B2 genetic analyses., Results: The normal values (median [interquartile range]) in children for serum F/E and cortisone (µg/dl) were 2.56 [2.21-3.69] and 2.54 [2.35-2.88], and in adults were 4.42 [3.70-4.90] and 2.23 [1.92-2.57], respectively. Case 1 showed a very high serum F/E 28.8 and low cortisone 0.46 µg/dl. His mother and sister were normotensives and heterozygous for D223N mutation with high F/E (13.2 and 6.0, respectively) and low cortisone (2.0 and 2.2, respectively). Case 2 showed a very high serum F/E 175 and suppressed cortisone 0.11 µg/dl. Her parents and sister were heterozygous for the R213C mutation with normal phenotype, but high F/E and low cortisone. Heterozygous subjects showed normal aldosterone, PRA, but lower fractional excretion of sodium and urinary Na/K ratio than controls., Conclusion: Serum F/E ratio and cortisone allow to identify partial 11βHSD2 deficiencies, as occurs in heterozygous subjects, who would be susceptible to develop arterial hypertension.

Objective: To identify novel biomarkers associated with pediatric primary hypertension., Methods: We recruited 350 participants (4-16 years). Anthropometric parameters and aldosterone, plasma renin activity, cortisol, cortisone, Homeostasis Model Assessment Insulin Resistance (HOMA-IR), high-sensitivity C-reactive protein, adiponectin, IL-6, plasminogen activator inhibitor type 1 levels and matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9 and MMP-2) activities were measured. Genomic DNA was isolated. Patients with altered glucose metabolism, severe obesity [BMI-SD score (BMI-SDS) > 2.5], renovascular disease, primary aldosteronism and apparent mineralocorticoid excess syndrome were excluded., Results: In selected participants (n = 320), SBP was positively correlated with BMI-SDS (r = 0.382, P < 0.001), HOMA-IR (r = 0.211, P < 0.001), MMP-9 activity (r = 0.215, P < 0.001) and the cortisol/cortisone ratio (r = 0.231, P < 0.001). DBP showed similar correlations with these variables. No correlation was observed with aldosterone or plasma renin activity. Participants were categorized as hypertensive (n = 59) or nonhypertensive (n = 261). In the univariate analysis, hypertensive patients had higher BMI-SDS (P < 0.001), HOMA-IR (P < 0.001), high-sensitivity C-reactive protein (P < 0.001), MMP-9 activity (P < 0.001), plasminogen activator inhibitor type 1 (P < 0.001) and cortisol/cortisone ratio (P < 0.001) than nonhypertensive patients. Multiple regression analysis showed that the variables that remained associated with hypertension were higher BMI-SDS [odds ratio (OR) = 3.74; 95% confidence interval (CI) = 1.84-7.58], a higher cortisol/cortisone ratio (OR = 3.92; 95% CI = 1.98-7.71) and increased MMP-9 activity (OR = 4.23; 95% CI = 2.15-8.32)., Conclusion: We report that MMP-9 activity and the cortisol/cortisone ratio were higher in pediatric primary hypertensive patients, and these associations were independent of the effect of obesity. The potential role of these novel biomarkers in predicting hypertension risk and blood pressure regulation warrants further investigation.

Background: Bariatric surgery is the most effective treatment alternative in morbid obesity. The mechanisms contributing to these benefits remain poorly understood. Bile acids (BAs) are mediators of different regulatory functions in glucose and cholesterol homeostasis and energy expenditure. Recent evidence suggests that BAs are critically important for the beneficial effects of sleeve gastrectomy (SG)., Objectives: The aim of this study was to evaluate the effect of SG on BA synthesis., Setting: University Hospital. Santiago, Chile., Methods: Obese patients were evaluated before and after SG (1, 3, 6, and 12 months). BA synthesis was evaluated through the serum marker, 7 α-hydroxy-4-cholesten-3-one (C4). Primary and secondary BA and C4 were determined by high performance liquid chromatography coupled with tandem mass spectrometry detection (HPLC-MS/MS)., Results: From June 2013 to January 2014, 19 patients (age 37.6±7.8 years; BMI 35.8±3.5 kg/m(2); 79% female) were included in this study. Mean weight loss at 1, 3, 6, and 12 months was 11.3, 17.5, 23.6, and 25.4 kg, respectively, equivalent to 11.8, 18.6, 24.8, and 26.9 of total body water percentage (%TBW) (P<.0001), respectively and 43.2, 68.2, 91, and 98.8 of percentage of excess weight loss (%EWL), respectively (P<.001). Serum C4 levels at baseline, 1, 3, 6, and 12 months were 23.4±21.1, 4.9±8.2, 8.7±12.1, 13.8±12.9, and 18.8±16.8 ng/mL (P<.0001), respectively. Fibroblast growth factor 19 (FGF19) levels at baseline, 1, 3, 6, and 12 months were 71±33.3, 130.5±66.2, 117.8±57.2, 134.6±91.7, and 124.3±85.9 pg/mL (P = .019), respectively., Conclusion: Serum levels of C4 decrease after SG, indicating a reduction in the synthesis of BA. FGF19 may play a role in decreasing BA synthesis. Further studies are necessary to characterize the effect of bariatric surgery on BA homeostasis., (Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)